Method of treating disorders caused by reduced neurotransmission of serotonin, norephnephrine or dopamine

Abstract

A heterocyclic compound represented by the general formula (1) or a salt thereof: ##STR00001## wherein m, l, and n respectively represent an integer of 1 or 2; X represents O or CH.sub.2; R.sup.1 represents hydrogen, a lower alkyl group, a hydroxy-lower alkyl group, a protecting group, or a tri-lower alkylsilyloxy-lower alkyl group; R.sup.2 and R.sup.3, which are the same or different, each independently represent hydrogen or a lower alkyl group; or R.sub.2 and R.sub.3 are bonded to form a cyclo-C3-C8 alkyl group; and R.sup.4 represents an aromatic group or a heterocyclic group, wherein the aromatic or heterocyclic group may have one or more arbitrary substituent(s).

Claims

1. A method for treating Tourette's Disorder, attention deficit hyperactivity disorder (ADHD), autism, Asperger syndrome and/or impulse control disorder, comprising administering to a subject in need a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof: ##STR01584## wherein m=2, l=1 and n=1; X represents CH.sub.2; R.sup.1 represents hydrogen, a C1-C6 alkyl group, a hydroxy C1-C6 alkyl group, a protecting group selected from unsubstituted C1-C6 alkanoyl, phthaloyl, C1-C6 alkoxycarbonyl, unsubstituted aralkyloxycarbonyl, 9-fluorenylmethoxycarbonyl, nitrophenylsulfenyl, aralkyl and C1-C6 alkylsilyl groups, or a tri C1-C6 alkylsilyloxy C1-C6 alkyl group; R.sup.2 and R.sup.3, which are the same or different, each independently represent hydrogen or a C1-C6 alkyl group; or R.sub.2 and R.sub.3 are bonded to form a cyclo-C3-C8 alkyl group; and R.sup.4 represents any of (1) a phenyl group, (2) an indolyl group, (3) a benzothienyl group, (4) a naphthyl group, (5) a benzofuryl group, (6) a quinolyl group, (7) an isoquinolyl group, (8) a pyridyl group, (9) a thienyl group, (10) a dihydrobenzoxazinyl group, (11) a dihydrobenzodioxinyl group, (12) a dihydroquinolyl group, (13) a chromanyl group, (14) a quinoxalinyl group, (15) a dihydroindenyl group, (16) a dihydrobenzofuryl group, (17) a benzodioxolyl group, (18) an indazolyl group, (19) a benzothiazolyl group, (20) an indolinyl group, (21) a thienopyridyl group, (22) a tetrahydrobenzazepinyl group, (23) a tetrahydrobenzodiazepinyl group, (24) a dihydrobenzodioxepinyl group, (25) a fluorenyl group, (26) a pyridazinyl group, (27) a tetrahydroquinolyl group, (28) a carbazolyl group, (29) a phenanthryl group, (30) a dihydroacenaphthylenyl group, (31) a pyrrolopyridyl group, (32) an anthryl group, (33) a benzodioxinyl group, (34) a pyrrolidinyl group, (35) a pyrazolyl group, (36) an oxadiazolyl group, (37) a pyrimidinyl group, (38) a tetrahydronaphthyl group, (39) a dihydroquinazolinyl group, (40) a benzoxazolyl group, (41) a thiazolyl group, (42) a quinazolinyl group, (43) a phthalazinyl group, (44) a pyrazinyl group, and (45) a chromenyl group, wherein these aromatic or heterocyclic groups may have one or more substituent(s) selected from (1-1) a halogen atom, (1-2) a C1-C6 alkyl group, (1-3) a C1-C6 alkanoyl group, (1-4) a halogen-substituted C1-C6 alkyl group, (1-5) a halogen-substituted C1-C6 alkoxy group, (1-6) a cyano group, (1-7) a C1-C6 alkoxy group, (1-8) a C1-C6 alkylthio group, (1-9) an imidazolyl group, (1-10) a tri C1-C6 alkylsilyl group, (1-11) an oxadiazolyl group which may have one or more C1-C6 alkyl group(s), (1-12) a pyrrolidinyl group which may have one or more oxo group(s), (1-13) a phenyl group which may have one or more C1-C6 alkoxy group(s), (1-14) a C1-C6 alkylamino C1-C6 alkyl group, (1-15) an oxo group, (1-16) a pyrazolyl group which may have one or more C1-C6 alkyl group(s), (1-17) a thienyl group, (1-18) a furyl group, (1-19) a thiazolyl group which may have one or more C1-C6 alkyl group(s), (1-20) a C1-C6 alkylamino group, (1-21) a pyrimidyl group which may have one or more C1-C6 alkyl group(s), (1-22) a phenyl C2-C6 alkenyl group, (1-23) a phenoxy group which may have one or more halogen atom(s), (1-24) a phenoxy C1-C6 alkyl group, (1-25) a pyrrolidinyl C1-C6 alkoxy group, (1-26) a C1-C6 alkylsulfamoyl group, (1-27) a pyridazinyloxy group which may have one or more C1-C6 alkyl group(s), (1-28) a phenyl C1-C6 alkyl group, (1-29) a C1-C6 alkylamino C1-C6 alkoxy group, (1-30) an imidazolyl C1-C6 alkyl group, (1-31) a phenyl C1-C6 alkoxy group, (1-32) a hydroxy group, (1-33) a C1-C6 alkoxycarbonyl group, (1-34) a hydroxyl C1-C6 alkyl group, (1-35) an oxazolyl group, (1-36) a piperidyl group, (1-37) a pyrrolyl group, (1-38) a morpholinyl C1-C6 alkyl group, (1-39) a piperazinyl C1-C6 alkyl group which may have one or more C1-C6 alkyl group(s), (1-40) a piperidyl C1-C6 alkyl group, (1-41) a pyrrolidinyl C1-C6 alkyl group, (1-42) a morpholinyl group, and (1-43) a piperazinyl group which may have one or more C1-C6 alkyl group(s).

2. The method according to claim 1, wherein in the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof R.sup.4 represents any of (1) a phenyl group, (2) an indolyl group, (3) a benzothienyl group, (4) a naphthyl group, (5) a benzofuryl group, (6) a quinolyl group, (7) an isoquinolyl group, (8) a pyridyl group, (9) a thienyl group, (10) a dihydrobenzoxazinyl group, (11) a dihydrobenzodioxinyl group, (12) a dihydroquinolyl group, (13) a chromanyl group, (14) a quinoxalinyl group, (15) a dihydroindenyl group, (16) a dihydrobenzofuryl group, (17) a benzodioxolyl group, (18) an indazolyl group, (19) a benzothiazolyl group, (20) an indolinyl group, (21) a thienopyridyl group, (22) a tetrahydrobenzazepinyl group, (23) a tetrahydrobenzodiazepinyl group, (24) a dihydrobenzodioxepinyl group, (25) a fluorenyl group, (26) a pyridazinyl group, (27) a tetrahydroquinolyl group, (28) a carbazolyl group, (29) a phenanthryl group, (30) a dihydroacenaphthylenyl group, (31) a pyrrolopyridyl group, (32) an anthryl group, (33) a benzodioxinyl group, (34) a pyrrolidinyl group, (35) a pyrazolyl group, (36) an oxadiazolyl group, (37) a pyrimidinyl group, (38) a tetrahydronaphthyl group, (39) a dihydroquinazolinyl group, (40) a benzoxazolyl group, (41) a thiazolyl group, (42) a quinazolinyl group, (43) a phthalazinyl group, (44) a pyrazinyl group, and (45) a chromenyl group, wherein these aromatic or heterocyclic groups may have 1 to 4 substituent(s) selected from (1-1) a halogen atom, (1-2) a C1-C6 alkyl group, (1-3) a C1-C6 alkanoyl group, (1-4) a halogen-substituted C1-C6 alkyl group, (1-5) a halogen-substituted C1-C6 alkoxy group, (1-6) a cyano group, (1-7) a C1-C6 alkoxy group, (1-8) a C1-C6 alkylthio group, (1-9) an imidazolyl group, (1-10) a tri C1-C6 alkylsilyl group, (1-11) an oxadiazolyl group which may have 1 C1-C6 alkyl group, (1-12) a pyrrolidinyl group which may have 1 oxo group, (1-13) a phenyl group which may have 1 C1-C6 alkoxy group, (1-14) a C1-C6 alkylamino C1-C6 alkyl group, (1-15) an oxo group, (1-16) a pyrazolyl group which may have 1 C1-C6 alkyl group, (1-17) a thienyl group, (1-18) a fury) group, (1-19) a thiazolyl group which may have 1 C1-C6 alkyl group, (1-20) a C1-C6 alkylamino group, (1-21) a pyrimidyl group which may have 1 C1-C6 alkyl group, (1-22) a phenyl C2-C6 alkenyl group, (1-23) a phenoxy group which may have 1 halogen atom, (1-24) a phenoxy C1-C6 alkyl group, (1-25) a pyrrolidinyl C1-C6 alkoxy group, (1-26) a C1-C6 alkylsulfamoyl group, (1-27) a pyridazinyloxy group which may have 1 C1-C6 alkyl group, (1-28) a phenyl C1-C6 alkyl group, (1-29) a C1-C6 alkylamino C1-C6 alkoxy group, (1-30) an imidazolyl C1-C6 alkyl group, (1-31) a phenyl C1-C6 alkoxy group, (1-32) a hydroxy group, (1-33) a C1-C6 alkoxycarbonyl group, (1-34) a hydroxy C1-C6 alkyl group, (1-35) an oxazolyl group, (1-36) a piperidyl group, (1-37) a pyrrolyl group, (1-38) a morpholinyl C1-C6 alkyl group, (1-39) a piperazinyl C1-C6 alkyl group which may have 1 C1-C6 alkyl group, (1-40) a piperidyl C1-C6 alkyl group, (1-41) a pyrrolidinyl C1-C6 alkyl group, (1-42) a morpholinyl group, and (1-43) a piperazinyl group which may have 1 C1-C6 alkyl group.

3. The method according to claim 1, wherein in the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof m represents 2; l and n respectively represent 1; X represents CH.sub.2; R.sup.1 represents hydrogen, a C1-C6 alkyl group, a hydroxy C1-C6 alkyl group, a benzyl group, or a tri C1-C6 alkylsilyloxy C1-C6 alkyl group; and R.sup.4 represents any of (1) a phenyl group, (2) an indolyl group, (4) a naphthyl group, (5) a benzofuryl group, and (31) a pyrrolopyridyl group, wherein these aromatic or heterocyclic groups may have 1 to 4 substituent(s) selected from (1-1) a halogen atom, (1-2) a C1-C6 alkyl group, (1-3) a C1-C6 alkanoyl group, (1-4) a halogen-substituted C1-C6 alkyl group, (1-5) a halogen-substituted C1-C6 alkoxy group, (1-6) a cyano group, (1-7) a C1-C6 alkoxy group, (1-8) a C1-C6 alkylthio group, (1-9) an imidazolyl group, (1-10) a tri C1-C6 alkylsilyl group, (1-11) an oxadiazolyl group which may have 1 C1-C6 alkyl group, (1-12) a pyrrolidinyl group which may have 1 oxo group, (1-13) a phenyl group which may have 1 C1-C6 alkoxy group, (1-14) a C1-C6 alkylamino C1-C6 alkyl group, (1-15) an oxo group, (1-16) a pyrazolyl group which may have 1 C1-C6 alkyl group, (1-17) a thienyl group, (1-18) a furyl group, (1-19) a thiazolyl group which may have 1 C1-C6 alkyl group, (1-20) a C1-C6 alkylamino group, (1-21) a pyrimidyl group which may have 1 C1-C6 alkyl group, (1-22) a phenyl C2-C6 alkenyl group, (1-23) a phenoxy group which may have 1 halogen atom, (1-24) a phenoxy C1-C6 alkyl group, (1-25) a pyrrolidinyl C1-C6 alkoxy group, (1-26) a C1-C6 alkylsulfamoyl group, (1-27) a pyridazinyloxy group which may have 1 C1-C6 alkyl group, (1-28) a phenyl C1-C6 alkyl group, (1-29) a C1-C6 alkylamino C1-C6 alkoxy group, (1-30) an imidazolyl C1-C6 alkyl group, (1-31) a phenyl C1-C6 alkoxy group, (1-32) a hydroxy group, (1-34) a hydroxy C1-C6 alkyl group, (1-35) an oxazolyl group, (1-36) a piperidyl group, (1-37) a pyrrolyl group, (1-38) a morpholinyl C1-C6 alkyl group, (1-39) a piperazinyl C1-C6 alkyl group which may have 1 C1-C6 alkyl group(s), (1-40) a piperidyl C1-C6 alkyl group, (1-41) a pyrrolidinyl C1-C6 alkyl group, (1-42) a morpholinyl group, and (1-43) a piperazinyl group which may have 1 C1-C6 alkyl group.

4. The method according to claim 1, wherein in the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof R.sup.1 represents hydrogen; R.sup.2 and R.sup.3, which are the same or different, each independently represent a C1-C6 alkyl group; or R.sup.2 and R.sup.3 are bonded to form a cyclo-C3-C8 alkyl group; and R.sup.4 represents any of (1) a phenyl group, (2) an indolyl group, (4) a naphthyl group, (5) a benzofuryl group, and (31) a pyrrolopyridyl group, wherein these aromatic or heterocyclic groups may have 1 to 2 substituent(s) selected from (1-1) a halogen atom, (1-2) a C1-C6 alkyl group, (1-5) a halogen-substituted C1-C6 alkoxy group, (1-6) a cyano group, and (1-7) a C1-C6 alkoxy group.

5. The method according to claim 1, wherein the compound represented by the formula (1) or a pharmaceutically acceptable salt thereof is selected from (4aS,8aR)-1-(4-chlorophenyl)-3,3-dimethyldecahydroquinoxaline, 2-chloro-4-((4aS,8 aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)benzonitrile, (4aS,8aR)-1-(3-chloro-4-fluorophenyl)-3,3-dimethyldecahydroquinoxaline, (4aS,8aR)-1-(7-fluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline, 5-((4aR,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)-1-methyl-1H-indole-2-carbonitrile, (4aR,8aS)-4-(7-methoxybenzofuran-4-yl)octahydro-1 H-spiro[cyclobutane-1,2-quinoxaline], (4aS,8aR)-1-(6,7-difluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline, 5-((4aS,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)-1H-indole-2-carbonitrile, (4aS,8aR)-1-(7-chloro-2,3-dihydro-1H-inden-4-yl)-3,3-dimethyldecahydroquinoxaline, 6-((4aS,8aS)-3,3-dimethyloctahydroquinoxalin-1(2H)-yl)-2-naphthonitrile, (4aS,8aS)-3,3-dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-4-yl)decahydroquinoxaline, (4aS,8aS)-1-(4-(difluoromethoxy)-3-fluorophenyl)-3,3-dimethyldecahydroquinoxaline, (4aS,8 aS)-1-(4-(difluoromethoxy)phenyl-3,3-dimethyldecahydroquinoxaline, and (4aR,8aR)-1-(4-difluoromethyoxy)-3-fluorophenyl-3,3-dimethyldecahydroquinoxaline.

Description

EXAMPLES

(1) Hereinafter, the present invention will be described more specifically with reference to Reference Examples, Examples, and Pharmacological Tests. The chemical structures of racemic bodies and optically active forms are indicated, for example, as shown below.

(2) Racemic Body

(3) Relative Configuration

(4) ##STR00010##
Optically Active Form
Absolute Configuration

(5) ##STR00011##

Reference Example 1

Production of cis-3,3-dimethyloctahydrocyclopentapyrazin-2-one

(6) Relative Configuration

(7) ##STR00012##

(8) 90% acetone cyanohydrin (9.79 g, 104 mmol) was added to an aqueous (100 mL) solution of cis-cyclopentane-1,2-diamine (9.88 g, 98.6 mmol) at room temperature, and the mixture was stirred under reflux for 16 hours. The solvent was removed from the reaction mixture under reduced pressure, followed by azeotropy with ethanol. The obtained residue was purified by silica gel column chromatography (methylene chloride/methanol=1/10) to obtain cis-3,3-dimethyloctahydrocyclopentapyrazin-2-one (5.00 g, 30%) in a white powder form.

(9) .sup.1H-NMR (CDCl.sub.3) ppm: 1.20 (1H, brs), 1.34 (3H, s), 1.39 (3H, s), 1.40-2.20 (6H, m), 3.50-3.70 (2H, m), 5.89 (1H, brs).

(10) Compounds of Reference Examples 2 to 12 shown below were produced in the same way as in Reference Example 1 using appropriate starting materials.

Reference Example 2

Trans-3,3-dimethyloctahydrocyclopentapyrazin-2-one

(11) Relative Configuration

(12) ##STR00013##
.sup.1H-NMR(CDCl.sub.3)ppm: 1.1-1.3(1H, m), 1.35-2.15(12H, m) 2.5-2.6(1H, m), 2.75-2.85(1H, m), 3.15-3.3(2H, m), 5.65(1H, br).

Reference Example 3

Cis-3,3-dimethylhexahydrofuro[3,4-b]pyrazin-2-one

(13) Relative Configuration

(14) ##STR00014##

(15) .sup.1H-NMR (CDCl.sub.3) ppm: 1.37 (3H, s), 1.40 (3H, s), 1.50-1.85 (1H, br), 3.73-4.10 (6H, m), 6.02-6.22 (1H, br).

Reference Example 4

Trans-3,3-dimethylhexahydrofuro[3,4-b]pyrazin-2-one

(16) Relative Configuration

(17) ##STR00015##

(18) .sup.1H-NMR (CDCl.sub.3) ppm: 1.38-1.43 (1H, br), 1.44 (3H, s), 1.47 (3H, s), 3.38-3.52 (1H, m), 3.52-3.65 (3H, m), 4.00-4.14 (2H, m), 6.28-6.45 (1H, br).

Reference Example 5

(4aS,8aS)-3,3-dimethyloctahydroquinoxalin-2-one

(19) ##STR00016##

(20) .sup.1H-NMR (CDCl.sub.3) ppm: 1.14-1.43 (6H, m), 1.38 (3H, s), 1.42 (3H, s), 1.69 (1H, brs), 1.74-1.84 (2H, m), 2.57-2.65 (1H, m), 2.96-3.04 (1H, m), 5.61 (1H, s)

Reference Example 6

(4aR,8aR)-3,3-dimethyloctahydroquinoxalin-2-one

(21) Absolute Configuration

(22) ##STR00017##

(23) .sup.1H-NMR (CDCl.sub.3) ppm: 1.14-1.43 (6H, m), 1.38 (3H, s), 1.42 (3H, s), 1.63 (1H, brs), 1.73-1.83 (2H, m), 2.57-2.66 (1H, m), 2.95-3.04 (1H, m), 5.55 (1H, s)

Reference Example 7

Trans-3,3-diethyloctahydroquinoxalin-2-one

(24) Relative Configuration

(25) ##STR00018##

(26) .sup.1H-NMR (CDCl.sub.3) ppm: 0.92 (3H, t, J=7.5 Hz), 0.93 (3H, t, J=7.3 Hz), 1.13-1.49 (7H, m), 1.60-1.99 (6H, m), 2.55-2.60 (1H, m), 2.91-3.00 (1H, m), 5.69 (1H, brs)

Reference Example 8

Trans-octahydro-1H-spiro[cyclobutane-1,2-quinoxalin]-3-one

(27) Relative Configuration

(28) ##STR00019##

(29) .sup.1H-NMR (CDCl.sub.3) ppm: 1.14-1.46 (4H, m), 1.70-2.17 (9H, m), 2.43-2.52 (1H, m), 2.55-2.66 (1H, m), 2.78-2.88 (1H, m), 2.97-3.06 (1H, m), 5.65 (1H, brs)

Reference Example 9

Cis-octahydro-1H-spiro[cyclobutane-1,2-quinoxalin]-3-one

(30) Relative Configuration

(31) ##STR00020##

(32) .sup.1H-NMR (CDCl.sub.3) ppm: 1.1-1.3 (1H, m), 1.35-2.15 (12H, m), 2.5-2.6 (1H, m), 2.75-2.85 (1H, m), 3.15-3.3 (2H, m), 5.65 (1H, br).

Reference Example 10

Trans-octahydro-1H-spiro[cyclohexane-1,2-quinoxalin]-3-one

(33) Relative Configuration

(34) ##STR00021##

(35) .sup.1H-NMR (CDCl.sub.3) ppm: 1.18-1.88 (18H, m), 2.03-2.13 (1H, m), 2.47-2.58 (1H, m), 2.92-3.00 (1H, m), 5.59 (1H, s)

Reference Example 11

Cis-3,3-dimethyldecahydrocycloheptapyrazin-2-one

(36) Relative Configuration

(37) ##STR00022##

(38) .sup.1H-NMR (CDCl.sub.3) ppm: 1.12-2.00 (16H, m), 2.03-2.20 (1H, m), 3.35-3.55 (2H, m), 5.88 (brs).

Reference Example 12

Trans-3,3-dimethyldecahydrocycloheptapyrazin-2-one

(39) Relative Configuration

(40) ##STR00023##

(41) .sup.1H-NMR (CDCl.sub.3) ppm: 1.35 (3H, s), 1.39 (3H, s), 1.42-1.90 (11H, m), 2.73-2.85 (1H, m), 3.13-3.26 (1H, m), 5.51 (1H, brs).

Reference Example 13

Production of cis-4,4-dimethyloctahydrocyclopenta[b][1,4]diazepin-2-one

(42) Relative Configuration

(43) ##STR00024##

(44) A toluene (200 mL) suspension of cis-cyclopentane-1,2-diamine (19.7 g, 197 mmol) and 3-methyl-2-butenoic acid (19.7 g, 197 mmol) was stirred under reflux for 24 hours under azeotropic conditions using a Dean-Stark apparatus. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure, and the deposited crystal was collected by filtration. The obtained crystal was washed with ether and then dried to obtain cis-4,4-dimethyloctahydrocyclopenta[b][1,4]diazepin-2-one (8.60 g, 24%) in a light brown powder form.

(45) .sup.1H-NMR (CDCl.sub.3) ppm: 1.10-1.56 (10H, m), 1.65-1.80 (1H, m), 2.02-2.30 (3H, m), 2.60 (1H, d, J=12.8 Hz), 3.18-3.37 (1H, m), 3.68-3.85 (1H, m), 5.73 (1H, brs).

(46) Compounds of Reference Examples 14 and 15 below were produced in the same way as in Reference Example 13 using appropriate starting materials.

Reference Example 14

(5aS,9aS)-4,4-dimethyldecahydro[b][1,4]diazepin-2-one

(47) Absolute Configuration

(48) ##STR00025##

(49) .sup.1H-NMR (CDCl.sub.3) ppm: 1.00-1.45 (11H, m), 1.63-1.83 (3H, m), 1.83-2.00 (1H, m), 2.31-2.43 (1H, m), 2.65-2.81 (2H, m), 3.00-3.16 (1H, m), 5.54-5.90 (1H, br).

Reference Example 15

(5aR,9aR)-4,4-dimethyldecahydro[b][1,4]diazepin-2-one

(50) Absolute Configuration

(51) ##STR00026##

(52) .sup.1H-NMR (CDCl.sub.3) ppm: 1.02-1.36 (11H, m), 1.64-1.83 (3H, m), 1.83-1.97 (1H, m), 2.37 (1H, dd, J=2.4, 13.9 Hz), 2.66-2.81 (2H, m), 3.01-3.15 (1H, m), 5.75-5.92 (1H, brs).

Reference Example 16

Production of cis-2,2-dimethyloctahydro-1H-cyclopenta[b]pyrazine

(53) Relative Configuration

(54) ##STR00027##

(55) Lithium aluminum hydride (541 mg, 14.3 mmol) was added to an anhydrous dioxane (40 mL) solution of cis-3,3-dimethyloctahydrocyclopentapyrazin-2-one (2.00 g, 11.9 mmol) with stirring at room temperature, and the mixture was gradually heated and stirred for 10 minutes under reflux. The reaction mixture was cooled to ice temperature. Then, sodium sulfate decahydrate was added thereto in small portions until no hydrogen gas was generated. Then, the mixture was stirred at room temperature for 1 hour. Insoluble matter was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=1/10) to obtain cis-2,2-dimethyloctahydro-1H-cyclopenta[b]pyrazine (1.67 g, 91%) in a pale yellow oil form.

(56) .sup.1H-NMR (CDCl.sub.3) ppm: 1.04 (3H, s), 1.16 (3H, s), 1.28-2.02 (8H, m), 2.37 (1H, d, J=12.9 Hz), 2.70 (1H, d, J=12.9 Hz), 3.00-3.15 (1H, m), 3.15-3.32 (1H, m).

(57) Compounds of Reference Examples 17 to 34 below were produced in the same way as in Reference Example 16 using appropriate starting materials.

Reference Example 17

Trans-2,2-dimethyloctahydro-1H-cyclopenta[b]pyrazine

(58) Relative Configuration

(59) ##STR00028##

(60) .sup.1H-NMR (CDCl.sub.3) ppm: 1.08 (3H, s), 1.19-1.92 (11H, m), 2.15-2.30 (1H, m), 2.55-2.74 (2H, m), 2.77 (1H, d, J=12.2 Hz).

Reference Example 18

Cis-2,2-dimethyldecahydrocyclopenta[b][1,4]diazepine

(61) Relative Configuration

(62) ##STR00029##

(63) .sup.1H-NMR (CDCl.sub.3) ppm: 1.11 (3H, s), 1.14 (3H, s), 1.14-1.45 (6H, m), 1.55-1.68 (1H, m), 1.67-1.77 (1H, m), 1.97-2.12 (2H, m), 2.68-2.80 (1H, m), 2.98-3.11 (2H, m), 3.16-3.28 (1H, m).

Reference Example 19

Cis-2,2-dimethyloctahydrofuro[3,4-b]pyrazine

(64) Relative Configuration

(65) ##STR00030##

(66) .sup.1H-NMR (CDCl.sub.3) ppm: 1.08 (3H, s), 1.18 (3H, s), 1.40-1.80 (2H, br), 2.41 (1H, d, J=13.2 Hz), 2.69 (1H, d, J=13.2 Hz), 3.33-3.43 (1H, m), 3.43-3.55 (1H, m), 3.63-3.72 (1H, m), 3.75-3.96 (3H, m).

Reference Example 20

Trans-2,2-dimethyloctahydrofuro[3,4-b]pyrazine

(67) Relative Configuration

(68) ##STR00031##

(69) .sup.1H-NMR (CDCl.sub.3) ppm: 1.13 (3H, s), 1.30 (3H, s), 1.44-1.65 (2H, m), 2.64-2.78 (2H, m), 2.83 (1H, d, J=12.2 Hz), 3.11-3.22 (1H, m), 3.46 (1H, dd, J=7.3, 10.5 Hz), 3.55 (1H, dd, J=7.4, 10.5 Hz), 3.94 (1H, t, J=7.1 Hz), 4.00 (1H, t, J=7.2 Hz).

Reference Example 21

Cis-2,2-dimethyldecahydro-1H-benzo[b][1,4]diazepine

(70) Relative Configuration

(71) ##STR00032##

(72) .sup.1H-NMR (CDCl.sub.3) ppm: 1.08 (3H, s), 1.13 (3H, s), 1.18-1.84 (12H, m), 2.65-2.93 (3H, m), 3.14-3.22 (1H, m).

Reference Example 22

(5aS,9aS)-2,2-dimethyldecahydro-1H-benzo[b][1,4]diazepine

(73) Absolute Configuration

(74) ##STR00033##

(75) .sup.1H-NMR (CDCl.sub.3) ppm: 1.00-1.35 (11H, m), 1.50-1.85 (7H, m), 2.20-2.31 (1H, m), 2.31-2.43 (1H, m), 2.79-2.90 (1H, m), 2.90-3.04 (1H, m).

Reference Example 23

(5aR,9aR)-2,2-dimethyldecahydro-1H-benzo[b][1,4]diazepine

(76) Absolute Configuration

(77) ##STR00034##

(78) .sup.1H-NMR (CDCl.sub.3) ppm: 1.00-1.35 (11H, m), 1.50-1.85 (7H, m), 2.20-2.31 (1H, m), 2.31-2.43 (1H, m), 2.79-2.90 (1H, m), 2.90-3.04 (1H, m).

Reference Example 24

Cis-2,2-dimethyldecahydroquinoxaline

(79) Relative Configuration

(80) ##STR00035##

(81) .sup.1H-NMR (CDCl.sub.3) ppm: 1.06 (3H, s), 1.19 (3H, s), 1.20-1.40 (5H, m), 1.53-1.60 (3H, m), 1.70-1.77 (1H, m), 1.92-2.15 (1H, m), 2.36 (1H, d, J=12.7 Hz), 2.66-2.72 (1H, m), 2.72 (1H, d, J=12.7 Hz), 3.16-3.28 (1H, m).

Reference Example 25

Trans-2,2-dimethyldecahydroquinoxaline

(82) Relative Configuration

(83) ##STR00036##

(84) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05 (3H, s), 1.08-1.74 (10H, m), 1.23 (3H, s), 2.02-2.12 (1H, m), 2.40-2.50 (1H, m), 2.60 (1H, d, J=12.1 Hz), 2.73 (1H, d, J=12.1 Hz).

Reference Example 26

(4aS,8aS)-2,2-dimethyldecahydroquinoxaline

(85) Absolute Configuration

(86) ##STR00037##

(87) .sup.1H-NMR (CDCl.sub.3) ppm: 1.01-1.43 (6H, m), 1.05 (3H, s), 1.23 (3H, s), 1.58-1.63 (1H, m), 1.68-1.74 (3H, m), 2.03-2.19 (1H, m), 2.40-2.49 (1H, m), 2.60 (1H, d, J=12.1 Hz), 2.73 (1H, d, J=12.1 Hz).

Reference Example 27

(4aR,8aR)-2,2-dimethyldecahydroquinoxaline

(88) Absolute Configuration

(89) ##STR00038##

(90) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05 (3H, s), 1.09-1.56 (6H, m), 1.23 (3H, s), 1.58-1.63 (1H, m), 1.66-1.75 (3H, m), 2.03-2.12 (1H, m), 2.41-2.50 (1H, m), 2.61 (1H, d, J=12.1 Hz), 2.75 (1H, d, J=12.1 Hz).

Reference Example 28

Trans-2,2-diethyldecahydroquinoxaline

(91) Relative Configuration

(92) ##STR00039##

(93) .sup.1H-NMR (CDCl.sub.3) ppm: 0.79 (3H, t, J=7.5 Hz), 0.81 (3H, t, J=7.5 Hz), 0.86-1.02 (1H, m), 1.08-1.40 (8H, m), 1.47-1.60 (2H, m), 1.67-1.87 (3H, m), 2.06-2.15 (1H, m), 2.33-2.42 (1H, m), 2.57 (1H, d, J=12.1 Hz), 2.81 (1H, d, J=12.1 Hz).

Reference Example 29

Trans-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(94) Relative Configuration

(95) ##STR00040##

(96) MS(M+1) 181

Reference Example 30

Cis-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(97) Relative Configuration

(98) ##STR00041##

(99) MS(M+1) 181

Reference Example 31

Trans-octahydro-1H-spiro[cyclopentane-1,2-quinoxaline]

(100) Relative Configuration

(101) ##STR00042##

(102) .sup.1H-NMR (CDCl.sub.3) ppm: 1.10-1.97 (18H, m), 2.10-2.21 (1H, m), 2.29-2.38 (1H, m), 2.71 (1H, d, J=12.2 Hz), 2.76 (1H, d, J=12.2 Hz).

Reference Example 32

Trans-octahydro-1H-spiro[cyclohexane-1,2-quinoxaline]

(103) Relative Configuration

(104) ##STR00043##

(105) .sup.1H-NMR (CDCl.sub.3) ppm: 1.12-1.76 (20H, m), 2.12-2.20 (1H, m), 2.44-2.53 (1H, m), 2.55 (1H, d, J=12.2 Hz), 2.98 (1H, d, J=12.2 Hz).

Reference Example 33

Cis-2,2-dimethyldecahydro-1H-cyclohepta[b]pyrazine

(106) Relative Configuration

(107) ##STR00044##

(108) .sup.1H-NMR (CDCl.sub.3) ppm: 1.00-2.02 (18H, m), 2.42 (1H, d, J=12.4 Hz), 2.58 (1H, d, J=12.4 Hz), 2.75-2.86 (1H, m), 3.13-3.25 (1H, m).

Reference Example 34

Trans-2,2-dimethyldecahydro-1H-cyclohepta[b]pyrazine

(109) Relative Configuration

(110) ##STR00045##

(111) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05 (3H, s), 1.21 (3H, s), 1.23-1.80 (12H, m), 2.09-2.20 (1H, m), 2.46-2.60 (2H, m), 2.68 (1H, d, J=11.8 Hz).

Reference Example 35

Production of (2RS,4aSR,8aSR)-2-ethyldecahydroquinoxaline

(112) Relative Configuration

(113) ##STR00046##

(114) Dichloro(pentamethylcyclopentadienyl)iridium (III) dimer (70 mg, 0.090 mmol) and sodium bicarbonate (73 mg, 0.87 mmol) were added to an aqueous (20 mL) solution of trans-cyclohexane-1,2-diamine (2.00 g, 17.5 mmol) and ()-1,2-butanediol (1.69 mL, 18.4 mmol) with stirring at room temperature. Degassing and argon substitution were repeated 3 times, and the mixture was then stirred for 24 hours under reflux. The reaction mixture was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (methylene chloride/methanol) to obtain (2R*,4aS*,8aS*)-2-ethyldecahydroquinoxaline (2.03 g, yield: 69%) in a yellow solid form.

(115) .sup.1H-NMR (CDCl.sub.3) ppm: 0.92 (3H, t, J=7.5 Hz), 1.10-1.60 (7H, m), 1.64-1.83 (5H, m), 2.16-2.31 (2H, m), 2.44 (1H, dd, J=11.5, 10.4 Hz), 2.58-2.67 (1H, m), 3.02 (1H, dd, J=11.5, 2.7 Hz).

Reference Example 36

Production of (4aS,8aS)-1-benzyldecahydroquinoxaline

(116) ##STR00047##

(117) Benzaldehyde (3.05 mL, 30.0 mmol) was added to a methanol (300 mL) solution of (1S,2S)-cyclohexane-1,2-diamine (3.43 g, 30.0 mmol) with stirring at room temperature, and the mixture was stirred overnight at the same temperature. The reaction mixture was cooled to 0 C. Sodium borohydride (2.27 g, 60.0 mmol) was added thereto, and the mixture was stirred at 0 C. for 2 hours. To the reaction mixture, water (30 mL) was added, and the product was extracted twice with methylene chloride (50 mL). The organic layers were combined and dried over magnesium sulfate, and the solvent was then distilled off under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane) to obtain (1S,2S)N-benzylcyclohexane-1,2-diamine (cas no. 207450-11-1) (2.95 g, yield: 48%) in a pale yellow oil form.

(118) The obtained (1S,2S)N-benzylcyclohexane-1,2-diamine (2.90 g, 14.2 mmol) was dissolved in methylene chloride (284 nL). To the solution, 60% sodium hydride (1.99 g, 49.7 mmol) was added with ice-cooling and stirring in a nitrogen atmosphere. After 5 minutes, (2-bromoethyl)diphenylsulfonium trifluoromethanesulfonate (6.92 g, 15.6 mmol) was added to the reaction mixture with ice-cooling and stirring, and the mixture was stirred overnight at room temperature. To the reaction mixture, a saturated aqueous solution of ammonium chloride was added dropwise in small portions, and the product was then extracted twice with methylene chloride (100 mL). The organic layers were combined and dried over magnesium sulfate, and the solvent was then distilled off under reduced pressure. The obtained residue was purified by NH-silica gel column chromatography (ethyl acetate/hexane) to obtain (4aS,8aS)-1-benzyldecahydroquinoxaline (2.28 g, 70%) in a light brown solid form.

(119) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.4 (4H, m), 1.50 (1H, br), 1.6-1.9 (4H, m), 2.05-2.2 (1H, m), 2.2-2.3 (1H, m), 2.4-2.5 (1H, m), 2.65-2.75 (1H, m), 2.8-2.95 (2H, m), 3.14 (1H, d, J=13.4 Hz), 4.11 (1H, d, J=13.4 Hz), 7.15-7.4 (5H, m).

(120) Compounds of Reference Examples 37 to 39 below were produced in the same way as in Reference Example 36 using appropriate starting materials.

Reference Example 37

(4aS,8aS)-1-benzyldecahydroquinoxaline

(121) Absolute Configuration

(122) ##STR00048##

(123) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.4 (4H, m), 1.50 (1H, br), 1.6-1.9 (4H, m), 2.05-2.2 (1H, m), 2.2-2.3 (1H, m), 2.4-2.5 (1H, m), 2.65-2.75 (1H, m), 2.8-2.95 (2H, m), 3.13 (1H, d, J=13.4 Hz), 4.11 (1H, d, J=13.4 Hz), 7.15-7.4 (5H, m).

Reference Example 38

Cis-decahydroquinoxaline-1-carboxylic acid tert-butyl ester

(124) Relative Configuration

(125) ##STR00049##

(126) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.15 (1H, m), 1.2-1.75 (19H, m), 1.75-1.85 (1H, m), 1.85-2.2 (1H, m), 3.70 (1H, br), 4.83 (1H, br).

Reference Example 39

Cis-1-benzyldecahydroquinoxaline

(127) Relative Configuration

(128) ##STR00050##

(129) .sup.1H-NMR (CDCl.sub.3) ppm: 1.0-2.0 (10H, m), 2.2-2.4 (1H, m), 2.45-2.7 (2H, m), 2.75-3.1 (2H, m), 3.63 (2H, br), 7.05-7.45 (5H, m).

Reference Example 40

Production of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline

(130) Absolute Configuration

(131) ##STR00051##

Reference Example 41

(4aS,8aR)-2,2-dimethyldecahydroquinoxaline

(132) Absolute Configuration

(133) ##STR00052##

(134) ()-dibenzoyl-L-tartaric acid monohydrate (13.8 g, 36.7 mmol) in ethanol (140 mL) was added to an ethanol (140 mL) solution of cis-2,2-dimethyldecahydroquinoxaline (13.7 g, 81.4 mmol) with stirring at room temperature. The reaction mixture was stirred for 30 minutes under reflux and cooled to room temperature, and the deposited white crystal was then collected by filtration. The obtained crystal was washed with ethanol (20 mL) and then dried to obtain a white solid <1> (13.1 g). The filtrate and washes obtained in obtaining the solid <1> were concentrated under reduced pressure. The obtained residue was dissolved in ethanol (100 mL). To the solution, an ethanol (130 mL) solution of (+)-dibenzoyl-D-tartaric acid (13.1 g, 36.6 mmol) was added with stirring at room temperature, and the deposited crystal was collected by filtration. The obtained crystal was washed with ethanol (20 mL) and then dried to obtain a light brown solid <2> (16.6 g).

(135) A methanol (130 mL)/water (10 mL) suspension of the solid <1> was stirred for 30 minutes under reflux. Then, the reaction mixture was cooled to room temperature, and the deposited crystal was collected by filtration. The deposited crystal was washed with methanol (10 mL) and then dried to obtain (4aR,8aS)-2,2-dimethyldecahydroquinoxaline dibenzoyl-L-tartrate (11.4 g, 21.6 mmol) in a white solid form (the absolute configuration of cis-2.2-dimethyldecahydroquinoxaline was determined by the X-ray crystallographic analysis of the white solid). This solid was dissolved in a 1 N aqueous sodium hydroxide solution (44 mL), and the product was extracted with ether (100 mL) three times and with methylene chloride (100 mL) three times. The extracted organic layers were combined, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (3.44 g, yield: 25%) in a white solid form.

(136) .sup.1H-NMR (CDCl.sub.3) ppm: 1.06 (3H, s), 1.20 (3H, s), 1.2-1.4 (4H, m), 1.45-1.95 (5H, m), 1.95-2.15 (1H, m), 2.36 (1H, d, J=12.7 Hz), 2.65-2.75 (2H, m), 3.15-3.25 (1H, m).

(137) A methanol (130 mL)/water (10 mL) suspension of the solid <2> was stirred for 1 hour under reflux. Then, the reaction mixture was cooled to room temperature, and the deposited crystal was collected by filtration. The deposited crystal was washed with methanol (10 mL) and then dried to obtain (4aS,8aR)-2,2-dimethyldecahydroquinoxaline dibenzoyl-D-tartrate (16.0 g, 30.4 mmol) in a white solid form. This solid was dissolved in a 1 N aqueous sodium hydroxide solution (65 mL), and the product was extracted with methylene chloride (100 mL) three times. The extracted organic layers were combined, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain (4aS,8aR)-2,2-dimethyldecahydroquinoxaline (4.63 g, yield: 34%) in a light brown solid form.

(138) .sup.1H-NMR (CDCl.sub.3) ppm: 1.06 (3H, s), 1.19 (3H, s), 1.2-1.45 (5H, m), 1.45-1.65 (3H, m), 1.65-1.8 (1H, m), 1.95-2.15 (1H, m), 2.36 (1H, d, J=12.7 Hz), 2.6-2.8 (2H, m), 3.15-3.25 (1H, m).

(139) Compounds of Reference Examples 42 to 45 below were produced in the same way as in Reference Examples 40 and 41 using appropriate starting materials.

Reference Example 42

(4aR,8aS)-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(140) ##STR00053##

(141) MS(M+1) 181

(142) .sup.1H-NMR (CDCl.sub.3) ppm: 1.20-2.20 (16H, m), 2.69 (1H, d, J=12.4 Hz), 2.72-2.82 (1H, m), 2.87-3.02 (2H, m).

Reference Example 43

(4aS,8aR)-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(143) Absolute Configuration

(144) ##STR00054##

(145) MS(M+1) 181

(146) .sup.1H-NMR (CDCl.sub.3) ppm: 1.20-2.20 (16H, m), 2.68 (1H, d, J=12.5 Hz), 2.72-2.82 (1H, m), 2.87-3.02 (2H, m).

Reference Example 44

(4aR,8aS)-1-benzyldecahydroquinoxaline

(147) Absolute Configuration

(148) ##STR00055##

(149) .sup.1H-NMR (CDCl.sub.3) ppm: 1.0-1.25 (1H, m), 1.25-1.65 (5H, m), 1.65-2.05 (3H, m), 2.2-2.4 (1H, m), 2.45-2.7 (2H, m), 2.75-3.1 (3H, m), 3.63 (2H, br), 7.15-7.4 (5H, m).

Reference Example 45

(4aS,8aR)-1-benzyldecahydroquinoxaline

(150) ##STR00056##

(151) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.25 (1H, m), 1.25-1.65 (5H, m), 1.65-2.05 (3H, m), 2.2-2.4 (1H, m), 2.5-2.7 (2H, m), 2.75-3.1 (3H, m), 3.63 (2H, br), 7.15-7.4 (5H, m).

Reference Example 46

Production of (trans-3-oxodecahydroquinoxalin-1-yl)acetic acid ethyl ester

(152) Relative Configuration

(153) ##STR00057##

(154) Trans-cyclohexane-1,2-diamine (3.00 g, 26.3 mmol) was diluted with ethanol (15 ml). To the solution, bromoethyl acetate (6.12 mL, 55.2 mmol) was added dropwise with ice-cooling, and the mixture was then stirred overnight at room temperature.

(155) To the reaction solution, water was added, and the mixture was stirred. The product was extracted with methylene chloride. The organic layer was washed with saturated saline and dried over magnesium sulfate, followed by filtration. The filtrate was concentrated under reduced pressure. The obtained residue was separated and purified by silica gel column chromatography (methylene chloride/methanol) to obtain (trans-3-oxodecahydroquinoxalin-1-yl)acetic acid ethyl ester (2.35 g, yield: 74.4%) in an orange particulate solid form.

(156) .sup.1H-NMR (CDCl.sub.3) ppm: 1.13-1.41 (4H, m), 1.28 (3H, t, J=7.1 Hz), 1.72-1.97 (4H, m), 2.59-2.67 (1H, m), 3.06-3.13 (1H, m), 3.35 (1H, d, J=17.4 Hz), 3.48 (1H, d, J=16.8 Hz), 3.52 (1H, d, J=17.4 Hz), 3.60 (1H, d, J=16.8 Hz), 4.17 (2H, q, J=7.1 Hz), 6.79 (1H, brs).

[Reference Example 47] Production of 2-(trans-decahydroquinoxalin-1-yl)ethanol

(157) Relative Configuration

(158) ##STR00058##

(159) Lithium aluminum hydride (1.00 g, 26.4 mmol) was suspended in anhydrous dioxane (40 ml). To the suspension, an anhydrous dioxane (10 ml) solution of (trans-3-oxodecahydroquinoxalin-1-yl)acetic acid ethyl ester (2.35 g, 9.78 mmol) was added dropwise with stirring at room temperature, and the mixture was then stirred under reflux for 10 minutes. The reaction mixture was cooled on ice, and sodium sulfate decahydrate was added thereto in small portions until no gas was generated. This mixture was filtered through celite and washed with methylene chloride, and the filtrate was then concentrated under reduced pressure to obtain 2-(trans-decahydroquinoxalin-1-yl)ethanol (1.74 g, yield: 97%) in a brown oil form.

(160) .sup.1H-NMR (CDCl.sub.3) ppm: 0.95-1.11 (1H, m), 1.15-1.44 (3H, m), 1.68-1.80 (5H, m), 1.85-1.94 (1H, m), 2.05-2.44 (4H, m), 2.87-2.97 (3H, m), 3.04-3.16 (1H, m), 3.46-3.54 (1H, m), 3.60-3.69 (1H, m).

Reference Example 48

Production of trans-1-[2-(tert-butyldimethylsilyloxy)ethyl]decahydroquinoxaline

(161) Relative Configuration

(162) ##STR00059##

(163) Triethylamine (4.61 mL, 33.0 mmol) and subsequently tert-butyldimethylsilyl chloride (4.27 g, 28.3 mmol) were added to a methylene chloride (40 mL) solution of 2-(trans-decahydroquinoxalin-1-yl)ethanol (1.74 g, 9.44 mmol) with ice-cooling and stirring, and the mixture was stirred overnight at room temperature. To the reaction mixture, water (100 mL) was added to terminate the reaction. The product was extracted with methylene chloride (100 mL). The organic layer was washed with water twice and with saturated saline once, then dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride/methanol) to obtain trans-1-[2-(tert-butyldimethylsilyloxy)ethyl]decahydroquinoxaline (2.00 g, yield: 71%) in a light brown oil form.

(164) .sup.1H-NMR (CDCl.sub.3) ppm: 0.06 (6H, s), 0.89 (9H, s), 0.98-1.36 (4H, m), 1.65-1.79 (4H, m), 1.85-1.95 (1H, m), 2.08-2.14 (1H, m), 2.24-2.39 (1H, m), 2.45-2.61 (2H, m), 2.79-3.03 (4H, m), 3.62-3.80 (2H, m).

(165) Compounds of Reference Examples 50 and 51 below were produced in the same way as in Reference Example 1 using appropriate starting materials.

Reference Example 50

(4aS, 8aS)-octahydro-1H-spiro[cyclobutane-1,2-quinoxalin]-3-one

(166) Absolute Configuration

(167) ##STR00060##

(168) .sup.1H-NMR (CDCl.sub.3) ppm: 0.99-1.38 (4H, m), 1.55-1.78 (5H, m), 1.78-1.94 (3H, m), 2.21-2.33 (2H, m), 2.48-2.59 (1H, m), 2.63 (1H, brs), 2.76-2.87 (1H, m), 7.36 (1H, s).

Reference Example 51

(4aR,8aR)-octahydro-1H-spiro[cyclobutane-1,2-quinoxalin]-3-one

(169) Absolute Configuration

(170) ##STR00061##

(171) .sup.1H-NMR (CDCl.sub.3) ppm: 0.97-1.36 (4H, m), 1.55-1.77 (5H, m), 1.77-1.92 (3H, m), 2.20-2.32 (2H, m), 2.47-2.57 (1H, m), 2.63 (1H, brs), 2.76-2.86 (1H, m), 7.36 (1H, s).

(172) Compounds of Reference Examples 52 and 53 below were produced in the same way as in Reference Example 16 using appropriate starting materials.

Reference Example 52

(4aS,8aS)-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(173) ##STR00062##

(174) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.90 (15H, m), 2.15-2.30 (3H, m), 2.69 (1H, dd, J=1.5, 12.2 Hz), 3.01 (1H, d, J=12.2 Hz).

Reference Example 53

(4aR,8aR)-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(175) Absolute Configuration

(176) ##STR00063##

(177) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.91 (15H, m), 2.15-2.30 (3H, m), 2.69 (1H, d, J=12.2 Hz), 3.01 (1H, d, J=12.2 Hz).

Reference Example 54

Production of (4aS,8aR)-tert-butyl 4-benzyldecahydroquinoxaline-1-carboxylate

(178) Absolute Configuration

(179) ##STR00064##

(180) Di-tert-butyl dicarbonate (1.70 g, 7.79 mmol) was added to a MeOH (16 ml) solution of (4aR,8aS)-1-benzyldecahydroquinoxaline (1.63 g, 7.08 mmol), and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off, and the residue was then purified by basic silica gel column chromatography (Hex-AcOEt) to obtain (4aS,8aR)-tert-butyl 4-benzyldecahydroquinoxaline-1-carboxylate (2.38 g, yield: quantitative) in a colorless oil form.

(181) .sup.1H-NMR (CDCl.sub.3) ppm:

(182) A compound of Reference Example 55 below was produced in the same way as in Reference Example 54 using appropriate starting materials.

Reference Example 55

(4aR,8aS)-tert-butyl 4-benzyldecahydroquinoxaline-1-carboxylate

(183) Absolute Configuration

(184) ##STR00065##

(185) .sup.1H-NMR (CDCl.sub.3) ppm: 1.26-1.66 (14H, m), 1.79-1.96 (2H, m), 2.14-2.33 (2H, m), 2.40-2.45 (1H, m), 2.65 (1H, brs), 2.86 (1H, d, J=13.2 Hz), 3.03 (1H, brs), 3.51-4.10 (2H, br), 4.16 (1H, d, J=13.2 Hz), 7.21-7.36 (5H, m).

Reference Example 56

Production Process of (4aS,8aR)-tert-butyl decahydroquinoxaline-1-carboxylate

(186) Absolute Configuration

(187) ##STR00066##

(188) Pearlman's catalyst (0.24 g) was added to an EtOH (25 ml) solution of (4aS,8aR)-tert-butyl 4-benzyldecahydroquinoxaline-1-carboxylate (2.4 g, 7.26 mmol). This suspension was stirred at room temperature for 1 hour in a hydrogen atmosphere. The catalyst was filtered through celite, and the residue was washed with EtOH. Then, the filtrate was concentrated under reduced pressure to obtain (4aS,8aR)-tert-butyl decahydroquinoxaline-1-carboxylate (1.67 g, yield: 96%) in a colorless oil form.

(189) .sup.1H-NMR (CDCl.sub.3) ppm: 1.16-1.53 (14H, m), 1.53-1.82 (3H, m), 1.83-2.00 (1H, m), 2.68-2.83 (1H, m), 2.85-3.10 (3H, m), 3.65-4.06 (2H, m).

(190) A compound of Reference Example 57 below was produced in the same way as in Reference Example 56 using appropriate starting materials.

Reference Example 57

(4aR,8aS)-tert-butyl decahydroquinoxaline-1-carboxylate

(191) ##STR00067##

(192) .sup.1H-NMR (CDCl.sub.3) ppm: 1.18-1.55 (14H, m), 1.55-1.82 (3H, m), 1.85-2.00 (1H, m), 2.68-2.82 (1H, m), 2.85-3.10 (3H, m), 3.65-4.04 (2H, m).

Reference Example 58

Production Process of cis tert-butyl 4-(4-chlorophenyl)decahydroquinoxaline-1-carboxylate

(193) Relative Configuration

(194) ##STR00068##

(195) A toluene (4 ml) suspension of cis tert-butyl decahydroquinoxaline-1-carboxylate (240 mg, 0.999 mmol), 1-bromo-4-chlorobenzene (211 mg, 1.10 mmol), Pd(OAc).sub.2 (11.2 mg, 0.0499 mmol), t-Bu.sub.3P.HBF.sub.4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 5 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Insoluble matter was filtered through celite, and the celite layer was washed with AcOEt (5 ml2). Then, the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a white solid (87 mg, yield: 25%).

(196) .sup.1H-NMR (CDCl.sub.3) ppm: 1.10-1.40 (4H, m), 1.40-1.52 (10H, m), 1.63-1.71 (1H, m), 1.73-1.82 (1H, m), 2.15-2.28 (1H, m), 2.74 (1H, dt, J=3.6, 11.8 Hz), 2.90-2.97 (1H, m), 3.05-3.11 (1H, m), 3.27 (1H, dt, J=3.4, 12.6 Hz), 3.77-3.86 (1H, m), 4.01-4.10 (1H, m), 7.08-7.13 (2H, m), 7.25-7.30 (2H, m).

(197) Compounds of Reference Examples 59 to 63 below were produced in the same way as in Reference Example 35 using appropriate starting materials.

Reference Example 59

(4aS,8aS)-decahydroquinoxaline

(198) Absolute Configuration

(199) ##STR00069##

(200) .sup.1H-NMR (CDCl.sub.3) ppm: 1.12-1.58 (6H, m), 1.62-1.78 (4H, m), 2.20-2.29 (2H, m), 2.82-3.02 (4H, m).

Reference Example 60

(4aR,8aR)-decahydroquinoxaline

(201) Absolute Configuration

(202) ##STR00070##

(203) .sup.1H-NMR (CDCl.sub.3) ppm: 1.14-1.27 (2H, m), 1.27-1.57 (4H, m), 1.62-1.79 (4H, m), 2.19-2.30 (2H, m), 2.83-3.03 (4H, m).

Reference Example 61

(2R,4aS,8aS)-2-methyldecahydroquinoxaline

(204) Absolute Configuration

(205) ##STR00071##

(206) .sup.1H-NMR (CDCl.sub.3) ppm: 1.02 (3H, d, J=6.3 Hz), 1.11-1.51 (6H, m), 1.62-1.79 (4H, m), 2.14-2.22 (1H, m), 2.24-2.33 (1H, m), 2.44 (1H, dd, J=10.2, 11.7 Hz), 2.81-2.91 (1H, m), 2.94 (1H, dd, J=2.9, 11.7 Hz).

Reference Example 62

(2S,4aR,8aR)-2-methyldecahydroquinoxaline

(207) ##STR00072##

(208) .sup.1H-NMR (CDCl.sub.3) ppm: 1.02 (3H, d, J=6.3 Hz), 1.10-1.49 (6H, m), 1.62-1.80 (4H, m), 2.14-2.22 (1H, m), 2.24-2.33 (1H, m), 2.44 (1H, dd, J=10.3, 11.7 Hz), 2.80-2.91 (1H, m), 2.94 (1H, dd, J=2.9, 11.7 Hz).

Reference Example 63

(2R,4aS,8aS)-2-ethyldecahydroquinoxaline

(209) Absolute Configuration

(210) ##STR00073##

(211) .sup.1H-NMR (CDCl.sub.3) ppm: 0.92 (3H, t, J=7.5 Hz), 1.1-1.55 (8H, m), 1.6-1.8 (4H, m), 2.14-2.32 (2H, m), 2.39-2.5 (1H, m), 2.57-2.68 (1H, m), 3.01 (1H, dd, J=2.6, 11.6 Hz).

Example 1

Production of (4aR,8aS)-3,3-dimethyl-1-(1-(triisopropylsilyl)-1H-indol-6-yl)decahydroquinoxaline

(212) Absolute Configuration

(213) ##STR00074##

(214) A toluene (8 mL) suspension of (4aS,8aR)-2,2-dimethyldecahydroquinoxaline (337 mg, 2.00 mmol), 6-bromo-1-(triisopropylsilyl)-1H-indole (846 mg, 2.40 mmol), sodium tert-butoxide (269 mg, 2.80 mmol), palladium (II) acetate (22.5 mg, 0.0902 mmol), and tri-tert-butylphosphine tetrafluoroborate (29.1 mg, 0.101 mmol) was stirred for 5 hours under reflux in a nitrogen atmosphere. The reaction mixture was cooled to room temperature. Then, water (0.5 mL) and ethyl acetate (10 mL) were added thereto, and the mixture was stirred, followed by addition of magnesium sulfate. Insoluble matter was filtered through celite, and the filtrate was then concentrated under reduced pressure. The obtained residue was purified by NH-silica gel column chromatography (n-hexane:ethyl acetate) to obtain colorless, amorphous (4aR,8aS)-3,3-dimethyl-1-(1-(triisopropylsilyl)-1H-indol-6-yl)decahydroquinoxaline (0.75 g, yield: 85%).

(215) .sup.1H-NMR (CDCl.sub.3) ppm: 1.1-1.2 (18H, m), 1.21 (3H, s), 1.29 (3H, s), 1.3-1.55 (5H, m), 1.55-1.8 (7H, m), 2.79 (1H, d, J=11.6 Hz), 2.91 (1H, d, J=11.6 Hz), 3.45-3.6 (2H, m), 6.49 (1H, dd, J=0.7, 3.2 Hz), 6.82 (1H, dd, J=2.0, 8.6 Hz), 6.93 (1H, s), 7.08 (1H, d, J=3.2 Hz), 7.45 (1H, d, J=8.6 Hz).

Example 2

Production of (4aR,8aS)-1-(1H-indol-6-yl)-3,3-dimethyldecahydroquinoxaline

(216) Absolute Configuration

(217) ##STR00075##

(218) Tetra-n-butyl ammonium fluoride (1 M in THF) (3.41 mL, 3.41 mol) was added to a tetrahydrofuran (15 mL) solution of (4aR,8aS)-3,3-dimethyl-1-(1-(triisopropylsilyl)-1H-indol-6-yl)decahydroquinoxaline (0.750 g, 1.71 mmol) with stirring at room temperature, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off from the reaction mixture under reduced pressure. The obtained residue was purified by NH-silica gel column chromatography (ethyl acetate/hexane) to obtain a white solid. The obtained solid was recrystallized from diisopropyl ether/hexane to obtain (4aR,8aS)-1-(1H-indol-6-yl)-3,3-dimethyldecahydroquinoxaline (305 mg, yield: 63%).

(219) .sup.1H-NMR (CDCl.sub.3) ppm: 1.0-1.55 (11H, m), 1.55-1.85 (4H, m), 2.79 (1H, d, J=11.6 Hz), 2.94 (1H, d, J=11.6 Hz), 3.45-3.55 (1H, m), 3.6-3.75 (1H, m), 6.35-6.5 (1H, m), 6.79 (1H, s), 6.86 (1H, dd, J=2.1, 8.7 Hz), 7.03 (1H, dd, J=2.7, 2.7 Hz), 7.47 (1H, d, J=8.6 Hz), 7.92 (1H, br).

Example 3

Production of (4aS,8aS)-1-(4-chlorophenyl)decahydroquinoxaline

(220) Absolute Configuration

(221) ##STR00076##

(222) 1-chloroethyl chloroformate (229 L, 2.10 mmol) was added to a methylene chloride (6.5 mL) solution of (4aS,8aS)-1-benzyl-4-(4-chlorophenyl)decahydroquinoxaline (0.650 g, 1.91 mmol) with ice-cooling and stirring. The mixture was stirred at room temperature for 15 hours, and the reaction mixture was then concentrated under reduced pressure. The obtained residue was dissolved in methanol (6.5 mL), and this solution was stirred for 1 hour under reflux. The solvent was distilled off from the reaction mixture. To the obtained residue, acetone (5 mL) was added, and the mixture was stirred. The deposited crystal was collected by filtration. The obtained crystal was washed with acetone (1 mL) and then dried to obtain (4aS,8aS)-1-(4-chlorophenyl)decahydroquinoxaline (253 mg, yield: 53%) in a white powder form.

(223) .sup.1H-NMR (DMSO-d.sub.6) ppm: 0.85-1.05 (1H, m), 1.1-1.4 (2H, m), 1.4-1.65 (3H, m), 1.65-1.8 (1H, m), 1.9-2.05 (1H, m), 2.8-3.05 (2H, m), 3.05-3.2 (3H, m), 3.2-3.5 (1H, m), 7.1-7.2 (2H, m), 7.35-7.45 (2H, m), 9.2-9.65 (2H, m).

Example 4

Production of cis-4-(benzo[b]thiophen-5-yl)-1,2,2-trimethyldecahydroquinoxaline hydrochloride

(224) Relative Configuration

(225) ##STR00077##

(226) A 37% aqueous formaldehyde solution (0.81 mL, 9.9 mmol) was added to a methanol (10 mL) solution of cis-1-(benzo[b]thiophen-5-yl)-3,3-dimethyldecahydroquinoxaline (298 mg, 0.992 mmol) with stirring at room temperature. After 30 minutes, sodium cyanoborohydride (311 mg, 4.96 mmol) and acetic acid (0.30 mL) were added to the reaction solution at room temperature, and the mixture was stirred overnight. The solvent was distilled off from the reaction mixture under reduced pressure. Then, a saturated aqueous solution of sodium bicarbonate (50 mL) was added thereto, followed by extraction with ethyl acetate (50 mL) twice. The organic layer was washed with water twice and with saturated saline once, then dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=10:1) to obtain a brown oil. 4 N hydrochloric acid/ethyl acetate (0.6 mL) was added to an ethanol solution of the obtained oil with stirring at room temperature, and the deposited crystal was collected by filtration. The obtained crystal was washed with ethyl acetate and then dried under reduced pressure to obtain cis-4-(benzo[b]thiophen-5-yl)-1,2,2-trimethyldecahydroquinoxaline hydrochloride (258 mg, yield: 74%) in a white powder form.

(227) .sup.1H-NMR (CDCl.sub.3) ppm: 1.17-1.34 (1H, m), 1.37-1.74 (2H, m), 1.47 (3H, s), 1.87-2.04 (1H, m), 1.90 (3H, s), 2.20-2.30 (1H, m), 2.39-2.54 (1H, m), 2.64-2.88 (2H, m), 2.75 (3H, d, J=4.9 Hz), 3.12 (1H, d, J=13.2 Hz), 3.69-3.74 (1H, m), 3.85-3.93 (1H, m), 3.87 (1H, d, J=13.2 Hz), 7.01 (1H, dd, J=8.8, 2.3 Hz), 7.21-7.32 (2H, m), 7.44 (1H, d, J=5.4 Hz), 7.75 (1H, d, J=8.8 Hz), 11.20 (1H, brs).

Example 5

Production of 2-(trans-4-(naphthalen-2-yl)decahydroquinoxalin-1-yl)ethanol dihydrochloride

(228) Relative Configuration

(229) ##STR00078##

(230) Tetra-n-butyl ammonium fluoride (1 M in THF) (2.1 mL, 2.1 mmol) was added to a THF (10 mL) solution of trans-1-(2-(tert-butyldimethylsilyloxy)ethyl)-4-(naphthalen-2-yl)decahydroquinoxaline (820 mg, 1.93 mmol) with stirring at room temperature, and the mixture was stirred overnight. To the reaction mixture, ethyl acetate was added, and the resultant mixture was washed with water twice and with saturated saline once, then dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (methylene chloride:methanol=10:1) to obtain a colorless, amorphous solid (534 mg). A 319 mg aliquot of the obtained solid was dissolved in ethanol. To the solution, 4 N hydrochloric acid/ethyl acetate (1.0 mL) was added with stirring at room temperature, and the deposited crystal was collected by filtration. The obtained crystal was washed with ethyl acetate and then dried under reduced pressure to obtain 2-(trans-4-(naphthalen-2-yl)decahydroquinoxalin-1-yl)ethanol dihydrochloride (365 mg, yield: 49%) in a white powder form.

(231) .sup.1H-NMR (CDCl.sub.3) ppm: 1.23-1.76 (4H, m), 1.86-2.08 (3H, m), 2.43-2.48 (1H, m), 3.18-3.25 (1H, m), 3.72-3.77 (2H, m), 3.93-3.98 (1H, m), 3.93-4.78 (1H, br), 4.08-4.20 (2H, m), 4.39-4.55 (1H, m), 4.57-4.78 (2H, m), 4.97-5.06 (1H, m), 7.61-7.68 (3H, m), 7.81-8.07 (3H, m), 8.17-8.69 (1H, br), 12.73 (1H, brs), 14.91 (1H, brs).

Example 77

Production of (4aS,8aR)-1-(7-fluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline

(232) Absolute Configuration

(233) ##STR00079##

(234) A toluene (4 ml) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (168 mg, 0.998 mmol), 4-bromo-7-fluorobenzofuran (258 mg, 1.20 mmol), Pd(OAc).sub.2 (11.2 mg, 0.0499 mmol), t-Bu.sub.3P.HBF.sub.4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 4 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Insoluble matter was filtered, and the residue was washed with AcOEt (5 ml2). Then, the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a colorless oil (167 mg). This oil was crystallized from hexane (1 mL) to obtain (4aS,8aR)-1-(7-fluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline (107 mg, yield: 35%) in a white powder form.

(235) .sup.1H-NMR (CDCl.sub.3) ppm: 1.0-1.45 (11H, m), 1.6-1.8 (3H, m), 1.8-1.95 (1H, m), 2.70 (1H, d, J=11.3 Hz), 3.04 (1H, d, J=11.3 Hz), 3.50 (1H, ddd, J=3.8, 3.8, 12.1 Hz), 3.55-3.65 (1H, m), 6.47 (1H, dd, J=3.4, 8.6 Hz), 6.84 (1H, dd, J=2.5, 2.5 Hz), 6.89 (1H, dd, J=8.6, 10.4 Hz), 7.60 (1H, d, J=2.2 Hz).

Example 106

Production of (4aS,8aR)-1-(4-chlorophenyl)-3,3-dimethyldecahydroquinoxaline hydrochloride

(236) Absolute Configuration

(237) ##STR00080##

(238) A toluene (10 ml) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (252 mg, 1.50 mmol), 1-bromo-4-chlorobenzene (345 mg, 1.80 mmol), Pd(OAc).sub.2 (16.8 mg, 0.0748 mmol), t-Bu.sub.3P.HBF.sub.4 (21.8 mg, 0.0751 mmol), and NaOt-Bu (202 mg, 2.10 mmol) was stirred for 5 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Then, insoluble matter was filtered through celite. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt). The obtained oil was dissolved in 1 N HCl-EtOH (3 mL), and the solvent was distilled off under reduced pressure. The deposited crystal was recrystallized from ethanol/acetone to obtain (4aS,8aR)-1-(4-chlorophenyl)-3,3-dimethyldecahydroquinoxaline hydrochloride (262 mg, yield: 55%) in a white powder form.

(239) .sup.1H-NMR (DMSO-d.sub.6) ppm: 1.2-1.45 (6H, m), 1.51 (3H, s), 1.6-2.1 (5H, m), 2.93 (1H, d, J=13.6 Hz), 3.40 (1H, d, J=13.8 Hz), 3.65-3.85 (1H, m), 3.9-4.1 (1H, m), 6.8-7.05 (2H, m), 7.1-7.35 (2H, m), 8.14 (1H, br), 9.77 (1H, br).

Example 112

Production of (4aS,8aR)-1-(3-chloro-4-fluorophenyl)-3,3-dimethyldecahydroquinoxaline hydrochloride

(240) Absolute Configuration

(241) ##STR00081##

(242) A toluene (10 ml) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (168 mg, 0.998 mmol), 4-bromo-2-chloro-1-fluorobenzene (251 mg, 1.20 mmol), Pd(OAc).sub.2 (11.2 mg, 0.0500 mmol), t-Bu.sub.3P.HBF.sub.4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 5 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Then, insoluble matter was filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt). The obtained oil was dissolved in 1 N HCl-EtOH (3 mL), and ethanol was distilled off under reduced pressure. The deposited crystal was recrystallized from ethanol/acetone to obtain (4aS,8aR)-1-(3-chloro-4-fluorophenyl)-3,3-dimethyldecahydroquinoxaline hydrochloride (153 mg, yield: 46%) in a white powder form.

(243) .sup.1H-NMR (DMSO-d.sub.6) ppm: 1.15-1.45 (6H, m), 1.51 (3H, s), 1.6-1.9 (4H, m), 1.9-2.05 (1H, s), 2.01 (1H, d, J=8.2 Hz), 3.3-3.45 (1H, m), 3.65-3.8 (1H, m), 3.95-4.1 (1H, m), 6.85-7.0 (1H, m), 7.12 (1H, dd, J=3.0, 6.2 Hz), 7.25 (1H, dd, J=9.1, 9.1 Hz), 8.13 (1H, br), 9.86 (1H, br).

Example 150

Production of 5-((4aR,8aS)-3,3-dimethyldecahydroquinoxalin-1-yl)-1-methyl-1H-indole-2-carbonitrile

(244) ##STR00082##

(245) A toluene (4 ml) suspension of (4aS,8aR)-2,2-dimethyldecahydroquinoxaline (168 mg, 0.998 mmol), 5-bromo-1-methyl-1H-indole-2-carbonitrile (259 mg, 1.10 mmol), Pd(OAc).sub.2 (11.2 mg, 0.0499 mmol), t-Bu.sub.3P.HBF.sub.4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 4 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Insoluble matter was filtered through celite, and the residue was washed with CH.sub.2Cl.sub.2:MeOH (3:1) (5 mL2). Then, the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a colorless oil. This oil was crystallized from hexane (1 mL) to obtain (4aS,8aR)-1-(7-fluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline (148 mg, yield: 46%) in a pale yellow powder form.

(246) .sup.1H-NMR (CDCl.sub.3) ppm: 0.7-2.3 (15H, m), 2.7-3.2 (2H, m), 3.5-3.8 (2H, m), 3.85 (3H, s), 6.95-7.05 (2H, m), 7.15-7.3 (2H, m).

Example 237

Production of (4aS,8aS)-1-(3-chloro-4-cyanophenyl)-3,3-dimethyldecahydroquinoxaline hydrochloride

(247) Absolute Configuration

(248) ##STR00083##

(249) A toluene (10 ml) suspension of (4aS,8aS)-2,2-dimethyldecahydroquinoxaline (400 mg, 2.38 mmol), 4-bromo-2-chlorobenzonitrile (669 mg, 3.09 mmol), Pd(OAc).sub.2 (53 mg, 0.24 mmol), t-Bu.sub.3P.HBF.sub.4 (70 mg, 0.24 mmol), and t-BuONa (320 mg, 3.33 mmol) was stirred for 5 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled. Then, insoluble matter was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (CH.sub.2Cl.sub.2/MeOH) to obtain an orange amorphous solid. This amorphous solid was dissolved in ethyl acetate (5 mL). A crystal deposited by the addition of 4 N HCl/AcOEt (0.6 mL) was collected by filtration and dried under reduced pressure to obtain (4aS,8aS)-1-(3-chloro-4-cyanophenyl)-3,3-dimethyldecahydroquinoxaline (304 mgm, 48%) in a pale orange powder form.

(250) .sup.1H-NMR (CDCl.sub.3) ppm: 1.05-1.20 (1H, m), 1.23-1.44 (2H, m), 1.54-2.10 (4H, m), 1.63 (3H, s), 1.68 (3H, s), 2.35-2.40 (1H, m), 2.89 (1H, d, J=12.7 Hz), 3.19 (2H, br), 3.34 (1H, d, J=12.7 Hz), 7.06 (1H, dd, J=8.4, 2.0 Hz), 7.20 (1H, d, J=2.0 Hz), 7.61 (1H, d, J=8.4 Hz), 9.62 (1H, brs), 9.90 (1H, br) Example 579

Production of (4aR,8aS)-4-(7-methoxybenzofuran-4-yl)octahydro-1H-spiro[cyclobutane-1,2-quinoxaline]

(251) Absolute Configuration

(252) ##STR00084##

(253) A toluene (4 ml) suspension of (4aR,8aS)-octahydro-1H-spiro[cyclobutane-1,2-quinoxaline] (180 mg, 0.998 mmol), 4-bromo-7-methoxybenzofuran (250 mg, 1.10 mmol), Pd(OAc).sub.2 (11.2 mg, 0.0499 mmol), t-Bu.sub.3P.HBF.sub.4 (14.5 mg, 0.0500 mmol), and NaOt-Bu (135 mg, 1.40 mmol) was stirred for 4 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Insoluble matter was filtered, and the residue was washed with AcOEt (5 mL2). Then, the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a colorless amorphous solid. This solid was crystallized from hexane (1 mL) to obtain (4aR,8aS)-4-(7-methoxybenzofuran-4-yl)octahydro-1H-spiro[cyclobutane-1,2-quinoxaline] (107 mg, yield: 35%) in a white powder form.

(254) .sup.1H-NMR (CDCl.sub.3) ppm: 0.95-1.1 (2H, m), 1.3-1.4 (1H, m), 1.4-2.1 (11H, m), 2.25-2.4 (1H, m), 3.01 (1H, d, J=11.0 Hz), 3.17 (1H, d, J=11.1 Hz), 3.40 (1H, br), 3.45-3.5 (1H, m), 3.97 (3H, s), 6.58 (1H, d, J=8.4 Hz), 6.70 (1H, d, J=8.4 Hz), 6.80 (1H, d, J=2.1 Hz), 7.58 (1H, d, J=2.1 Hz).

Example 580

Production of (4aS,8aR)-1-(6,7-difluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline hydrochloride

(255) Absolute Configuration

(256) ##STR00085##

(257) A toluene (6 ml) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (252 mg, 1.50 mmol), 4-bromo-6,7-difluorobenzofuran (384 mg, 1.65 mmol), Pd(OAc).sub.2 (16.8 mg, 0.0748 mmol), t-Bu.sub.3P.HBF.sub.4 (21.8 mg, 0.0751 mmol), and NaOt-Bu (202 mg, 2.10 mmol) was stirred for 3 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Then, insoluble matter was filtered through celite. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a pale yellow oil (193 mg). This oil was dissolved in ethanol (2 mL). To the solution, 1 N HCl-EtOH (1.2 mL) was added, and the mixture was stirred. The deposited crystal was collected by filtration, washed with ethyl acetate, and then dried under reduced pressure to obtain (4aS,8aR)-1-(6,7-difluorobenzofuran-4-yl)-3,3-dimethyldecahydroquinoxaline hydrochloride (167 mg, yield: 31%) in a white powder form.

(258) .sup.1H-NMR (DMSO-d.sub.6) ppm: 1.01-1.17 (2H, m), 1.34-1.44 (1H, m), 1.48 (3H, s), 1.52 (3H, s), 1.59-2.07 (5H, m), 3.00 (1H, d, J=13.0 Hz), 3.28 (1H, d, J=13.2 Hz), 3.75-3.9 (1H, m), 4.0-4.15 (1H, m), 6.83 (1H, dd, J=5.9, 13.5 Hz), 7.36 (1H, dd, J=2.6, 2.6 Hz), 8.0-8.2 (2H, m), 9.7-9.9 (1H, m).

Example 581

Production of (4aS,8aS)-1-(2-cyano-1-(triisopropylsilyl)-1H-indol-5-yl) 3,3-dimethyldecahydroquinoxaline

(259) Absolute Configuration

(260) ##STR00086##

(261) A toluene (5 ml) suspension of (4aS,8aS)-2,2-dimethyldecahydroquinoxaline (200 mg, 1.19 mmol), 5-bromo-1-(triisopropylsilyl)-1H-indole-2-carbonitrile (493 mg, 1.31 mmol), Pd(OAc).sub.2 (13.3 mg, 0.0594 mmol), tBu.sub.3P.HBF.sub.4 (17.2 mg, 0.0594 mmol), and t-BuONa (137 mg, 1.43 mmol) was stirred at 100 C. for 4 hours in a nitrogen atmosphere. Insoluble matter was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by basic silica gel column chromatography (AcOEt/hexane) to obtain (4aS,8aS)-1-(2-cyano-1-(triisopropylsilyl)-1H-indol-5-yl) 3,3-dimethyldecahydroquinoxaline (430 mg, 78%) in a white amorphous solid form.

(262) .sup.1H-NMR (CDCl.sub.3) ppm: 0.75-1.38 (26H, m), 1.41 (3H, s), 1.54-1.77 (4H, m), 2.01 (1H, sextet, J=7.5 Hz), 2.25-2.32 (1H, m), 2.65 (1H, d, J=11.2 Hz), 2.75-2.85 (2H, m), 7.11 (1H, dd, J=2.0, 9.1 Hz), 7.32 (1H, d, J=2.0 Hz), 7.33 (1H, d, J=0.5 Hz), 7.50 (1H, d, J=9.1 Hz).

Example 582

Production of (4aS,8aS)-1-(2-cyano-1H-indol-5-yl) 3,3-dimethyldecahydroquinoxaline

(263) ##STR00087##

(264) Tetrabutylammonium fluoride (1 M THF solution, 0.73 mL, 0.73 mmol) was added to an anhydrous tetrahydrofuran (5 mL) solution of (4aS,8aS)-1-(2-cyano-1-(triisopropylsilyl)-1H-indol-5-yl) 3,3-dimethyldecahydroquinoxaline (170 mg, 0.366 mmol) at room temperature, and the reaction solution was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (AcOEt/hexane=1/10.fwdarw.1/1). The solvent was removed under reduced pressure. The obtained residue was recrystallized from ethyl acetate/n-hexane to obtain (4aS,8aS)-1-(2-cyano-1H-indol-5-yl) 3,3-dimethyldecahydroquinoxaline (30 mg, yield: 27%) in a white powder form.

(265) .sup.1H-NMR (DMSO-d.sub.6) ppm: 0.82-1.00 (4H, m), 1.18-1.34 (6H, m), 1.42-1.67 (5H, m), 2.19-2.27 (1H, m), 2.55 (1H, d, J=10.9 Hz), 2.59-2.69 (2H, m), 7.11 (1H, dd, J=1.8, 8.8 Hz), 7.26 (1H, d, J=0.8 Hz), 7.32 (1H, d, J=1.8 Hz), 7.36 (1J, d, J=8.8 Hz).

Example 583

Production of (4aS,8aR)-1-(7-chloro-2,3-dihydro-1H-inden-4-yl)-3,3-dimethyldecahydroquinoxaline

(266) Absolute Configuration

(267) ##STR00088##

(268) A toluene (1 mL) solution of bis(tri-tert-butylphosphine)palladium (25.6 mg, 0.0501 mmol) was added to a toluene (4 ml) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (168 mg, 0.998 mmol), 4-bromo-7-chloro-2,3-dihydro-1H-indene (255 mg, 1.10 mmol), and NaOt-Bu (135 mg, 1.40 mmol), and the mixture was stirred for 4 hours under reflux in a nitrogen atmosphere. The reaction solution was cooled to room temperature. Then, water (0.5 mL) and AcOEt (10 mL) were added thereto, and the mixture was stirred. MgSO.sub.4 was further added thereto, and the mixture was stirred. Insoluble matter was filtered through celite, and the residue was washed with AcOEt (5 mL2). Then, the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (Hex-AcOEt) to obtain a white solid (167 mg). This solid was recrystallized from ethanol/water to obtain (4aS,8aR)-1-(7-chloro-2,3-dihydro-1H-inden-4-yl)-3,3-dimethyldecahydroquinoxaline (136 mg, yield: 43%) in a white powder form.

Example 584

Production of (4aS,8aS)-1-(6-cyanonaphthalen-2-yl)-3,3-dimethyldecahydroquinoxaline dihydrochloride

(269) Absolute Configuration

(270) ##STR00089##

(271) A toluene (5 mL) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (200 mg, 1.19 mmol), 6-bromo-2-naphthonitrile (303 mg, 1.31 mmol), Pd(OAc).sub.2 (13.3 mg, 0.0594 mmol), tBu.sub.3P.HBF.sub.4 (17.2 mg, 0.0594 mmol), and t-BuONa (137 mg, 1.43 mmol) was stirred at 100 C. for 4 hours. Insoluble matter was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by basic silica gel column chromatography (AcOEt/hexane). The solvent was removed under reduced pressure. The obtained residue was dissolved in ethyl acetate. To this solution, 1 N hydrochloric acid-ethanol was added, and the deposited crystal was collected by filtration. The obtained crystal was dried under reduced pressure to obtain (4aS,8aS)-1-(6-cyanonaphthalen-2-yl)-3,3-dimethyldecahydroquinoxaline dihydrochloride (303 mg, yield: 65%) in a white powder form.

(272) .sup.1H-NMR (DMSO-d.sub.6) ppm: 1.10-1.50 (6H, m), 1.56-1.90 (7H, m), 2.00-2.14 (1H, m), 3.08-3.45 (4H, m), 7.45 (1H, dd, J=2.0, 8.9 Hz), 7.64 (1H, d, J=1.8 Hz), 7.73 (1H, dd, J=1.6, 8.6 Hz), 8.00 (1H, d, J=8.6 Hz), 8.04 (1H, d, J=8.6 Hz), 8.49 (1H, s), 9.10-9.28 (1H, br), 10.04-10.28 (1H, br).

Example 585

Production of (4aS,8aS)-3,3-dimethyl-1-(1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)decahydroquinoxaline

(273) Absolute Configuration

(274) ##STR00090##

(275) A toluene (5 mL) suspension of (4aS,8aS)-2,2-dimethyldecahydroquinoxaline (200 mg, 1.19 mmol), 4-bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (462 mg, 1.31 mmol), Pd(OAc).sub.2 (13.3 mg, 0.0594 mmol), tBu.sub.3P.HBF.sub.4 (17.2 mg, 0.0594 mmol), and t-BuONa (137 mg, 1.43 mmol) was stirred at 100 C. for 4 hours in a nitrogen atmosphere. Insoluble matter was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by basic silica gel column chromatography (AcOEt/hexane) to obtain (4aS,8aS)-3,3-dimethyl-1-(1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)decahydroquinoxaline (439 mg, 84%) in a white amorphous solid form.

(276) .sup.1H-NMR (CDCl.sub.3) ppm: 0.95-1.20 (22H, m), 1.36-1.45 (3H, m), 1.52 (3H, s), 1.65-1.92 (7H, m), 2.11-2.20 (1H, m), 2.57-2.67 (2H, m), 2.83-2.95 (1H, m), 3.26-(1H, d, J=11.7 Hz), 6.55 (1H, d, J=3.5 Hz), 6.63 (1H, d, J=5.3 Hz), 7.18 (1H, d, J=3.5 Hz), 8.12 (1H, d, J=5.3 Hz).

Example 586

Production of (4aS,8aS)-3,3-dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-4-yl)decahydroquinoxaline fumarate

(277) ##STR00091##

(278) Tetrabutylammonium fluoride (1 M THF solution, 1.95 mL, 1.95 mmol) was added to an anhydrous tetrahydrofuran (5 mL) solution of (4aS,8aS)-3,3-dimethyl-1-(1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)decahydroquinoxaline (430 mg, 0.976 nmol), and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (AcOEt/hexane=1/10.fwdarw.1/1) to obtain a product (370 mg, 1.30 mmol) in an oil form. This oil was dissolved in ethanol (5 mL). To this solution, an ethanol (5 mL) solution of fumaric acid (151 mg) was added, and ethanol was removed under reduced pressure. The obtained solid was recrystallized from ethanol/ethyl acetate to obtain 5-((4aS,8aS)-3,3-dimethyldecahydroquinoxalin-1-yl)-1H-indole-2-carbonitrile (246 mg, yield: 63%) in a white powder form.

(279) .sup.1H-NMR (DMSO-d.sub.6) ppm: 0.94-1.09 (1H, m), 1.20 (3H, s), 1.26-1.55 (7H, m), 1.68-1.78 (1H, m), 1.85-2.04 (2H, m), 2.81-2.93 (1H, m), 2.95-3.23 (3H, m), 6.36-6.42 (1H, m), 6.49 (2H, s), 6.71 (1H, d, J=5.2 Hz), 7.32-7.38 (1H, m), 8.09 (1H, d, J=5.2 Hz), 8.50-11.20 (1H, br), 11.59 (1H, s).

Example 587

Production of (4aS,8aS)-1-(4-(difluoromethoxy)-3-fluorophenyl)-3,3-dimethyldecahydroquinoxaline dihydrochloride

(280) Absolute Configuration

(281) ##STR00092##

(282) A toluene (5 mL) suspension of (4aR,8aS)-2,2-dimethyldecahydroquinoxaline (200 mg, 1.19 mmol), 4-bromo-1-difluoromethoxy-2-fluorobenzene (315 mg, 1.31 mmol), Pd(OAc).sub.2 (13.3 mg, 0.0594 mmol), tBu.sub.3P.HBF.sub.4 (17.2 mg, 0.0594 mmol), and t-BuONa (137 mg, 1.43 mmol) was stirred at 100 C. for 4 hours. Insoluble matter was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by basic silica gel column chromatography (AcOEt/hexane). The solvent was removed under reduced pressure. The obtained residue was dissolved in ethyl acetate. To this solution, 1 N hydrochloric acid-ethanol was added, and the deposited crystal was collected by filtration. The obtained crystal was dried under reduced pressure to obtain (4aS,8aS)-1-(4-difluoromethoxy-3-fluorophenyl)-3,3-dimethyldecahydroquinoxaline dihydrochloride (303 mg, yield: 65%) in a white powder form.

(283) .sup.1H-NMR (DMSO-d.sub.6) ppm: 1.01-1.39 (6H, m), 1.49-1.67 (6H, m), 1.67-1.77 (1H, m), 1.96-2.05 (1H, m), 2.81-2.95 (2H, m), 3.02 (1H, d, J=12.5 Hz), 3.10-3.23 (1H, m), 6.96-7.01 (1H, m), 7.02 (0.25H, s), 7.17 (1H, dd, J=2.5, 12.1 Hz), 7.20 (0.5H, s), 7.33 (1H, t, J=8.9 Hz), 7.39 (0.25H, s), 9.04-9.21 (1H, m), 9.70-9.85 (1H, m).

(284) Compounds of Examples 6 to 76, 78 to 105, 107 to 111, 113 to 149, 151 to 236, 238 to 578, 588 to 1656 shown in tables below were produced in the same way as in the Examples using corresponding appropriate starting materials. In these tables, for example, the produced compounds have physical properties such as a crystalline form, m.p. (melting point), salt, .sup.1H-NMR, and MS (mass spectrum).

(285) TABLE-US-00001 TABLE 1 Relative configuration Exam- ple X R.sup.4 1H-NMR Salt 6 CH.sub.3 1H-NMR (DMSO-d6) ppm: 1.39 (3H, s), 1.49 (3H, s), 1.56-2.20 (6 H, m), 3.04 (1H, d, J = 13.3 Hz), 3.61 (1H, d, J = 13.3 Hz), 3.75-3.90 (1H, m), 4.40-4.55 (1 H, m), 7.17-7.30 (2 H, m), 7.33-7.45 (2 H, m), 7.65-7.63 (3 H, m), 8.35-8.80 (1 H, brr), 9.70-9.95 (1 H, brr). Hydro- chloride 7 CH.sub.3 1H-NMR (DMSO-d6) ppm: 1.39 (3H, s), 1.48 (3H, s), 1.55-2.19 (5H, m), 3.01 (1H, d, J = 13.2 Hz), 3.45 (1H, d, J = 13.2 Hz), 3.70-3.87 (1H, m), 4.25-4.45 (1H, m), 7.17 (1H, dd, J = 2.2, 9.0 Hz), 7.29 (1H, d, J = 6.4 Hz), 7.37 (1H, d, J = 2.2 Hz), 7.67 (1H, d, J = 6.4 Hz), 7.81 (1H, J =8.9 Hz), 8.42-8.65 (1H, br), 9.80-10.05 (1H, br). Hydro- chloride 8 O 1H-NMR (DMSO-d6) ppm: 1.42 (3H, s), 1.49 (3H, s), 3.07 (1H, d, J = 13.4 Hz), 3.53 (1H, d, J = 13.4 Hz), 3.72 (1H, t, J = 8.6 Hz), 3.90-4.17 (4H, m), 4.79-4.94 (1H, m), 7.19 (1H, dd, J = 2.4, 5.9 Hz), 7.30 (1H, dd, J = 0.5, 5.4 Hz), 7.41 (1H, d, J = 2.4 Hz), 7.69 (1H, d, J = 5.4 Hz), 7.83 (1H, d, J = 6.9 Hz), 8.60-8.85 (1H, br), 10.41-10.65 (1H, br). Hydro- chloride 9 CH.sub.3 1H-NMR (DMSO-d6) ppm: 1.33 (3H, s), 1.44 (3H, s), 1.55-2.19 (6H, m), 2.92 (1H, d, J = 13.5 Hz), 3.45 (1H, d, J = 13.5 Hz), 3.68-3.82 (1H, m), 4.20-4.35 (1H, m), 6.98 (2H, d, J = 9.0 Hz), 7.23 (2H, d, J = 9.0 Hz), 8.40-8.86 (1H, br), 9.75-10.05 (1H, br). Hydro- chloride 10 CH.sub.3 1H-NMR (DMSO-d6) ppm: 1.32 (3H, s), 1.43 (3H, s), 1.55-2.15 (6H, m), 2.95 (1H, d, J = 13.6 Hz), 3.58 (1H, d, J = 13.8 Hz), 3.65-3.82 (1H, m), 4.20-4.40 (1H, m), 5.97 (1H, dd, J = 2.9, 9.0 Hz), 7,19 (1H, d, J = 2.9 Hz), 7.40 (1H, d, J = 9.0 Hz), 8.40-8.52 (1H, br), 9.70-9.95 (1H, br). Hydro- chloride 11 O 1H-NMR (DMSO-d6) ppm: 1.34 (3H, s), 1.44 (3H, s), 2.99 (1H, d, J = 13.5 Hz), 3.50-3.73 (2H, m), 3.85-4.11 (4H, m), 4.71-4.90 (1H, m), 6.95-7.08 (1H, m), 7.20-7.30 (1H, m), 7.42 (1H, d, J 9.0 Hz), 8.60-8.89 (1H, br), 10.20-10.61 (1H, br). Hydro- chloride

(286) TABLE-US-00002 TABLE 2 Relative configuration 00 Exam- ple X R.sup.4 NMR Salt 12 CH.sub.3 01 1H-NMR (DMSO-d6) ppm: 1.30-1.50 (4H, m), 1.80 (3H, s), 1.55-2.05 (4H, m), 2.05-2.23 (1H, m), 2.82-2.96 (1H, m), 3.06-3.25 (1H, m), 3.25-3.45 (2H, m), 4.00-5.25 (1H, br), 7.29 (1H, dd, J = 2.1, 8.8 Hz), 7.35-7.60 (3H, m), 7.76-7.94 (3H, m), 9.29-9.57 (1H, br), 9.78-10.08 (1H, br). Dihydro- chloride 13 CH.sub.3 02 1H-NMR (DMSO-d6) ppm: 1.30-1.50 (4H, m), 1.80 (3H, s), 1.55-2.07 (6H, m), 2.94 (1H, d, J = 12.4 Hz), 3.05-3.45 (3H, m), 4.40-5.88 (1H, br), 7.18 (1H, dd, J = 1.7, 8.7 Hz), 7.42 (1H, d, J = 5.4 Hz), 7.55 (1H, d, J = 1.7 Hz), 7.76 (1H, d, J = 5.4 Hz), 7.93 (1H, d, J = 5.7 Hz), 9.40-9.70 (1H, br), 9.80-10.12 (1H, br). Dihydro- chloride 14 O 03 1H-NMR (DMSO-d6) ppm: 1.44 (3H, s), 1.62 (3H, s), 2.90 (1H, d, J = 12.7 Hz), 3.34 (1H, d, J = 12.7 Hz), 3.48-3.51 (2H, m), 3.75-9.95 (2H, m), 4.00-4.10 (1H, m), 4.11-4.28 (1H, m), 4.75-5.01 (1H, br), 7.12 (1H, dd, J = 2.1, 8.7 Hz), 7.40 (1H, d, J = 5.4 Hz), 7.62 (1H, d, J = 2.1 Hz), 7.75 (1H, d, J = 5.4 Hz), 7.91 (1H, d, J = 5.7 Hz), 9.88-10.08 (1H, br), 10.08-10.80 (1H, br). Dihydro- chloride 15 CH.sub.3 04 1H-NMR (DMSO-d6) ppm: 1.25-1.45 (4H, m), 1.52 (3H, s), 1.65-1.88 (3H, m), 1.88-2.10 (2H, m), 2.84 (1H, d, J = 12.8 Hz), 2.94-3.10 (1H, m), 3.18-3.39 (2H, m), 4.03-4.70 (1H, br), 7.09 (1H, dd, J = 2.6, 6.7 Hz), 7.33 (1H, d, J = 2.6 Hz), 7.52 (1H, d, J = 8.7 Hz), 9.25-9.83 (1H, br), 9.72-10.04 (1H, br). Dihydro- chloride 16 CH.sub.3 05 1H-NMR (DMSO-d6) ppm: 1.24-1.45 (4H, m), 1.56 (3H, s), 1.83-2.04 (6H, m), 2.82 (1H, d, J = 12.8 Hz), 2.90-3.08 (1H, m), 3.13 (1H, d, J = 12.8 Hz), 3.26-3.28 (1H, m), 4.35-5.05 (1H, br), 7.05-7.18 (2H, m), 7.30-7.40 (2H, m), 9.30-9.55 (1H, br), 9.75-10.02 (1H, br). Dihydro- chloride 17 O 06 1H-NMR (DMSO-d6) ppm: 1.46 (3H, s), 1.84 (3H, s), 2.89 (1H, d, J = 12.9 Hz), 3.47-3.88 (3H, m), 3.81-3.97 (2H, m), 4.01-4.15 (1H, m), 4.34-4.46 (1H, m), 7.28 (1H, dd, J = 2.3, 5.8 Hz), 7.38-7.44 (1H, m), 7.44-7.50 (1H, m), 7.50-7.54 (1H, m), 7.80-7.87 (2H, m), 7.59 (1H, d, J = 8.1 Hz), 9.84-10.04 (1H, br), 10.04-10.20 (1H, br). Hydro- chloride

(287) TABLE-US-00003 TABLE 3 Relative configuration 07 Example R.sup.4 NMR Salt 18 08 1H-NMR (DMSO-d6) ppm (80 C.): 1.40 (3 H, s), 1.43-1.70 (5 H, m), 1.72-1.92 (2 H, m), 1.95-2.23 (4 H, m), 3.39-3.52 (2 H, m), 3.55-4.02 (1 H, br), 4.02-4.14 (1 H, m), 5.64-6.00 (1 H, br), 7.31-7.38 (1 H, m), 7.38-7.47 (2 H, m), 7.50-7.57 (1H, m), 7.72-7.85 (3 H, m), 8.44-8.80 (1 H, br), 9.04-9.40 (1 H, br). Dihydro- chloride 19 09 1H-NMR (DMSO-d6) ppm (80 C.): 1.31-1.51 (5H, m), 1.54 (3H, s), 1.83-1.76 (2H, m), 1.87-2.12 (3H, m), 2.12-2.23 (1H, m), 3.22-3.44 (2H, m), 3.85-4.02 (2H, m), 5.00-5.90 (1H, br), 7.33 (1H, d, J = 6.6 Hz), 7.36 (1H, d, J = 5.4 Hz), 7.70 (1H, d, J = 5.4 Hz), 7.77 (1H, s), 7.89 (1H, d, J = 8.8 Hz), 8.25-8.74 (1H, br), 9.00-9.54 (1H, br). Dihydro- chloride 20 0 1H-NMR (DMSO-d6) ppm: 1.34 (3H, s), 1.39-1.55 (5H, m), 1.67-1.90 (3H, m), 1.90-2.15 (3H, m), 3.17-3.35 (2H, m), 3.75-4.02 (2H, m), 7.10-7.20 (2H, m), 7.25-7.37 (2H, m), 7.37-7.90 (1H, br), 5.45-6.69 (1H, br), 5.59-9.19 (1H, br). Dihydro- chloride

(288) TABLE-US-00004 TABLE 4 Relative configuration Exam- ple R.sup.4 NMR Salt 21 1H-NMR (DMSO-d6) ppm (80 C.): 1.43 (3H, s), 1.47 (3H, s), 1.61-1.65 (1H, m), 1.72-1.90 (3H, m), 1.93-2.09 (2H, m), 2.12-2.29 (2H, m), 3.59-3.80 (1H, m), 3.81-3.92 (1H, m), 3.98-4.11 (1H, m), 4.11-4.70 (2H, br), 7.22-7.45 (4H, m), 7.70-7.85 (3H, m), 9.15-9.49 (1H, br), 9.49-9.58 (1H, br). Dihydro- chloride 22 1H-NMR (DMSO-d6) ppm (80 C.): 1.48 (3H, s), 1.49 (3H, s), 1.85-1.94 (5H, m), 2.10-2.44 (3H, m), 3.89-3.90 (1H, m), 3.85-4.00 (1H, m), 4.00-4.20 (1H, m), 4.80-4.96 (1H, m), 4.95-6.06 (1H, br), 7.36-7.55 (2H, m), 7.76 (1H, d, J = 5.4 Hz), 7.78 (1H, brs), 7.98 (1H, d, J = 6.8 Hz), 9.40-9.65 (1H, br), 9.86-10.11 (1H, br). Dihydro- chloride 23 1H-NMR (DMSO-d6) ppm (80 C.): 1.44 (6H, m), 1.47-1.84 (1H, m), 1.67-1.54 (3H, m), 1.85-2.13 (3H, m), 2.14-2.30 (1H, m), 3.60-3.80 (2H, m), 3.92-4.07 (1H, m), 5.80-5.70 (1H, br), 7.04 (1H, d, J = 6.9 Hz), 7.25 (1H, d, J = 5.9 Hz), 9.40-9.75 (2H, br). Dihydro- chloride

(289) TABLE-US-00005 TABLE 5 Relative configuration Ex- am- ple R.sup.1 R.sup.4 NMR Salt 24 H 1H-NMR (DMSO) ppm: 1.29-1.67 (3H, m), 1.46 (3H, s), 1.57 (3H, s), 1.89-1.91 (4H, m), 1.98-2.09 (1H, m), 3.07 (1H, d, J = 13.5 Hz), 3.51 (1H, d, J = 13.5 Hz), 3.73-3.92 (1H, m), 4.11-4.30 (1H, m), 7.18 (1H, d, J = 2.2 Hz), 7.22-7.28 (1H, m), 7.36-7.43 (2H, m), 7.88-7.50 (3H, m), 5.02-8.51 (1H, m), 9.52-9.91 (1H, br) Hydro- chloride 25 CH.sub.3 1H-NMR (CDCl3) ppm: 1.21-1.35 (1H, m), 1.40-1.53 (1H, m), 1.48 (3H, s), 1.55-1.77 (2H, m), 1.93 (3H, s), 1.98-2.05 (1H, m), 2.18-2.34 (1H, m), 2.37-2.58 (1H, m), 2.87-2.58 (1H, m), 2.82 (3H, d, J = 4.9 Hz), 3.26 (1H, d, J = 13.4 Hz), 3.64-3.77 (1H, m), 3.91 (1H, d, J = 13.4 Hz), 3.97-4.04 (1H, m), 7.07-7.09 (1H, m), 7.17-7.22 (1H, m), 7.30-7.35 (1H, m), 7.40-7.46 (1H, m), 7.68-7.53 (3H, m), 11.27 (1H, brs) Hydro- chloride 26 H 1H-NMR (DMSO-d6) ppm: 1.2-1.5 (6H, m), 1.57 (3H, s), 1.6-1.95 (4H, m), 1.95-2.15 (1H, m), 3.05 (1H, d, J = 13.3 Hz), 3.40 (1H, d, J = 13.4 Hz), 3.75-3.9 (4H, m), 4.05-4.2 (1H, m), 4.93 (1H, br), 7.07 (1H, dd, J = 2.5, 8.9 Hz), 7.1-7.2 (2H, m), 7.36 (1H, dd, J = 2.3, 9.1 Hz), 7.65 (1H, d, J = 9.0 Hz), 7.70 (1H, d, J = 9.1 Hz), 6.06-8.3 (1H, m), 9.76-10.05 (1H, m). Dihydro- chloride 27 H 1H-NMR (DMSO-d6) ppm: 0.9-1.1 (2H, m), 1.25-1.45 (1H, m), 1.45-1.7 (7H, m), 1.7-2.1 (4H, m), 2.55 (1H, d, J = 12.7 Hz), 3.43 (1H, d, J = 12.5 Hz), 3.55-3.7 (1H, m), 4.1-4.3 (1H, m), 6.02 (1H, d, J = 7.7 Hz), 7.28 (1H, dd, J = 7.8, 7.6 Hz), 7.5-7.7 (2H, m), 7.74 (1H, d, J = 5.5 Hz), 7.9-8.2 (1H, m), 9.55-9.85 (1H, m). Hydro- chloride 28 H 0 1H-NMR (CDCl3) ppm: 1.18-1.28 (1H, m), 1.38-1.50 (2H, m), 1.55 (3H, s), 1.72-2.00 (2H, m), 1.90 (3H, s), 2.07-2.22 (1H, m), 2.39-2.52 (2H, m), 3.05 (1H, d, J = 12.8 Hz), 8.43 (1H, d, J = 1.25 Hz), 3.77-3.90 (1H, m), 3.91-4.01 (1H, m), 7.04 (1H, dd, J = 8.8, 2.2 Hz), 7.21-7.25 (2H, m), 7.43 (1H, d, J = 5.4 Hz), 7.75 (1H, d, J = 8.5 Hz), 8.55-8.97 (1H, br), 9.99-10.37 (1H, br) Hydro- chloride 29 CH.sub.3 1H-NMR (CDCl3) ppm: 1.17-1.34 (1H, m), 1.37-1.74 (2H, m), 1.47 (3H, s), 1.57-2.04 (1H, m), 1.90 (3H, s), 2.20-2.30 (1H, m), 2.39-2.54 (1H, m), 2.84-2.88 (2H, m), 2.75 (3H, d, J = 4.9 Hz), 3.12 (1H, d, J = 13.2 Hz), 3.89-3.74 (1H, m), 3.85-3.93 (1H, m), 3.87 (1H, d, J = 13.2 Hz), 7.01 (1H, dd, J = 5.6, 2.2 Hz), 7.21-7.32 (2H, m), 7.44 (1H, d, J = 5.4 Hz), 7.75 (1H, d, J = 5.8 Hz), 11.20 (1H, brs) Hydro- chloride 30 H 1H-NMR (CDCl3) ppm: 1.11-1.33 (1H, m), 1.35-1.54 (2H, m), 1.85 (3H, s), 1.72-2.00 (2H, m), 1.90 (3H, s), 2.07-2.29 (1H, m), 2.34-2.50 (2H, m), 3.03 (1H, d, J = 13.2 Hz), 3.42 (1H, d, J = 13.2 Hz), 3.76-4.02 (2H, m), 7.02 (1H, dd, J = 8.7, 2.2 Hz), 7.17-7.31 (3H, m), 7.70 (1H, d, J = 5.7 Hz), 8.64-9.00 (1H, br), 10.08-10.37 (1H, br) Hydro- chloride 31 CH.sub.3 1H-NMR (CDCl3) ppm: 1.20-1.35 (1H, m), 1.38-1.74 (3H, m), 1.45 (3H, s), 1.90 (3H, s), 1.97-2.11 (1H, m), 2.20-2.30 (1H, m), 2.41-2.56 (1H, m), 2.85-2.89 (1H, m), 2.81 (3H, d, J = 4.5 Hz), 3.16 (1H, d, J = 13.3 Hz), 3.61-3.74 (1H, m), 3.88 (1H, d, J = 13.3 Hz), 3.89-3.99 (1H, m), 6.99 (1H, dd, J = 5.7, 2.1 Hz), 7.20-7.31 (3H, m), 7.70 (1H, d, J = 8.7 Hz), 11.04-11.44 (1H, br) Hydro- chloride 32 H 1H-NMR (DMSO-d6) ppm: 0.9-1.2 (2H, m), 1.25-1.45 (1H, m), 1.53 (5H, s), 1.8-1.7 (1H, m), 1.7-1.9 (2H, m), 1.9-2.15 (2H, m), 2.92 (1H, d, J = 2.8 Hz), 3.46 (1H, d, J = 12.7 Hz), 3.75-4.0 (2H, m), 7.02 (1H, d, J = 7.5 Hz), 7.34 (1H, dd, J = 7.7, 7.7 Hz), 7.48 (1H, d, J = 5.4 Hz), 7.51 (1H, d, J = 7.8 Hz), 7.78 (1H, d, J = 5.4 Hz), 8.17 (1H, br), 9.75 (1H, br). Hydro- chloride 33 H 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (2H, m), 1.3-1.45 (1H, m), 1.51 (3H, s), 1.53 (3H, s), 1.6-2.1 (8H, m), 3.04 (1H, d, J = 12.9 Hz), 3.2-3.45 (1H, m), 3.75-3.95 (1H, m), 3.95-4.15 (1H, m), 8.6-8.8 (1H, m), 7.1-7.3 (3H, m), 7.94 (1H, d, J = 2.1 Hz), 8.07 (1H, br), 9.77 (1H, br). Hydro- chloride

(290) TABLE-US-00006 TABLE 6 Relative configuration Ex- am- ple R.sup.1 R.sup.4 NMR Salt 34 H 1H-NMR (CDCl3) ppm: 1.15 (18H, d, J = 7.5 Hz), 1.20 (3H, s), 1.25-1.45 (8H, m), 1.45-1.8 (8H, m), 1.8-2.0 (1H, m), 2.83 (1H, d, J = 11.5 Hz), 3.11 (1H, d, J = 11.5 Hz), 3.6-3.65 (1H, m), 3.67-3.8 (1H, m), 6.50 (1H, d, J = 7.2 Hz), 8.64 (1H, d, J = 2.7 Hz), 7.00 (1H, dd, J = 7.9, 7.9 Hz), 7.11 (1H, d, J = 8.3 Hz), 7.16 (1H, d, J = 3.2 Hz). 35 H 1H-NMR (CDCl3) ppm: 1.13 (18H, d, J = 7.5 Hz), 1.21 (3H, s), 1.25-1,3 (5H, m), 1.35-1.45 (2H, m), 1.53 (1H, br), 1.6-1.8 (7H, m), 2.80 (1H, d, J = 11.7 Hz), 2.93 (1H, d, J = 11.5 Hz), 3.45-3.55 (1H, m), 3.55-3.65 (1H, m), 5.48 (1H, d, J = 2.6 Hz), 6.85 (1H, dd, J = 2.4, 9.0 Hz), 7.02 (1H, d, J = 2.4 Hz), 7.16 (1H, d, J = 3.2 Hz), 7.36 (1H, d, J = 9.1 Hz). 36 H 1H-NMR (CDCl3) ppm: 1.1-1.2 (1H, m), 1.21 (3H, s), 1.25-1.3 (4H, m), 1.3-1.85 (11H, m), 2.79 (1H, d, J = 11.6 Hz), 2.91 (1H, d, J = 11.5 Hz), 3.45-3.65 (2H, m), 5.45-6.5 (1H, m), 6.82 (1H, dd, J = 2.0, 8.8 Hz), 6.93 (1H, s), 7.08 (1H, d, J = 3.2 Hz), 7.45 (1H, d, J = 8.6 Hz).

(291) TABLE-US-00007 TABLE 7 Relative configuration 0 Example R.sup.1 R.sup.4 NMR Salt 37 H 1H-NMR (CDCl3) ppm: 0.95-1.15 (3H, m), 1.21 (3H, s), 1.25-1.45 (6H, m), 1.45-1.8 (2H, m), 1.6-1.95 (1H, m), 2.83 (1H, d, J = 11.5 Hz), 3.11 (1H, d, J = 11.5 Hz), 3.6-3.7 (1H, m), 3.75-3.85 (1H, m), 6.50 (1H, dd, J = 0.9, 7.4 Hz), 6.55-6.6 (1H, m), 7.00 (1H, d, J = 8.1 Hz), 7.07 (1H, dd, J = 7.7, 7.7 Hz), 7.14 (1H, dd, J = 2.8, 2.8 Hz), 8.18 (1H, br). 38 CH.sub.3 1H-NMR (CDCl3) ppm: 1.0-1.15 (5H, m), 1.19 (3H, s), 1.2-1.5 (3H, m), 1.6-1.7 (1H, m), 2.8-2.3 (5H, m), 2.76 (1H, d, J = 11.5 Hz), 3.05-3.15 (1H, m), 3.38 (1H, d, J = 11.4 Hz), 3.8-3.9 (1H, m), 8.49 (1H, d, J = 7.4 Hz), 6.55-6.6 (1H, m), 6.99 (1H, d, J = 7.4 Hz), 7.07 (1H, dd, J = 7.8, 7.8 Hz), 7.13 (1H, dd, J = 2.8, 2.8 Hz), 8.11 (1H, br). 39 H 1H-NMR (CDCl3) ppm: 1.0-1.85 (15H, m), 2.82 (1H, d, J = 11.5 Hz), 2.88 (1H, d, J = 11.5 Hz), 3.45-3.55 (1H, m), 3.55-3.65 (1H, m), 8.4-6.45 (1H, m), 6.95 (1H, dd, J = 2.3, 8.8 Hz), 7.04 (1H, d, J = 2.2 Hz), 7.13 (1H, dd, J = 2.8, 2.8 Hz), 7.25-7.3 (1H, m), 7.98 (1H, br). 40 CH.sub.3 1H-NMR (CDCl3) ppm: 1.06 (3H, s), 1.1-1.55 (8H, m), 1.6-1.75 (1H, m), 1.95-2.15 (2H, m), 2.16 (3H, s), 2.80 (1H, d, J = 11.4 Hz), 2.95-3.0 (1H, m), 3.10 (1H, d, J = 11.4 Hz), 3.55-3.7 (1H, m), 6.35-5.45 (1H, m), 6.94 (1H, dd, J = 2.3, 5.6 Hz), 7.03 (1H, d, J = 2.0 Hz), 7.12 (1H, dd, J = 2.8, 2.8 Hz), 7.2-7.3 (1H, m), 7.94 (1H, br). 41 H 1H-NMR (DMSO-d6) ppm: 1.0-1.4 (9H, m), 1.4-1.9 (5H, m), 2.62 (1H, d, J = 11.9 Hz), 2.95 (1H, d, J = 12.0 Hz), 3.0-4.5 (4H, m), 6.25 (1H, dd, J = 2.4, 2.4 Hz), 6.47 (1H, s), 6.7-8.8 (2H, m), 7.10 (1H, dd, J = 2.7, 2.7 Hz), 7.34 (1H, d, J = 9.3 Hz), 10.65 (1H, s). Hemi- fumarate 42 CH.sub.3 1H-NMR (DMSO-d6) ppm: 0.95-1.5 (1H, m), 1.55-1.7 (1H, m), 1.55-2.1 (2H, m), 2.16 (3H, s), 2.65-4.2 (6H, m), 6.2-6.25 (1H, m), 6.80 (2H, s), 5.7-6.6 (2H, s), 7.09 (1H, dd, J = 2.4, 3.0 Hz), 7.33 (1H, d, J = 6.6 Hz), 10.80 (1H, s). Fumarate 43 H 1H-NMR (DMSO-d6) ppm: 0.95-1.4 (9H, m), 1.45-1.9 (5H, m), 2.88 (2H, dd, J = 12.3, 15.1 Hz), 3.5-3.8 (1H, m), 3.6-3.75 (4H, m), 6.24 (1H, dd, J = 0.6, 3.0 Hz), 6.47 (1H, s), 6.85-7.0 (2H, m), 7.18 (1H, d, J = 3.0 Hz), 7.27 (1H, d, J = 9.5 Hz). Hemi- fumarate 44 H 1H-NMR (DMSO-d6) ppm: 1.1-1.4 (9H, m), 1.4-1.9 (6H, m), 2.65 (1H, d, J = 12.1 Hz), 3.03 (1H, d, J = 12.1 Hz), 3.5-3.6 (1H, m), 3.69 (3H, s), 3.75-3.85 (1H, m), 6.24 (1H, d, J = 3.1 Hz), 6.49 (2H, s), 6.7-6.85 (2H, m), 7.07 (1H, d, J = 3.1 H), 7.34 (1H, d, J = 5.6 Hz). Fumarate 45 H 1H-NMR (DMSO-d6) ppm: 1.0-1.3 (2H, m), 1.3-1.45 (7H, m), 1.5-1.95 (5H, m), 2.9-3.1 (2H, m), 3.71 (1H, br), 3.8-3.95 (1H, m), 3.98 (3H, s), 6.54 (3H, s), 7.04 (1H, s), 7.27 (1H, dd, J = 1.9, 9.2 Hz), 7.51 (1H, d, J = 9.1 Hz), 7.83 (1H, s), 10.8 (4H, br). 3/2 Fumarate 46 H 0 1H-NMR (DMSO-d6) ppm: 1.1-1.35 (2H, m), 1.35-1.45 (4H, m), 1.50 (3H, s), 1.6-1.9 (4H, m), 1.9-2.1 (1H, m), 2.92 (1H, d, J = 13.2 Hz), 3.11 (1H, d, J = 13.2 Hz), 3.5-4.05 (3H, m), 5.91 (2H, d, J = 1.0 Hz), 6.32 (1H, dd, J = 2.4, 8.5 Hz), 6.71 (1H, d, J = 2.3 Hz), 6.76 (1H, d, J = 8.4 Hz), 8.06 (1H, br), 9.83 (1H, br). Dihydro- chloride

(292) TABLE-US-00008 TABLE 8 Relative configuration Ex- am- ple R.sup.1 R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 47 H H H F H H 1H-NMR (DMSO-d6) ppm: 1.1-1.35 (2H, m), 1.35-1.5 (4H, m), 1.53 (3H, s), Dihydro- 1.6-1.95 (4H, m), 1.95-2.15 (1H, m), 2.94 (1H, d, J = 13.3 Hz), 3.24 (1H, d, chloride J = 13.2 Hz), 3.65-3.85 (1H, m), 3.85-4.0 (1H, m), 5.30 (1H, br), 6.9-7.0 (2H, m), 7.0-7.1 (2H, m), 8.0-8.35 (1H, m), 10.03 (1H, d, J = 10.5 Hz). 48 H H H F F H 1H-NMR (DMSO-d6) ppm: 1.2-1.35 (6H, m), 1.52 (3H, s), 1.6-1.95 (4H, m), Hydro- 1.96-2.15 (1H, m), 2.93 (1H, d, J = 13.5 Hz), 3.36 (1H, d, J = 13.5 Hz), 3.65-3.8 chloride (1H, m), 3.9-4.1 (1H, m), 5.5-6.5 (1H, m), 6.9-7.1 (1H, m), 7.25 (1H, dd, J = 9.5, 19.7 Hz), 8.0-8.4 (1H, m), 10.02 (1H, d, J = 11.3 Hz). 49 H H F H F H 1H-NMR (DMSO-d6) ppm: 1.25-1.6 (9H, m), 1.8-2.05 (5H, m), 2.95 (1H, d, Hydro- J = 14.5 Hz), 3.56 (1H, d, J = 13.9 Hz), 3.6-3.75 (1H, m), 4.0-4.15 (1H, m), chloride 6.35-6.55 (1H, m), 8.5-8.75 (2H, m), 5.05-8.4 (1H, m), 9.65-10.2 (1H, m). 50 H H F OCH.sub.3 F H 1H-NMR (DMSO-d6) ppm: 1.21-1.45 (6H, m), 1.80 (3H, s), 1.8-1.9 (4H, m), Hydro- 1.9-2.05 (1H, m), 2.90 (1H, d, J = 13.7 Hz), 3.42 (1H, d, J = 13.7 Hz), 3.8-3.75 chloride (1H, m), 3.78 (3H, s), 3.9-4.05 (1H, m), 6.65-6.8 (2H, m), 8.17 (1H, br), 9.86 (1H, br). 51 CH.sub.3 H F OCH.sub.3 F H 1H-NMR (DMSO-d6) ppm: 0.96 (3H, s), 1.05-1.2 (4H, m), 1.2-1.5 (4H, m), 3/2 1.55-1.75 (1H, m), 1.85-2.1 (2H, m), 2.16 (3H, s), 2.75-2.9 (2H, m), 3.12 Fumarate (1H, d, J = 12.4 Hz), 3.65-3.85 (4H, m), 8.55-8.85 (5H, m). 52 H H Cl H H H 1H-NMR (DMSO-d6) ppm: 1.2-1.45 (6H, m), 1.51 (3H, s), 1.6-2.05 (5H, m), Hydro- 2.94 (1H, d, J = 13.7 Hz), 3.48 (1H, d, J = 14.0 Hz), 3.65-3.8 (1H, m), 4.0-4.15 chloride (1H, m), 6.77 (1H, dd, J = 1.5, 7.8 Hz), 6.90 (1H, dd, J = 2.3, 8.4 Hz), 6.95-7.0 (1H, m), 7.21 (1H, dd, J = 8.1, 8.1 Hz), 8.14 (1H, br), 9.55-10.0 (1H, m). 53 CH.sub.3 H Cl H H H 1H-NMR (DMSO-d6) ppm: 0.97 (3H, s), 1.05-1.2 (4H, m), 1.2-1.8 (4H, m), Fumarate 1.6-1.75 (1H, m), 1.9-2.1 (2H, m), 2.15 (3H, s), 2.85-5.05 (6H, m), 6.61 (2H, s), 6.86 (1H, dd, J = 1.2, 7.8 Hz), 6.75-6.9 (2H, m), 7.15 (1H, dd, J = 8.1, 8.1 Hz). 54 H H H Cl H H 1H-NMR (DMSO-d6) ppm: 1.15-1.45 (8H, m), 1.62 (3H, s), 1.6-2.1 (5H, m), Hydro- 2.93 (1H, d, J = 13.5 Hz), 3.39 (1H, d, J = 13.9 Hz), 3.65-3.8 (1H, m), 3.9-4.1 chloride (1H, m), 5.9-7.0 (2H, m), 7.15-7.3 (2H, m), 7.95-8.4 (1H, m), 9.65-10.1 (1H, m). 55 CH.sub.3 H H Cl H H 1H-NMR (DMSO-d6) ppm: 0.99 (3H, s), 1.06-1.5 (8H, m), 1.55-1.75 (1H, Fumarate m), 1.54-2.1 (2H, m), 2.17 (3H, s), 2.8-2.95 (2H, m), 3.12 (1H, d, J = 12.3 Hz), 3.7-3.85 (1H, m), 6.61 (2H, s), 6.6-6.9 (2H, m), 7.1-7.2 (2H, m). 56 H H Cl Cl H H 1H-NMR (DMSO-d6) ppm: 1.21-1.62 (2H, m), 1.38 (3H, s), 1.53 (3H, s), Hydro- 1.67-2.09 (6H, m), 2.95 (1H, d, J = 13.6 Hz), 3.48 (1H, d, J = 13.6 Hz), 3.70-3.74 chloride (1H, m), 4.04-4.10 (1H, m), 6.95 (1H, dd, J = 8.7, 2.6 Hz), 7.17 (1H, d, J = 2.8 Hz), 7.40 (1H, d, J = 6.7 Hz), 8.03-8.52 (1H, br), 9.77-10.21 (1H, br) 57 CH.sub.3 H Cl Cl H H 1H-NMR (CDCl3) ppm: 1.23-1.72 (4H, m), 1.42 (3H, s), 1.89 (3H, s), Hydro- 2.01-2.11 (1H, m), 2.20-2.29 (1H, m), 2.37-2.65 (1H, m), 2.68-2.83 (1H, m), chloride 2.79 (3H, d, J =4.8 Hz), 3.09 (1H, d, J = 13.5 Hz), 3.54-3.65 (1H, m), 3.75-3.83 (1H, m), 3.76 (1H,d, J = 13.5 Hz), 8.88 (1H, dd, J = 9.0, 2.9 Hz), 6.92 (1H, d, J = 2.9 Hz), 7.30 (1H, d, J = 9.0 Hz), 11.48 (1H, brs) 58 H H Cl F H H 1H-NMR (DMSO) ppm: 1.24-1.57 (3H, m), 1.37 (3H, s), 1.52 (3H, s), Hydro- 1.64-1.81 (4H, m), 1.87-2.01 (1H, m), 2.92 (1H, d, J = 13.1 Hz), 3.45 (1H, d, J = chloride 13.1 Hz), 3.65-3.79 (1H, m), 3.90-4.06 (1H, m), 6.89-6.94 (1H, m), 7.08-7.11 (1H, m), 7.20-7.27 (1H, m), 7.90-8.21 (1H, br), 9.55-9.81 (1H, br)

(293) TABLE-US-00009 TABLE 9 Absolute configuration Ex- am- ple R.sup.1 R.sup.4 NMR Salt 59 H 1H-NMR (CDCl3) ppm: 1.15-1.35 (5H, m), 1.35-1.86 (7H, m), 2.82 (1H, d, J = 11.7 Hz), 3.05 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.88 (3H, s), 8.97 (1H, d, J = 2.4 Hz), 7.0-7.1 (2H, m), 7.22-7.29 (1H, m), 7.55 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 9.0 Hz). 60 H 1H-NMR (CDCl3) ppm: 1.15-1.3 (8H, m), 1.3-1.5 (6H, m), 1.85-1.86 (4H, m), 2.82 (1H, d, J = 11.7 Hz), 3.04 (1H, d, J = 11.7 Hz), 3.45-3.85 (1H, m), 3.7-3.78 (1H, m), 4.11 (2H, q, J = 7.0 Hz), 8.96 (1H, d, J = 2.4 Hz), 7.03 (1H, d, J = 2.4 Hz), 7.08 (1H, dd, J = 2.5, 5.8 Hz), 7.2-7.3 (1H, m), 7.55 (1H, d, J = 8.9 Hz), 7.59 (1H, d, J = 9.0 Hz). 61 H 1H-NMR (DMSO-d6) ppm: 1.26-1.5 (8H, m), 1.56 (3H, s), 1.85-2.1 (5H, m), 3.06 (1H, d, J = 13.4 Hz), 3.46 (1H, d, J = 13.4 Hz), 3.8-3.9 (1H, m), 4.1-4.2 (1H, m), 4.42 (1H, br), 7.24 (1H, d, J = 2.3 Hz), 7.31 (1H, ddd, J = 4.5, 12.6, 12.5 Hz), 7.47 (1H, dd, J = 2.3, 9.2 Hz), 7.54 (1H, dd, J = 2.8, 10.2 Hz), 7.75-7.8 (2H, m), 8.1-8.25 (1H, m), 9.75-9.95 (1H, m). Dihydro- chloride 62 H 1H-NMR (DMSO-d6) ppm: 0.9-1.1 (2H, m), 1.3-1.4 (1H, m), 1.5-1.86 (7H, m), 1.65-1.85 (2H, m), 1.9-2.1 (2H, m), 2.81 (1H, d, J = 1.25 Hz), 3.4-3.5 (2H, m), 4.2-4.35 (1H, m), 7.13 (1H, d, J = 7.0 Hz), 7.43 (1H, dd, J = 7.8, 7.5 Hz), 7.5-7.8 (2H, m), 7.65 (1H, d, J = 8.2 Hz), 7.55-7.95 (1H, m), 7.95-8.15 (1H, m), 5.2-8.3 (1H, m), 9.65-9.85 (1H, m). Hydro- chloride 63 H 1H-NMR (DMSO-d6) ppm: 0.9-1.15 (2H, m), 1.3-1.4 (1H, m), 1.5-1.7 (7H, m), 1.7-1.85 (2H, m), 1.9-2.1 (2H, m), 2.77 (1H, d, J = 12.5 Hz), 3.3-3.45 (1H, m), 3.52 (1H, d, J = 12.5 Hz), 4.2-4.3 (1H, m), 7.05-7.15 (1H, m), 7.25 (1H, dd, J = 8.2, 10.5 Hz), 7.6-7.7 (2H, m), 8.0-8.15 (2H, m), 8.3-8.4 (1H, m), 9.7-9.95 (1H, m). Hydro- chloride

(294) TABLE-US-00010 TABLE 10 Absolute configuration Ex- am- ple R.sup.1 R.sup.4 NMR Salt 64 H 1H-NMR (DMSO-d6) ppm: 0.9-1.1 (2H, m), 1.3-1.4 (1H, m), 1.5-1.7 (7H, m), 1.7-1.9 (2H, m), 1.95-2.15 (2H, m), 2.89 (1H, d, J = 12.7 Hz), 3.0-4.2 (4H, m), 4.3-4.4 (1H, m), 7.35-7.5 (1H, m), 7.8-8.05 (3H, m), 8.05-8.3 (1H, m), 9.1-9.4 (2H, m), 10.0-10.25 (1H, m). Trihydro- chloride 65 H 0 1H-NMR (CDCl3) ppm: 0.9-1.05 (3H, m), 1.24 (3H, s), 1.36-1.45 (5H, m), 1.55-1.8 (3H, m), 1.9-2.05 (1H, m), 2.71 (1H, d, J = 11.3 Hz), 3.25 (1H, d, J = 11.3 Hz), 3.85-3.75 (1H, m), 3.75-3.85 (1H, m), 8.76 (1H, d, J = 5.0 Hz), 7.45-7.8 (1H, m), 7.5-7.7 (1H, m), 8.0-8.1 (2H, m), 8.88 (1H, d, J = 5.0 Hz). 66 H 1H-NMR (DMSO-d6) ppm: 1.36-1.5 (5H, m), 1.82 (3H, s), 1.7-2.0 (3H, m), 2.6-2.15 (2H, m), 2.7-4.3 (4H, m), 4.25-4.4 (1H, m), 7.67 (1H, d, J = 2.5 Hz), 7.80 (1H, d, J = 5.2, 5.6 Hz), 5.04 (1H, dd, J = 2.7, 9.6 Hz), 8.24 (1H, d, J = 9.5 Hz), 8.5-8.8 (1H, m), 8.79 (1H, d, J = 8.4 Hz), 8.98 (1H, dd, J = 1.5, 6.2 Hz), 10.22 (1H, d, J = 10.1 Hz). Dihydro- chloride 67 H 1H-NMR (DMSO-d6) ppm: 1.41 (3H, s), 1.45-1.8 (3H, m), 1.82 (3H, s), 1.7-1.85 (2H, m), 1.55-2.0 (1H, m), 2.05-2.25 (2H, m), 3.27 (1H, d, J = 14.5 Hz), 3.37 (1H, br), 3.75-3.85 (1H, m), 4.09 (1H, d, J = 14.4 Hz), 4.4-4.5 (1H, m), 7.80 (1H, d, J = 2.1 Hz), 7.85 (1H, dd, J = 2.4, 9.5 Hz), 7.93 (1H, d, J = 8.8 Hz), 8.25-5.35 (2H, m), 8.6-8.75 (1H, m), 9.36 (1H, s), 10.2-10.4 (1H, m). Dihydro- chloride

(295) TABLE-US-00011 TABLE 11 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 68 H 1H-NMR (CDCl3) ppm: 0.9-1.1 (2H, m), 1.22 (3H, s), 1.3-1.45 (6H, m), 1.45-1.8 (3H, m), 1.8-2.0 (1H, m), 2.65 (1H, d, J = 11.3 Hz), 3.19 (1H, d, J = 11.3 Hz), 3.45-3.85 (1H, m), 3.65-3.75 (1H, m), 6.79 (1H, d, J = 7.6 Hz), 7.15-7.3 (1H, m), 7.38 (1H, d, J = 5.8 Hz), 7.44 (1H, d, J = 5.5 Hz), 7.51 (1H, d, J = 8.0 Hz). 69 H 1H-NMR (DMDO-d6) ppm: 1.1-1.35 (2H, m), 1.35-1.5 (4H, m), 1.65 (3H, s), 1.8-2.15 (5H, m), 3.08 (1H, d, J = 13.2 Hz), 3.35 (1H, d, J = 13.2 Hz), 3.71 (1H, br), 3.75-3.9 (1H, m), 3.95-4.15 (1H, m), 7.18 (1H, dd, J = 2.1, 9.0 Hz), 7.29 (1H, d, J = 5.4 Hz), 7.35 (1H, d, J = 2.0 Hz), 7.68 (1H, d, J = 5.4 Hz), 7.82 (1H, d, J = 8.9 Hz), 6.05-8.25 (1H, m), 9.75-10.0 (1H, m). Dihydro- chloride 70 CH.sub.3 1H-NMR (DMDO-d6) ppm: 0.95-1.5 (11H, m), 1.55-1.75 (1H, m), 1.85-2.1 (2H, m), 2.19 (3H, s), 2.85-5.05 (5H, m), 6.61 (2H, s), 7.10 (1H, dd, J = 2.4, 9.0 Hz), 7.24 (1H, d, J = 2.3 Hz), 7.27 (1H, dd, J = 0.5, 5.4 Hz), 7.62 (1H, d, J = 5.4 Hz), 7.75 (1H, d, J = 8.9 Hz). Fumarate 71 H 1H-NMR (DMDO-d6) ppm: 1.2-1.5 (6H, m), 1.54 (3H, s), 1.8-2.1 (5H, m), 3.03 (1H, d, J = 13.4 Hz), 3.43 (1H, d, J = 13.5 Hz), 3.7-3.9 (1H, m), 4.0-4.2 (1H, m), 7.14 (1H, dd, J = 2.2, 8.9 Hz), 7.27 (1H, d, J = 5.4 Hz), 7.4-7.55 (2H, m), 7.71 (1H, d, J = 5.8 Hz), 8.14 (1H, br), 9.84 1H, br). Hydro- chloride 72 H 1H-NMR (DMDO-d6) ppm: 0.95-1.2 (2H, m), 1.3-1.45 (1H, m), 1.45-1.7 (7H, m), 1.7-1.9 (2H, m), 1.9-2.2 (2H, m), 2.91 (1H, d, J = 12.8 Hz), 3.48 (1H, d, J = 12.9 Hz), 3.75-4.0 (2H, m), 7.01 (1H, d, J = 7.5 Hz), 7.34 (1H, dd, J = 7.7, 7.7 Hz), 7.48 (1H, d, J = 5.4 Hz), 7.61 (1H, d, J = 7.7 Hz), 7.76 (1H, d, J = 5.4 Hz), 8.24 (1H, br), 9.94 (1H, br). Hydro- chloride

(296) TABLE-US-00012 TABLE 12 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 73 H 0 1H-NMR (DMDO-d6) ppm: 0.95-1.15 (2H, m), 1.3-1.45 (1H, m), 1.51 (3H, s), 1.53 (3H, s), 1.65-2.05 (5H, m), 3.04 (1H, d, J = 1.29 Hz), 3.2-.34 (1H, m), 3.75-3.9 (1H, m), 4.0-4.15 (1H, m), 6.71 (1H, dd, J = 3.0, 5.5 Hz), 7.15-7.25 (3H, m), 7.94 (1H, d, J = 2.2 Hz), 8.08 (1H, br), 9.80 (1H, br). Hydro- chloride 74 H 1H-NMR (DMDO-d6) ppm: 1.1-1.35 (2H, m), 1.35-1.5 (4H, m), 1.54 (3H, s), 1.6-1.86 (4H, m), 1.35-2.1 (1H, m), 3.03 (1H, d, J = 13.1 Hz), 3.21 (1H, d, J = 13.1 Hz), 3.75-3.9 (1H, m), 3.9-4.0 (1H, m), 4.53 (1H, br), 5.5-5.85 (1H, m), 7.03 (1H, dd, J = 2.5, 9.0 Hz), 7.18 (1H, d, J = 2.4 Hz), 7.46 (1H, d, J = 9.0 Hz), 7.90 (1H, d, J = 2.2 Hz), 8.11 (1H, br), 9.91 (1H, br). Dihydro- chloride 75 H 1H-NMR (DMDO-d6) ppm: 1.15-1.5 (8H, m), 1.65 (3H, s), 1.6-1.95 (4H, m), 1.95-2.15 (1H, m), 3.01 (1H, d, J = 13.4 Hz), 3.36 (1H, d, J = 13.1 Hz), 3.7-3.85 (1H, m), 3.95-4.05 (1H, m), 4.50 (1H, br), 6.80 (1H, d, J = 2.1 Hz), 6.96 (1H, dd, J = 1.9, 8.7 Hz), 7.13 (1H, s), 7.47 (1H, d, J = 6.6 Hz), 7.79 (1H, d, J = 0.7H), 8.20 (1H, br), 9.85-10.2 (1H, m). Dihydro- chloride 76 H 1H-NMR (DMDO-d6) ppm: 1.1-1.3 (2H, m), 1.35-1.45 (1H, m), 1.50 (3H, s), 1.54 (3H, s), 1.6-1.9 (3H, m), 1.9-2.1 (2H, m), 3.2-3.4 (2H, m), 3.9-4.0 (1H, m), 4.15-4.25 (1H, m), 6.50 (1H, d, J = 7.2 Hz), 6.93 (1H, d, J = 2.2 Hz), 7.12 (1H, dd, J = 7.7, 7.7 Hz), 7.21 (1H, dd, J = 0.8, 7.7 Hz), 7.97 (1H, d, J = 2.2 Hz), 8.1-8.35 (1H, m), 9.7-9.9 (1H, m). Hydro- chloride 77 H 1H-NMR (CDCl3) ppm: 1.0-1.45 (11H, m), 1.6-1.8 (3H, m), 1.6-1.95 (1H, m), 2.70 (1H, d, J = 11.3 Hz), 3.04 (1H, d, J = 11.3 Hz), 3.50 (1H, ddd, J = 3.8, 3.8, 12.1 Hz), 3.55-3.85 (1H, m), 8.47 (1H, dd, J = 3.4, 8.6 Hz), 6.84 (1H, dd, J = 2.5, 2.5 Hz), 6.89 (1H, dd, J = 8.8, 10.4 Hz), 7.60 (1H, d, J = 2.2 Hz). 78 H 1H-NMR (CDCl3) ppm: 1.0-1.15 (2H, m), 1.20 (3H, s), 1.25-1.45 (5H, m), 1.6-1.8 (3H, m), 1.8-1.95 (1H, m), 2.79 (1H, d, J = 11.5 Hz), 3.05 (1H, d, J = 11.4 Hz), 3.55-3.64 (2H, m), 6.53 (1H, d, J = 8.4 Hz), 6.84 (1H, d, J = 2.2 Hz), 7.14 (1H, d, J = 8.4 Hz), 7.51 (1H, d, J = 2.2 Hz). 79 H 1H-NMR (DMDO-d6) ppm: 0.95-1.1 (2H, m), 1.3-1.4 (1H, m), 1.51 (3H, s), 1.52 (3H, s), 1.5-1.7 (1H, m), 1.7-1.95 (3H, m), 1.95-2.05 (1H, m), 2.39 (3H, s), 2.95 (1H, d, J = 12.8 Hz), 3.28 (1H, d, J = 12.9 Hz), 3.7-3.8 (1H, m), 4.0-4.15 (1H, m), 8.61 (1H, d, J = 7.9 Hz), 6.99 (1H, d, J = 8.0 Hz), 7.20 (1H, d, J = 2.2 Hz), 7.95 (1H, d, J = 2.2 Hz), 7.95-5.16 (1H, m), 9.7-9.9 (1H, m). Hydro- chloride 80 H 1H-NMR (DMDO-d6) ppm: 0.95-1.1 (2H, m), 1.3-1.4 (1H, m), 1.52 (8H, s), 1.55-1.65 (1H, m), 1.55-1.95 (3H, m), 1.95-2.1 (1H, m), 2.85 (1H, d, J = 12.7 Hz), 3.27 (1H, d, J = 12.8 Hz), 3.6-3.7 (1H, m), 3.87 (3H s), 4.0-4.15 (1H, m), 6.51 (1H, d, J = 8.4 Hz), 8.79 (1H, d, J = 8.4 Hz), 7.21 (1H, d, J = 2.2 Hz), 7.95 (1H, d, J = 2.2 Hz), 7.95-8.15 (1H, m), 9.75-10.0 (1H, m). Hydro- chloride 81 H 1H-NMR (DMDO-d6) ppm: 1.05-1.25 (2H, m), 1.35-1.45 (1H, m), 1.50 (3H, s), 1.53 (3H, s), 1.6-1.9 (3H, m), 1.9-2.1 (2H, m), 3.17 (1H, d, J = 13.0 Hz), 3.29 (1H, d, J = 13.2 Hz), 3.9-4.0 (1H, m), 4.0-4.1 (1H, m), 6.80 (1H, dd, J = 4.4, 8.7 Hz), 6.98 (1H, dd, J = 8.9, 5.9 Hz), 7.06 (1H, d, J = 2.2 Hz), 5.06 (1H, d, J = 2.2 Hz), 8.1-8.3 (1H, m), 9.7-9.9 (1H, m). Hydro- chloride

(297) TABLE-US-00013 TABLE 13 Absolute configuration Ex- am- ple R.sup.1 R.sup.4 NMR Salt 82 H 0 1H-NMR (CDCl3) ppm: 1.1-1.2 (20H, m), 1.20 (3H, s), 1.3-1.45 (6H, m), 1.55-1.8 (6H, m), 1.8-2.0 (1H, m), 2.53 (1H, d, J = 11.5 Hz), 3.11 (1H, d, J = 11.5 Hz), 3.6-3.7 (1H, m), 3.7-3.8 (1H, m), 5.50 (1H, d, J = 7.4 Hz), 5.64 (1H, d, J = 3.1 Hz), 7.00 (1H, dd, J = 7.9, 7.9 Hz), 7.11 (1H, d, J = 8.3 Hz), 7.16 (1H, d, J = 3.2 Hz). 83 H 1H-NMR (CDCl3) ppm: 1.13 (18H, d, J = 7.5 Hz), 1.21 (3H, s), 1.25 (3H, s), 1.3-1.6 (5H, m), 1.85-1.8 (7H, m), 2.80 (1H, d, J = 11.6 Hz), 2.93 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.55-3.85 (1H, m), 6.48 (1H, d, J = 3.1 Hz), 6.85 (1H, dd, J = 2.4, 9.0 Hz), 7.02 (1H, d, J = 2.4 Hz), 7.18 (1H, d, J = 3.1 Hz), 7.35 (1H, d, J = 9.0 Hz). 84 H 1H-NMR (CDCl3) ppm: 1.1-1.2 (18H, m), 1.21 (3H, s), 1.20 (3H, s), 1.3-1.5 (5H, m), 1.55-1.8 (7H, m), 2.79 (1H, d, J = 11.6 Hz), 2.91 (1H, d, J = 11.6 Hz), 3.45-3.6 (2H, m), 6.46 (1H, d, J = 3.2 Hz), 5.82 (1H, dd, J = 2.0, 8.6 Hz), 5.93 (1H, s), 7.08 (1H, d, J = 3.2 Hz), 7.45 (1H, d, J = 8.8 Hz).

(298) TABLE-US-00014 TABLE 14 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 85 H 1H-NMR (CDC13) ppm: 0.9-1.15 (2H, m), 1.21 (3H, s), 1.25-1.45 (5H, m), 1.5-1.8 (4H, m), 1.8-2.0 (1H, m), 2.83 (1H, d, J = 11.5 Hz), 3.11 (1H, d, J = 1.5 Hz), 3.6-3.75 (1H, m), 3.75-3.85 (1H, m), 6.50 (1H, dd, J = 0.9, 7.4 Hz), 6.55- 6.6 (1H, m), 6.95-7.05 (1H, m), 7.07 (1H, dd, J = 7.7, 7.7 Hz), 7.14 (1H, dd, J = 2.8, 2.8 Hz), 8.15 (1H, br). 86 H 1H-NMR (DMSO-d6) ppm: 1.0-1.25 (2H, m), 1.35 (7H, bs), 1.45-1.9 (5H, m), 2.93 (2H, s), 3.6-3.8 (2H, m), 6.2-6.3 (1H, m), 6.50 (2H, s), 6.86 (1H, dd, J = 2.1 8.8 Hz), 6.95 (1H, d, J = 1.8 Hz), 7.15- 7.3 (2H, m), 10.80 (1H, s). Fuma- rate 87 H 1H-NMR (CDC13) ppm: 1.05-1.85 (15H, m), 2.79 (1H, d, J = 11.6 Hz), 2.94 (1H, d, J = 11.6 Hz), 3.45-3.55 (1H, m), 3.6-3.75 (1H, m), 6.35-6.45 (1H, m), 6.79 (1H, s), 6.86 (1H, dd, J = 2.1, 8.7 Hz), 7.03 (1H, dd, J = 2.4, 3.2 Hz), 7.47 (1H, d, J = 8.7 Hz), 7.89 (1H, br).

(299) TABLE-US-00015 TABLE 15 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 88 H 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (2H, m), 1.25-1.4 (4H, m), 1.40 (3H, s), 1.5-2.0 (5H, m), 2.82 (1H, d, J = 8.2 Hz), 3.21 (1H, d, J = 12.2 Hz), 3.74 (3H, s), 3.8-3.9 (2H, m), 6.44 (1H, dd, J = 2.5, 5.8 Hz), 6.5-6.55 (3H, m), 6.95-7.05 (2H, m), 7.22 (1H, d, J = 3.1 Hz). Fumarate 89 H 1H-NMR (DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.32 (7H, bs), 1.45-1.85 (6H, m), 2.85-2.95 (2H, m), 3.63 (1H, br), 3.65-3.8 (4H, m), 6.24 (1H, dd, J = 0.6, 3.0 Hz), 6.50 (2H, s) 6.9-7.0 (2H, m), 7.19 (1H, d, J = 3.0 Hz), 7.28 (1H, d, J = 8.6 Hz). Fumarate 90 H 0 1H-NMR (DMSO-d6) ppm: 1.05-1.3 (2H, m), 1.3-1.45 (7H, m), 1.5-1.9 (5H, m), 2.90 (1H, d, J = 12.4 Hz), 3.08 (1H, d, J = 12.3 Hz), 3.62 (1H, br), 3.70 (3H, s), 3.8-3.9 (1H, m), 6.25 (1H, d, J = 3.0 Hz), 6.52 (2H, s), 6.75-6.85 (2H, m), 7.09 (1H, d, J = 3.1 Hz), 7.35 (1H, d, J = 8.6 Hz). Fumarate 91 H 1H-NMR (CDCl3) ppm: 0.6-2.4 (15H, m), 2.7-3.3 (2H, m), 3.4-3.8 (2H, m), 3.85 (3H, s), 6.95-7.05 (2H, m), 7.15-7.3 (2H, m).

(300) TABLE-US-00016 TABLE 16 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 92 H H-NMR (DMSO-d6 ) ppm: 1.1-1.4 (9H, m), 1.45-1.75 (4H, m), 1.8-1.95 (1H, m), 2.80 (1H, d, J = 12.3 Hz), 3.20 (1H, d, J = 12.3 Hz), 3.4-3.5 (1H, m) 3.8-3.9 (1H, m), 6.51 (1H, s), 7.20 (1H, dd, J = 2.5 9.1 Hz), 7.51 (1H, d, J = 2.4 Hz), 7.85 (1H, d, J = 9.1 Hz), 9.01 (1H, s). Hemi- fumarate 93 H 1H-NMR (DMSO-d6) ppm : 1.0-1.2 (2H, m), 1.3-1.45 (1H, m), 1.48 (3H, s), 1.50 (3H, s), 1.55-1.7 (1H, m), 1.7-2.15 (6H, m), 2.7-2.95 (5H, m), 3.28 (1H, d, J = 12.8 Hz), 3.35-3.45 (1H, m), 3.75- 3.95 (1H, m), 6.68 (1H, d, J = 7.8 Hz), 6.90 (1H, d, J = 7.2 Hz), 7.05 (1H, dd, J = 7.6, 7.6 Hz), 7.95-8.2 (1H, m), 9.75- 10.0 (1H, m). Hydro- chloride 94 H 1H-NMR (DMSO-d6) ppm: 1.15-1.3 (2H, m), 1.3-1.5 (4H, m), 1.53 (3H, s), 1.6-1.9 (4H, m), 1.9-2.1 (3H, m), 2.74 (2H, t, J = 7.3 Hz), 2.79 (2H, t, J = 7.4 Hz), 2.93 (1H, d, J = 13.2 Hz), 3.22 (1H, d, J = 13.3 Hz), 3.65-3.8 (1H, m), 3.85-4.0 (1H, m), 6.70 (1H, dd, J = 2.2, 8.2 Hz), 6.8-6.85 (1H, m), 7.05 (1H, d, J = 8.2 Hz), 7.6-8.4 (2H, m), 9.85-10.2 (1H, m). Dihydro- chloride 95 H 1H-NMR (DMSO-d6) ppm: 1.1-1.3 (2H, m), 1.35-1.5 (4H, m), 1.51 (3H, s), 1.6-1.9 (4H, m), 2.0-2.1 (1H, m), 2.95 (1H, d, J = 13.0 Hz), 3.02 (1H, d, J = , 13.0 Hz), 3.11 (2H, t, J = 8.6 Hz), 3.7- 3.85 (2H, m), 4.44 (2H, t, J = 8.6 Hz), 4.7-5.5 (1H, m), 6.6-6.7 (2H, m), 6.85- 6.95 (1H, m), 8.09 (1H, br), 9.94 (1H, br). Dihydro- chloride

(301) TABLE-US-00017 TABLE 17 Absolute configuration Example R.sup.1 R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 96 H F H H H H 1H-NMR (DMSO-d6) ppm: 1.1-1.25 (2H, m), 1.35-1.45 (1H, m), 1.46 (3H, s), 1.49 (3H, s), 1.6-1.85 (3H, m), 1.85-2.05 (2H, m), 2.93 (1H, d, J = 13.1 Hz), 3.27 (1H, d, J = 13.82 Hz), 3.55-3.65 (1H, m), 3.8-3.9 (1H, m), 6.95-7.05 (1H, m), 7.05-7.2 (3H, m), 8.0-8.2 (1H, m), 9.55-9.75 (1H, m). Hydro- chloride 97 H H H F H H 1H-NMR (DMSO-d6) ppm: 1.1-1.35 (2H, m), 1.35-1.45 (4H, m), 1.53 (3H, s), 1.6-1.95 (4H, m), 1.95-2.15 (1H, m), 2.94 (1H, d, J = 13.3 Hz), 3.24 (1H, d, J = 13.3 Hz), 3.65-3.85 (1H, m), 3.85-4.0 (1H, m), 4.2-5.8 (1H, m), 6.85-7.0 (2H, m), 7.0-7.1 (2H, m), 8.19 (1H, br), 10.05 (1H, br). Dihydro- chloride 98 H H F OCH.sub.3 H H 1H-NMR (DMSO-d6) ppm: 1.2-1.35 (2H, m), 1.35-1.45 (4H, m), 1.52 (3H, s), 1.6-1.9 (4H, m), 2.0-2.1 (1H, m), 2.90 (1H, d, J = 13.3 Hz), 3.22 (1H, d, J = 13.2 Hz), 3.65-3.8 (4H, m), 3.85-3.95 (1H, m), 6.6-6.7 (1H, m), 6.89 (1H, dd, J = 2.9, 14.7 Hz), 7.02 (1H, dd, J = 9.5, 9.5 Hz), 8.05-8.25 (1H, m), 9.94 (1H, br). Dihydro- chloride 99 H H OCH.sub.3 F H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.45 (6H, m), 1.55 (3H, s), 1.6-1.95 (4H, m), 2.0-2.15 (1H, m), 2.95 ( 1H, d, J = 13.2 Hz), 3.24 (1H, d, J = 13.2 Hz), 3.7-3.8 (1H, m), 3.82 (3H, s), 3.9-4.0 (1H, m), 6.4-6.5 (1H, m), 6.70 (1H, dd, J = 2.8, 7.6 Hz), 7.03 (1H, dd, J = 8.9, 11.3 Hz), 8.0 (1H, br), 8.15-8.35 (1H, m), 10.0-10.15 (1H, m). Dihydro- chloride 100 H F F H H H 1H-NMR (DMSO-d6) ppm: 1.15-1.3 (2H, m), 1.35-1.45 (1H, m), 1.46 (3H, s), 1.50 (3H, s), 1.6-1.85 (3H, m), 1.9-2.05 (2H, m), 3.00 (1H, d, J = 3.2 Hz), 3.28 (1H, d, J = 13.2 Hz), 3.6-3.7 (1H, m), 3.8-3.9 (1H, m) 6.85-6.95 (1H, m), 6.95-7.05 (1H, m), 7.05-7.15 (1H, m), 8.05- 8.35 (1H, m), 9.7-9.9 (1H, m). Hydro- chloride 101 H H H F F H 1H-NMR (DMSO-d6 ) ppm: 1.05-1.4 (9H, m), 1.4-1.9 (5H, m), 2.72 (1H, d, J = 12.5 Hz), 2.8-4.6 (6H, m), 6.54 (2H, s), 6.6-6.7 (1H, m), 6.85-7.0 (1H, m), 7.20 (1H, dd, J = 9.5, 19.9 Hz). Fuma- rate 102 H H F F F H 1H-NMR (DMSO-d6 ) ppm: 1.25-1.5 (6H, m), 1.51 (3H, s), 1.65-2.1 (5H, m) 2.92 (1H, d, J = 13.8 Hz), 3.46 (1H d, J = 13.8 Hz), 3.65-3.75 (1H, m), 4.0-4.1 (1H, m), 6.8-6.95 (2H, m), 8.15-8.35 (1H, m), 9.85-10.1 (1H, m). Hydro- chloride 103 H H F OCH.sub.3 F H 1H-NMR (DMSO-d6) ppm: 1.25-1.55 (9H, m), 1.6-1.85 (4H, m), 1.85-2.05 (1H, m), 2.90 (1H, d, J = 13.8 Hz), 3.43 (1H, d, J = 12.8 Hz), 3.65-3.75 (1H, m), 3.78 (3H, s), 3.95-4.05 (1H, m), 6.6-6.8 (2H, m), 8.06 (1H, br), 9.57 (1H, br). Hydro- chloride 104 H Cl H H H H 1H-NMR (DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.3-1.4 (1H, m), 1.48 (3H, s), 1.50 (3H, s), 1.6-1.85 (3H, m), 1.85-2.1 (2H, m), 2.74 (1H, d, J = 12.8 Hz), 3.41 (1H, d, J = 13.1 Hz), 3.5-3.6 (1H, m), 3.8-3.9 (1H, m), 7.05-7.15 (1H, m), 7.17 (1H, dd, J = 1.4, 8.0 Hz), 7.25-7.35 (1H, m), 7.44 (1H, d, J = 1.5, 7.9 Hz), 8.02 (1H, br), 9.63 (1H, br). Hydro- chloride 105 H H Cl OCH.sub.3 H H 1H-NMR (DMSO-d6 ) ppm: 1.15-1.45 (6H, m), 1.51 (3H, s), 1.6-1.9 (4H, m) 1.95-2.1 (1H, m) 2.92 (1H, d, J = 13.3 Hz), 3.20 (1H, d, J = 13.1 Hz), 3.7-3.8 (4H, m), 3.9-4.0 (1H, m), 5.9 (1H, br), 6.88 (1H, dd, J = 2.9, 9.1 Hz), 7.0-7.05 (1H, m), 8.11 (1H, br), 9.90 (1H, br). Dihydro- chloride 106 H H H Cl H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.45 (6H, m), 1.51 (3H, s), 1.6-2.1 (5H, m) 2.93 (1H, d, J = 13.6 Hz), 3.40 (1H d, J = 13.8 Hz), 3.65-3.85 (1H, m), 3.9-4.1 (1H, m), 6.8-7.05 (2H, m), 7.1-7.35 (2H, m), 8.14 (1H, br), 9.77 (1H, br). Hydro- chloride 107 CH.sub.3 H H Cl H H 1H-NMR (DMSO-d6 ) ppm: 0.98 (3H, s), 1.05-1.2 (4H, m), 1.2-1.45 (4H, m), 1.55-1.75 (1H, m), 1.85-2.1 (2H, m), 2.16 (3H, s), 2.65-4.2 (4H, m), 6.61 (2H, s), 6.8-6.9 (2H, m), 7.1-7.2 (2H, m), 12.8 (2H, br). Fuma- rate 108 H H OCH.sub.3 Cl H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.5 (6H, m), 1.5-1.6 (3H, m), 1.6-1.95 (4H, m), 2.0-2.1 (1H, m), 2.95 (1H, d, J = 13.5 Hz), 3.3-3.5 (1H, m), 3.7-3.8 (1H, m), 3.84 (3H, s), 4.0-4.1 (1H, m), 6.52 (1H, dd, J = 2.6, 8.9 Hz), 6.63 (1H, d, J = 2.6 Hz), 7.19 (1H, d, J = 8.8 Hz), 8.19 (1H, br), 9.75-10.1 (1H, m). Hydro- chloride 109 H Cl Cl H H H 1H-NMR (DMSO-d6) ppm: 1.05-1.25 (2H, m), 1.35-1.45 (1H, m), 1.47 (3H, s), 1.49 (3H, s), 1.6-1.85 (3H, m), 1.85-2.05 (2H, m), 2.76 (1H, d, J = 12.8 Hz), 3.42 (1H, d, J = 13.0 Hz), 3.5-3.6 (1H, m), 3.8-3.9 (1H, m), 7.18 (1H, dd, J = 1.6, 7.9 Hz), 7.31 (1H, dd, J = 8.0, 8.0 Hz), 7.37 (1H, dd, J = 1.5, 8.0 Hz), 8.01 (1H, br), 9.5-9.7 (1H, m). Hydro- chloride 110 H H Cl Cl H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.45 (6H, m), 1.52 (3H, s), 1.6-2.15 (5H, m) 2.95 (1H d, J = 13.7 Hz), 3.49 (1H, d, J = 13.4 Hz), 3.6-3.8 (1H, m), 3.95-4.15 (1H, m), 6.95 (1H, dd, J = 2.6, 9.1 Hz), 7.05-7.25 (1H, m), 7.40 (1H, d, J = 9.0 Hz), 7.95-8.4 (1H, m), 9.6-10.15 (1H, m). Hydro- chloride 111 CH.sub.3 H Cl Cl H H 1H-NMR (DMSO-d6 ) ppm: 0.96 (3H, s), 1.05-1.2 (4H, m), 1.2-1.5 (4H, m) 1.6-1.75 (1H, m) 1.85-2.05 (2H, m) 2.14 (3H, s) 2.75-2.95 (2H, m), 3.17 (1H, d, J = 12.4 Hz), 3.7-3.9 (1H, m), 6.62 (3H, s), 6.87(1H, dd, J = 2.9, 9.1 Hz), 7.04(1H, d, J = 2.9 Hz), 7.33(1H, d, J = 9.0 Hz), 11.0 (3H, br). 3/2 Fuma- rate 112 H H Cl F H H 1H-NMR (DMSO-d6) ppm: 1.15-1.45 (6H, m), 1.51 (3H, s), 1.6-1.9 (4H, m) 1.9-2.05 (1H, s) 2.01 (1H, d, J = 8.2 Hz), 3.3-3.45 (1H, m) 3.65-3.8 (1H, m), 3.95-4.1 (1H, m), 6.85-7.0 (1H, m), 7.12 (1H, dd, J = 3.0, 6.2 Hz), 7.25 (1H, dd, J = 9.1, 9.1 Hz), 8.13 (1H, br), 9.86 (1H, br). Hydro- chloride 113 H H F Cl H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.45 (6H, m), 1.51 (3H, s), 1.6-2.1 (5H, m), 2.94 (1H, d, J = 13.7 Hz), 3.50 (1H, d, J = 13.6 Hz), 3.65-3.8 (1H, m), 3.95-4.15 (1H, m), 6.80 (1H, dd, J = 2.6, 9.1 Hz), 7.01 (1H, dd, J = 2.7, 13.4 Hz), 7.34 (1H, dd, J = 9.0, 9.0 Hz), 8.22 (1H, br), 9.90 (1H, br). Hydro- chloride

(302) TABLE-US-00018 TABLE 18 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 114 H 1H-NMR (CDCl3 ) ppm: 1.15-1.35 (8H, m), 1.35-1.85 (7H, m), 2.82 (1H, d, J = 11.7 Hz), 3.05 (1H, d, J = 11.7 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.88 (3H, s), 6.97 (1H, d, J = 2.3 Hz), 7.03 (1H, d, J = 2.4 Hz), 7.06 (1H, dd, J = 2.6, 8.8 Hz), 7.26 (1H, dd, J = 2.5, 9.0 Hz), 7.55 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 9.0 Hz). 115 CH.sub.3 0 1H-NMR (CDCl3) ppm: 1.05 (3H, s), 1.15-1.5 (8H, m), 1.65-1.8 (1H, m), 2.0-2.15 (2H, m), 2.18 (3H, s), 2.9-3.0 (2H, m), 3.09 (1H, d, J = 11.7 Hz), 3.7-3.8 (1H, m), 3.88 (3H, s), 6.95 (1H, d, J = 2.4 Hz), 7.0-7.1 (2H, m), 7.15-7.3 (1H, m), 7.55(1H, d, J = 8.7 Hz), 7.59 (1H, d, J = 9.1 Hz). 116 H 1H-NMR (CDCl3) ppm: 1.15-1.3 (8H, m), 1.3-1.85 (10H, m), 2.82 (1H, d, J = 11.7 Hz), 3.04 (1H, d, J = 11.7 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 4.11 (2H, q, J = 7.0 Hz), 6.96 (1H, d, J = 2.4 Hz) 7.03 (1H, d, J = 2.4 Hz), 7.06 (1H, dd, J = 2.5, 8.8 Hz), 7.2-7.3 (1H, m), 7.55 (1H, d, J = 8.9 Hz), 7.59 (1H, d, J = 9.0 Hz). 117 H 1H-NMR (DMSO-d6) ppm: 1.25-1.5 (6H, m), 1.57 (3H, s), 1.65-2.15 (5H, m), 3.06 (1H, d, J = 13.4 Hz), 3.47 (1H, d, J = 13.5 Hz), 3.8-3.9 (1H, m), 4.15-4.25 (1H, m), 5.02 (1H, br), 7.24 (1H, d, J = 2.2 Hz), 7.31 (1H, ddd, J = 4.5, 12.8, 12.8 Hz), 7.47 (1H, dd, J = 2.2, 9.2 Hz), 7.54 (1H, dd, J = 2.6, 10.2 Hz), 7.75-7.8 (2H, m), 8.15-8.3 (1H, m), 9.9-10.0 (1H, m). Dihydro- chloride 118 H 1H-NMR (DMSO-d6) ppm: 0.85-1.1 (2H, m), 1.3-1.45 (1H, m), 1.45-1.7 (7H, m), 1.7-1.9 (2H, m), 1.9-2.1 (2H, m), 2.81 (1H, d, J = 12.6 Hz), 3.45-3.6 (2H, m), 4.15-4.3 (1H, m), 7.12 (1H, d, J = 7.1 Hz), 7.43 (1H, dd, J = 7.8, 7.8 Hz), 7.5-7.6 (2H, m), 7.65 (1H, d, J = 8.2 Hz), 7.85-7.95 (1H, m), 8.0-8.2 (1H, m), 8.2-8.3 (1H, m), 9.7-9.95 (1H, m). Hydro- chloride 119 H 1H-NMR (DMSO-d6) ppm: 0.9-1.15 (2H, m), 1.3-1.4 (1H, m), 1.5-1.7 (7H, m), 1.7-1.9 (2H, m) 1.9-2.1 (2H, m) 2.77 (1H d, J = 12.6 Hz), 3.3-3.45 (1H m) 3.52 (1H, d, J = 12.6 Hz), 4.2-4.3 (1H, m), 7.05-7.15 (1H, m), 7.25 (1H, dd, J = 8.2, 10.5 Hz), 7.6-7.7 (2H, m), 8.0-8.2 (2H, m), 8.3-8.4 (1H, m), 9.8-10.0 (1H, m). Hydro- chloride

(303) TABLE-US-00019 TABLE 19 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 120 H 1H-NMR (DMSO-d6 ) ppm: 0.9-1.1 (2H, m), 1.3-1.4 (1H, m), 1.5-1.7 (7H, m), 1.7-1.85 (2H, m), 1.95-2.1 (2H, m), 2.89 (1H, d, J = 12.8 Hz), 3.0-3.9 (4H, m), 4.3-4.4 (1H, m), 7.41 (1H, d, J = 7.0 Hz) , 7.8-7.9 (1H, m), 7.9-8.0 (2H, m), 8.1-8.2 (1H, m), 9.1-9.25 (2H, m), 9.98 (1H, br). Trihydro- chloride 121 H 1H-NMR (CDCl3 ) ppm: 0.9-1.05 (3H, m), 1.24 (3H, s), 1.35-1.45 (5H, m), 1.55-1.8 (3H, m), 1.9-2.05 (1H, m), 2.71 (1H, d, J = 11.3 Hz), 3.25 (1H, d, J = 11.4 Hz), 3.65-3.75 (1H, m), 3.75-3.85 (1H, m), 6.76 (1H, d, J = 5.0 Hz), 7.45-7.5 (1H, m), 7.6-7.7 (1H, m),8.0-8.1 (2H, m), 8.68 (1H, d, J = 5.0 Hz). 122 H 1H-NMR (DMSO-d6) ppm: 1.35-1.5 (6H, m), 1.61 (3H, s), 1.7-2.0 (3H, m), 2.0-2.15 (2H, m), 2.8-4.2 (4H, m), 4.25- 4.4 (1H, m), 7.56 (1H, d, J = 2.6 Hz), 7.89 (1H, d, J = 5.2, 8.5 Hz), 8.04 (1H, dd, J = 2.7, 9.6 Hz), 8.23 (1H, d, J = 9.5 Hz), 8.45-8.6 (1H, m), 8.78 (1H, d, J = 8.3 Hz), 8.92 (1H, dd, J = 1.3, 5.2 Hz), 10.21 (1H, d, J = 10.6 Hz). Dihydro- chloride 123 H 1H-NMR (DMSO-d6 ) ppm: 1.41 (3H, s), 1.45-1.6 (3H, m), 1.63 (3H, s), 1.7-1.85 (2H, m), 1.85-2.05 (1H, m), 2.05-2.25 (2H, m), 3.28 (1H, d, J = 14.5 Hz), 3.39 (1H, br), 3.75-3.85 (1H, m), 4.10 (1H, d, J = 14.4 Hz), 4.4-4.5 (1H, m), 7.51 (1H, d, J = 2.0 Hz), 7.86 (1H, dd, J = 2.4, 9.5 Hz), 7.94 (1H, d, J = 6.8 Hz), 8.25-8.35 (2H, m), 8.65- 8.85 (1H, m), 9.37 (1H, s), 10.3- 10.45 (1H, m). Dihydro- chloride

(304) TABLE-US-00020 TABLE 20 Absolute configuration 00 Example R.sup.1 R.sup.4 NMR Salt 124 H 01 1H-NMR (CDCl3) ppm: 0.9-1.15 (2H, m), 1.21 (3H, s), 1.3-1.45 (5H, m), 1.45-1.8 (4H, m) 1.8-2.0 (1H, m) 2.64 (1H, d, J = 11.2 Hz), 3.18 (1H, d, J = 11.2 Hz), 3.45-3.55 (1H, m), 3.65-3.75 (1H, m), 6.78 (1H, d, J = 7.7 Hz), 7.15-7.3 (1H, m), 7.37 (1H, d, J = 5.5 Hz), 7.45 (1H, d, J = 5.6 Hz), 7.51 (1H, d, J = 8.0 Hz). 125 H 02 1H-NMR (DMSO-d6) ppm: 0.8-1.05 (2H, m), 1.13 (3H, s), 1.15-1.45 (6H, m), 1.5-1.65 (1H, m) 2.0-2.2 (2H, m) 2.23 (3H, s) 2.61 (1H, d, J = 11.6 Hz), 2.8-3.9 (3H, m), 6.61 (4H, s), 6.81 (1H, d, J = 7.6 Hz), 7.24 (1H, dd, J = 7.8, 7.8 Hz), 7.46 (1H, d, J = 5.6 Hz), 7.58 (1H, d, J = 8.0 Hz), 7.69 (1H, d, J = 5.5 Hz), 13.0 (4H, br). Difumarate 126 H 03 1H-NMR( DMSO-d6) ppm: 1.2-1.35 (2H, m), 1.35-1.5 (4H, m), 1.54 (3H, s), 1.6-2.1 (5H, m), 3.03 (1H, d, J = 13.2 Hz), 3.25-3.4 (1H, m), 3.75- 3.9 (1H, m), 3.95-4.15 (1H, m), 7.16 (1H, dd, J = 2.2, 8.9 Hz), 7.29(1H, d, J = 5.4 Hz), 7.35 (1H, d, J = 2.1 Hz), 7.68 (1H, d, J = 5.4 Hz), 7.82 (1H, d, J = 8.9 Hz), 7.95-8.3 (1H, m), 9.65-9.95 (1H, m). Hydrochloride 127 CH.sub.3 04 1H-NMR (DMSO-d6) ppm: 0.95-1.5 (11H, m), 1.55-1.75 (1H, m), 1.85-2.1 (2H, m), 2.18 (3H, s), 2.6-4.75 (6H, m), 6.61 (2H, s), 7.10 (1H, dd, J = 2.4, 9.0 Hz), 7.24 (1H, d, J = 2.3 Hz), 7.27 (1H, d, J = 5.4 Hz), 7.62 (1H, d, J = 5.3 Hz), 7.75 (1H, d, J = 8.9 Hz). Fumarate 128 H 05 1H-NMR (DMSO-d6 ) ppm: 1.2-1.5 (6H, m), 1.53 (3H, s), 1.6-2.05 (5H, m), 3.03 (1H, d, J = 13.5 Hz), 3.44(1H, d, J = 13.5 Hz), 3.75- 3.9 (1H, m), 4.0-4.15 (1H, m), 7.14 (1H, dd, J = 2.2, 8.9 Hz), 7.27 (1H, d, J = 5.4 Hz), 7.44 (1H, d, J = 5.4 Hz), 7.48 (1H, d, J = 1.8Hz), 7.71 (1H, d, J = 8.8Hz), 7.95-8.2 (1H, m), 9.55- 9.8 (1H, m). Hydrochloride 129 CH.sub.3 06 1H-NMR (DMSO-d6 ) ppm: 1.25-1.5 (6H, m), 1.61 (3H, s), 1.65-1.9 (3H, m), 2.05-2.3 (2H, m), 2.74 (3H, d, J = 4.7 Hz), 3.27 (1H, d, J = 13.9 Hz), 3.58 (1H d, J = 13.8 Hz), 3.7-3.85 (1H, m), 4.1-4.25 (1H, m), 7.15 (1H, dd, J = 2.3, 8.9 Hz), 7.28 (1H, d, J = 5.4 Hz), 7.44 (1H, d, J = 5.4 Hz), 7.49 (1H, d, J = 1.9 Hz), 7.72 (1H, d, J = 8.8 Hz), 9.42 (1H, br). Hydrochloride 130 H 07 1H-NMR (DMSO-d6 ) ppm: 0.95-1.2 (2H, m), 1.3-1.45 (1H, m), 1.53 (6H, s), 1.55-1.7 (1H, m), 1.7-1.9 (2H, m), 1.9-2.15 (2H, m), 2.92 (1H, d, J = 12.9 Hz), 3.48 (1H, d, J = 12.8 Hz), 3.75-4.0 (2H, m ), 7.02 (1H, d, J = 7.6 Hz), 7.35 (1H, dd, J = 7.7, 7.7 Hz), 7.48 (1H, d, J = 5.4 Hz), 7.61 (1H, d, J = 7.9 Hz), 7.76 (1H, d, J = 5.4 Hz), 8.18 (1H, br), 9.81 (1H, br). Hydrochloride

(305) TABLE-US-00021 TABLE 21 Absolute configuration 08 Example R.sup.1 R.sup.4 NMR Salt 131 H 09 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (2H, m), 1.3-1.45 (1H, m), 1.52 (3H, s), 1.54 (3H, s), 1.6-2.1 (5H, m), 3.03 (1H, d, J = 13.0 Hz), 3.30 (1H, d, J = 13.4Hz), 3.75-3.9 (1H, m), 4.0-4.15(1H, m), 6.65-6.75(1H, m), 7.1-7.25 (3H, m), 7.94 (1H d, J = 2.2 Hz), 8.0-8.25 (1H, m), 9.7-10.05 (1H, m). Hydro- chloride 132 CH.sub.3 0 1H-NMR (DMSO-d6) ppm: 1.0-1.25 (2H, m), 1.3-1.4 (1H, m), 1.43 (3H, s), 1.55-1.9 (6H, m), 2.1-2.35 (2H, m), 2.75 (3H, d, J = 4.7 Hz), 3.21 (1H, d, J = 13.3 Hz), 3.55 (1H, d, J = 13.3 Hz), 3.85-4.1 (2H, m), 6.65-6.75 (1H, m), 7.15-7.25 (3H, m), 7.95 (1H, d, J = 2.2 Hz), 9.48 (1H, br). Hydro- chloride 133 H 1H-NMR (DMSO-d6 ) ppm: 1.1-1.35 (2H, m), 1.35-1.5 (4H, m), 1.55 (3H, s), 1.6-1.95 (4H, m), 1.95-2.1 (1H, m), 3.03 (1H, d, J = 13.1 Hz), 3.20 (1H, d, J = 12.9 Hz), 3.75-3.9 (1H, m), 3.9-4.0 (1H, m), 5.29 (1H, br), 6.8-6.85 (1H, m), 7.03 (1H, dd, J = 2.4, 9.0 Hz), 7.13 (1H, d, J = 2.3 Hz), 7.45 (1H, d, J = 9.0 Hz), 7.89 (1H, d, J = 2.2 Hz), 8.15 (1H, br), 9.99 (1H, br). Dihydro- chloride 134 H 1H-NMR (DMSO-d6) ppm: 1.2-1.5 (6H, m), 1.56 (3H, s), 1.6-2.0 (4H, m), 2.0-2.15 (1H, m), 3.01 (1H, d, J = 13.4 Hz ), 3.35 (1H, d, J = 13.3 Hz), 3.65-3.85 (1H, m), 3.95-4.15 (1H, m), 6.75-6.85 (1H, m), 6.98 (1H, dd, J = 2.1, 8.7 Hz), 7.13 (1H, s), 7.47 (1H, d, J = 8.6 Hz), 7.5-8.0 (2H, m), 8.15-8.35 (1H, m), 10.0-10.2 (1H, m). Dihydro- chloride 135 H 1H-NMR (DMSO-d6 ) ppm: 1.1-1.3 (2H, m), 1.35-1.45 (1H, m), 1.50 (3H, s), 1.55 (3H, s), 1.6-1.9 (3H, m), 1.9-2.1 (2H, m), 3.2-3.4 (2H, m), 3.85-4.0 (1H, m), 4.15-4.25 (1H, m), 6.80 (1H, d, J = 7.0 Hz), 6.94 (1H, d, J = 2.2 Hz), 7.12 (1H, dd, J = 7.7, 7.7 Hz), 7.21 (1H, dd, J = 0.8, 7.7 Hz), 7.97 (1H, d, J = 2.2 Hz), 8.1-8.35 (1H, m), 9.75-9.95 (1H, m). Hydro- chloride 136 H 1H-NMR (CDCI3 ) ppm: 1.0-1.45 (11H, m), 1.6-1.8 (3H, m), 1.8-1.95 (1H, m), 2.70 (1H, d, J = 11.3 Hz), 3.04 (1H, d, J = 11.4 Hz), 3.45-3.55 (1H, m), 3.55-3.65 (1H, m), 6.47 (1H, dd, J = 3.4, 8.6 Hz), 6.84 (1H, dd, J = 2.5, 2.5 Hz), 6.89 (1H, dd, J = 8.6, 10.4 Hz), 7.60 (1H, d, J = 2.1 Hz). 137 H 1H-NMR (CDC13 ) ppm: 1.0-1.15 (2H, m), 1.20 (3H, s), 1.25-1.45 (6H, m), 1.6-1.8 (3H, m), 1.8-1.95 (1H, m), 2.79 (1H, d, J = 11.5 Hz), 3.05 (1H, d, J = 11.4 Hz), 3.55-3.65 (2H, m), 6.53 (1H, d, J = 8.4 Hz), 6.84 (1H, d, J = 2.2 Hz), 7.14 (1H, d, J = 8.4 Hz), 7.61 (1H, d, J = 2.2 Hz). 138 H 1H-NMR (DMSO-d6) ppm: 0.95-1.1 (2H, m), 1.3-1.4(1H, m), 1.51 (3H, s), 1.53 (3H, s), 1.6- 1.7 (1H, m), 1.7-2.0 (3H, m), 2.0-2.05 (1H, m), 2.39 (3H, s), 2.95 (1H, d, J = 12.8 Hz), 3.28 (1H, d, J = 12.9 Hz), 3.7-3.8 (1H, m), 4.0-4.15 (1H, m), 6.61 (1H, d, J = 7.9 Hz), 6.99 (1H, d, J = 8.1 Hz), 7.20 (1H, d, J = 2.2 Hz), 7.95 (1H, d, J = 2.2 Hz), 8.0-8.15 (1H, m), 9.57-9.95 (1H, m). Hydro- chloride 139 H 1H-NMR (DMSO-d6 ) ppm: 0.9-1.1 (2H, m), 1.3-1.4 (1H, m), 1.52 (6H, s), 1.55-1.65 (1H, m), 1.65-1.95 (3H, m), 1.95-2.1 (1H, m), 2.86 (1H, d, J = 12.8 Hz), 3.27 (1H, d, J = 12.8 Hz), 3.6-3.7 (1H, m), 3.87 (3H, s), 4.0-4.15 (1H, m), 6.61 (1H, d, J = 8.4 Hz), 6.79 (1H, d, J = 8.4 Hz), 7.21 (1H, d, J = 2.2 Hz), 7.95 (1H, d, J = 2.1 Hz), 7.95-8.15 (1H, m), 9.7-9.9 (1H, m). Hydro- chloride 140 H 1H-NMR (DMSO-d6 ) ppm: 1.05-1.25 (2H, m), 1.35-1.45 (1H, m), 1.50 (3H, s), 1.54 (3H, s), 1.6-1.9 (3H, m), 1.9-2.1 (2H, m), 3.17 (1H, d, J = 13.1 Hz), 3.29 (1H, d, J = 13.2 Hz), 3.9-4.0 (1H, m), 4.0-4.1 (1H, m), 6.80 (1H, dd, J = 4.4, 8.7 Hz), 6.98 (1H, dd, J = 8.9, 8.9 Hz), 7.06 (1H, d, J = 2.2 Hz), 8.06 (1H, d, J = 2.2 Hz), 8.1-8.3 (1H, m), 9.75-9.95 (1H, m). Hydro- chloride

(306) TABLE-US-00022 TABLE 22 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 141 H 0 1H-NMR (CDCl3) ppm: 1.1-1.2 (20H, m), 1.20 (3H, s), 1.3-1.45 (6H, m), 1.55-1.8 (6H, m), 1.8-2.0 (1H, m), 2.83 (1H, d, J = 11.5 Hz), 3.11 (1H, d, J = 11.6 Hz), 3.6-3.7 (1H, m), 3.7-3.8 (1H, m), 6.50 (1H, d, J = 7.5 Hz), 6.64 (1H, d, J = 3.2 Hz), 7.00 (1H, dd, J = 7.9, 7.9 Hz), 7.11 (1H, d, J = 8.3 Hz), 7.16 (1H, d, J = 3.2 Hz). 142 H 1H-NMR (CDCl3) ppm: 1.13 (18H, d, J = 7.5 Hz), 1.21 (3H, s), 1.28 (3H, s), 1.3-1.6 (5H, m), 1.6- 1.8 (7H, m), 2.80 (1H, d, J = 11.7 Hz), 2.93(1H, d, J = 11.6 Hz), 3.45-3.55 (1H, m), 3.55-3.65 (1H, m), 6.48 (1H, dd, J = 0.7, 3.1 Hz), 6.85 (1H, dd, J = 2.4, 9.0 Hz), 7.02 (1H, d, J =2.3 Hz), 7.16 (11-1, d, J = 3.1 Hz), 7.36 (1H, d, J = 9.0 Hz).

(307) TABLE-US-00023 TABLE 23 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 143 H 1H-NMR (CDCl3) ppm: 0.9-1.15 (2H, m), 1.21 (3H, s), 1.25-1.45 (5H, m), 1.45-1.8 (4H, m), 1.8-2.0 (1H, m), 2.83 (1H, d, J = 11.5 Hz), 3.11 (1H, d, J = 11.5 Hz), 3.6-3.75 (1H, m), 3.75-3.9 (1H, m), 6.50 (1H, d, J = 7.3 Hz), 6.55- 6.65 (1H, m), 7.00 (1H, d, J = 8.0 Hz), 7.07 (1H, dd, J = 7.7, 7.7 Hz), 7.14 (1H, dd, J = 2.8, 2.8 Hz), 8.16 (1H, br). 144 H 1H-NMR (DMSO-d6) ppm: 1.0-1.25 (2H, m), 1.33 (7H, bs), 1.45-1.9 (5H, m), 2.8-3.0 (2H, m), 3.0-4.05 (5H, m), 6.2-6.3 (1H, m), 6.50 (2H, s), 6.86 (1H, dd, J = 2.2, 8.8 Hz), 6.95 (1H, d, J = 1.9 Hz), 7.15-7.3 (2H, m), 10.79 (1H, s). Fumarate 145 H 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (2H, m), 1.25-1.4 (4H, m), 1.42 (3H, s), 1.5-2.0 (5H, m), 2.84 (1H, d, J = 12.3 Hz), 3.24 (1H, d, J = 12.3 Hz), 3.74 (3H, s), 3.8-3.95 (2H, m), 6.45 (1H, dd, J = 2.2, 6.2 Hz), 6.5-6.55 (3H, m), 6.95-7.05 (2H, m), 7.23 (1H, d, J = 3.1 Hz). Fumarate 146 H 1H-NMR (CDCl3) ppm: 1.0-1.5 (11H, m), 1.6-1.7 (1H, m), 2.05-2.3 (5H, m), 2.75 (1H, d, J = 11.4 Hz), 3.05-3.15 (1H, m), 3.38 (1H, d, J = 11.5 Hz), 3.75 (3H, s), 3.8-3.9 (1H, m), 6.45-6.55 (2H, m), 6.92 (1H, d, J = 8.2 Hz), 6.96 (1H, d, J = 3.1 Hz), 7.10 (1H, dd, J = 0.7, 3.1 Hz). 147 H 1H-NMR (DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.33 (7H, bs), 1.45-1.85 (6H, m), 2.85-2.95 (2H, m), 3.64 (1H, br), 3.7-3.8 (4H, m), 6.24 (1H, dd, J = 0.7, 3.0 Hz), 6.51 (2H, s), 6.9- 7.0 (2H, m), 7.19 (1H, d, J = 3.0 Hz), 7.28 (1H, d, J = 8.6 Hz). Fumarate 148 H 1H-NMR (DMSO-d6) ppm: 1.05-1.3 (2H, m), 1.3-1.45 (7H, m), 1.5-1.9 (5H, m), 2.93 (1H, d, J = 12.3 Hz), 3.09 (1H, d, J = 12.4 Hz), 3.65 (1H, br), 3.70 (3H, s), 3.8-3.95 (1H, m), 6.25 (1H, d, J = 3.0 Hz), 6.51 (2H, s), 6.75-6.85 (2H, m), 7.09 (1H, d, J = 3.1 Hz), 7.36 (1H, d, J = 9. 2 Hz). Fumarate 149 H 1H-NMR (CDCl3) ppm: 1.06 (3H, s), 1.1-1.5 (8H, m), 1.65-1.75 (1H, m), 2.0-2.15 (2H, m), 2.18 (3H, s), 2.87 (1H, d, J = 11.4 Hz), 2.95-3.0 (1H, m), 3.10 (1H, d, J = 11.4 Hz), 3.65-3.75 (4H, m), 6.34 (1H, dd, J = 0.7, 3.1 Hz), 6.62 (1H, d, J = 1.8 Hz), 6.8-6.9 (2H, m), 7.44 (1H, d, J = 8.7 Hz). 150 H 0 1H-NMR (CDCl3) ppm: 0.7-2.3 (15H, m), 2.7-3.2 (2H, m), 3.5-3.8 (2H, m), 3.85 (3H, s), 6.95-7.05 (2H, m), 7.15-7.3 (2H, m).

(308) TABLE-US-00024 TABLE 24 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 151 H 1H-NMR (DMSO-d6) ppm: 1.1-1.4 (9H, m), 1.45-1.8 (4H, m), 1.8-1.95 (1H, m), 2.81 (1H, d, J = 12.3 Hz), 3.22 (1H, d, J = 12.4 Hz), 3.45- 3.5 (1H, m), 3.85-3.95 (1H, m), 6.52 (1H, s), 7.20 (1H, dd, J = 2.5, 9.1 Hz), 7.51 (1H, d, J = 2.4 Hz), 7.85 (1H, d, J = 9.1 Hz), 9.02 (1H, s). Hemifumarate 152 H 1H-NMR ( DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.3-1.45 (1H, m), 1.48 (3H, s), 1.50 (3H, s), 1.55-1.7 (1H, m), 1.7-2.15 (6H, m), 2.7-2.95 (5H, m), 3.28 (1H, d, J = 12.8 Hz), 3.35-3.45 (1H, m), 3.8-3.9 (1H, m), 6.68 (1H, d, J = 7.8 Hz), 6.90 (1H, d, J = 7.3 Hz), 7.05 (1H, dd, J = 7.6, 7.6 Hz), 7.95-8.2 (1H, m), 9.7-9.95 (1H, m). Hydrochloride 153 H 1H-NMR (DMSO-d6) ppm: 1.15-1.3 (2H, m), 1.35-1.5 (4H, m), 1.53 (3H, s), 1.6-1.9 (4H, m), 1.9-2.1 (3H, m), 2.74 (2H, t, J = 7.3 Hz), 2.79 (2H, t, J = 7.4 Hz), 2.93 (1H, d, J = 13.3 Hz), 3.22 (1H, d, J = 13.3 Hz), 3.65-3.8 (1H, m), 3.85-4.0 (1H, m), 6.70 (1H, dd, J = 2.2, 8.2 Hz), 6.8-6.85 (1H, m), 7.05 (1H, d, J = 8.2 Hz), 7.33 (1H, br), 8.0-8.3 (1H, m), 9.9-10.1 (1H, m). Dihydrochloride 154 H 1H-NMR (DMSO-d6) ppm: 1.1-1.3 ( 2H, m), 1.35-1.5 (4H, m), 1.52 (3H, s), 1.6-1.9 (4H, m), 2.0-2.1 (1H, m), 2.95 (1H, d, J = 13.0 Hz), 3.02 (1H, d, J = , 13.0 Hz), 3.11 (2H, t, J = 8.6 Hz), 3.7-3.85 (2H, m), 4.44 (2H, t, J = 8.6 Hz), 5.96 (1H, br), 6.6-6.7 (2H, m), 6.85-6.95 (1H, m), 8.0-8.25 (1H, m), 9.9-10.2 (1H, m). Dihydrochloride

(309) TABLE-US-00025 TABLE 25 Absolute configuration Example R.sup.1 R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 155 H F H H H H 1H-NMR (DMSO-d6) ppm: 1.1-1.25 (2H, m), 1.3-1.45 (1H, m), 1.46 (3H, s), 1.49 (3H, s), 1.65- 1.85 (3H, m), 1.85-2.05 (2H, m), 2.93 (1H, d, J = 13.0 Hz), 3.27 (1H, d, J = 13.1 Hz), 3.55- 3.65 (1H, m), 3.8-3.9 (1H, m), 6.95-7.05 (1H, m), 7.05-7.2 (3H, m), 8.09 (1H, br), 9.68 (1H, br). Hydrochloride 156 H H H F H H 1H-NMR (DMSO-d6 ) ppm: 1.15-1.45 (6H, m), 1.52 (3H, s), 1.6-2.15 (5H, m), 2.94 (1H, d, J = 13.3 Hz), 3.25 (1H, d, J = 13.1 Hz), 3.35-3.4 (3H, m), 6.85-7.0 (2H, m), 7.0-7.1 (2H, m), 8.16 (1H, br), 9.94 (1H, br). Dihydrochloride 157 CH.sub.3 H H F H H 1H-NMR (DMSO-d6) ppm: 0.98 (3H, s), 1.0-1.1 (1H, m), 1.16 (3H, s), 1.2-1.45 (4H, m), 1.55-1.7 (1H, m), 1.85-2.05 (2H, s), 2.15 (3H, s), 2.35-4.55 (4H, m), 6.59 (2H, s), 6.8-6.9 (2H, m), 6.9-7.05 (2H, m), 12.9 (2H, br). Fumarate 158 H H F OCH.sub.3 H H 1H-NMR (DMSO-d6) ppm: 1.2-1.35 (2H, m), 1.35-1.45 (4H, m), 1.51 (3H, s), 1.6-1.9 (4H, m), 1.95-2.1 (1H, m), 2.90 (1H, d, J = 13.4 Hz), 3.22 (1H, d, J = 13.3 Hz), 3.65-3.8 (4H, m), 3.85-3.95 (1H, m), 6.6-6.7 (1H, m), 6.89 (1H, dd, J = 2.9, 14.7 Hz), 7.02 (1H, dd, J = 9.5, 9 5 Hz), 8.12 (1H, m), 9.90 (1H, br). Hydrochloride 159 H H OCH.sub.3 F H H 1H-NMR (DMSO-d6) ppm: 1.2-1.5 (6H, m), 1.54 (3H, s), 1.6-1.95 (4H, m), 2.0-2.15 (1H, m), 2.95 (1H, d, J = 13.3 Hz), 3.24 (1H, d, J = 13.2 Hz), 3.7-3.8 (1H, m), 3.82 (3H, s), 3.9-4.05 (1H, m), 6.4-6.5 (1H, m), 6.70 (1H, dd, J = 2.8, 7.6 Hz), 7.03 (1H, dd, J = 8.9, 11.3 Hz), 7.75 (1H, br), 8.15-8.35 (1H, m), 10.0-10.15 (1H, m). Hydrochloride 160 H F F H H H 1H-NMR (DMSO-d6) ppm: 1.15-1.3 (2H, m), 1.35-1.45 (1H, m), 1.46 (3H, s), 1.50 (3H, s), 1.6-1.85 (4H, m), 1.9-2.05 (3H, m), 3.00 (1H, d, J = 13.2 Hz), 3.28 (1H, d, J = 13.4 Hz), 3.6-3.7 (1H, m), 3.8-3.9 (1H, m), 6.85-6.95 (1H, m), 6.95-7.05 (1H, m), 7.05-7.15 (1H, m), 8.1-8.3 (1H, m), 9.7-9.9 (1H, m). Hydrochloride 161 H H F F H H 1H-NMR (DMSO-d6) ppm: 1.2-1.5 (6H, m), 1.52 (3H, s), 1.6-2.15 (5H, m) 2.93 (1H, d, J = 13.5 Hz), 3.2-3.45 (1H, m), 3.65-3.8 (1H, m), 3.9-4.1 (1H, m), 6.65-6.8 (1H, m), 6.95-7.1 (1H, m), 7.25 (1H, dd, J = 9.4, 19.8 Hz), 8.0-8.35 (1H, m), 9.75-10.1 (1H, m). Hydrochloride 162 CH.sub.3 H F F H H 1H-NMR (DMSO-d6 ) ppm: 0.97 (3H, s), 1.05-1.2 (4H, m), 1.2-1.45 (4H, m) 1.6-1.75 (1H, m) 1.85-2.05 (2H, s) 2.14 (3H, s) 2.65-4.05 (4H, m), 6.55-6.7 (3H, m), 6.8-6.95 (1H, m), 7.18 (1H, dd, J = 9.5, 20.0 Hz), 13.0 (2H, br). Fumarate 163 H H F F F H 1H-NMR (DMSO-d6) ppm: 1.25-1.5 (6H, m), 1.50 (3H, s), 1.65-1.9 (4H, m), 1.95-2.05 (1H, m), 2.92 (1H, d, J = 13.8 Hz), 3.47 (1H, d, J = 13.8 Hz), 3.65-3.8 (1H, m), 4.0-4.1 (1H, m), 6.8-6.95 (2H, m), 8.1-8.3 (1H, m), 9.75-9.95 (1H, m). Hydrochloride 164 H H F OCH.sub.3 F H 1H-NMR (DMSO-d6) ppm: 1.2-1.45 (6H, m), 1.50 (3H, s), 1.6-1.9 (4H, m) 1.9-2.1 (1H, m) 2.90 (1H, d, J = 13.6 Hz), 3.42 (1H, d, J = 13.8 Hz), 3.6-3.75 (1H, m), 3.78 (3H, s), 3.95-4.05 (1H, m ), 6.6-6.85 (2H, m), 8.16 (1H, br), 9.85 (1H, br). Hydrochloride 165 H Cl H H H H 1H-NMR (DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.3-1.45 (1H, m), 1.49 (3H, s), 1.51 (3H, s), 1.6-1.85 (3H, m), 1.9-2.1 (2H, m), 2.73 (1H, d, J = 12.8 Hz), 3.41 (1H, d, J = 12.8 Hz ), 3.45-3.55 (1H, m), 3.75-3.9 (1H, m), 7.05-7.15 (1H, m), 7.17 (1H, dd, J = 1.4, 8.0 Hz), 7.25-7.35 (1H, m), 7.44 (1H, d, J = 1.5, 8.0 Hz), 8.09 (1H, br), 9.7-9.9 (1H, m). Hydrochloride 166 H H Cl CH.sub.3 H H 1H-NMR (DMSO-d6) ppm: 1.15-1.45 (6H, m), 1.52 (3H, s), 1.6-1.9 (4H, m) 2.0-2.1 (1H, m) 2.92 (1H, d, J = 13.2 Hz), 3.19 (1H, d, J = 13.1 Hz), 3.7-3.8 (4H, m), 3.85-3.95 (1H, m), 5.9 (1H, br), 6.88 (1H, dd, J = 2.9, 9.0 Hz), 7.0-7.05 (1H, m), 8.15 (1H, br), 10.00 (1H, br). Dihydrochloride 167 H H H Cl H H 1H-NMR (DMSO-d6) ppm: 1.2-1.45 (6H, m), 1.51 (3H, s), 1.6-2.1 (5H, m) 2.93 (1H, d, J = 13.7 Hz), 3.2-3.5 (1H, m) 3.65-3.85 (1H, m) 3.9-4.1 (1H, m), 6.96 (2H, d, J = 9.0 Hz), 7.24 (2H, d, J = 8.9 Hz), 8.14 (1H, br), 9.45-10.0 (1H, m). Hydrochloride 168 CH.sub.3 H H Cl H H 1H-NMR (DMSO-d6 ) ppm: 0.97 (3H, s), 1.05-1.2 (4H, m), 1.2-1.45 (4H, m), 1.6-1.75 (1H, m), 1.85-2.05 (2H, m), 2.14 (3H, s), 2.65- 4.35 (4H, m), 6.61 (2H, s), 6.8-6.9 (2H, m), 7.1-7.2 (2H, m), 12.9 (2H, br). Fumarate 169 H Cl Cl H H H 1H-NMR (DMSO-d6) ppm: 1.05-1.25 (2H, m), 1.35-1.45 (1H, m), 1.47 (3H, s), 1.49 (3H, s), 1.6-1.85 (3H, m), 1.9-2.05 (2H, m), 2.76 (1H, d, J = 12.8 Hz), 3.42 (1H, d, J = 13.0 Hz), 3.5- 3.6 (1H, m), 3.8-3.9 (1H, m), 7.18 (1H, dd, J = 1.5, 7.9 Hz), 7.31 (1H, dd, J = 8.0 8.0 Hz), 7.37 (1H, dd, J = 1.5, 8.0 Hz), 8.02 (1H, br), 9.61 (1H, br). Hydrochloride 170 H H Cl Cl H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.45 (6H, m), 1.51 (3H, s), 1.6-2.1 (5H, m) 2.95 (1H, d, J = 13.7 Hz), 3.49 (1H d, J = 13.7 Hz), 3.65-3.8 (1H, m), 4.0-4.15 (1H, m), 6.95 (1H, dd, J = 3.0, 9.1 Hz), 7.18 (1H, d, J = 2.9 Hz), 7.40 (1H, d, J = 9.0 Hz), 7.95-8.35 (1H, m), 9.6-10.05 (1H, m). Hydrochloride 171 CH.sub.3 H Cl Cl H H 1H-NMR (DMSO-d6 ) ppm: 0.95 (3H, s), 1.05-1.2 (4H, m), 1.2-1.5 (4H, m), 1.55-1.75 (1H, m), 1.85-2.05 (2H, m), 2.13 (3H, s), 2.75-2.9 (2H, m), 3.17 (1H, d, J = 12.4 Hz), 3.75-3.85 (1H, m), 6.62 (3H, s), 6.87 (1H, dd, J = 2.9, 9.1 Hz), 7.04 (1H, d, J = 2.9 Hz), 7.33 (1H, d, J = 9.0 Hz), 11.0 (3H, br). 3/2 Fumarate 172 H H Cl F H H 1H-NMR (DMSO-d6 ) ppm: 1.1-1.45 (6H, m), 1.50 (3H, s), 1.6-1.9 (4H, m) 1.9-2.1 (1H, s) 2.00 (1H, d, J = 8.2 Hz), 3.25-3.45 (1H, m) 3.65-3.85 (1H, m), 3.9-4.1 (1H, m), 6.85-7.0 (1H, m), 7.12 (1H, dd, J = 3.0, 6.3 Hz), 7.25 (1H, dd, J = 9.1 9.1 Hz), 8.12 (1H, br), 9.82 (1H, br). Hydrochloride 173 H H F Cl H H 1H-NMR ( DMSO-d6) ppm: 1.2-1.45 (6H, m), 1.50 (3H, s) 1.6-2.1 (5H, m) 2.94 (1H, d, J = 13.8 Hz ), 3.51 (1H d, J = 13.9 Hz), 3.65-3.85 (1H, m), 3.95-4.15 (1H, m), 6.80 (1H, dd, J = 2.5, 8.9 Hz), 7.01 (1H, dd, J = 2.8, 13.4 Hz), 7.34 (1H, dd, J = 9.0, 9.0 Hz), 8.16 (1H, br), 9.77 (1H, br). Hydrochloride 174 H H OCH.sub.3 Cl H H 1H-NMR (DMSO-d6 ) ppm: 1.2-1.5 (6H, m), 1.53 (3H, s), 1.65-1.95 (4H, m), 1.95-2.1 (1H, m), 2.95 (1H, d, J = 13.5 Hz), 3.3-3.45 (1H, m), 3.7-3.8 (1H, m), 3.84 (3H, s), 4.0-4.1 (1H, m), 6.52 (1H, dd, J = 2.7, 8.9 Hz), 6.63 (1H, d, J = 2.6 Hz), 7.19 (1H, d, J = 8.8 Hz), 8.18(1H, br), 9.88 (1H, br). Hydrochloride

(310) TABLE-US-00026 Relative configuration Example R.sup.1 R.sup.4 NMR Salt 175 H 1H-NMR (CDCl3) ppm: 1.04-1.21 (1H, m), 1.25-1.46 (2H, m), 1.64-1.88 (3H, m), 1.67 (3H, s), 1.77 (3H, s), 2.00-2.12 (1H, m), 2.34-2.40 (1H, m), 2.88 (1H, d, J = 12.5 Hz), 3.13-3.29 (2H, m), 3.42 (1H, d, J = 12.5 Hz), 7.29-7.34 (1H, m), 7.41-7.51 (2H, m), 7.60 (1H, s), 7.77-7.82 (3H, m), 9.51 (1H, brs), 9.79 (1H, brs) Hydro- chloride 176 H 1H-NMR (CDCl3) ppm: 1.00-1.11 (1H, m), 1.25-1.39 (2H, m), 1.58-1.81 (3H, m), 1.65 (3H, s), 1.75 (3H, s), 1.96-2.10 (1H, m), 2.32-2.37 (1H, m), 2.82 (1H, d, J = 12.5 Hz), 3.06-3.15 (1H, m), 3.18-3.36 (2H, m), 3.39 (1H, d, J = 12.5 Hz), 7.19 (1H, d, J = 8.5 Hz), 7.2 (1H, d, J = 5.4 Hz), 7.47 (1H, d, J = 5.4 Hz), 7.64 (1H, s), 7.81 (11-1, d, J = 8.5 Hz), 9.46 (1H, brs), 9.75 (1H, brs) Hydro- chloride 177 H 0 1H-NMR (DMSO) ppm: 0.92-1.37 (3H, m), 1.27 (3H, s), 1.40-1.60 (3H, m), 1.52 (3H, s), 1.60-1.75 (1H, m), 1.80-1.90 (1H, m), 2.60- 2.73 (1H, m), 2.78 (1H, d, J = 12.1 Hz), 2.97 (1H, d, J = 12.1 Hz), 3.00-3.12 (1H, m), 3.13-3.69 (3H, br), 3.76 (3H, s), 6.36 (1H, d, J = 3.0 Hz), 6.50 (2H, s), 6.94 (1H, dd, J = 8.6, 1.6 Hz), 7.28 (1H, d, J = 1.6 Hz), 7.30 (1H, d, J = 3.0 Hz), 7.36 (1H, d, J = 8.6 Hz) Fumarate 178 H 1H-NMR (CDCl3) ppm: 0.97-1.09 (1H, m), 1.23-1.38 (2H, m), 1.62-1.68 (3H, m), 1.63 (3H, s), 1.68 (3H, s), 1.92-2.05 (1H, m), 2.29-2.36 (1H, m), 2.73 (1H, d, J = 12.4 Hz), 2.94-3.03 (1H, m), 3.11-3.22 (1H, m), 3.28 (1H, d, J = 12.4 Hz), 7.02 (1H, dd, J = 8.5, 2.4 Hz), 7.25 (1H, d, J = 2.4 Hz), 7.39 (1H, d, J = 8.5 Hz), 9.50 (1H, brs), 9.78 (1H, brs) Hydro- chloride

(311) TABLE-US-00027 TABLE 27 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 179 H 1H-NMR (CDCl3) ppm : 1.26-2.30 (8H, m), 1.79 (3H, s), 2.17 (3H, s), 2.51-2.57 (1H,m), 3.36 (1H, d, J = 13.2 Hz), 3.90-4.30 (2H, m), 4.08 (1H, d, J = 13.2 Hz), 7.56-7.69 (2H, m), 7.83-8.01 (4H, m), 8.50 (1H, brs), 10.07 (1H, brs), 10.26 (1H, brs) Dihydrochloride 180 CH.sub.3 1H-NMR (CDCl3) ppm : 1.20-1.36 (1H, m), 1.42-1.76 (4H, m), 1.76 (3H, s), 1.91-1.93 (1H, m), 2.03-2.18 (1H, m), 2.16 (3H, s), 2.30-2.53 (2H, m), 2.85 (3H, d, J = 4.9 Hz), 3.49 (1H, d, J = 13.6 Hz), 4.06-4.21 (1H, m), 4.68 (1H, d, J = 13.6 Hz), 4.95-5.05 (1H, m), 7.55-7.67 (2H, m), 7.89-8.05 (4H, m), 8.95 (1H, br), 13.17 (1H, brs) Dihydrochloride 181 H 1H-NMR (DMSO-d6) ppm: 0.94-1.25 (2H, m), 1.25-1.45 (5H, m), 1.45-1.55 (1H, m), 1.55-1.80 (5H, m), 1.95-2.10 (1H, m), 2.82 (1H, d, J = 12.4 Hz), 2.97-3.11 (2H, m), 3.36-3.51 (1H, m), 7.40 (1H, d, J = 7.3 Hz), 7.50-7.59 (3H, m), 7.79 (1H, d, J = 8.2 Hz), 7.89-7.96 (1H, m), 8.42-8.48 (1H, m), 8.97-9.24 (1H, br), 9.50-9.80 (1H, br). Hydrochloride 182 H 1H-NMR (CDCl3) ppm : 1.21-2.12 (8H, m), 1.77 (3H, s), 2.11 (3H, s), 2.49-2.55 (1H, m), 3.27 (1H, d, J = 13.1 Hz), 3.64-4.22 (3H, m), 3.94 (3H, s), 7.15-7.24 (2H, m), 7.68-7.85(3H, m), 8.25 (1H, brs), 10.04 (2H, brs) Dihydrochloride 183 CH.sub.3 1H-NMR (CDCl3) ppm : 1.20-1.50 (2H, m), 1.63-2.28 (7H, m), 1.70 (3H, s), 1.95 (3H, s), 2.81 (3H, d, J = 4.9 Hz), 3.27 (1H, d, J = 13.2 Hz), 3.49-3.85 (1H, m), 3.94 (3H, s ), 4.22-4.70 (2H, br), 7.14-7.25 (2H, m), 7.68-7.82 (3H, m), 7.97-8.60 (1H, br), 12.21 (1H, brs) Dihydrochloride 184 H 1H-NMR (DMSO-d6) ppm : 1.01-1.48 (6H, m), 1.48-1.85 (7H, m), 1.95-2.12 (1H, m), 2.88-3.33 (4H, m), 4.45-5.45 (1H, br), 7.30-7.48 (2H, m), 7.62-7.75 (2H, m), 7.89 (1H, d, J = 8.8 Hz), 7.99(1H, dd, J = 5.8, 9.1 Hz), 9.07-9.38 (1H, br), 9.60-9.88 (1H, br). Dihydrochloride

(312) TABLE-US-00028 TABLE 28 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 185 H 0 1H-NMR (CDCl3) ppm : 0.96-1.07 (1H, m), 1.25-1.33 (2H, m), 1.48-1.86 (3H, m), 1.65 (3H, s), 1.85 (3H, s), 1.95-2.12 (1H, m), 2.37-2.42 (1H, m), 2.86 (1H, d, J = 12.7 Hz), 3.20-3.35 (2H, m), 3.32 (1H, d, J = 12.7 Hz), 7.26 (1H, d, J = 7.7 Hz), 7.35 (1H, dd, J = 7.7, 7.7 Hz), 7.41 (1H, d, J = 5.5 Hz), 7.53 (1H, d, J = 5.5 Hz), 7.72 (1H, d, J = 7.7 Hz), 9.57 (1H, brs), 9.87 (1H, brs) Hydrochloride 186 H 1H-NMR (CDCl3) ppm : 1.18-2.18 (8H, m), 1.76 (3H, s), 2.17 (3H, s), 2.47-2.54 (1H, m), 3.26 (1H, d, J = 12.9 Hz), 3.72-4.05 (2H, m), 3.92 (1H, d, J = 12.9 Hz), 7.41 (1H, d, J = 5.5 Hz), 7.59 (1H, d, J = 5.5 Hz), 7.65-7.80 (1H, m), 7.96 (1H, d, J = 8.7 Hz), 8.34 (1H, brs), 10.15 (2H, brs) Dihydrochloride 187 CH.sub.3 1H-NMR (CDCl3) ppm : 1.23-1.76 (5H, m), 1.75 (3H, s), 1.84-2.21 (2H, m), 2.14 (3H, s), 2.24-2.44 (2H, m), 2.86 (3H, d, J = 4.9 Hz), 3.49 (1H, d, J = 13.6 Hz), 4.06-4.20 (1H, m), 4.65 (1H, d, J = 13.6 Hz), 4.90-5.01 (1H, m), 7.46 (1H, d, J = 5.5 Hz), 7.65 (1H, d, J = 5.5 Hz), 7.74-9.30 (2H, br), 7.97-8.10 (1H, m), 13.12 (1H, brs) Dihydrochloride 188 H 1H-NMR (CDCl3) ppm : 1.26-2.06 (8H, m), 1.75 (3H, s), 2.05 (3H, s), 2.46-2.52 (1H, m), 3.23 (1H, d, J = 13.4 Hz), 3.70-4.05 (2H, br), 3.86 (1H, d, J = 13.4 Hz), 7.36 (1H, d, J = 5.5 Hz), 7.56 (1H, d, J = 5.5 Hz), 7.67 (1H, brs), 7.89 (1H, d, J = 8.6 Hz), 8.38 (1H, brs), 10.03 (2H, brs) Dihydrochloride 189 CH.sub.3 1H-NMR (CDCl3) ppm : 1.18-1.35 (1H, m), 1.39-1.53 (1H, m), 1.55-1.75 (2H, m), 1.74 (3H, s), 1.84-1.96 (1H, m), 2.02-2.39 (4H, m), 2.08 (3H, s), 2.84 (3H, d, J = 4.9 Hz), 3.42 (1H, d, J = 13.5 Hz), 3.96-4.07 (1H, m), 4.56 (1H, d, J = 13.5 Hz), 4.76-4.84 (1H, m), 7.39 (1H, d, J = 5.5 Hz), 7.63 (1H, d, J = 5.5 Hz), 7.90-7.99 (2H, m), 8.780 (1H, br), 13.05 (1H, brs) Dihydrochloride 190 H 1H-NMR (DMSO-d6) ppm : 0.95-1.48 (6H, m), 1.48-1.80 (7H, m), 1.90-2.07 (1H, m), 2.87-3.16 (3H, m), 3.16-3.32 (1H, m), 7.23 (1H, d, J = 7.5 Hz), 7.40-7.52 (2H, m), 7.67-7.79 (2H, m), 8.92-9.22 (1H, br), 9.40-9.70 (1H, br). Hydrochloride

(313) TABLE-US-00029 TABLE 29 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 191 H 1H-NMR (DMSO-d6) ppm : 0.95-1.46 (6H, m), 1.46-1.85 (7H, m), 1.95-2.12 (1H, m), 2.80-3.40 (4H, m), 5.50-6.60 (1H, br), 6.75-7.20 (2H, m), 7.20-7.37 (1H, m), 7.37-1.53 (1H, m), 7.99 (1H, s), 9.00-9.50 (1H, br), 9.60-10.05 (1H, br). Dihydrochloride 192 H 1H-NMR (DMSO-d6) ppm at 80 C.: 0.96-1.26 (2H, m), 1.26-1.51 (5H, m), 1.51-1.61 (1H, m), 1.61-1.78 (5H, m), 1.99-2.08 (1H, m), 2.80 (1H, d, J = 12.3 Hz), 3.05-3.32 (3H, m),3.58-4.12 (1H, br), 7.01 (1H, dd, J = 3.8, 8.5 Hz), 7.08-7.18 (2H, m), 8.01 (1H, d, J = 2.1 Hz), 9.10-9.35 (1H, br), 9.38-9.75 (1H, br). Dihydrochloride 193 H 1H-NMR (DMSO-d6) ppm at 80 C.: 0.98-1.27 (2H, m), 1.27-1.46 (4H, m), 1.46-1.60 (2H, m) 1.60-1.80 (5H, m), 1.98-2.10 (1H, m), 2.84 (1H d, J = 12.4 Hz), 3.05-3.35 (3H, m), 3.45-3.90 (1H, br), 7.05 (1H, d, J = 8.2 Hz), 7.08-7.13 (1H, br), 7.36 (1H, d, J = 8.2 Hz), 8.03 (1H, d, J = 2.2 Hz), 8.98-9.35 (1H, br), 9.35-9.72 (1H, br). Dihydrochloride 194 H 0 1H-NMR (CDCl3) ppm: 0.82-1.05 (2H, m), 1.07 (3H, s), 1.19-1.43 (3H, m), 1.49 (3H, s), 1.56-1.68 (1H, m), 1.68-1.90 (3H, m), 2.35-2.51 (4H, m), 2.51-2.70 (1H, m), 2.78-2.92 (2H, m), 6.83-6.89 (2H, m), 7.01 (1H, d, J = 7.8 Hz), 7.56 (1H, d, J = 2.1 Hz). 195 H 1H-NMR (DMSO-d6) ppm at 80 C.: 0.96-1.25 (2H, m), 1.25-1.60 (6H, m), 1.60-1.79 (5H, m), 1.98-2.10 (1H, m), 2.76 (1H, d, J = 12.3 Hz), 2.99-3.37 (3H, m), 3.93 (3H, s), 4.52-4.86 (1H, br), 6.86 (1H, d, J = 8.4 Hz), 6.95 (1H, d = 8.4 Hz), 6.98-7.09 (1H, br), 7.87 (1H, d, J = 2.1 Hz), 9.02-9.40 (1H, br), 9.40-9.75 (1H, br). Dihydrochloride 196 H 1H-NMR (CDCl3) ppm: 1.18-1.36 (1H, m), 1.41-1.63 (2H, m), 1.73-2.10 (5H, m), 1.78 (3H, s), 2.17 (3H, s), 2.36-2.69 (1H, m), 3.36 (1H, d, J = 12.8 Hz), 3.82-4.40 (2H, br), 4.09 (1H, d, J = 12.8 Hz), 6.88 (1H, d, J = 2.0 Hz), 7.62 (1H, d, J = 8.7 Hz), 7.74 (1H, d, J = 2.0 Hz), 7.70-8.76 (2H, br), 9.50-10.65 (2H, br) Dihydrochloride 197 H 1H-NMR (DMSO-d6) ppm at 80 C.: 1.03-1.44 (6H, m), 1.51-1.79 (7H, m), 2.00-2.10 (1H, m), 2.87 (1H, d, J = 12.4 Hz), 2.94-3.05 (1H, m), 3.10-3.23 (2H, m), 4.64-5.12 (1H, br), 6.88(1H, d, J = 1.4 Hz), 7.05-7.09 (1H, m), 7.33-7.36 (1H, br), 7.59 (1H, d, J = 8.2 Hz), 7.89 (1H, J = 2.2 Hz), 8.97-9.26 (1H, br), 9.45-9.82 (1H, br). Dihydrochloride

(314) TABLE-US-00030 TABLE 30 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 198 H 1H-NMR(CDCl3) ppm : 0.93-1.80 (35H, m), 1.80-2.05 (1H, br), 2.40-2.70 (2H, m), 2.81-2.95 (1H, m), 3.00-3.15 (1H, m), 6.72 (1H, d, J = 2.7 Hz), 6.80 (1H, d, J = 7.4 Hz), 7.00-7.13 (1H, m), 7.17 (1H, d, J = 3.2 Hz), 7.23-7.34 (1H, m). 199 H 1H-NMR (CDCl3) ppm : 0.99-1.50 (5H, m), 1.07 (3H, s), 1.13 (9H, s), 1.15 (9H, s), 1.42 (3H, s), 1.58-1.73 (7H, m), 2.23-2.31 (1H, m), 2.68 (1H, d, J = 11.2 Hz), 2.73-2.79 (1H, m), 2.83 (1H, d, J = 11.2 Hz), 6.55 (1H, dd, J = 3.2, 0.7 Hz), 6.92 (1H, dd, J = 8.8, 2.1 Hz), 7.21 (1H, d, J = 3.2 Hz), 7.34 (1H, d, J = 2.1 Hz), 7.37 (1H, d, J = 8.8 Hz) 200 H 1H-NMR (CDCl3) ppm : 0.85-1.85 (36H, m), 2.25-2.39 (1H, m), 2.60 (1H, d, J = 11.2 Hz), 2.76-2.90 (2H, m), 6.54-6.60 (1H, m), 6.90 (1H, dd, J = 1.7, 8.3 Hz), 7.17-7.32 (2H, m), 7.50 (1H, d, J = 8.3 Hz). 201 H 1H-NMR (CDCl3) ppm : 1.01-1.44 (5H, m), 1.08 (3H, s), 1.13 (9H, s), 1.15 (9H, s), 1.42 (3H, s), 1.56-1.83 (7H, m), 2.25-2.33 (1H, m), 2.67 (1H, d, J = 11.3 Hz), 2.77-2.83 (1H, m), 2.82 (1H, d, J = 11.3 Hz), 7.13 (1H, dd, J = 8.9, 2.0 Hz), 7.43 (1H, d, J = 2.0 Hz), 7.45 (1H, d, J = 8.9 Hz), 8.15 (1H, d, J = 0.8 Hz)

(315) TABLE-US-00031 TABLE 31 Absolute configuration Melting Example R.sup.1 R.sup.4 NMR point ( C.) Salt 202 H 0 1H-NMR (CDCl3) ppm : 0.80-1.18 (5H, m), 1.18-1.46 (3H, m), 1.46-1.66 (4H, m), 1.66-2.05 (3H, m), 2.40-2.70 (2H, m), 2.80-2.98 (1H, m), 3.03 (1H, d, J = 11.3 Hz), 6.64-6.72 (1H, m), 6.83 (1H, dd, J = 1.6, 6.6 Hz), 7.07-7.20 (3H, m), 8.16-8.35 (1H, br). 203 H 1H-NMR (CDCl3) ppm : 0.95-1.08 (1H, m), 1.07 (3H, s), 1.13-1.37 (4H, m), 1.43 (3H, s), 1.55-1.73 (4H, m), 2.25-2.33 (1H, m), 2.68 (1H, d, J = 11.1 Hz), 2.75-2.83 (1H, m), 2.81 (1H, d, J = 11.1 Hz), 6.48-6.50 (1H, m), 7.01 (1H, dd, J = 8.6, 1.9 Hz), 7.17-7.20 (1H, m), 7.30 (1H, d, J = 8.6 Hz), 7.38 (1H, d, J = 1.9 Hz), 8.11 (1H, brs) 204 CH.sub.3 1H-NMR (CDCl3) ppm : 1.01-1.30 (3H, m), 1.09 (3H, s), 1.22 (3H, s), 1.50-1.76 (4H, m), 1.99-2.15 (1H, m), 2.25 (3H, s), 2.27-2.36 (1H, m), 2.54-2.64 (1H, m), 2.70 (1H, d, J = 11.2 Hz), 2.91 (1H, d, J = 11.2 Hz), 6.48-6.50 (1H, m), 7.02 (1H, dd, J = 8.6, 1.5 Hz), 7.17-7.20 (1H, m), 7.31 (1H, d, J = 8.6 Hz), 7.39(1H, s), 8.10 (1H, brs) 205 H 1H-NMR (CDCl3) ppm : 0.80-1.40 (8H, m), 1.43 (3H, s), 1.55-1.86 (4H, m), 2.27-2.40 (1H, m), 2.68 (1H, d, J = 11.3 Hz), 2.75-2.91 (2H, m), 6.48-6.56 (1H, m), 6.94 (1H, dd, J = 1.8, 8.4 Hz), 7.13-7.22 (2H, m), 7.53 (1H, d, J = 8.4 Hz), 8.15-8.48 (1H, br). 206 H 1H-NMR (MeOH-d4) ppm : 0.87-1.95 (14H, m), 2.66-3.02 (3H, m), 3.09-3.30 (3H, m), 3.69 (3H, s), 6.43 (1H, s), 6.58 (1H, s), 6.77 (1H, d, J = 7.6 Hz), 6.93-7.20 (3H, m). Hemifumarate 207 CH.sub.3 1H-NMR (DMSO-d6) ppm : 0.85-1.55 (11H, m), 1.63-1.85 (2H, m), 2.05-2.20 (1H, m), 2.41 (3H, brs), 2.60-3.00 (4H, m), 3.00-4.80 (5H, m), 6.35-6.52 (1H, br), 6.56 (2H, s), 6.79 (1H, d, J = 7.5 Hz), 7.03-7.15 (1H, m), 7.15-7.30 (2H, m). Fumarate 208 CH.sub.3 1H-NMR (DMSO-d6) ppm : 0.89-1.40 (10H, m), 10.40-10.58 (2H, m), 10.63-10.80 (1H, m), 2.01-2.27 (1H, m), 2.39 (3H, s), 2.55-2.78 (3H, m), 2.92-3.06 (1H,m), 4.65 (5H, m), 6.35 (1H, d, J = 2.6 Hz), 6.55 (2H, s), 6.90-7.00 (1H, m), 7.24-7.32 (2H, m), 7.34 (1H, d, J = 8.6 Hz). Fumarate 209 H 1H-NMR (DMSO-d6) ppm : 0.90-1.63 (12H, m), 1.63-1.77 (1H, m), 1.82-1.99 (1H, m), 2.60-2.88 (2H, m), 2.91-3.14 (2H, m), 3.75 (3H, s), 3.80-5.30 (2H, br), 6.36 (1H, d, J = 3.0 Hz), 6.48 (2H, s), 6.85 (1H, d, J = 8.4 Hz), 7.14 (1H, s), 7.27 (1H, d, J = 3.0 Hz), 7.46 (1H, d, J = 8.4 Hz), 8.76-10.00 (1H, br). Fumarate 210 CH.sub.3 1H-NMR (DMSO-d6) ppm : 0.90-1.35 (10H, m), 1.40-1.55 (2H, m), 1.55-1.80 (1H, m), 2.02-2.16 (1H, m), 2.39 (3H, s), 2.55-2.80 (31-1,m ), 2.90-3.08 (1H, m), 3.15-4.70 (5H,m), 6.32-6.40 (1H, m), 6.56 (2H, s), 6.85 (1H, dd, J = 1.5 8.4 Hz), 7.14 (1H, s), 7.26 (1H, d, J = 3.1 Hz), 7.45 (1H, d, J = 8.4 Hz). Fumarate 211 H 209.8- 214.2 Fumarate 212 H 0 1H-NMR (CDCl3) ppm : 0.96-1.16 (1H, m), 1.09 (3H, s), 1.19-1.39 (4H, m), 1.44(3H, s), 1.52-1.62(2H, m), 1.69-1.82 (2H, m), 2.27-2.35 (1H, m), 2.68 (1H, d, J = 11.1 Hz), 2.75-2.85 (1H, m), 2.81 (1H, d, J = 11.1 Hz), 7.22 (1H, dd, J = 8.8, 1.9 Hz), 7.37-7.46 (2H, m), 8.01 (1H, s), 9.54-10.80 (1H, br) 213 CH.sub.3 1H-NMR (CDCl3) ppm : 0.99-1.30 (4H, m), 1.10 (3H, s), 1.22 (3H, s), 1.41-1.67 (2H, br), 1.70-1.80 (1H, m), 1.98-2.16 (1H, m), 2.26 (3H, s), 2.20-2.37 (1H, m), 2.57-2.64 (1H, m), 2.69 (1H, d, J = 11.1 Hz), 2.89 (1H, d, J= 11.1 Hz), 5.85 (1H, s), 7.21-7.28 (1H, m), 7.40-7.53 (2H, m), 8.01 (1H, s) 214 H 1H-NMR (DMSO-d6) ppm : 1.00-1.51 (7H, m), 1.51-1.85 (6H, m), 1.92-2.20 (1H, brs), 2.60-3.70 (4H, m), 4.04 (3H, s), 6.85-7.90 (3H, m), 7.90-8.18 (1H, brs), 8.75-10.40 (3H, brm). Dihydrochloride 215 H 1H-NMR (DMSO-d6) ppm : 0.95-1.40 (6H, m), 1.40-1.65 (6H, m), 1.65-1.80 (1H, m), 1.85-2.00 (1H, m), 2.65-2.80(2H, m), 2.85-3.00 (1H, m), 3.00-3.21(1H, m), 3.98-4.55 (1H, br), 6.00 (2H, s), 6.55-6.65 (1H, m), 6.73 (1H, d, J = 1.6 Hz), 6.86 (1H, d, J = 8.2 Hz), 8.65-8.95 (1H, br), 9.22-9.52 (1H, br). Dihydrochloride 216 H 1H-NMR (DMSO) ppm : 1.04-1.46 (4H, m), 1.35 (3H, s), 1.50-1.75 (4H, m), 1.59 (3H, s), 1.94-1.99 (1H, m), 2.82-2.92 (1H, m), 2.97 (1H, d, J = 12.3 Hz), 3.07 (1H, d, J = 12.3 Hz), 3.13-3.28 (1H, m), 7.28 (1H, dd, J = 8.5,1.8 Hz), 7.81 (1H, d, J = 1.8 Hz), 8.12 (1H, d, J = 8.5 Hz), 8.85-9.05 (1H, br), 9.41 (1H, s), 9.48-9.56 (1H, br) Dihydrochloride 211 H 209.8- 214.2 Fumarate 212 H 1H-NMR (CDCl3) ppm : 0.96-1.16 (1H, m), 1.09 (3H, s), 1.19-1.39 (4H, m), 1.44(3H, s), 1.52-1.62(2H, m), 1.69-1.82(2H, m), 2.27-2.35 (1H, m), 2.68 (1H, d, J = 11.1 Hz), 2.75-2.85 (1H, m), 2.81 (1H, d, J = 11.1 Hz), 7.22 (1H, dd, J = 8.8, 1.9 Hz), 7.37-7.46 (2H, m), 8.01 (1H, s), 9.54-10.80 (1H, br) 213 CH.sub.3 1H-NMR (CDCl3) ppm : 0.99-1.30 (4H, m), 1.10 (3H, s), 1.22 (3H, s), 1.41-1.67 (2H, br), 1.70-1.80 (1H, m), 1.98-2.16 (1H, m), 2.26 (3H, s), 2.20-2.37 (1H, m), 2.57-2.64 (1H, m), 2.69 (1H, d, J = 11.1 Hz), 2.89 (1H, d, J= 11.1 Hz), 5.85 (1H, s), 7.21-7.28 (1H, m), 7.40-7.53 (2H, m), 8.01 (1H, s) 214 H 1H-NMR (DMSO-d6) ppm : 1.00-1.51 (7H, m), 1.51-1.85 (6H, m), 1.92-2.20 (1H, brs), 2.60-3.70 (4H, m), 4.04 (3H, s), 6.85- 7.90 (3H, m), 7.90-8.18 (1H, brs), 8.75-10.40 (3H, brm). Dihydrochloride 215 H 1H-NMR (DMSO-d6) ppm : 0.95-1.40 (6H, m), 1.40-1.65 (6H, m), 1.65-1.80 (1H, m), 1.85-2.00 (1H, m), 2.65-2.80(2H, m), 2.85-3.00 (1H, m), 3.00-3.21(1H, m), 3.98-4.55 (1H, br), 6.00 (2H, s), 6.55-6.65 (1H, m), 6.73 (1H, d, J = 1.6 Hz), 6.86 (1H, d, J = 8.2 Hz), 8.65-8.95 (1H, br), 9.22-9.52 (1H, br). Dihydrochloride 216 H 0 1H-NMR (DMSO) ppm : 1.04-1.46 (4H, m), 1.35 (3H, s), 1.50-1.75 (4H, m), 1.59 (3H, s), 1.94-1.99 (1H, m), 2.82-2.92 (1H, m), 2.97 (1H, d, J = 12.3 Hz), 3.07 (1H, d, J = 12.3 Hz), 3.13-3.28 (1H, m), 7.28 (1H, dd, J = 8.5,1.8 Hz), 7.81 (1H, d, J = 1.8 Hz), 8.12 (1H, d, J = 8.5 Hz), 8.85-9.05 (1H, br), 9.41 (1H, s), 9.48-9.56 (1H, br) Dihydrochloride

(316) TABLE-US-00032 TABLE 32 Absolute configuration Melting Example R.sup.1 R.sup.4 NMR point ( C.) Salt 217 H 1H-NMR (DMSO-d6) ppm: 1.00-1.44 (6H, m), 1.50-1.79 (7H, m), 1.96-2.08 (1H, m), 2.82-3.00 (2H, m), 3.00-3.25 (2H, m), 3.61 (3H, s), 6.62 (1H, d, J = 9.5 Hz), 7.38-7.46 (1H, m), 7.48-7.58 (2H, m), 7.91 (1H, d, J = 9.5 Hz), 7.98-8.62 (1H, br), 9.14-9.37 (1H, br), 9.65-9.88 (1H, br). Dihydrochloride 218 H 1H-NMR (CDCl3) ppm: 0.87-1.03 (1H, m), 1.09 (3H, m), 1.15-1.46 (4H, m), 1.46-1.65 (5H, m), 1.65-1.88 (2H, m), 2.47-2.60 (1H, m), 2.65 (1H, d, J = 11.3 Hz), 2.76 (1H, d, J = 11.3 Hz), 2.90-3.04 (1H, m), 7.25 (1H, d, J = 7.3 Hz), 7.40 (1H, dd, J = 4.2, 8.5 Hz), 7.65-7.72 (1H, m), 7.91 (1H, d, J = 8.5 Hz), 8.85(1H, d, J= 8.5 Hz), 8.90 (1H, dd, J = 1.7, 4.2 Hz). 219 H 1H-NMR (CDCl3) ppm: 0.93-1.12 (5H, m), 1.22-1.48 (3H, m), 1.55-1.70 (4H, m), 1.73-1.90 (3H, m), 2.50 (1H, d, J = 11.5 Hz), 2.55-2.65 (1H, m), 2.92-3.05 (2H, m), 7.09 (1H, d, J = 4.8 Hz), 7.49-7.56 (1H, m), 7.65-7.72 (1H, m), 8.05-8.10 (1H, m), 8.36 (1H, dd, J = 1.0 8.4 Hz), 8.84 (1H, d, J = 4.8 Hz). 220 H 1H-NMR (CDCl3) ppm: 0.80-1.17 (5H, m), 1.21-1.50 (6H, m), 1.61-1.88 (4H, m), 2.42-2.50 (1H, m), 2.74 (1H, d, J = 11.4 Hz), 2.80-2.90 (1H, m), 2.96 (1H, d, J = 11.4 Hz), 7.31-7.39 (2H, m), 7.50 (1H, dd, J = 2.4, 9.0 Hz), 8.01 (1H, d, J = 9.0 Hz), 8.06 (1H, dd, J = 1.1, 8.3 Hz), 8.81 (1H, dd, J = 1.7, 4.2 Hz). 221 H 1H-NMR (CDCl3) ppm: 1.04-1.20 (4H, m), 1.20-1.48 (7H, m), 1.67-1.86 (3H, m), 1.96 (1H, dd, J = 3.0, 13.0), 2.61-2.70 (1H, m), 2.82-2.95 (2H, m), 3.07 (1H, d, J = 12.0 Hz), 7.20 (1H, d, J = 1.8 Hz), 7.32 (1H, dd, J = 2.1, 8.8 Hz), 7.50 (1H, d, J = 5.8 Hz), 7.84 (1H, d, J = 8.8 Hz), 8.41 (1H, d, J = 5.8 Hz), 9.09 (1H, s).

(317) TABLE-US-00033 TABLE 33 Absolute configuration Example R.sup.1 R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 222 H H H F H H 1H-NMR (CDCl3) ppm : 1.21-1.36 (1H, m), Dihydrochloride 1.44-1.61 (2H, m), 1.68-2.00 (3H, m), 1.78 (3H, s), 2.09-2.33 (1H, m), 2.22 (3H, s), 2.51-2.55 (1H, m), 3.42 (1H, d, J = 13.2 Hz), 3.92-4.12 (1H, m), 4.15 (1H, d, J = 13.2 Hz), 4.37-4.44 (1H, m), 7.22-7.27 (4H, m), 7.90-8.46 (1H, br), 9.90-10.18 (1H, m), 10.32-10.60 (1H, brs) 223 CH.sub.3 H H F H H 1H-NMR (CDCl3) ppm : 0.90-1.10 (1H, m), Dihydrochloride 1.14-1.38 (2H, m), 1.40-1.75 (2H, m), 1.53 (3H, s), 1.59 (3H, s), 1.85-1.95 (1H, m), 2.01-2.23 (2H, m), 2.72 (3H, d, J = 5.0 Hz), 2.75 (1H, d, J = 12.9 Hz), 2.87-3.06 (1H, m), 3.40-3.50 (1H, m), 3.80 (1H, d, J = 12.9 Hz), 6.98-7.04 (2H, m), 7.18-7.23 (2H, m), 12.10 (1H, brs) 224 H H F F H H 1H-NMR (CDCl3) ppm : 1.17-1.46 (3H, m), Hydrochloride 1.53-1.74 (2H, m), 1.66 (3H, s), 1.79 (3H, s), 1.79 (1H, brs), 1.88-2.05 (1H, m), 2.24-2.46 (1H, m), 2.88 (1H, d, J = 12.5 Hz), 3.10-3.40 (2H, m), 3.43 (1H, d, J = 12.5 Hz), 7.13-7.18 (2H, m), 7.20-7.28 (1H, m), 9.40-9.75 (1H, br), 9.76-10.08 (1H, 225 CH.sub.3 H F F H H 1H-NMR (CDCl3) ppm :1.19-1.41 (3H, m), Hydrochloride 1.61 (8H, brs), 1.80-2.02 (1H, m), 2.04-2.24 (2H, m), 2.74 (3H, d, J = 5.0 Hz), 2.87 (1H, d, J = 12.8 Hz), 3.08-3.20 (1H, m), 3.62-3.78 (1H, m), 3.92 (1H, d, J = 12.8 Hz), 7.11-7.19 (2H, m), 7.27-7.32 (1H, m), 12.08 (1H, brs) 226 H H Cl F H H 1H-NMR (CDCl3) ppm : 1.13-1.42 (3H, m), Hydrochloride 1.47-1.81 (3H, m), 1.65 (3H, s), 1.74(3H, s), 1.88-2.05 (1H, m), 2.32-2.38 (1H, m), 2.80 (1H, d, J = 12.5 Hz), 3.07-3.16 (1H, m), 3.19-3.29 (1H, m), 3.36 (1H, d, J = 12.5 Hz), 7.07-7.21 (2H, m), 7.34 (1H, dd, J = 6.5 2.3 Hz), 9.56 (1H, brs), 9.82-9.86 (1H, br) 227 H H CH.sub.3 F H H 1H-NMR (DMSO-d6) ppm : 1.00-1.45 Dihydrochloride (6H, m), 1.45-1.81 (7H, m), 1.81-2.10 (1H, m), 2.22 (3H, d, J = 1.5 Hz), 2.78-3.00 (2H, m), 3.00-3.27 (2H, m), 4.10-4.98 (1H, br), 6.96-7.23 (3H, m), 9.00-9.40 (1H, br), 9.58-9.92 (1H, br). 228 H H OCH.sub.3 F H H 1H-NMR (DMSO-d6) ppm at 80 C.: Dihydrochloride 1.00-1.43 (6H, m), 1.49-1.77 (7H, m), 1.97-2.08 (1H, m), 2.81 (1H, d, J = 12.3 Hz), 2.84-2.93 (1H, m), 3.04-3.18(2H, m), 3.83(3H, s), 4.30-4.57 (1H, br), 6.68-6.74 (1H, m), 6.86 (1H, dd, J = 2.5, 7.9 Hz), 7.11 (1H, dd, J = 8.6, 11.4 Hz), 8.94-9.25 (1H, br), 9.49-9.80 (1H, br). 229 H H F CH.sub.3 H H 1H-NMR (CDCl3) ppm : 1.21-1.51 (2H, m), Hydrochloride 1.62-1.97 (5H, m), 1.72 (3H, s), 2.03 (3H, s), 2.29 (3H, s), 2.44-2.49 (1H, m), 3.21 (1H, d, J = 12.9 Hz), 3.66-3.87 (2H, m), 3.21 (1H, d, J = 12.9 Hz), 7.25-7.31 (1H, m), 7.47-7.62 (2H, m), 10.00 (2H, brs) 230 CH.sub.3 H F CH.sub.3 H H 1H-NMR (CDCl3) ppm : 1.20-1.40 (3H, m), Hydrochloride 1.48-1.75 (2H, m), 1.61 (3H, s), 1.64 (3H, s), 1.84-1.93 (1H, m), 2.11-2.16 (2H, m), 2.26 (3H, d, J = 1.9 Hz), 2.73 (3H, d, J = 5.0 Hz), 2.90 (1H, d, J = 12.9 Hz), 3.12-3.24 (1H, m), 3.65-3.80 (1H, m), 3.92 (1H, d, J = 12.9 Hz), 7.09-7.21 (3H, m), 12.33 (1H, brs) 231 H H F Cl H H 1H-NMR (CDCl3) ppm : 1.01-1.12 (1H, m), Hydrochloride 1.20-1.39 (2H, m), 1.56-2.04 (4H, m), 1.63(3H, s), 1.69 (3H, s), 2.31-2.36 (1H, m), 2.76 (1H, d, J= 12.4 Hz), 2.97-3.04 (1H, m), 3.13-3.24 (1H, m), 3.29 (1H, d, J = 12.4 Hz), 6.91-7.01 (2H, m), 7.34 (1H, dd, J = 8.4, 8.3 Hz), 9.50 (1H, brs), 9.80 (1H, brs) 232 CH.sub.3 H F Cl H H 1H-NMR (CDCl3) ppm : 1.00-1.13 (1H, m), Hydrochloride 1.17-1.40 (2H, m), 1.53 (3H, s), 1.60 (3H, s), 1.60-1.81 (3H, m), 1.90-1.94 (1H, m), 2.04-2.25 (1H, m), 2.72 (3H, d, J = 4.9 Hz), 2.78 (1H, d, J = 12.8 Hz), 2.92-3.04 (1H, m), 3.46-3.55 (1H, m), 3.81 (1H, d, J = 12.8 Hz), 7.00-7.08 (2H, m), 7.32-7.39 (1H, m), 12.26 (1H, brs) 233 H H F OCH.sub.3 F H 1H-NMR (DMSO-d6) ppm : 1.02-1.34 (3H, m), Dihydrochloride 1.33 (3H, s), 1.51 (3H, s), 1.54-1.73 (4H, m), 1.96-2.01 (1H, m), 2.76-2.83 (1H, m), 2.89 (1H, d, J = 12.5 Hz), 2.98 (1H, d, J = 12.5 Hz), 3.08-3.18 (1H, m), 3.87 (3H, s), 4.76 (1H, s), 6.86-6.96 (2H, m), 9.01-9.09 (1H, m), 9.70-9.75 (1H, m) 234 H H F OCH.sub.3 H H 1H-NMR (DMSO-d6) ppm : 1.05-1.45 (6H, m), Dihydrochloride 1.45-1.80 (7H, m), 1.95-2.08 (1H, m), 2.70-2.90 (2H, m), 2.95-3.23 (2H, m), 3.81 (3H, s), 4.65-5.40 (1H, br), 6.88-7.08 (2H, m), 7.08-7.22 (1H, m), 8.90-9.25 (1H, br), 9.55-9.85 (1H, br). 235 H H Cl H H H 1H-NMR (CDCl3) ppm : 1.05-1.13 (1H, m), Hydrochloride 1.23-1.35 (2H, m), 1.50-1.78 (3H, m), 1.63 (3H, s), 1.71 (3H, s), 1.92-2.08 (1H, m), 2.31-2.36 (1H, m), 2.78 (1H, d, J = 12.7 Hz), 3.00-3.09 (1H, m), 3.15-3.26 (1H, m), 3.31 (1H, d, J = 12.7 Hz), 7.07-7.10 (1H, m), 7.15-7.19 (2H, m), 7.23-7.29 (1H, m), 9.50 (1H, brs), 9.79 (1H, brs) 236 CH.sub.3 H Cl H H H 1H-NMR (CDCl3) ppm : 1.18-1.50 (2H, m), Dihydrochloride 1.60-1.81 (2H, m), 1.71 (3H, s), 1.91-2.30 (5H, m), 2.00 (3H, s), 2.80 (3H, d, J = 4.9 Hz), 3.32 (1H, d, J = 13.4 Hz), 3.81-3.94 (1H, m), 4.42 (1H, d, J = 13.4 Hz), 4.61-4.70 (1H, m), 7.42-7.50 (2H, m), 7.97 (1H, brs), 8.13 (1H, brs), 13.7 (1H, brs) 237 H H Cl CN H H 1H-NMR (CDCl3) ppm : 1.05-1.20 (1H, m), Hydrochloride 1.23-1.44 (2H, m), 1.54-2.10 (4H, m), 1.63 (3H, s), 1.68 (3H, s), 2.35-2.40 (1H, m), 2.89 (1H, d, J = 12.7 Hz), 3.19 (2H, br), 3.34 (1 H, d, J = 12.7 Hz), 7.06 (1H, dd, J = 8.4, 2.0 Hz), 7.20 (1H, d, J = 2.0 Hz), 7.61 (1H, d, J = 8.4 Hz), 9.62 (1H, brs), 9.90 (1H, br) 238 CH.sub.3 H Cl CN H H 1H-NMR (C0Cl3) ppm : 1.01-1.15 (1H, m), Hydrochloride 1.23-1.46 (2H, m), 1.50 (3H, s), 1.61 (3H, s), 1.61-1.98 (3H, m), 2.09-2.27 (2H, m), 2.72 (3H, d, J = 4.9 Hz), 2.87 (1H, d, J = 13.0 Hz), 2.91-3.03 (1H, m), 3.63-3.72 (1H, m), 3.84 (1H, d, J = 13.0 Hz), 7.14 (1H, dd, J = 8.4, 2.1 Hz), 7.26 (1H, d, J = 2.1 Hz), 7.62 (1H, d, J = 8.4 Hz), 12.38 (1H, brs) 239 H H Cl CH.sub.3 H H 1H-NMR (CDCl3) ppm :1.25-2.04 (7H, m), Hydrochloride 1.75 (3H, s), 2.13 (3H, s), 2.40 (3H, s), 2.48-2.53 (1H, m), 3.33 (1H, d, J = 13.1 Hz), 3.88-3.92 (1H, m), 3.97 (1H, d, J = 13.1 Hz), 4.10-4.17 (1H, m), 7.36 (1H, d, J = 8.4 Hz), 7.78 (1H, d, J = 8.4 Hz), 8.00 (1H, s), 10.03-10.07 (1H, m), 10.20-10.30 (1H, m) 240 CH.sub.3 H Cl CH.sub.3 H H 1H-NMR (CDCl3) ppm : 1.14-1.41 (3H, m), Hydrochloride 1.47-1.74 (2H, m), 1.58 (3H, s), 1.60 (3H, s), 1.89-1.93 (1H, m), 2.10-2.22 (2H, m), 2.35 (3H, s), 2.72 (3H, d, J = 4.9 Hz), 2.83 (1H, d, J = 12.9 Hz), 3.00-3.15 (1H, m) 3.45-3.67 (1H, m), 3.85 (1H, d, J = 12.9 Hz), 7.11-7.22 (2H, m), 7.32 (1H, s), 12.24 (1H, brs) 241 H H Cl OCH.sub.3 H H 1H-NMR (DMSO-d6) ppm : 0.95-1.41 Dihydrochloride (6H, m), 1.41-1.80 (7H,m ), 1.88-2.05 (1H, m), 2.69-2.90 (2H, m), 2.93-3.05 (1H, m), 3.05-3.24 (1H, m ), 3.83(3H, s), 4.15-5.35 (1H, br), 7.02-7.25(3H, m), 8.87-9.18 (1H, br), 9.40-9.72 (1H, br). 242 H H H Cl H H 1H-NMR (CDCl3) ppm : 1.13-1.24 (1H, m), Hydrochloride 1.25-1.36 (2H, m), 1.60-1.83 (3H, m), 1.64 (3H, s), 1.74 (3H, s), 1.89-2.02 (1H, m), 2.32-2.37 (1H, M), 2.80 (1H, d, J = 12.5 Hz), 3.12-3.16 (1H, m), 3.22-3.29 (1H, m), 3.36 (1H, d, J = 12.5 Hz), 7.19-7.22 (2H, m), 7.29-7.33 (2H, m), 9.52 (1H, brs), 9.81 (1H, brs) 243 CH.sub.3 H H Cl H H 1H-NMR (CDCl3) ppm : 1.02-1.40 (3H, m), Hydrochloride 1.48-1.75 (2H, m), 1.61 (3H, s), 1.63 (3H, s), 1.80-2.02 (1H, m), 2.11-2.16 (2H, m), 2.74 (3H, d, J = 5.0 Hz), 2.88 (1H, d, J = 12.9 Hz), 3.10-3.22 (1H, m), 3.66-3.78 (1H, m), 3.93 (1H, d, J = 12.9 Hz), 7.30-7.38 (4H, m), 12.28 (1H, brs) 244 H H CH.sub.3 Cl H H 1H-NMR (DMSO-d6) ppm : 0.90-1.79 Fumarate (13H, m), 1.79-1.95 (1H, m), 2.29 (3H, s), 2.58-3.08 (4H, m), 3.10-4.90 (3H, br), 6.48 (2H, s), 6.89-7.00 (1H, m), 7.07 (1H, d, J = 2.3 Hz), 7.33 (1H, d, J = 8.5 Hz). 245 H H OCH.sub.3 Cl H H 1H-NMR (DMSO-d6) ppm : 1.00-1.45 Dihydrochloride (6H ,m), 1.45-1.82 (7H, m), 1.95-2.10 (1H, m), 2.78-3.10 (3H, m), 3.10-3.27 (1H, m), 3.85 (3H, s), 4.00-4.55 (1H, br), 6.73 (1H, dd, J = 2.1, 8,4 Hz), 6.80 (1H, d, J = 2.1 Hz), 7.37 (1H, d, J = 8.4 Hz), 8.90-9.19 (1H, br), 9.51-9.85 (1H, br). 246 H H Cl Cl H H 1H-NMR (CDCl3) ppm : 1.15-1.45 (3H, m), Hydrochloride 1.58-1.81 (3H, m), 1.65 (3H, s), 1.75(3H, s), 1.88-2.04 (1H, m), 2.32-2.38 (1H, m), 2.82 (1H, d, J = 12.6 Hz), 3.12-3.31 (2H, m), 3.38 (1H, d, J = 12.6 Hz), 7.15 (1H, dd, J = 8.5, 2.3 Hz), 7.40 (1H, d, J = 2.3 Hz), 7.42 (1H, d, J = 8.5 Hz), 9.57 (1H, br), 9.82 (1H, br) 247 CH.sub.3 H Cl Cl H H 1H-NMR (CDCl3) ppm : 1.23-1.49 (2H, m), Hydrochloride 1.60-1.75 (2H, m), 1.69 (3H, s), 1.91 (3H, s), 1.91-2.15 (3H, m), 2.22-2.28 (1H, m), 2.79 (3H, d, J = 4.9 Hz), 3.23 (1H, d, J = 13.2 Hz), 3.64-3.76 (1H, m), 4.33 (1H, d, J = 13.2 Hz), 4.43-4.52 (1H, m), 7.56(1H, d, J = 8.7 Hz), 7.82 (1H, dd, J = 8.7, 2.3 Hz), 8.14 (1H, d, J = 2.3 Hz), 12.88 (1H, brs) 248 H H H OCH.sub.3 H H 1H-NMR (DMSO-d6) ppm : 1.02-1.50 (7H, m), Dihydrochloride 1.50-1.82 (6H, m), 1.96-2.18 (1H, m), 2.60-3.60 (4H, m), 3.76 (3H, s), 6.85-7.10 (2H, m), 7.10-7.68(2H, m), 8.60-10.90 (3H, m). 249 H H OCH.sub.3 F H H 1H-NMR (DMSO-d6) ppm at 80 C.: Dihydrochloride 1.00-1.43 (6H, m), 1.49-1.77 (7H, m), 1.97-2.08 (1H, m), 2.81 (1H, d, J = 12.3 Hz), 2.84-2.93 (1H, m), 3.04-3.18 (2H, m), 3.83 (3H, s), 4.30-4.57 (1H, br), 6.68-6.74 (1H, m), 6.86 (1H, dd, J = 2.5, 7.9 Hz), 7.11 (1H, dd, J = 8.6, 11.4 Hz), 8.94-9.25 (1H, br), 9.49-9.80 (1H, br).

(318) TABLE-US-00034 TABLE 34 Absolute configuration Example R.sup.1 R.sup.4 NMR Salt 250 H 1H-NMR (CDCl3) ppm : 1.10-1.47 (3H, m) 1.48-2.16 (4H, m), 1.69 (3H, s), 1.78 (3H, s), 2.30-2.54 (1H, m), 2.95 (1H, d, J = 12.5 Hz), 3.20-3.50 (2H, br), 3.52 (1H, d, J = 12.5 Hz), 7.37-7.52 (2H, m), 7.60-8.00 (4H, m), 9.18-10.05 (2H, br) Hydrochloride 251 CH.sub.3 00 1H-NMR (CDCl3) ppm : 1.20-1.35 (1H, m), 1.41-1.55 (1H, m), 1.59-1.82 (2H, m), 1.75 (3H, s), 1.91-2.01 (1H, m), 2.02-2.15 (2H, m), 2.14 (3H, s), 2.30-2.44 (2H, m), 2.85 (3H, d, J = 4.8 Hz), 3.49 (1H, d, J = 13.5 Hz), 4.07-4.19 (1H, m), 4.66 (1H, d, J = 13.5 Hz), 4.92-5.01 (1H, m), 7.59-7.66 (2H, m), 7.89-8.04 (4H, m), 8.87 (1H, br), 13.11 (1H, brs) Dihydrochloride 252 H 01 1H-NMR (DMSO-d6) ppm : 0.94-1.25 (2H, m), 1.25-1.45 (5H, m), 1.45-1.55 (1H, m), 1.55-1.80 (5H, m), 1.95-2.10 (1H, m), 2.82 (1H, d, J = 12.4 Hz), 2.97-3.11 (2H, m), 3.36-3.51 (1H, m), 7.40 (1H, d, J = 7 .3 Hz), 7.50-7.59 (3H, m), 7.79 (1H, d, J = 8.2 Hz), 7.89-7.96 (1H, m), 8.42-8.48 (1H, m), 8.97-9.24 (1H, br), 9.50-9.80 (1H, br). Hydrochloride 253 H 02 1H-NMR (CDCl3) ppm : 1.23-2.17 (8H, m), 1.76 (3H, s), 2.09 (3H, s), 2.48-2.53 (1H, m), 3.27 (1H, d, J = 1.23 Hz), 3.66-4.18 (3H, m), 3.94 (3H,$), 7.15 (1H, d, J = 2.4 Hz), 7.23 (1H, dd, J = 9.0, 2.4 Hz), 7.74 (1H, brs), 7.79-7.85 (2H, m), 8.24 (1H, brs), 9.87-10.19 (2H, br) Dihydrochloride 254 H 03 1H-NMR (CDCl3) ppm : 1.20-2.05 (8H, m), 1.73 (3H, s), 2.00 (3H, s), 2.44-2.48 (1H, m), 3.15 (1H, d, J = 10.7 Hz), 3.55-3.88 (3H, br), 7.38 (1H, d, J = 5.5 Hz), 7.49-7.69 (1H, m), 7.55 (1H, d, J = 5.5 Hz), 7.92 (1H, d, J = 8.6 Hz), 8.14 (1H, brs), 9.94 (2H, brs) Dihydrochloride

(319) TABLE-US-00035 TABLE 35 Absolute configuration 04 Example R.sup.1 R.sup.4 NMR Salt 255 H 05 1H-NMR (DMSO-d6) ppm : 0.95-1.82 (13H, m), 1.97-2.12 (1H, m), 2.80-3.35 (4H, m), 6.07-6.72 (1H, br), 6.72-7.20 (2H, m), 7.23-7.35 (1H, m), 7.35-7.53 (1H, m), 7.99 (1H, brs), 9.00-9.50 (1H, br), 9.55-10.10 (1H, br). Dihydrochloride 256 H 06 1H-NMR (DMSO-d6) ppm at 80 C.: 0.96-1.26 (2H, m), 1.26-1.51 (5H, m), 1.51-1.61 (1H, m), 1.61-1.78 (5H, m), 1.99-2.08 (1H, m), 2.80 (1H, d, J = 12.3 Hz), 3.05-3.32 (3H, m),3.58-4.12 (1H, br), 7.01 (1H, dd, J = 3.8, 8.5 Hz), 7.08-7.18 (2H, m), 8.01 (1H, d, J = 2.1 Hz), 9.10-9.35 (1H, br), 9.38-9.75 (1H, br). Dihydrochloride 257 H 07 1H-NMR (DMSO-d6) ppm at 80 C.: 0.98-1.27 (2H, m), 1.27-1.46 (4H, m), 1.46-1.60 (2H, m), 1.60-1.80 (5H, m), 1.98-2.10 (1H, m), 2.84 (1H, d, J = 12.4 Hz), 3.05-3.35 (3H, m), 3.45-3.90 (1H, br), 7.05 (1H, d, J = 8.2 Hz), 7.08-7.13 (1H, br), 7.36 (1H, d, J = 8.2 Hz), 8.03 (1H, d, J = 2.2 Hz), 8.98-9.35 (1H, br), 9.35-9.72 (1H, br). Dihydrochloride 258 H 08 1H-NMR (CDCl3) ppm: 0.82-1.05 (2H, m), 1.07 (3H, s), 1.19-1.43 (3H, m), 1.49 (3H, s), 1.56-1.68 (1H, m), 1.68-1.90 (3H, m), 2.35-2.51 (4H, m), 2.51-2.70 (1H, m), 2.78-2.92 (2H m), 6.83-6.89 (2H, m), 7.01 (1H, d, J = 7.8 Hz), 7.56 (1H, d, J = 2.1 Hz). 259 H 09 1H-NMR (DMSO-d6) ppm at 80 C.: 0.96-1.25 (2H, m), 1.25-1.60 (6H, m), 1.60-1.79 (5H, m), 1.98-2.10 (1H, m), 2.76 (1H, d, J = 12.3 Hz), 2.99-3.37 (3H, m), 3.93 (3H, s), 4.52-4.86 (1H, br), 6.86 (1H, d, J = 8.4 Hz), 6.95 (1H, d, = 8.4 Hz), 6.98-7.09 (1H, br), 7.87 (1H, d, J = 2.1 Hz), 9.02-9.40 (1H, br), 9.40-9.75 (1H, br). Dihydrochloride 260 H 0 1H-NMR (DMSO-d6) ppm at 80 C.: 1.03-1.44 (6H, m), 1.51-1.79 (7H, m), 2.00-2.10 (1H, m), 2.87 (1H, d, J = 12.4 Hz), 2.94-3.05 (1H, m), 3.10-3.23 (2H, m), 4.64-5.12 (1H, br), 6.88 (1H, d, J = 1.4 Hz), 7.05-7.09 (1H, m), 7.33-7.36 (1H, br), 7.59 (1H, d, J = 8.2 Hz), 7.89 (1H, J = 2.2 Hz), 8.97-9.26 (1H, br), 9.45-9.82 (1H, br). Dihydrochloride

(320) TABLE-US-00036 TABLE 36 Absolute configuration Example R.sup.1 R.sup.4 NMR Melting point ( C.) Salt 261 H 209.8-214.2 Fumarate 262 H 1H-NMR (DMSO-d6) ppm: 1.00-1.44 (6H, m), 1.50-1.79 (7H, m), 1.96-2.08 (1H, m), 2.82-3.00 (2H, m), 3.00-3.25 (2H, m), 3.61 (3H, s), 6.62 (1H, d, J = 9.5 Hz), 7.38-7.46 (1H, m), 7.48-7.58 (2H, m), 7.91 (1H, d, J = 9.5 Hz), 7.98-8.62 (1H, br), 9.14-9.37 (1H, br), 9.65-9.88 (1H, br). Dihydrochloride 263 H 1H-NMR (CDCl3) ppm: 0.87-1.03 (1H, m), 1.09 (3H, m), 1.15-1.46 (4H, m), 1.46-1.65 (5H, m), 1.65-1.88 (2H, m), 2.47-2.60 (1H, m), 2.65 (1H, d, J = 11.3 Hz), 2.76 (1H, d, J = 11.3 Hz), 2.90-3.04 (1H, m), 7.25 (1H, d, J = 7.3 Hz), 7.40 (1H, dd, J = 4.2, 8.5 Hz), 7.65-7.72 (1H, m), 7.91 (1H, d, J = 8.5 Hz), 8.85 (1H, d, J = 8.5 Hz), 8.90 (1H, dd, J = 1.7, 4.2 Hz). 264 H 1H-NMR (CDCl3) ppm: 0.93-1.12 (5H, m), 1.22-1.48 (3H, m), 1.55-1.70 (4H, m), 1.73-1.90 (3H, m), 2.50 (1H, d, J = 11.5 Hz), 2.55-2.65 (1H, m), 2.92-3.05 (2H, m), 7.09 (1H, d, J = 4.8 Hz), 7.49-7.56 (1H, m), 7.65-7.72 (1H, m), 8.05-8.10 (1H, m), 8.36 (1H, dd, J = 1.0, 8.4 Hz), 8.84 (1H, d, J = 4.8 Hz). 265 H 1H-NMR (CDCl3) ppm: 0.80-1.17 (5H, m), 1.21-1.50 (6H, m), 1.61-1.88 (4H, m), 2.42-2.50 (1H, m), 2.74 (1H, d, J = 11.4 Hz), 2.80-2.90 (1H, m), 2.96 (1H, d, J = 11.4 Hz), 7.31-7.39 (2H, m), 7.50 (1H, dd, J = 2.4, 9.0 Hz), 8.01 (1H, d, J = 9.0 Hz), 8.06 (1H, dd, J = 1.1, 8.3 Hz), 8.81 (1H, dd, J = 1.7, 4.2 Hz). 266 H 1H-NMR (CDCl3) ppm: 1.04-1.20 (4H, m), 1.20-1.48 (7H, m), 1.67-1.86 (3H, m), 1.96 (1H, dd, J = 3.0,13.0), 2.61-2.70 (1H, m), 2.82-2.95 (2H, m), 3.07 (1H, d, J = 12.0 Hz), 7.20 (1H, d, J = 1.8 Hz), 7.32 (1H, dd, J = 2.1, 8.8 Hz), 7.50 (1H, d, J = 5.8 Hz), 7.84 (1H, d, J = 8.8 Hz), 8.41 (1H, d, J = 5.8 Hz), 9.09 (1H, s).

(321) TABLE-US-00037 TABLE 37 Absolute configuration Example R1 R5 R6 R7 R8 R9 NMR Salt 267 H H H F H H 1H-NMR (DMSO-d6) ppm : 0.99-1.44 Dihydrochloride (6H, m), 1.44-1.80 (7H, m), 1.93-2.10 (1H, m), 2.75-2.99 (2H, m), 2.99-3.28 (2H, m), 5.08-6.80 (1H, br), 7.10-7.33 (4H, m), 8.96-9.42 (1H, br), 9.58-9.94 (1H, br). 268 H H OCH.sub.3 F H H 1H-NMR (DMSO-d6) ppm at 80 C.: Dihydrochloride 1.00-1.43 (6H, m), 1.49-1.77 (7H, m), 1.97-2.08 (1H, m), 2.81 (1H, d, J = 12.3 Hz), 2.84-2.93 (1H, m), 3.04-3.18 (2H, m), 3.83 (3H, s), 4.30-457 (1H, br), 6.68-6.74 (1H, m), 6.86 (1H, dd, J = 2.5, 7.9 Hz), 7.11 (1H, dd, J = 8.6, 11.4 Hz), 8.94-9.25 (1H, br), 9.49-9.80 (1H, br). 269 H H Cl CN H H 1H-NMR (CDCl3) ppm : 1.02-1.17 (1H, m), Hydrochloride 1.25-1.44 (2H, m), 1.62-2.05 (4H, m), 1.63 (3H, s), 1.68 (3H, s), 2.35-2.41 (1H, m), 2.89 (1H, d, J = 12.8 Hz), 3.20 (2H, br), 3.35 (1H, d, J = 12.8 Hz), 7.07 (1H, dd, J = 8.4, 2.0 Hz), 7.20 (1H, d, J = 2.0 Hz), 7.61 (1H, d, J = 8.4 Hz), 9.61 (1H, brs), 9.89 (1H, br) 270 H H H Cl H H 1H-NMR (DMSO-d6) ppm : 0.95-1.45 Dihydrochloride (6H, m), 1.45-1.80 (7H, m), 1.88-2.06 (1H, m), 2.70-3.05 (3H, m), 3.08-3.28 (1H, m), 3.50-3.94 (1H, br), 7.13 (2H, d, J = 8.7 Hz), 7.39 (2H, d, J = 8.7 Hz), 8.66-9.20 (1H, br), 9.20-9.80 (1H, br). 271 H H OCH.sub.3 Cl H H 1H-NMR (DMSO-d6) ppm. 1.00-1.45 (6H, m), Hydrochloride 1.45-1.83 (7H, m), 1.90-2.08 (1H, m), 2.70-2.87 (1H, m), 2.87-3.08 (2H, m), 3.08-3.28 (1H, m), 3.85 (3H, s), 6.72 (1H, dd, J = 2.2, 8.4 Hz), 6.79 (1H, d, J = 2.2 Hz), 7.36 (1H, d, J = 8.4 Hz), 8.73-9.10 (1H, br), 9.34-9.70 (1H, br). 272 H H Cl Cl H H 1H-NMR (CDCl3) ppm : 0.98-1.14 (1H, m), Hydrochloride 1.26-1.39 (2H, m), 1.55-1.78 (3H, m), 1.62(3H, s), 1.68 (3H, s), 1.92-2.05 (1H, m), 2.30-2.35 (1H, m), 2.73 (1H, d, J = 12.5 Hz), 2.95-3.03 (1H, m), 3.11-3.23 (1H, m), 3.28 (1H, d, J = 12.5 Hz), 7.20 (1H, dd, J = 8.5, 2.4 Hz), 7.25 (1H, d, J = 2.4 Hz), 7.39 (1H, d, J = 8.5 Hz), 9.49 (1H, br), 9.79 (1H, br) 273 CH.sub.3 H Cl Cl H H 1H-NMR (CDCl3) ppm :1.23-1.49 (2H, m), Hydrochloride 1.60-1.74 (2H, m), 1.69 (3H, s), 1.87-2.15 (3H, m), 1.91 (3H, s), 2.21-2.28 (1H, m), 2.78 (3H, d, J = 4.9 Hz), 3.22 (1H, d, J = 13.2 Hz), 3.63-3.75 (1H, m), 4.32 (1H, d, J = 13.2 Hz), 4.42-4.51 (1H, m), 7.56(1H, d, J = 8.7 Hz), 7.81 (1H, dd, J = 8.7, 2.0 Hz), 8.14 (1H, d, J = 2.0 Hz), 12.71 (1H, brs)

(322) TABLE-US-00038 TABLE 38 Absolute configuration Example R.sup.1 R.sup.2, R.sup.3 R.sup.4 NMR Salt 274 0 H, H 1H-NMR (CDCl3) ppm: 1.25-1.7 (5H, m), 1.75-1.9 (1H, m), 2.05-2.2 (2H, m), 2.3-2.4 (1H, m), 2.6-2.7 (1H, m), 2.8-2.9 (1H, m), 2.92 (1H, d, J = 13.1 Hz), 3.0-3.15 (2H, m), 3.65-3.75 (1H, m), 4.20 (1H, d, J = 13.1 Hz), 6.7-6.8 (2H, m), 7.1-7.2 (2H, m), 7.2-7.3 (1H, m), 7.3-7.4 (4H, m). 275 H H, H 1H-NMR (DMSO-d6) ppm: 1.2-1.4 (2H, m), 1.4-1.5 (1H, m), 1.5-1.95 (4H, m) 1.95-2.05 (1H, m), 2.95-3.2 (2H, m), 3.25-3.4 (1H, m), 3.4-3.6 (2H, m), 3.95-4.1 (1H, m), 6.48 (1H, br), 6.80 (1H, dd, J = 7.2, 7.2 Hz), 6.9-7.0 (2H, m), 7.2-7.3 (2H, m), 9.22 (1H, br), 9.87 (1H, br). Dihydrochloride 276 H (CH.sub.2).sub.3 1H-NMR (DMSO-d6) ppm: 1.25-1.4 (2H, m), 1.4-2.35 (10H, m), 2.3-2.6 (2H, m), 3.04 (1H, d, J = 13.3 Hz), 3.35-3.5 (1H, m), 3.67 (1H, d, J = 13.4 Hz), 3.7-4.3 (2H, m), 6.95-7.05 (2H, m), 7.2-7.3 (2H, m), 8.95-9.2 (1H, m), 10.1-10.3 (1H, m). Dihydrochloride 277 H (CH.sub.2).sub.3 1H-NMR (CDCl3) ppm: 1.05-1.35 (3H, m), 1.35-1.45 (1H, m), 1.45-1.65 (3H, m), 1.65-1.9 (5H, m), 1.9-2.0 (1H, m), 2.0-2.1 (1H, m), 2.2-2.3 (1H, m), 2.93 (1H, d, J = 11.4 Hz), 3.25-3.35 (1H, m), 3.39 (1H, d, J = 11.4 Hz), 3.7-3.8 (1H, m), 3.89 (3H, s), 7.01 (1H, d, J = 2.4 Hz), 7.04 (1H, d, J = 2.5 Hz), 7.07 (1H, dd, J = 2.6, 8.8 Hz), 7.25-7.3 (1H, m), 7.58 (1H, d, J = 8.9 Hz), 7.61 (1H, d, J = 9.1 Hz). 278 H (CH.sub.2).sub.3 1H-NMR (DMSO-d6) ppm: 1.2-1.35 (2H, m), 1.4-2.15 (10H, m), 2.35-2.6 (2H, m), 3.14 (1H, d, J = 12.5 Hz), 3.4-3.55 (1H, m), 3.64 (1H, d, J = 13.1 Hz), 3.95-4.05 (1H, m), 4.05-4.4 (1H, m), 7.19 (1H, dd, J = 2.4, 8.9 Hz), 7.31 (1H, d, J = 5.3 Hz), 7.41 (1H, d, J = 2.0 Hz), 7.69 (1H, d, J = 5.4 Hz), 7.83 (1H, d, J = 8.9 Hz), 8.9-9.1 (1H, m), 11-12.5 (1H, m). Dihydrochloride

(323) TABLE-US-00039 TABLE 39 Absolute configuration Ex- Melting am- point ple R.sup.1 R.sup.2, R.sup.3 R.sup.4 NMR ( C.) Salt 279 H, H 1H-NMR (CDCl3) ppm: 1.25-1.5 (4H, m), 1.55-1.7 (1H, m), 1.75-1.85 (1H, m), 2.05-2.2 (2H, m), 2.3-2.4 (1H, m), 2.6-2.7 (1H, m), 2.8-2.9 (1H, m), 2.92 (1H, d, J = 13.2 Hz), 3.0-3.15 (2H, m), 3.65-3.8 (1H, m), 4.20 (1H, d, J = 13.1 Hz), 6.7-6.8 (2H, m), 7.1-7.2 (2H, m), 7.2-7.3 (1H, m), 7.3-7.4 (4H, m). 280 H H, H 1H-NMR (DMSO-d6) ppm: 1.2-1.4 (2H, m), 1.4- 1.5 (1H, m), 1.5-1.95 (4H, m), 1.95-2.05 (1H, m), 3.0-3.2 (2H, m), 3.25-3.4 (1H, m), 3.4-3.6 (2H, m), 3.95-4.1 (1H, m), 5.65 (1H, br), 6.79 (1H, dd, J = 7.2, 7.2 Hz), 6.9-7.0 (2H, m), 7.2-7.3 (2H, m), 9.16 (1H, br), 9.81 (1H, br). Di- hydro- chloride 281 H (CH.sub.2).sub.3 0 1H-NMR (DMSO-d6) ppm: 1.25-1.4 (2H, m), 1.4-2.15 (10H, m), 2.3-2.6 (2H, m), 3.03 (1H, d, J = 12.5 Hz), 3.35-3.5 (1H, m), 3.65-3.85 (2H, m), 3.9-4.0 (1H, m), 6.95-7.05 (2H, m), 7.2-7.3 (2H, m), 8.9-9.15 (1H, m), 10.05-12.5 (1H, m). Di- hydro- chloride 282 H (CH.sub.2).sub.3 1H-NMR (CDCl3) ppm: 1.05-1.35 (3H, m), 1.35-1.45 (1H, m), 1.45-1.65 (3H, m), 1.65-1.9 (5H, m), 1.9-2.0 (1H, m), 2.0-2.1 (1H, m), 2.2-2.3 (1H, m), 2.93 (1H, d, J = 11.4 Hz), 3.25-3.35 (1H, m), 3.39 (1H, d, J = 11.4 Hz), 3.7-3.8 (1H, m), 3.89 (3H, s), 7.01 (1H, d, J = 2.4 Hz), 7.04 (1H, d, J = 2.5 Hz), 7.07 (1H, dd, J = 2.6, 8.8 Hz), 7.25-7.3 (1H, m), 7.58 283 H (CH.sub.2).sub.3 1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 9.0 Hz). 1H-NMR (DMSO-d6) ppm: 1.2-1.35 (2H, m), 1.4-2.15 (10H, m), 2.4-2.6 (2H, m), 3.15 (1H, d, J = 12.1 Hz), 3.4-3.55 (1H, m) 3.64 (1H, d, J = 13.0 Hz), 3.95-4.1(1H, m), 4.2-4.6 (1H, m), 7.19 (1H, dd, J = 2.4, 8.9 Hz), 7.31 (1H, d, J = 5.2 Hz), 7.41 (1H, d, J = 2.0 Hz), 7.69 (1H, d, J = 5.4 Hz), 7.83 (1H, d,J = 8.9 Hz), 8.9-9.1 (1H, m), 10.1-10.3 (1H, m). Di- hydro- chloride

(324) TABLE-US-00040 TABLE 40 Relative configuration Ex- ample R.sup.1 R.sup.2 R.sup.3 R.sup.4 NMR Salt 284 H H CH.sub.3 1H-NMR (CDCl3) ppm: 1.18-1.48 (2H, m), 1.62-2.08 (8H, m), 2.56-2.61 (1H, m), 3.63-3.66 (1H, m), 4.23 (1H, brs), 4.67 (3H, brs), 7.61-8.26 (7H, m), 9.60-9.81 (1H, m), 11.36 (1H, br), 14.02 (1H, brs) Dihydro- chloride 285 H H CH.sub.3 1H-NMR (DMSO) ppm: 1.02-1.43 (3H, m), 1.30 (3H, d, J = 6.4 Hz), 1.44-1.88 (4H, m), 1.95-2.20 (1H, m), 2.97-3.53 (6H, m), 7.26-7.46 (1H, br), 7.50 (1H, d, J = 5.4 Hz), 7.69-8.00 (1H, br), 7.86 (1H, d, J = 5.4 Hz), 8.09 (1H, d, J = 8.2 Hz), 9.28-10.12 (2H, br) Dihydro- chloride 286 H H CH.sub.3 1H-NMR (DMSO) ppm: 0.87-1.06 (1H, m), 1.17-1.35 (2H, m), 1.24 (3H, d, J = 6.3 Hz), 1.41-1.84 (4H, m), 1.92-2.07 (1H, m), 2.88-3.08 (3H, m), 3.24 (1H, d, J = 12.4 Hz), 3.31-3.52 (1H, br), 7.16 (1H, dd, J = 8.6, 2.1 Hz), 7.40 (1H, d, J = 2.1 Hz), 7.60 (1H, d, J = 8.6 Hz), 9.02-9.33 (1H, br), 9.50-9.85 (1H, br) Hydro- chloride 287 H H C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 1.05 (3H, t, J = 7.3 Hz), 1.24-1.48 (2H, m), 1.51-2.14 (6H, br), 2.18-2.41 (1H, br), 2.43-2.76 (1H, m), 2.83-5.31 (5H, br), 7.33-8.24 (6H, br), 9.15-10.20 (1.3H, br), 11.04-11.78 (0.3H, br), 13.30-13.79 (0.4H, br) Hydro- chloride 288 CH.sub.3 H C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 1.06 (3H, t, J = 7.5 Hz), 1.22-2.25 (10H, m), 2.26-2.45 (2H, m), 2.94 (3H, s), 3.31-4.97 (4H, br), 7.36-8.02 (7H, m), 12.47-13.27 (1H, br) Dihydro- chloride 289 H C.sub.2H.sub.5 C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 0.80-2.47 (11H, m), 0.99 (3H, t, J = 7.4 Hz), 1.17 (3H, t, J = 7.3 Hz), 2.66-2.76 (1H, m), 2.86-3.18 (1H, br), 3.38-3.43 (1H, m), 3.65-4.01 (2H, m), 4.02-4.36 (1H, m), 7.54-7.61 (2H, m), 7.80-7.96 (5H, m), 9.37 (1H, brs), 9.80-10.49 (1H, br) Dihydro- chloride 290 H H C.sub.2H.sub.5 0 1H-NMR (CDCl3) ppm: 1.07 (3H, t, J = 7.5 Hz), 1.25-1.42 (2H, m), 1.48-1.85 (7H, m), 1.93-2.10 (2H, m), 2.16-2.40 (1H, m), 2.50-2.69 (1H, m). 2.91-5.05 (4H, br), 7.33-8.76 (4H, br & m), 9.19-9.85 (1H, br), 11.09-11.67 (0.4H, br), 13.40-13.82 (0.6H, br) Dihydro- chloride 291 H C.sub.2H.sub.5 C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 0.80-2.44 (11H, m), 0.97 (3H, t, J = 7.4 Hz), 1.15 (3H, t, J = 7.4 Hz), 2.60-2.66 (1H, m), 2.78-3.09 (1H, m), 3.20-3.37 (1H, m), 3.45-4.16 (3H, m), 7.37 (1H, d, J = 5.4 Hz), 7.49-7.71 (1H, m), 7.55 (1H, d, J = 5.4 Hz), 7.86-7.96 (1H, m), 8.01-8.47 (1H, br), 9.02-9.48 (1H, br), 9.69-10.18 (1H, br) Dihydro- chloride 292 H H C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 1.07 (3H, t, J = 7.5 Hz), 1.23-1.50 (3H, m), 1.51-2.13 (8H, m), 2.16-2.39 (1H, m), 2.50-2.71 (1H, m), 2.90-5.09 (4H, br), 7.30-7.46 (1H, m), 7.46-8.33 (3H, br), 9.10-9.91 (1H, br), 10.95-11.65 (0.4H, br), 13.37-13.92 (0.6H, br) Dihydro- chloride 293 H C.sub.2H.sub.5 C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 0.80-2.45 (10H, m), 0.97 (3H, t, J = 7.3 Hz), 1.45 (3H, t, J = 7.3 Hz), 2.60-2.66 (1H, m), 2.74-3.05 (1H, m), 3.11-3.42 (1H, m), 3.51-3.97 (3H, m), 7.37 (1H, d, J = 5.4 Hz), 7.50-7.68 (2H, m), 7.53 (1H, d, J = 5.5 Hz), 7.83-7.88 (1H, m), 8.02-8.53 (1H, br), 9.12-9.46 (1H, br), 9.66-10.18 (1H, br) Dihydro- chloride 294 H C.sub.2H.sub.5 C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 0.87-2.38 (11H, m), 0.98 (3H, t, J = 7.4 Hz), 1.14 (3H, t, J = 7.2 Hz), 2.49-2.73 (1H, m), 2.73-3.11 (1H, m), 3.31-3.42 (1H, m), 3.52-4.26 (3H, m), 6.82 (1H, d, J = 1.9 Hz), 7.54-7.68 (2H, m), 7.71 (1H, d, J = 1.9 Hz), 7.79-8.30 (1H, br), 8.94-9.51 (1H, br), 9.75-10.34 (1H, br) Dihydro- chloride 295 H H C.sub.2H.sub.5 1H-NMR (CDCl3) ppm: 1.08 (3H, t, J = 7.5 Hz), 1.25-1.43 (2H, m), 1.54-2.05 (6H, m), 2.15-2.34 (1H, m), 2.50-2.64 (1H, m), 3.56 (1H, d, J = 11.1 Hz), 3.84-4.04 (1H m), 4.10-4.46 (3H, m), 7.62 (1H, d, J = 8.6 Hz), 7.72 (1H, d, J = 8.6 Hz), 7.97 (1H, s), 9.25-9.53 (1H, br), 10.75-11.16 (1H, br) Hydro- chloride 296 H H C.sub.3H.sub.7 1H-NMR (DMSO-d6) ppm: 0.93 (3H, t, J = 7.3 Hz), 1.2-1.4 (2H, m), 1.4-1.6 (3H, m), 1.6-1.9 (6H, m), 2.05-2.15 (1H, m), 2.8-2.9 (1H, m), 3.25 (1H, br), 3.5-3.6 (2H, m), 4.0-4.1 (1H, m), 6.95-7.05 (2H, m), 7.2-7.3 (2H m), 8.35-8.6 (1H, m), 9.3-9.5 (1H, m). Hydro- chloride

(325) TABLE-US-00041 TABLE 41 Relative configuration Ex- ample R.sup.10 R.sup.4 NMR Salt 297 1H-NMR (CDCl3) ppm: 0.08 (6H, s), 0.91 (9H, s), 1.04-1.35 (4H, m), 1.53-1.80 (3H, m), 2.18-2.33 (2H, m), 2.60-2.76 (2H, m), 2.80-3.01 (3H, m), 3.09-3.13 (2H, m), 3.69-3.85 (2H, m), 7.29-7.48 (3H, m), 7.52-7.53 (1H, m), 7.73-7.80 (3H, m) 298 0 1H-NMR (CDCl3) ppm: 0.06 (6H, s), 0.90 (9H, s), 1.04-1.37 (5H, m), 1.61-1.75 (2H, m), 1.79-1.84 (2H, m), 2.15-2.20 (1H, m), 2.32-2.40 (1H, m), 2.58-2.68 (1H, m), 2.71-2.90 (3H, m), 2.97-3.14 (2H, m), 3.19-3.26 (1H, m), 3.64-3.79 (2H, m), 6.93 (1H, dd, J = 8.5, 2.1 Hz), 7.07 (1H, d, J = 2.1 Hz), 7.52 (1H, d, J = 8.5 Hz) 299 1H-NMR (CDCl3) ppm: 0.07 (6H, s), 0.81-1.90 (3H, m), 0.90 (9H, s), 1.55-1.78 (4H, m), 2.14-2.24 (2H, m), 2.46-2.54 (1H, m), 2.57-2.67 (1H, m), 2.72-2.82 (1H, m), 2.85-2.97 (4H, m), 3.66-3.81 (2H, m), 6.97 (1H, dd, J = 8.6, 2.4 Hz), 7.22 (1H, d, J = 2.4 Hz), 7.34 (1H, d, J= 8.6 Hz) 300 H 1H-NMR (CDCl3) ppm: 1.25-1.53 (2H, m), 1.61-1.70 (1H, m), 1.74-1.80 (2H, m), 1.89-2.04 (2H, m), 2.38-2.43 (1H, m), 3.08-3.16 (1H, m), 3.53-3.59(1H, m), 3.66-3.73 (1H, m), 3.88-3.94 (1H, m), 4.06-4.14 (3H, m), 4.35-4.43 (2H, m), 4.61-4.78 (1H, m), 7.61 (1H, d, J = 8.7 Hz), 7.71 (1H, d, J = 8.7 Hz), 8.00 (1H, brs), 12.52 (1H, brs) Hydro- chloride

(326) TABLE-US-00042 TABLE 42 Relative configuration Ex- ample R.sup.4 NMR Salt 301 1H-NMR (CDCl3) ppm: 1.25-1.50 (2H, m), 1.60-2.05 (5H, m), 2.35-2.70 (1H, m), 2.81-5.38 (6H, br), 7.32-8.89 (7H, br), 9.47-10.31 (1H, br), 10.55-11.77 (0.45H, br), 13.51-14.36 (0.55H, br) Hydro- chloride 302 1H-NMR (CDCl3) ppm: 1.25-1.51 (2H, m), 1.63-2.09 (5H, m), 2.50-2.56 (1H, m), 3.56-3.91 (2H, m), 3.91-5.16 (4H, br), 7.46 (1H, d, J = 5.5 Hz), 7.55-8.76 (3H, br), 7.66 (1H, d, J = 5.5 Hz), 9.46-10.11 (1H, br), 10.94-11.83 (1H, br), 13.61-14.25 (1H, br) Dihydro- chloride 303 1H-NMR (CDCl3) ppm : 1.24-1.49 (2H, br), 1.51-2.00 (5H, m), 2.33-2.54 (1H, m), 3.30-3.79 (5H, m), 3.81-4.15 (1H, br), 7.34 (1H, d, J = 8.6 Hz), 7.50 (1H, d, J = 8.6 Hz), 7.59 (1H, s), 10.01 (1H, brs), 10.14-10.56 (1H, br) Hydro- chloride

(327) TABLE-US-00043 TABLE 43 Relative configuration Ex- ample R.sup.1 R.sup.2, R.sup.3 R.sup.4 NMR Salt 304 H (CH.sub.2).sub.3 0 1H-NMR (DMSO-d6) ppm: 1.2-1.35 (2H, m), 1.4-2.1 (10H, m), 2.3-2.5 (2H, m), 3.03 (1H, d, J = 13.2 Hz), 3.35-3.45 (1H, m), 3.68 (1H, d, J = 13.4 Hz), 3.9-4.0 (1H, m), 4.35 (1H, br), 6.95-7.05 (2H, m), 7.2-7.3 (2H, m), 8.9-9.1 (1H, m), 10.0-10.15(1H, m). Dihydro- chloride 305 H (CH.sub.2).sub.4 1H-NMR (CDCl3) ppm: 1.20-1.58 (2H, m), 1.60-2.17 (10H, m), 2.29-2.37 (1H, m), 2.46-2.67 (2H, m), 2.96-3.29 (1H, br), 3.33 (1H, d, J = 13.2 Hz), 3.60-3.98 (1H, br), 3.98-4.41 (2H, br), 7.56-7.60 (2H, m), 7.80-7.98 (4H, m), 8.11-8.71 (1H, br), 9.63-10.08 (1H, br), 10.13-10.87 (1H, br) Hydro- chloride 306 CH3 (CH.sub.2).sub.4 1H-NMR (CDCl3) ppm: 1.20-1.33 (1H, m), 1.40-2.08 (12H, m), 2.24-2.44 (2H, m), 2.58-2.69 (1H, m), 2.83 (3H, d, J = 4.8 Hz), 3.45 (1H, d, J = 13.4 Hz), 3.58-3.83 (1H, m), 3.87-4.14 (1H, m), 4.08 (1H, d, J = 13.4 Hz), 4.74-4.96 (1H, m), 7.55-7.65 (2H, m), 7.88-8.03 (4H, m), 8.42-9.20 (1H, br), 13.33 (1H, brs) Dihydro- chloride 307 H (CH.sub.2).sub.4 1H-NMR (CDCl3) ppm: 1.18-1.35 (1H, m), 1.41-2.17 (12H, m), 2.30-2.38 (1H, m), 2.51-2.67 (2H, m), 3.00-3.32 (1H, br), 3.36 (1H, d, J = 12.4 Hz), 3.65-4.47 (3H, br), 7.43 (1H, d, J = 5.5 Hz), 7.61 (1H, d, J = 5.5 Hz), 7.66-7.96 (1H, br), 7.99 (1H, d, J = 8.6 Hz), 8.12-8.19 (1H, br), 9.65-10.02 (1H, br), 10.29-10.83 (1H, br) Dihydro- chloride 308 H (CH.sub.2).sub.4 1H-NMR (CDCl3) ppm: 1.20-1.36 (1H, m), 1.41-2.21 (12H, m), 2.29-2.37 (1H, m), 2.49-2.58 (1H, m), 2.61-2.67 (1H, m), 3.07-3.30 (1H, br), 3.36 (1H, d, J = 13.1 Hz), 3.66-3.97 (1H, br), 3.98-4.32 (2H, br), 7.38 (1H, d, J = 5.5 Hz), 7.59 (1H, d, J = 5.5 Hz), 7.67-7.90 (1H, br), 7.93 (1H, d, J = 8.6 Hz), 8.11-8.93 (1H, br), 9.56-10.03 (1H, br), 10.20-10.81 (1H, br) Dihydro- chloride 309 H (CH.sub.2).sub.4 1H-NMR (CDCl3) ppm: 0.91-1.13 (1H, m), 1.23-1.38 (2H, m), 1.46-2.12 (10H, m), 2.33-2.48 (3H, m), 2.76 (1H, d, J = 12.5 Hz), 2.94-3.12 (2H, m), 3.32 (1H, d, J = 12.5 Hz), 7.03 (1H, dd, J = 8.5, 2.4 Hz), 7.26 (1H, d, J = 2.4 Hz), 7.39 (1H, d, J = 8.5 Hz), 9.75 (2H, brs) Hydro- chloride 310 H (CH.sub.2).sub.4 1H-NMR (DMSO) ppm: 0.96-2.27 (16H, m), 2.97-3.59 (4H, m), 7.10 (1H, d, J = 8.7 Hz), 7.31 (1H, s), 7.78 (1H, d, J = 8.7 Hz), 8.93-9.28 (1H, br), 9.32-9.67 (1H, br) Hydro- chloride 311 H (CH.sub.2).sub.5 1H-NMR (CDCl3) ppm: 1.18-2.19 (16H, m), 2.30-2.35 (1H, m), 2.47-2.52 (1H, m), 3.04 (1H, br), 3.44-3.67 (3H, m), 7.47-7.61 (3H, m), 7.83-7.89 (4H, m), 9.64 (2H, br) Hydro- chloride 312 H (CH.sub.2).sub.5 1H-NMR (CDCl3) ppm: 0.89-1.01 (1H, m), 1.08-1.70 (15H, m), 1.86-1.90 (1H, m), 2.42-2.47 (1H, m), 2.64-2.73 (1H, m), 2.79 (1H, d, J = 12.2 Hz), 3.00-3.08 (1H, m), 3.15 (1H, d, J = 12.2 Hz), 3.76 (3H, s), 3.47-4.70 (3H, br), 6.36 (1H, d, J = 3.0 Hz), 6.49 (2H, s), 6.93 (1H, dd, J = 8.6, 1.4 Hz), 7.27 (1H, d, J = 1.4 Hz), 7.29 (1H, d, J = 3.0 Hz), 7.36 (1H, d, J = 8.6 Hz) Fumarate 313 H (CH.sub.2).sub.5 1H-NMR (CDCl3) ppm: 0.96-1.08 (1H, m), 1.23-1.45 (6H, m), 1.06-2.13 (8H, m), 2.20-2.25 (1H, m), 2.35-2.40 (1H, m), 2.62-2.67 (1H, m), 3.03-3.31 (4H, m), 7.03 (1H, dd, J = 8.5, 2.4 Hz), 7.26 (1H, d, J = 2.4 Hz), 7.40 (1H, d, J = 8.5 Hz), 9.49 (2H, brs) Hydro- chloride

(328) TABLE-US-00044 TABLE 44 Absolute configuration 0 Ex- ample R.sup.1 NMR Salt 314 1H-NMR (CDCl3) ppm: 0.9-1.1 (1H, m), 1.15-1.4 (3H, m), 1.55-1.7 (2H, m), 1.75-1.85 (1H, m), 2.1-2.2 (1H, m), 2.25-2.45 (2H, m), 2.55-2.7 (1H, m), 2.7-2.8 (1H, m), 2.85-2.95 (2H, m), 3.21 (1H, d, J = 13.4 Hz), 4.18 (1H, d, J = 13.4 Hz), 7.05-7.1 (2H, m), 7.2-7.35(7H, m). 315 H 1H-NMR (CDCl3) ppm: 0.9-1.4 (4H, m), 1.5-1.65 (2H, m), 1.7-1.9 (2H, m), 2.05-2.2 (1H, m), 2.32 (3H, s), 2.45- 2.6 (2H, m), 2.8-2.9 (1H, m), 2.9-3.1 (2H, m), 7.0-7.1 (2H, m), 7.2-7.3 (2H, m).

(329) TABLE-US-00045 TABLE 45 Absolute configuration Example R.sup.1 NMR Salt 316 1H-NMR (CDCl3) ppm: 0.95-1.1 (1H, m), 1.15-1.45 (3H, m), 1.5-1.7 (2H, m), 1.75-1.85 (1H, m), 2.1-2.25 (1H, m), 2.25-2.45 (2H, m), 2.55- 2.7 (1H, m), 2.7-2.8 1H, m), 2.85-3.0 (2H, m), 3.21 (1H, d, J = 13.3 Hz), 4.18 (1H, d, J = 13.4 Hz), 7.0-7.1 (2H, m), 7.2-7.35 (7H, m) 317 H 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (1H, m), 1.1-1.4 (2H, m), Hydro- 1.4-1.65 (3H, m), 1.65-1.8 (1H, m), 1.9-2.05 (1H, m), 2.8-3.0 (2H, m), chloride 3.0-3.2 (3H, m), 3.2-3.5 (1H, m), 7.1-7.2 (2H, m), 7.35-7.45 (2H, m), 9.2-9.7 (2H, m). 318 CH.sub.3 1H-NMR (CDCl3) ppm: 0.9-1.4 (4H, m), 1.5-1.65 (2H, m), 1.7-1.9 (2H, m), 2.05-2.2 (1H, m), 2.32 (3H, s), 2.45-2.6 (2H, m), 2.8-2.9 (1H, m), 2.9-3.1 (2H, m), 7.0-7.15 (2H, m), 7.2-7.3 (2H, m).

(330) TABLE-US-00046 TABLE 46 Relative configuration Ex- ample R.sup.4 NMR Salt 319 1H-NMR (DMSO-d6) ppm: 1.35 (3H, s), 1.45-1.67 (6H, m), 1.67-2.00 (4H, m), 2.16- 2.30 (2H, m), 2.30-2.43 (1H, m), 3.39-3.48 (1H, m), 3.62-3.72 (1H, m), 3.88-3.96 (1H, m), 3.09-4.08 (1H, m), 6.05-6.75 (1H, br), 7.10 (1H, s), 7.20-7.25 (1H, m), 7.25-7.34 (1H, m), 7.33-7.40 (1H, m), 7.66-7.80 (3H, m), 8.22-8.35 (1H, br), 9.30-9.45 (1H, br). Dihydro- chloride 320 1H-NMR (DMSO-d6) ppm at 80 C.: 1.37-1.55 (5H, m), 1.55-1.70 (4H, m), 1.71- 2.00 (4H, m), 2.19-2.40 (3H, m), 3.35-3.50 (1H, m), 3.52-3.66 (1H, m), 3.84-3.97 (2H, m), 5.53-5.86 (1H, br), 7.06 (1H, dd, J = 2.4, 8.9 Hz), 7.28 (1H, d, J = 5.4 Hz), 7.36 (1H, d, J = 2.4 Hz), 7.60 (1H, d, J = 5.4 Hz), 7.76 (1H, d, J = 8.9 Hz), 8.07-8.40 (1H, br), 9.20-9.57 (1H, br). Dihydro- chloride 321 1H-NMR (DMSO-d6) ppm: 1.32 (3H, s), 1.43-1.61 (6H, m), 1.65-1.89 (4H, m), 2.07- 2.17 (1H, m), 2.17-2.27 (1H, m), 2.27-2.40 (1H, m), 3.27-3.36 (1H, m), 3.40-3.55 (1H, m), 3.79-3.90 (2H, m), 5.00-6.60 (1H, br), 6.84 (2H, d, J = 8.9 Hz), 7.19 (2H, d, J = 8.9 Hz), 8.19-8.35 (1H, br), 9.25-9.44 (1H, br). Dihydro- chloride 322 1H-NMR (DMSO-d6) ppm: 1.32 (3H, s), 1.40-1.63 (6H, m), 1.63-1.90 (4H, m), 2.07- 2.25 (2H, m), 2.30-2.33 (1H, m), 3.27-3.38 (1H, m), 3.48-3.59 (1H, m), 3.78-3.86 (1H, m), 3.86-3.95 (1H, m), 5.30-6.75 (1H, br), 6.83 (1H, d, J = 3.0, 9.1 Hz), 7.02 (1H, d, J = 3.0 Hz), 7.35 (1H, d, J = 9.1 Hz), 8.23-8.40 (1H, br), 9.22-9.45 (1H, br). Dihydro- chloride

(331) TABLE-US-00047 TABLE 47 Relative configuration Example R.sup.4 NMR Salt 323 0 1H-NMR (DMSO-d6) ppm: 1.39 (3H, s), 1.43-1.65 (7H, m), 1.71-1.90 (4H, m), 1.93-2.06 (1H, m), 2.35-2.45 (1H, m), 3.60-3.79 (4H, m), 5.40-6.15 (1H, br), 6.90 (1H, s), 7.09-7.20 (2H, m), 7.30-7.40 (1H, m), 7.65-7.72 (2H, m), 7.75 (1H, d, J = 9.0 Hz), 8.60-8.80 (1H, br), 8.80-9.00 (1H, br). Dihydro- chloride 324 1H-NMR (DMSO-d6) ppm at 80 C.: 1.38-1.54 (10H, m), 1.69-2.02 (5H, m), 2.41-2.50 (1H, m), 3.55-3.85 (4H, m), 4.97-5.80 (1H, br), 6.94-7.10 (1H, br), 7.18-7.40 (2H, m), 7.59 (1H, d, J= 5.4 Hz), 7.78 (1H, d, J = 8.9 Hz), 8.75-8.92 (1H, br), 8.92-9.30 (1H, br). Dihydro- chloride 325 1H-NMR (DMSO-d6) ppm: 1.33-1.52 (10H, m), 1.64-1.82 (4H, m), 1.82-1.93 (1H, m), 2.30-2.40 (1H, m), 3.40-3.54 (2H, m), 3.54-3.70 (2H, m), 4.45-5.20 (1H, br), 6.66 (2H, d, J = 9.0 Hz), 7.19 (2H, d, J = 9.0 Hz), 8.55-8.70 (1H, br), 8.75-8.92 (1H, br). Dihydro- chloride 326 1H-NMR (DMSO-d6) ppm: 1.33-1.59 (10H, m), 1.61-1.90 (5H, m), 2.33-2.45 (1H, m), 3.45-3.56 (2H, m), 3.56-3.71 (2H, m), 5.05-6.00 (1H, br), 6.65 (1H, dd, J = 2.8, 9.1 Hz), 6.78 (1H, d, J = 2.8 Hz), 7.34 (1H, d, J = 9.1 Hz), 8.70- 8.89 (1H, br), 9.00-9.15 (1H, br). Dihydro- chloride

(332) TABLE-US-00048 TABLE 48 Absolute configuration Example R.sup.4 NMR Salt 327 1H-NMR (DMSO-d6) ppm: 1.35 (3H, s), 1.45-1.67 (6H, m), 1.67-2.00 (4H, m), 2.16-2.30 (2H, m), 2.30-2.43 (1H, m), 3.39-3.48 (1H, m), 3.62-3.72 (1H, m), 3.88-3.96 (1H, m), 3.09-4.08 (1H, m), 6.05-6.75 (1H, br), 7.10 (1H, s), 7.20-7.25 (1H, m), 7.25-7.34 (1H, m), 7.33-7.40 (1H, m), 7.66-7.80 (3H, m), 8.22-8.35 (1H, br), 9.30-9.45 (1H, br). Dihydro- chloride 328 1H-NMR (DMSO-d6) ppm at 80 C.: 1.37-1.55 (5H, m), 1.55-1.70 (4H, m), 1.71-2.00 (4H, m), 2.19-2.40 (3H, m), 3.35-3.50 (1H, m), 3.52-3.66 (1H, m), 3.84-3.97 (2H, m), 5.53-5.86 (1H, br), 7.06 (1H, dd, J = 2.4, 8.9 Hz), 7.28 (1H, d, J = 5.4 Hz), 7.36 (1H, d, J = 2.4 Hz), 7.60 (1H, d, J = 5.4 Hz), 7.76 (1H, d, J = 8.9 Hz), 8.07-8.40 (1H, br), 9.20-9.57 (1H, br). Dihydro- chloride 329 1H-NMR (DMSO-d6) ppm: 1.33-1.52 (10H, m), 1.64-1.82 (4H, m), 1.82-1.93 (1H, m), 2.30-2.40 (1H, m), 3.40-3.54 (2H, m), 3.54-3.70 (2H, m), 4.45-5.20 (1H, br), 6.66 (2H, d, J = 9.0 Hz), 7.19 (2H, d, J = 9.0 Hz), 8.55-8.70 (1H, br), 8.75-8.92 (1H, br). Dihydro- chloride 330 1H-NMR (DMSO-d6) ppm: 1.32 (3H, s), 1.40-1.63 (6H, m), 1.63-1.90 (4H, m), 2.07-2.25 (2H, m), 2.30-2.33 (1H, m), 3.27-3.38 (1H, m), 3.48-3.59 (1H, m), 3.78-3.86 (1H, m), 3.86-3.95 (1H, m), 5.30-6.75 (1H, br), 6.83 (1H, d, J = 3.0, 9.1 Hz), 7.02 (1H, d, J = 3.0 Hz), 7.35 (1H, d, J = 9.1 Hz), 8.23-8.40 (1H, br), 9.22-9.45 (1H, br). Dihydro- chloride

(333) TABLE-US-00049 TABLE 49 Absolute configuration Ex- ample R.sup.4 NMR Salt 331 0 1H-NMR (DMSO-d6) ppm: 1.35 (3H, s), 1.45-1.67 (6H, m), 1.67-2.00 (4H, m), 2.16-2.30(2H, m), 2.30-2.43 (1H, m), 3.39-3.48 (1H, m), 3.62-3.72 (1H, m), 3.88-3.96 (1H, m), 3.09-4.08 (1H, m), 6.05-6.75 (1H, br), 7.10 (1H, s), 7.20-7.25 (1H, m), 7.25-7.34 (1H, m), 7.33-7.40 (1H, m), 7.66-7.80 (3H, m), 8.22-8.35 (1H, br), 9.30-9.45 (1H, br). Di- hydro- chloride 332 1H-NMR (DMSO-d6) ppm at 80 C.: 1.37-1.55 (5H, m), 1.55-1.70 (4H, m), 1.71-2.00 (4H, m), 2.19-2.40 (3H, m), 3.35-3.50 (1H, m), 3.52-3.66 (1H, m), 3.84-3.97 (2H, m), 5.53-5.86 (1H, br), 7.06 (1H, dd, J = 2.4, 8.9 Hz), 7.28 (1H, d, J = 5.4 Hz), 7.36 (1H, d, J = 2.4 Hz), 7.60(1H, d, J = 5.4 Hz), 7.76 (1H, d, J = 8.9 Hz), 8.07-8.40 (1H, br),9.20-9.57 (1H, br). Di- hydro- chloride 333 1H-NMR (DMSO-d6) ppm: 1.33-1.52 (10H, m), 1.64-1.82 (4H, m), 1.82-1.93 (1H, m), 2.30-2.40 (1H, m), 3.40-3.54 (2H, m), 3.54-3.70 (2H, m), 4.45-5.20 (1H, br), 6.66 (2H, d, J = 9.0 Hz), 7.19 (2H, d, J = 9.0 Hz), 8.55-8.70 (1H, br), 8.75-8.92 (1H, br). Di- hydro- chloride 334 1H-NMR (DMSO-d6) ppm: 1.32 (3H, s), 1.40-1.63 (6H, m), 1.63-1.90 (4H, m), 2.07-2.25 (2H, m), 2.30-2.33 (1H, m), 3.27-3.38 (1H, m), 3.48-3.59 (1H, m), 3.78-3.86 (1H, m), 3.86-3.95 (1H, m), 5.30-6.75 (1H, br), 6.83 (1H, d, J = 3.0, 9.1 Hz), 7.02 (1H, d, J = 3.0 Hz), 7.35 (1H, d, J = 9.1 Hz), 8.23- 8.40 (1H, br), 9.22-9.45 (1H, br). Di- hydro- chloride

(334) TABLE-US-00050 TABLE 50 Absolute configuration Example R.sup.4 NMR Salt 335 1H-NMR (DMSO-d6) ppm: 1.39 (3H, s), 1.43-1.65 (7H, m), 1.71-1.90 (4H, m), 1.93-2.06 (1H, m), 2.35-2.45 (1H, m), 3.60-3.79 (4H, m), 5.40-6.15 (1H, br), 6.90 (1H, s), 7.09-7.20 (2H, m), 7.30-7.40 (1H, m), 7.65-7.72 (2H, m), 7.75 (1H, d, J = 9.0 Hz), 8.60-8.80 (1H, br), 8.80-9.00 (1H, br). Dihydro- chloride 336 1H-NMR (DMSO-d6) ppm at 80 C.: 1.38-1.54 (10H, m), 1.69-2.02 (5H, m), 2.41-2.50 (1H, m), 3.55-3.85 (4H, m), 4.97-5.80 (1H, br), 6.94-7.10 (1H, br), 7.18-7.40 (2H, m), 7.59 (1H, d, J = 5.4 Hz), 7.78 (1H, d, J = 8.9 Hz), 8.75-8.92 (1H, br), 8.92-9.30 (1H, br). Dihydro- chloride 337 1H-NMR (DMSO-d6) ppm: 1.33-1.52 (10H, m), 1.64-1.82 (4H, m), 1.82-1.93 (1H, m), 2.30-2.40 (1H, m), 3.40-3.54 (2H, m), 3.54-3.70 (2H, m), 4.45-5.20 (1H, br), 6.66 (2H, d, J = 9.0 Hz), 7.19 (2H, d, J = 9.0 Hz), 8.55- 8.70 (1H, br), 8.75-8.92 (1H, br). Dihydro- chloride 338 1H-NMR (DMSO-d6) ppm: 1.33-1.59 (10H, m), 1.61-1.90 (5H, m), 2.33- 2.45 (1H, m), 3.45-3.56 (2H, m), 3.56-3.71 (2H, m), 5.05-6.00 (1H, br), 6.65 (1H, dd, J = 2.8, 9.1 Hz), 6.78 (1H, d, J = 2.8 Hz), 7.34 (1H, d, J = 9.1 Hz), 8.70-8.89 (1H, br), 9.00-9.15 (1H, br). Dihydro- chloride

(335) TABLE-US-00051 TABLE 51 Absolute configuration Example R.sup.4 NMR Salt 339 00 1H-NMR (DMSO-d6) ppm: 1.39 (3H, s), 1.43-1.65 (7H, m), 1.71-1.90 (4H, m), 1.93-2.06 (1H, m), 2.35-2.45 (1H, m), 3.60-3.79 (4H, m), 5.40-6.15 (1H, br), 6.90 (1H, s), 7.09-7.20 (2H, m), 7.30-7.40 (1H, m), 7.65-7.72 (2H, m), 7.75 (1H, d, J = 9.0 Hz), 8.60-8.80 (1H, br), 8.80-9.00 (1H, br). Dihydro- chloride 340 01 1H-NMR (DMSO-d6) ppm at 80 C.: 1.38-1.54 (10H, m), 1.69-2.02 (5H, m), 2.41-2.50 (1H, m), 3.55-3.85 (4H, m), 4.97-5.80 (1H, br), 6.94-7.10 (1H, br), 7.18-7.40 (2H, m), 7.59 (1H, d, J = 5.4 Hz), 7.78 (1H, d, J = 8.9 Hz), 8.75-8.92 (1H, br), 8.92-9.30 (1H, br). Dihydro- chloride 341 02 1H-NMR (DMSO-d6) ppm: 1.33-1.52 (10H, m), 1.64-1.82 (4H, m), 1.82-1.93 (1H, m), 2.30-2.40 (1H, m), 3.40-3.54 (2H, m), 3.54-3.70 (2H, m), 4.45-5.20 (1H, br), 6.66 (2H, d, J = 9.0 Hz), 7.19 (2H, d, J = 9.0 Hz), 8.55-8.70 (1H, br), 8.75-8.92 (1H, br). Dihydro- chloride 342 03 1H-NMR (DMSO-d6) ppm: 1.33-1.59 (10H, m), 1.61-1.90 (5H, m), 2.33-2.45 (1H, m), 3.45-3.56 (2H, m), 3.56-3.71 (2H, m), 5.05-6.00 (1H, br), 6.65 (1H, dd, J = 2.8, 9.1 Hz), 6.78 (1H, d, J = 2.8 Hz), 7.34 (1H, d, J = 9.1 Hz), 8.70-8.89 (1H, br), 9.00-9.15 (1H, br). Dihydro- chloride

(336) TABLE-US-00052 TABLE 52 Relative configuration 04 Example R.sup.4 NMR Salt 343 05 1H-NMR (DMSO-d6) ppm: 1.10-1.92 (14H, m), 2.23-2.44 (2H, m), 2.94 (1H, d, J = 13.3), 3.51 (1H, d, J = 13.3 Hz), 3.76-3.94 (1H, m), 4.10-4.22 (1H, m), 5.80-6.30 (1H, br), 7.11 (1H, d, J = 1.6 Hz), 7.22-7.31 (1H, m), 7.36-7.50 (2H, m), 7.66-7.85 (3H, m), 8.66-8.92 (1H, br), 9.80-9.08 (1H, br). Dihydro- chloride 344 06 1H-NMR (DMSO-d6) ppm: 1.10-1.38 (3H, m), 1.38-1.65(8H, m), 1.65-1.92(3H, m), 2.15-2.40 (2H, m), 2.89 (1H, d, J = 13.3 Hz), 3.37 (1H, d, J = 13.3 Hz), 3.77-3.95 (1H, m), 4.00-4.14 (1H, m), 7.17 (1H, dd, J = 2.3, 8.9 Hz), 7.28-7.38 (2H, m), 7.68 (1H, d, J = 5.4 Hz), 7.83 (1H, d, J = 8.9 Hz), 8.44-8.74 (1H, br), 9.65-9.90 (1H, br). Hydro- chloride 345 07 1H-NMR (DMSO-d6) ppm: 1.10-1.95 (14H, m), 2.16-2.45 (2H, m), 2.82 (1H, d, J = 13.5), 3.40 (1H, d, J = 13.5 Hz), 3.70-3.89 (1H, m), 3.89-4.07 (1H, m), 6.93(2H, d, J = 9.0 Hz), 7.26 (2H, d, J = 9.0 Hz), 8.54-8.88 (1H, br), 9.66-9.99 (1H, br). Hydro- chloride 346 08 1H-NMR (DMSO-d6) ppm: 1.10-1.90 (14H, m), 2.19-2.45 (2H, m), 2.83 (1H, d, J = 13.6 Hz), 3.50 (1H, d, J = 13.6 Hz), 3.68-3.86 (1H, br), 3.94-4.07 (1H, br), 6.92 (1H, dd, J = 2.9, 9.0 Hz), 7.14 (1H, d, J = 2.9 Hz), 7.42 (1H, d, J = 9.0 Hz), 8.55-8.88 (1H, br), 9.62-9.98 (1H, br). Hydro- chloride

(337) TABLE-US-00053 TABLE 53 Relative configuration 09 Ex- ample R.sup.4 NMR Salt 347 0 1H-NMR (DMSO-d6) ppm: 1.37 (3H, s), 1.42-1.88 (12H, m), 2.10-2.25 (1H, m), 3.13 (1H, d, J = 13.4 Hz), 3.28-3.63 (3H, m), 3.92-4.48 (1H, br), 7.26-7.51 (4H, m), 7.76-7.92 (3H, m), 8.85-9.15 (1H, br), 9.50-9.70 (1H, br). Dihydro- chloride 348 1H-NMR (DMSO-d6) ppm: 1.00 (3H, s), 1.20-1.70 (13H, m), 1.70-1.85 (1H, m), 2.70-2.95 (4H, m), 7.05 (1H, dd, J = 2.1, 8.7 Hz), 7.34 (1H, d, J = 5.4 Hz), 7.39 (1H, d, J = 2.1 Hz), 7.67 (1H, d, J = 5.4 Hz), 7.82 (1H, d, J = 8.7 Hz). 349 1H-NMR (DMSO-d6) ppm: 1.33 (3H, s), 1.37-1.81 (12H, m), 2.07-2.22 (1H, m), 3.00 (1H, d, J = 13.6 Hz), 3.21-3.50 (3H, m), 3.88-4.20 (1H, br), 6.97 (2H, d, J = 8.8 Hz), 7.31 (2H, d, J = 8.8 Hz), 8.66-9.00 (1H, br), 9.33-9.65 (1H, m). Dihydro- chloride 350 1H-NMR (DMSO-d6) ppm: 1.33 (3H, s), 1.36 (3H, s), 1.50-1.90 (9H, m), 2.07-2.28 (1H, m), 3.07 (1H, d, J = 14.2 Hz), 3.32-3.66 (3H, m), 6.88 (1H, dd, J = 2.8, 8.9 Hz), 7.09 (1H, d, J = 2.8 Hz), 7.43 (1H, d, J = 8.9 Hz), 8.70-8.92 (1H, br), 9.35-9.58 (1H, br). Hydro- chloride

(338) TABLE-US-00054 TABLE 54 Relative configuration Ex- MS am- (M + ple R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 1) 351 H H H H H 245 352 H H CH.sub.3 H H 259 353 H CH.sub.3 H H H 259 354 H F H H H 263 355 H H CN H H 270 356 H CH.sub.3 CH.sub.3 H H 273 357 H C.sub.2H.sub.5 H H H 273 358 H CH.sub.3 H CH.sub.3 H 273 359 H H C.sub.2H.sub.5 H H 273 360 H OCH.sub.3 H H H 275 361 H F H F H 281 362 H CH.sub.3 CN H H 284 363 H H (CH.sub.2).sub.2CH.sub.3 H H 287 364 H CH(CH.sub.3).sub.2 H H H 287 365 H H CH(CH.sub.3).sub.2 H H 287 366 H F CN H H 288 367 H CN H F H 288 368 H N(CH.sub.3).sub.2 H H H 288 369 H H N(CH.sub.3).sub.2 H H 288 370 H OC.sub.2H.sub.5 H H H 289 371 H CH.sub.3 OCH.sub.3 H H 289 372 H H OCH.sub.2CH.sub.3 H H 289 373 H CH.sub.3 F CH.sub.3 H 291 374 H H SCH.sub.3 H H 291 375 H SCH.sub.3 H H H 291 376 OCH.sub.3 H H F H 293 377 H F H Cl H 297 378 H F F F H 299 379 H H C(CH.sub.3).sub.3 H H 301 380 H CH.sub.3 OCH.sub.3 CH.sub.3 H 303 381 H OCH(CH.sub.3).sub.2 H H H 303 382 H OCH.sub.3 OCH.sub.3 H H 305 383 H H SCH.sub.2CH.sub.3 H H 305 384 OCH.sub.3 H H Cl H 309 385 H OCH.sub.3 F F H 311 386 H H H H 311 387 H CF.sub.3 H H H 313 388 H H CF.sub.3 H H 313 389 Cl H Cl H H 313 390 H Cl H Cl H 313 391 H CF.sub.3 CH.sub.3 H H 327 392 H H H H 328 393 H H OCF.sub.3 H H 329 394 H CF.sub.3 H F H 331 395 F H CF.sub.3 H H 331 396 H F CF.sub.3 H H 331 397 F CF.sub.3 H H H 331 398 H CF.sub.3 F H H 331 399 H CF.sub.3 OCH.sub.3 H H 343 400 H CF.sub.3 Cl H H 347

(339) TABLE-US-00055 TABLE 55 Relative configuration Example R.sup.4 MS(M + 1) 401 285 402 285 403 0 287 404 299 405 302 406 303 407 303 408 310 409 313 410 316 411 317 412 333

(340) TABLE-US-00056 TABLE 56 Relative configuration 0 Example R.sup.4 MS(M + 1) 413 251 414 260 415 260 416 276 417 296 418 296 419 296 420 297 421 302 422 0 302 423 310 424 310 425 326 426 326 427 326 428 330 429 332 430 364

(341) TABLE-US-00057 TABLE 57 Absolute configuration Example R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 MS(M + 1) 431 H H H H H 245 432 H H CH.sub.3 H H 259 433 H CH.sub.3 H H H 259 434 CH.sub.3 H H H H 259 435 H CN H H H 270 436 CN H H H H 270 437 H H CN H H 270 438 H CH.sub.3 CH.sub.3 H H 273 439 H CH.sub.3 H CH.sub.3 H 273 440 CH.sub.3 CH.sub.3 H H H 273 441 H H C.sub.2H.sub.5 H H 273 442 H OCH.sub.3 H H H 275 443 OCH.sub.3 H H H H 275 444 CH.sub.3 F H H H 277 445 H CH.sub.3 F H H 277 446 F H H CH.sub.3 H 277 447 H F CH.sub.3 H H 277 448 CH.sub.3 H F H H 277 449 F H H F H 281 450 F H F H H 281 451 H CH.sub.3 CN H H 284 452 H C(O)CH.sub.3 H H H 287 453 H H C(O)CH.sub.3 H H 287 454 CH.sub.3 H CH.sub.3 CH.sub.3 H 287 455 H H CH(CH.sub.3).sub.2 H H 287 456 F H CN H H 288 457 H F CN H H 288 458 H CN F H H 288 459 H N(CH.sub.3).sub.2 H H H 288 460 H H N(CH.sub.3).sub.2 H H 288 461 CH.sub.3 H OCH.sub.3 H H 289 462 H CH.sub.3 OCH.sub.3 H H 289 463 H CH.sub.3 F CH.sub.3 H 291 464 CH.sub.3 F CH.sub.3 H H 291 465 H H SCH.sub.3 H H 291 466 H SCH.sub.3 H H H 291 467 OCH.sub.3 H H F H 293 468 CH.sub.3 Cl H H H 293 469 H CH.sub.3 Cl H H 293 470 H Cl CH.sub.3 H H 293 471 CH.sub.3 H Cl H H 293 472 F H H Cl H 297 473 H F H Cl H 297 474 F H Cl H H 297 475 F F H F H 299 476 H H (CH.sub.2).sub.3CH.sub.3 H H 301 477 H H C(CH.sub.3).sub.3 H H 301 478 H H CH.sub.2N(CH.sub.3).sub.2 H H 302 479 H CH.sub.2N(CH.sub.3).sub.2 H H H 302 480 OCH(CH.sub.3).sub.2 H H H H 303 481 H CH.sub.3 OCH.sub.3 CH.sub.3 H 303 482 H Cl CN H H 304 483 H OCH.sub.3 H OCH.sub.3 H 305 484 H OCH.sub.3 OCH.sub.3 H H 305 485 OCH.sub.3 H H OCH.sub.3 H 305 486 OCH.sub.3 F H F H 311 487 H OCH.sub.3 F F H 311 488 OCH.sub.3 H F F H 311 489 H H OCHF.sub.2 H H 311 490 0 H H H H 311 491 H H H H 311 492 H H H H 311 493 H H H H 311 494 CF.sub.3 H H H H 313 495 H CF.sub.3 H H H 313 496 H H CF.sub.3 H H 313 497 Cl H Cl H H 313 498 H Cl H Cl H 313 499 H H H H 314 500 H CH.sub.3 N(CH.sub.3).sub.2 CH.sub.3 H 316 501 H H H H 321 502 H H H H 321 503 H H H H 321 504 H Cl OC.sub.2H.sub.5 H H 323 505 H H H H 325 506 H H H H 325 507 H H 0 H H 325 508 H H H H 325 509 H CF.sub.3 CH.sub.3 H H 327 510 H H H H 327 511 H H H H 327 512 H H H H 327 513 H H H H 328 514 H OCF.sub.3 H H H 329 515 OCF.sub.3 H H H H 329 516 H H OCF.sub.3 H H 329 517 H F CF.sub.3 H H 331 518 H CF.sub.3 F H H 331 519 H H O(CH.sub.2).sub.2N(CH.sub.3).sub.2 H H 332 520 H OCH.sub.3 OCH.sub.3 OCH.sub.3 H 335 521 H H H H 335 522 H H H H 335 523 H H H H 337 524 H H H H 337 525 H H 0 H H 342 526 H CF.sub.3 OCH.sub.3 H H 343 527 H H O(CH.sub.2).sub.5CH.sub.3 H H 345 528 H H O(CH.sub.2).sub.3N(CH.sub.3).sub.2 H H 346 529 H H H H 347 530 H Cl CF.sub.3 H H 347 531 H CF.sub.3 Cl H H 347 532 Cl Cl H Cl H 347 533 H H H H 351 534 H H H H 351 535 H H H H 351 536 H H H H 351 537 H H SO.sub.2N(CH.sub.3).sub.2 H H 352 538 H H H H 353 539 H H H H 355 540 H H H H 358 541 H H CH.sub.2N(i-Pr).sub.2 H H 358 542 H CF.sub.3 H CF.sub.3 H 381

(342) TABLE-US-00058 TABLE 58 Absolute configuration Example R.sup.4 MS(M + 1) 543 0 287 544 289 545 295 546 296 547 296 548 297 549 298 550 300 551 301 552 303 553 0 303 554 309 555 310 556 313 557 316 558 316 559 317 560 325 561 325 562 325 563 00 325 564 01 328 565 02 333 566 03 342 567 04 371 568 05 375 569 06 375

(343) TABLE-US-00059 TABLE 59 Absolute configuration 07 Example R.sup.4 MS(M + 1) 570 08 246 571 09 251 572 0 260 573 260 574 265 575 276 576 296 577 301 578 314

(344) TABLE-US-00060 TABLE 63 relative configuration Ex. No. R.sup.4 NMR Salt 588 1H-NMR (DMSO-d6) ppm: 1.29-1.57 (3H, m), 1.46 (3H, s), 1.57 (3H, s), 1.69-1.91 (5H, m), 1.98-2.09 (1H, m), 3.07 (1H, d, J = 13.5 Hz), 3.51 (1H, d, J = 13.5 Hz), 3.73-3.92 (1H, m), 4.11-4.30 (1H, m), 7.18 (1H, d, J = 2.2 Hz), 7.22-7.28 (1H, m), 7.36-7.43 (2H, m), 7.68- 7.80 (3H, m), 8.02-8.31 (1H, m), 9.62-9.91 (1H, br) 2 Hydrochloride

(345) TABLE-US-00061 TABLE 64 absolute configuration Ex. No. R.sup.4 NMR Salt 589 0 1H-NMR (CDCl3) ppm: 1.07-1.15 (18H, m), 1.17-1.34 (12H, m), 1.35-1.50 (2H, m), 1.64-1.86 (4H, m), 2.82 (1H, d, J = 11.6 Hz), 3.04 (1H, d, J = 11.7 Hz), 3.47-3.53 (1H, m), 3.69-3.78 (1H, m), 6.95 (1H, d, J = 2.3 Hz), 7.03 (1H, dd, J = 2.4, 8.8 Hz), 7.10 (1H, d, J = 2.4 Hz), 7.23 (1H, d, J = 2.4, 9.1 Hz), 7.51 (1H, d, J = 8.9 Hz), 7.55 (1H, d, J = 9.1 Hz). 590 1H-NMR (CDCl3) ppm: 1.13 (18H, d, J = 7.3 Hz), 1.20-1.36 (12H, m), 1.36-1.64 (2H, m), 1.68-1.86 (4H, m), 2.83 (1H, d, J = 12.0 Hz), 3.12 (1H, d, J = 11.9 Hz), 3.45-3.55 (1H, m), 3.75-3.85 (1H, m), 6.82 (1H, d, J = 2.3 Hz), 6.86 (1H, dd, J = 2.4, 8.7 Hz), 7.02 (1H, d, J = 2.3 Hz), 7.10 (1H, dd, J = 2.4, 9.0 Hz), 7.53 (1H, d, J = 8.7 Hz), 7.59 (1H, d, J = 9.0 Hz). 591 1H-NMR (CDCl3) ppm: 1.03-1.12 (18H, m), 1.12-1.32 (12H, m), 1.32-1.65 (2H, m), 1.66-1.84 (4H, m), 2.82 (1H, d, J = 11.7 Hz), 3.08 (1H, d, J = 11.8 Hz), 3.47-3.53 (1H, m), 3.73-3.81 (1H, m), 3.88 (3H, s), 5.17 (1H, d, J = 11.0 Hz), 5.24 (1H, d, J = 11.0 Hz), 6.94 (1H, d, J = 2.5 Hz), 7.16 (1H, d, J = 9.0 Hz), 7.31 (1H, dd, J = 2.5, 9.4 Hz), 7.58 (1H, d, J = 9.0 Hz), 8.12 (1H, d, J = 9.4 Hz). 592 1H-NMR (CDCl3) ppm: 1.14 (18H, d, J = 6.6 Hz), 1.19-1.35 (13H, m), 1.35-1.65 (1H, m), 1.65-1.84 (4H, m), 2.83 (1H, d, J = 11.6 Hz), 3.04 (1H, d, J = 11.6 Hz), 3.5-3.6 (1H, m), 3.7-3.8 (1H, m), 3.87 (3H, s), 4.93 (2H, d, J = 1.0 Hz), 6.96 (1H, s), 6.99 (1H, d, J = 2.2 Hz), 7.21 (1H, dd, J = 2.4, 9.0 Hz), 7.59 (1H, d, J = 9.0 Hz), 7.77 (1H, s).

(346) TABLE-US-00062 TABLE 65 absolute configuration Ex. No. R.sup.4 NMR Salt 593 1H-NMR (CDCl3) ppm: 1.15-1.33 (9H, m), 1.33-1.50 (2H, m), 1.64-1.84 (4H, m), 2.82 (1H, d, J = 11.8 Hz), 3.04 (1H, d, J = 11.8 Hz), 3.49-3.56 (1H, m), 3.69-3.78 (1H, m), 6.96 (1H, d, J = 2.4 Hz), 6.99-7.06 (2H, m), 7.22- 7.28 (1H, m), 7.52-7.58 (2H, m). 594 1H-NMR (CDCl3) ppm: 1.17-1.36 (9H, m), 1.36-1.52 (2H, m), 1.65-1.86 (4H, m), 2.83 (1H, d, J = 11.9 Hz), 3.13 (1H, d, J = 12.0 Hz), 3.45-3.55 (1H, m), 3.75-3.85 (1H, m), 6.8- 6.85 (2H, m), 6.94 (1H, d, J = 2.4 Hz), 7.10 (1H, d, J = 2.4, 9.1 Hz), 7.57 (1H, d, J = 8.7 Hz), 7.60 (1H, d, J = 9.1 Hz). 595 1H-NMR (DMSO-d6) ppm: 1.1-1.2 (1H, m), 1.2-1.4 (8H, m), 1.5-1.9 (5H, m), 2.89 (1H, d, J = 12.4 Hz), 3.22 (1H, d, J = 12.5 Hz), 3.62 (1H, br), 3.85 (3H, s), 3.95- 4.05 (1H, m), 4.85 (2H, s), 6.53 (2H, s), 7.07 (1H, d, J = 2.4 Hz), 7.28 (1H, d, J = 9.1 Hz), 7.39 (1H, dd, J = 2.5, 9.5 Hz), 7.67 (1H, d, J = 9.0H), 7.98 (1H, d, J = 9.4 Hz). Fumarate 596 1H-NMR (CDCl3) ppm: 0.99 (1H, br), 1.15- 1.35 (8H, m), 1.35-1.5 (2H, m), 1.5-1.85 (4H, m), 2.44 (1H, br), 2.81 (1H, d, J = 11.7 Hz), 3.05 (1H, d, J = 11.8H), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.93 (3H, s), 4.79 (2H, s), 6.98 (1H, d, J = 2.4 Hz), 7.02 (1H, s), 7.21-7.28 (1H, m), 7.54 (1H, s), 7.60 (1H, d, J = 9.0 Hz).

(347) TABLE-US-00063 TABLE 66 absolute configuration Ex. No. R.sup.4 NMR Salt 597 0 1H-NMR (CDCl3) ppm: 1.15-1.65 (11H, m), 1.65-1.9 (4H, m), 2.84 (1H, d, J = 12.0 Hz), 3.13 (1H, d, J = 11.9 Hz), 3.50 (1H, bs), 3.75- 3.85 (1H, m), 3.89 (3H, s), 6.89 (1H, dd, J = 2.5, 8.8 Hz), 6.92 (1H, d, J = 2.3 Hz), 6.97 (1H, d, J = 2.4 Hz), 7.11 (1H, dd, J = 2.4, 9.0 Hz), 7.57 (1H, d, J = 8.8 Hz), 7.60 (1H, d, J = 9.0 Hz). 598 1H-NMR (CDCl3) ppm: 1.08 (1H, br), 1.15- 1.35 (8H, m), 1.35-1.5 (2H, m), 1.65-1.85 (4H, m), 2.50 (3H, s), 2.82 (1H, d, J = 11.8 Hz), 3.07 (1H, d, J = 11.7 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.90 (3H, s), 6.96 (1H, d, J = 2.6 Hz), 7.18 (1H, d, J = 9.0 Hz), 7.30 (1H, dd, J = 2.6, 9.4 Hz), 7.51 (1H, d, J = 8.9 Hz), 7.81 (1H, d, J = 9.4 Hz). 599 1H-NMR (CDCl3) ppm: 0.81-1.00 (1H, m), 1.03-1.13 (1H, m), 1.27 (3H, s), 1.33-1.43 (2H, m), 1.46 (3H, s), 1.54-1.72 (2H, m), 1.72-1.82 (1H, m), 1.85-2.0 (1H, m), 2.69 (1H, d, J = 11.1 Hz), 3.3-3.4 (2H, m), 3.75- 3.85 (1H, m), 7.15 (1H, s), 7.5-7.55 (2H, m), 7.6-7.7 (2H, m), 7.7-7.8 (1H, m), 8.3-8.4 (1H, m), 8.55-8.65 (1H, m), 8.65-8.75 (1H, m). 600 1H-NMR (CDCl3) ppm: 1.00 (1H, br), 1.19- 1.37 (8H, m), 1.39-1.51 (2H, m), 1.68-1.79 (3H, m), 1.79-1.93 (1H, m), 2.90 (1H, d, J = 11.8 Hz), 3.18 (1H, d, J = 11.9 Hz), 3.5-3.6 (1H, m), 3.8-3.9 (1H, m), 7.05 (1H, d, J = 2.1 Hz), 7.3-7.45 (3H, m), 7.8-7.95 (3H, m), 8.15 (1H, s), 8.25 (1H, s). 601 1H-NMR (DMSO-d6) ppm: 0.85-1.0 (1H, m), 1.0-1.1 (1H, m), 1.3-1.4 (1H, m), 1.5- 1.65 (7H, m), 1.65-1.85 (2H, m), 1.85-2.1 (2H, m), 2.59 (3H, s), 2.76 (1H, d, J = 12.6 Hz), 3.3-3.5 (1H, m), 3.51 (1H, d, J = 13.1 Hz), 4.15-4.3 (1H, m), 7.02 (1H, d, J = 7.5 Hz), 7.28 (1H, d, J = 8.0 Hz), 7.5-7.65 (2H, m), 7.95-8.15 (2H, m), 8.25-8.35 (1H, m), 9.6-9.8 (1H, m). Hydrochloride 602 1H-NMR (DMSO-d6) ppm: 1.29-1.51 (6H, m), 1.56 (3H, s), 1.65-2.1 (5H, m), 3.09 (1H, d, J = 13.6 Hz), 3.62 (1H, d, J = 13.5 Hz), 3.8- 3.9 (1H, m), 4.2-4.3 (1H, m), 7.32 (1H, d, J = 2.2 Hz), 7.50 (1H, dd, J = 1.6, 8.4 Hz), 7.63 (1H, dd, J = 2.5, 9.2 Hz), 7.87-7.98 (2H, m), 8.11-8.29 (2H, m), 9.74 (1H, br). Hydrochloride 603 1H-NMR (DMSO-d6) ppm: 1.32-1.54 (6H, m), 1.58 (3H, s), 1.67-1.90 (3H, m), 1.90- 2.14 (2H, m), 3.11 (1H, d, J = 13.8 Hz), 3.71 (1H, d, J = 13.8 Hz), 3.75-3.9 (1H, m), 4.25- 4.35 (1H, m), 7.29 (1H, d, J = 2.2 Hz), 7.5- 7.65 (2H, m), 7.81 (1H, d, J = 8.6 Hz), 7.91 (1H, d, J = 9.2 Hz), 8.25-8.45 (2H, m), 9.9- 10.1 (1H, m). Hydrochloride 604 1H-NMR (CDCl3) ppm: 0.96 (1H, br), 1.15- 1.35 (8H, m), 1.35-1.5 (2H, m), 1.65-1.9 (4H, m), 2.83 (1H, d, J = 11.8 Hz), 3.09 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.75-3.85 (1H, m), 3.99 (3H, s), 6.95 (1H, d, J = 2.4 Hz), 7.20 (1H, d, J = 9.0 Hz), 7.37 (1H, dd, J = 2.5, 9.4 Hz), 7.56 (1H, d, J = 9.0 Hz), 8.06 (1H, d, J = 9.3 Hz). 605 1H-NMR (DMSO-d6) ppm: 0.9-1.0 (1H, m), 1.1-1.2 (1H, m), 1.3-1.4 (1H, m), 1.52 (3H, s), 1.55-1.7 (4H, m), 1.7-1.85 (2H, m), 1.85- 2.05 (2H, m), 2.73 (1H, d, J = 12.5 Hz), 3.3- 3.6 (2H, m), 3.94 (3H, s), 4.15-4.3 (1H, m), 6.88 (1H, d, J = 8.2 Hz), 7.06 (1H, d, J = 8.1 Hz), 7.5-7.55 (1H, m), 7.55-7.6 (1H, m), 7.95 (1H, br), 8.16 (1H, dd, J = 1.0, 8.3 Hz), 8.24 (1H, d, J = 8.1 Hz), 9.45-9.6 (1H, m). Hydrochloride 606 1H-NMR (DMSO-d6) ppm: 1.26-1.51 (6H, m), 1.57 (3H, s), 1.66-2.12 (5H, m), 3.06 (1H, d, J = 13.6 Hz), 3.57 (1H, d, J = 13.6 Hz), 3.74-3.86 (1H, m), 4.15-4.26 (1H, m), 7.05 (1H, d, J = 1.8 Hz), 7.28-7.37 (2H, m), 7.43- 7.52 (1H, m), 7.75 (1H, d, J = 8.4 Hz), 7.84 (1H, d, J = 8.2 Hz), 8.23 (1H, br), 9.90 (1H, br). Hydrochloride 607 0 1H-NMR (DMSO-d6) ppm: 1.28-1.52 (6H, m), 1.57 (3H, s), 1.64-1.97 (4H, m), 2.02- 2.16 (1H, m), 3.08 (1H, d, J = 13.5 Hz), 3.56 (1H, d, J = 13.6 Hz), 3.8-3.9 (1H, m), 3.95-4.1 (1H, m), 7.23 (1H, d, J = 2.0 Hz), 7.36-7.45 (1H, m), 7.45-7.54 (1H, m), 7.65 (1H, d, J = 2.3 Hz), 7.78 (1H, d, J = 8.1 Hz), 7.97 (1H, d, J = 8.3 Hz), 8.1-8.35 (1H, m), 9.90 (1H, br). Hydrochloride 608 1H-NMR (DMSO-d6) ppm: 1.26-1.52 (6H, m), 1.57 (3H, s), 1.66-2.02 (4H, m), 2.02- 2.12 (1H, m), 3.07 (1H, d, J = 13.4 Hz), 3.51 (1H, d, J = 13.4 Hz), 3.65-3.9 (2H, m), 4.15- 4.25 (1H, m), 7.18 (1H, d, J = 2.2 Hz), 7.22- 7.3 (1H, m), 7.35-7.47 (2H, m), 7.65-7.85 (3H, m), 8.1-8.3 (1H, m), 9.8-10.0 (1H, m). 2 Hydrochloride 609 1H-NMR (DMSO-d6) ppm: 1.06-1.16 (1H, m), 1.16-1.39 (8H, m), 1.46-1.78 (4H, m), 1.78-1.93 (1H, m), 2.81 (1H, d, J = 12.2 Hz), 2.9-4.0 (5H, m), 4.30-4.42 (2H, m), 6.27-6.58 (2H, m), 7.06 (1H, d, J = 2.1 Hz), 7.10 (1H, dd, J = 2.6, 8.9 Hz), 7.26 (1H, d, J = 2.5 Hz), 7.35 (1H, dd, J = 2.6, 9.4 Hz), 7.61-7.68 (2H, m). Fumarate 610 1H-NMR (DMSO-d6) ppm: 1.23-1.52 (6H, m), 1.59 (3H, s), 1.64-2.03 (4H, m), 2.03- 2.16 (1H, m), 3.07 (1H, d, J = 13.3 Hz), 3.45 (1H, d, J = 14.0 Hz), 3.75-3.85 (1H, m), 3.95 (3H, s), 4.1-4.2 (1H, m), 4.77 (1H, br), 7.25 (1H, d, J = 2.2 Hz), 7.46 (1H, s), 7.58 (1H, dd, J = 2.4, 9.2 Hz), 7.81 (1H, d, J = 9.2 Hz), 8.23 (1H, s), 8.25-8.4 (1H, m), 10.13 (1H, br). 2 Hydrochloride 611 1H-NMR (DMSO-d6) ppm: 1.12-1.20 (1H, m), 1.21-1.39 (8H, m), 1.47-1.79 (4H, m), 1.79-1.95 (1H, m), 2.84 (1H, d, J = 12.3 Hz), 2.85-3.75 (5H, m), 3.9-4.0 (1H, m), 6.54 (2H, s), 7.12 (1H, d, J = 2.2 Hz), 7.34 (1H, dd, J = 2.2, 8.7 Hz), 7.43 (1H, dd, J = 2.4, 9.2 Hz), 7.65-7.75 (2H, m), 7.80 (1H, d, J = 2.1 Hz). Fumarate 612 1H-NMR (DMSO-d6) ppm: 1.05-1.19 (1H, m), 1.19-1.40 (8H, m), 1.46-1.80 (4H, m), 1.80-1.96 (1H, m), 2.83 (1H, d, J = 12.3 Hz), 2.9-4.3 (5H, m), 6.51 (1H, s), 7.05-7.45 (4H, m), 7.49 (1H, d, J = 2.3 Hz), 7.7-7.8 (2H, m). Fumarate 613 1H-NMR (DMSO-d6) ppm: 1.0-1.15 (2H, m), 1.3-1.4 (1H, m), 1.48 (3H, s), 1.50 (3H, s), 1.55-1.65 (1H, m), 1.7-1.8 (2H, m), 1.8- 2.0 (2H, m), 2.25-2.35 (1H, m), 2.4-2.5 (1H, m), 2.6-2.75 (2H, m), 2.95-3.1 (2H, m), 3.21 (3H, s), 3.3-3.5 (1H, m), 3.78 (3H, s), 3.85- 3.95 (1H, m), 6.78 (1H, d, J = 8.9 Hz), 6.93 (1H, d, J = 8.9 Hz), 7.99 (1H, br), 9.64 (1H, br). Hydrochloride 614 1H-NMR (DMSO-d6) ppm: 1.08-1.37 (9H, m), 1.42 (6H, s), 1.47-1.85 (5H, m), 2.76 (1H, d, J = 12.4 Hz), 2.95 (1H, d, J = 12.3 Hz), 3.53 (1H, br), 3.63-3.73 (1H, m), 4.74 (2H, s), 6.52 (2H, s), 6.58 (1H, d, J = 2.7 Hz), 6.65 (1H, d, J = 8.9 Hz), 6.76 (1H, dd, J = 2.8, 9.0 Hz). Fumarate

(348) TABLE-US-00064 TABLE 67 absolute configuration Ex. No. R.sup.4 NMR Salt 615 1H-NMR (CDCl3) ppm: 0.91-1.09 (3H, m), 1.20 (3H, s), 1.31-1.43 (5H, m), 1.54-1.78 (3H, m), 1.81-1.95 (1H, m), 2.55-2.65 (4H, m), 3.15 (1H, d, J = 11.2 Hz), 3.4-3.5 (1H, m), 3.65-3.7 (1H, m), 6.72-6.77 (1H, m), 7.05 (1H, s), 7.13 (1H, dd, J = 7.8, 7.8 Hz), 7.37 (1H, d, J = 8.0 Hz). 616 0 1H-NMR (CDCl3) ppm: 0.85-1.08 (3H, m), 1.21 (3H, s), 1.29-1.42 (5H, m), 1.52-1.68 (2H, m), 1.68-1.88 (2H, m), 2.58 (1H, d, J = 11.0 Hz), 2.77 (3H, d, J = 0.9 Hz), 3.02-3.12 (1H, m), 3.20 (1H, d, J = 11.0 Hz), 3.66 (1H, br), 6.91 (1H, d, J = 7.5 Hz), 6.98 (1H, d, J = 0.8 Hz), 7.19 (1H, dd, J = 7.8, 7.8 Hz), 7.52 (1H, dd, J = 0.7, 8.0 Hz). 617 1H-NMR (CDCl3) ppm: 0.90-1.08 (3H, m), 1.20 (3H, s), 1.32-1.43 (5H, m), 1.45-1.78 (3H, m), 1.81-1.95 (1H, m), 2.57 (1H, d, J = 11.1 Hz), 3.14 (1H, d, J = 11.1 Hz), 3.33-3.42 (1H, m), 3.62-3.71 (1H, m), 6.71 (1H, dd, J = 4.1, 8.4 Hz), 6.92 (1H, dd, J = 8.9, 8.9 Hz), 7.41 (1H, d, J = 5.4 hz), 7.46 (1H, dd, J = 3.7, 5.4 Hz). 618 1H-NMR (CDCl3) ppm: 0.9-1.1 (2H, m), 1.20 (3H, s), 1.3-1.45 (5H, m), 1.45-1.8 (4H, m), 1.8-1.95 (1H, m), 2.56 (1H, d, J = 11.1 Hz), 3.14 (1H, d, J = 11.1 Hz), 3.3-3.4 (1H, m), 3.6-3.7 (1H, m), 3.96 (3H, s), 6.66 (1H, d, J = 8.2 Hz), 6.74 (1H, d, J = 8.2 Hz), 7.39 (1H, d, J = 5.4 Hz), 7.45 (1H, d, J = 5.4 Hz). 619 1H-NMR (CDCl3) ppm: 0.92-1.08 (3H, m), 1.20 (3H, s), 1.30-1.43 (5H, m), 1.47-1.78 (3H, m), 1.82-1.96 (1H, m), 2.61 (1H, d, J = 11.2 Hz), 3.13 (1H, d, J = 11.2 Hz), 3.42-3.52 (1H, m), 3.63-3.71 (1H, m), 6.74 (1H, d, J = 8.2 Hz), 7.21 (1H, d, J = 8.2 Hz), 7.43 (1H, d, J = 5.5 Hz), 7.47 (1H, d, J = 5.5 Hz). 620 1H-NMR (CDCl3) ppm: 0.94 (1H, br), 1.14- 1.33 (8H, m), 1.33-1.49 (2H, m), 1.65-1.85 (4H, m), 2.80 (1H, d, J = 11.7 Hz), 2.97 (1H, d, J = 11.6 Hz), 3.45-3.55 (1H, m), 3.6-3.7 (1H, m), 7.04 (1H, d, J = 2.1 Hz), 7.10 (1H, d, J = 2.2 Hz), 7.20 (1H, d, J = 5.4 Hz), 7.41 (1H, d, J = 5.5 Hz). 621 1H-NMR (DMSO-d6) ppm: 1.02-1.19 (2H, m), 1.32-1.44 (1H, m), 1.51 (3H, s), 1.52 (3H, s), 1.58-1.88 (3H, m), 1.92-2.09 (2H, m), 3.00 (1H, d, J = 13.0 Hz), 3.46 (1H, d, J = 13.1 Hz), 3.9-4.0 (1H, m), 3.95-4.08 (1H, m), 6.96 (1H, dd, J = 2.0, 11.0 Hz), 7.41 (1H, dd, J = 2.2, 9.1 Hz), 7.46 (1H, d, J = 5.4 Hz), 7.86 (1H, d, J = 5.4 Hz), 8.14 (1H, br), 9.76 (1H, br). Hydrochloride 622 1H-NMR (CDCl3) ppm: 0.92-1.12 (2H, m), 1.13-2.02 (13H, m), 2.66 (1H, d, J = 11.6 Hz), 3.22 (1H, br), 3.45-3.6 (1H, m), 3.77 (1H, br), 3.96 (3H, s), 6.81 (1H, d, J = 7.6 Hz), 7.33 (1H, dd, J = 7.8, 7.8 Hz), 7.46 (1H, d, J = 7.8 Hz), 8.13 (1H, s). 623 1H-NMR (DMSO-d6) ppm: 0.94-1.12 (2H, m), 1.28-1.43 (1H, m), 1.51 (3H, s), 1.53 (3H, s), 1.58-2.07 (5H, m), 2.84 (1H, d, J = 2.6 Hz), 3.41 (1H, d, J = 13.0 Hz), 3.6-3.7 (1H, m), 4.15-4.25 (1H, m), 7.11 (1H, dd, J = 6.5, 12.6 Hz), 7.77 (1H, dd, J = 3.8, 5.4 Hz), 7.84 (1H, d, J = 5.4 Hz), 8.05 (1H, br), 9.85 (1H, br). Hydrochloride 624 1H-NMR (DMSO-d6) ppm: 1.17-1.52 (6H, m), 1.52-1.63 (3H, m), 1.63-1.74 (1H, m), 1.74-1.98 (3H, m), 1.98-2.16 (1H, m), 2.33 (3H, d, J = 1.0 Hz), 3.03 (1H, d, J = 13.4 Hz), 3.33-3.5 (1H, m), 3.53-3.97 (2H, m), 4.03- 4.18 (1H, m), 7.03-7.12 (1H, m), 7.15 (1H, dd, J = 2.1, 8.9 Hz), 7.4-7.5 (1H, m), 7.59 (1H, d, J = 8.8 Hz), 8.1-8.35 (1H, m), 9.8-10.1 (1H, m). 2 Hydrochloride 625 1H-NMR (DMSO-d6) ppm: 1.1-1.4 (9H, m), 1.49-1.93 (6H, m), 2.31 (3H, d, J = 1.2 Hz), 2.83 (1H, d, J = 12.4 Hz), 3.19 (1H, d, J = 12.4 Hz), 3.25-3.85 (3H, m), 3.85-3.95 (1H, m), 6.52 (2H, s), 7.01 (1H, d, J = 1.2 Hz), 7.10 (1H, dd, J = 2.3, 9.0 Hz), 7.34 (1H, d, J = 2.2 Hz), 7.55 (1H, d, J = 8.8 Hz). Fumarate 626 0 1H-NMR (DMSO-d6) ppm: 1.09-1.17 (1H, m), 1.17-1.41 (8H, m), 1.45-1.76 (4H, m), 1.76-1.89 (1H, m), 2.47 (3H, d, J = 1.1 Hz), 2.78 (1H, d, J = 12.2 Hz), 3.11 (1H, d, J = 12.2 Hz), 3.47 (3H, m), 3.75-3.85 (1H, m), 6.50 (1H, s), 6.90 (1H, s), 6.99 (1H, dd, J = 2.3, 8.9 Hz), 7.25 (1H, d, J = 2.2 Hz), 7.48 (1H, d, J = 8.8 Hz). Fumarate

(349) TABLE-US-00065 TABLE 68 absolute configuration Ex. No. R.sup.4 NMR Salt 627 1H-NMR (CDCl3) ppm: 0.99 (1H, br), 1.20 (3H, s), 1.22 (3H, s), 1.29-1.51 (4H, m), 1.68-1.82 (3H, m), 1.82-1.95 (1H, m), 2.79 (1H, d, J = 12.8 Hz), 3.35-3.45 (1H, m), 3.91 (1H, d, J = 12.8 Hz), 4.2-4.3 (1H, m), 6.66 (1H, d, J = 9.0 Hz), 7.03 (2H, s), 7.77 (1H, d, J = 8.9 Hz). 628 1H-NMR (DMSO-d6) ppm: 1.35-1.63 (9H, m), 1.69-1.97 (3H, m), 1.97-2.16 (2H, m), 3.05-3.35 (1H, m), 3.35-4.3 (2H, m), 4.3-4.8 (2H, m), 7.1-7.35 (1H, m), 7.4-7.75 (1H, m), 8.0-8.2 (1H, m), 8.25-8.7 (2H, m), 9.85-10.35 (1H, m). 2 Hydrochloride 629 1H-NMR (DMSO-d6) ppm: 1.43-1.54 (5H, m), 1.64 (3H, s), 1.71-1.83 (2H, m), 1.83- 2.06 (2H, m), 2.06-2.17 (1H, m), 2.4-2.6 (1H, m), 3.25-3.5 (2H, m), 3.56 (1H, d, J = 15.1 Hz), 3.85-4.0 (1H, m), 4.25 (1H, d, J = 15.0 Hz), 4.65-4.75 (1H, m), 7.28 (1H, d, J = 7.2 Hz), 7.69 (1H, d, J = 5.7 Hz), 8.5-8.6 (2H, m), 8.9-9.1 (1H, m), 10.35-10.65 (1H, m), 15.15 (1H, br). 2 Hydrochloride

(350) TABLE-US-00066 TABLE 69 absolute configuration Ex. No. R.sup.4 NMR Salt 630 1H-NMR (CDCl3) ppm: 0.85-1.17 (3H, m), 1.20 (3H, s), 1.31 (3H, s), 1.33-1.45 (2H, m), 1.5-1.78 (3H, m), 1.81-1.95 (1H, m), 2.45 (3H, d, J = 1.0 Hz), 2.80 (1H, d, J = 11.5 Hz), 3.05 (1H, d, J = 11.5 Hz), 3.55-3.64 (2H, m), 6.39 (1H, s), 6.56 (1H, dd, J = 0.5, 7.7 Hz), 6.99 (1H, d, J = 8.2 Hz), 7.06 (1H, dd, J = 7.9, 7.9 Hz). 631 1H-NMR (CDCl3) ppm: 1.10-1.27 (5H, m), 1.29 (3H, s), 1.35-1.48 (2H, m), 1.48-1.83 (5H, m), 2.77-2.89 (2H, m), 3.49-3.55 (1H, m), 3.55-3.63 (1H, m), 4.01 (3H, s), 6.50 (1H, d, J = 2.0 Hz), 6.58 (1H, d, J = 2.1 Hz), 6.63 (1H, d, J = 2.1 Hz), 7.53 (1H, d, J = 2.0 Hz). 632 1H-NMR (DMSO-d6) ppm: 1.05-1.22 (2H, m), 1.34-1.45 (1H, m), 1.48 (3H, s), 1.53 (3H, s), 1.60-2.07 (5H, m), 3.13 (1H, d, J = 13.2 Hz), 3.28 (1H, d, J = 13.4 Hz), 3.88-3.89 (1H, m), 3.89-4.02 (1H, m), 6.62 (1H, dd, J = 2.1, 12.3 Hz), 7.09 (1H, dd, J = 1.3, 8.7 Hz), 7.22 (1H, dd, J = 0.7, 2.2 Hz), 7.96 (1H, d, J = 2.3 Hz), 8.05-8.2 (1H, m), 9.7-9.95 (1H, m). Hydrochloride 633 1H-NMR (DMSO-d6) ppm: 1.16-1.35 (2H, m), 1.35-1.45 (1H, m), 1.47 (3H, s), 1.54 (3H, s), 1.66-1.92 (3H, m), 1.92-2.14 (2H, m), 3.25 (1H, d, J = 13.5 Hz), 3.45 (1H, d, J = 13.4 Hz), 3.85-4.0 (1H, m), 4.2-4.35 (1H, m), 6.68 (1H, dd, J = 2.4, 12.1 Hz), 6.89-7.04 (2H, m), 8.02 (1H, d, J = 2.2 Hz), 8.26 (1H, br), 9.89 (1H, br). Hydrochloride 634 0 1H-NMR (DMSO-d6) ppm: 1.18-1.36 (2H, m), 1.36-1.49 (4H, m), 1.49-1.57 (3H, m), 1.62-1.94 (4H, m), 1.94-2.12 (1H, m), 3.03 (1H, d, J = 13.3 Hz), 3.25-3.4 (1H, m), 3.75- 3.9 (1H, m), 3.95-4.15 (1H, m), 7.22 (1H, s), 7.37 (1H, dd, J = 2.5, 9.3 Hz), 7.62 (1H, d, J = 9.2 Hz), 7.95 (1H, s), 8.18 (1H, br), 9.6-10.1 (1H, m). Hydrochloride 635 1H-NMR (DMSO-d6) ppm: 0.85-1.1 (2H, m), 1.2-1.35 (7H, m), 1.45-1.85 (4H, m), 1.85-2.05 (1H, m), 2.81 (1H, d, J = 12.0 Hz), 2.9-4.4 (5.5H, m), 6.52 (1.5H, s), 6.60 (1H, d, J = 8.6 Hz), 7.0-7.4 (3H, m), 8.00 (1H, d, J = 2.2 Hz). Fumarate 636 1H-NMR (DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.35-1.44 (1H, m), 1.50 (3H, s), 1.53 (3H, s), 1.59-2.07 (5H, m), 3.05 (1H, d, J = 12.8 Hz), 3.27 (1H, d, J = 13.0 Hz), 3.84 (3H, s), 3.89-4.02 (2H, m), 6.66 (1H, d, J = 8.5 Hz), 6.75 (1H, d, J = 8.4 Hz), 6.93 (1H, J = 2.2 Hz), 7.92 (1H, d, J = 2.2 Hz), 8.0-8.2 (1H, m), 9.55-9.8 (1H, m). Hydrochloride 637 1H-NMR (DMSO-d6) ppm: 1.21-1.37 (2H, m), 1.37-1.49 (4H, m), 1.52 (3H, s), 1.63- 1.92 (4H, m), 1.92-2.10 (1H, m), 3.02 (1H, d, J = 13.2 Hz), 3.29 (1H, d, J = 13.5 Hz), 3.75- 3.9 (1H, m), 3.95-4.1 (1H, m), 6.92 (1H, d, J = 2.2 Hz), 7.12 (1H, d, J = 2.1 Hz), 7.16 (1H, d, J = 2.1 Hz), 8.01 (1H, d, J = 2.1 Hz), 8.06 (1H, br), 9.72 (1H, br) Hydrochloride 638 1H-NMR (DMSO-d6) ppm: 1.18-1.37 (2H, m), 1.37-1.48 (4H, m), 1.55 (3H, s), 1.61- 1.98 (4H, m), 1.99-2.15 (1H, m), 2.38 (3H, s), 3.00 (1H, d, J = 13.3 Hz), 3.28 (1H, d, J = 13.2 Hz), 3.7-3.85 (1H, m), 3.95-4.05 (1H, m), 4.34 (1H, br), 6.40 (1H, s), 6.89 (1H, dd, J = 2.1, 8.6 Hz), 7.05 (1H, d, J = 1.4 Hz), 7.33 (1H, d, J = 8.5 Hz), 8.22 (1H, br), 10.07 (1H, br). 2 Hydrochloride 639 1H-NMR (DMSO-d6) ppm: 1.28-1.48 (6H, m), 1.52 (3H, s), 1.64-1.93 (4H, m), 1.95- 2.06 (1H, m), 2.99 (1H, d, J = 13.6 Hz), 3.46 (1H, d, J = 13.4 Hz), 3.5-3.95 (2H, m), 4.05- 4.15 (1H, m), 6.83-6.92 (2H, m), 7.01 (1H, s), 7.83 (1H, d, J = 2.1 Hz), 8.14 (1H, br), 9.82 (1H, br). 2 Hydrochloride 640 1H-NMR (DMSO-d6) ppm: 1.18-1.49 (6H, m), 1.53 (3H, s), 1.62-1.93 (4H, m), 1.95- 2.12 (1H, m), 3.00 (1H, d, J = 13.2 Hz), 3.30 (1H, d, J = 13.2 Hz), 3.7-3.85 (1H, m), 3.95- 4.1 (1H, m), 4.95 (1H, br), 6.91 (1H, dd, J = 2.1, 3.0 Hz), 6.94 (1H, d, J 2.1 Hz), 7.01 (1H, dd, J = 2.1, 14.3 Hz), 7.99 (1H, d, J = 2.1 Hz), 8.14 (1H, br), 9.89 (1H, br). 2 Hydrochloride 641 1H-NMR (DMSO-d6) ppm: 1.12-1.29 (8H, m), 1.29-1.40 (2H, m), 1.45-1.76 (4H, m), 1.82-1.96 (1H, m), 2.80 (1H, d, J = 12.6 Hz), 2.85-3.85 (4H, m), 3.85-3.95 (1H, m), 6.55 (2H, s), 7.08 (1H, s), 7.12 (1H, dd, J = 2.1, 9.0 Hz), 7.56 (1H, d, J = 8.9 Hz), 7.88 (1H, d, J = 0.6 Hz). Fumarate

(351) TABLE-US-00067 TABLE 70 absolute configuration Ex. No. R.sup.4 NMR Salt 642 1H-NMR (CDCl3) ppm: 1.10-1.20 (20H, m), 1.22 (3H, s), 1.25-1.36 (4H, m), 1.37-1.50 (2H, m), 1.64-1.88 (7H, m), 2.82 (1H, d, J = 11.8 Hz), 3.02 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.6-3.7 (1H, m), 6.82 (1H, s), 6.86 (1H, dd, J = 2.0, 8.9 Hz), 7.54 (1H, d, J = 8.8 Hz), 8.04 (1H, d, J = 0.9 Hz). 643 0 1H-NMR (CDCl3) ppm: 1.11-1.19 (19H, m), 1.21 (3H, s), 1.23-1.32 (2H, m), 1.35 (3H, s), 1.37-1.47 (2H, m), 1.63-1.86 (6H, m), 1.90-2.04 (1H, m), 3.04 (1H, d, J = 11.9 Hz), 3.09 (1H, d, J = 12.0 Hz), 3.55-3.65 (1H, m), 3.8-3.9 (1H, m), 6.41 (1H, d, J = 7.5 Hz), 7.05 (1H, d, J = 8.5 Hz), 7.16 (1H, dd, J = 7.6, 8.3 Hz), 8.26 (1H, d, J = 0.8 Hz). 644 1H-NMR (CDCl3) ppm: 1.14-1.23 (21H, m), 1.23-1.33 (6H, m), 1.38-1.50 (2H, m), 1.63- 1.88 (4H, m), 1.93-2.06 (3H, m), 2.82 (1H, d, J = 11.8 Hz), 3.00 (1H, d, J = 11.8 Hz), 3.44- 3.50 (1H, m), 3.56-3.65 (1H, m), 6.88-6.94 (2H, m), 7.28 (1H, d, J = 0.4 Hz), 7.42-7.47 (1H, m). 645 1H-NMR (CDCl3) ppm: 1.02-1.17 (21H, m), 1.19 (3H, s), 1.31-1.42 (5H, m), 1.59-1.77 (6H, m), 1.79-1.92 (1H, m), 2.67 (1H, d, J = 11.3 Hz), 3.09 (1H, d, J = 11.3 Hz), 3.45-3.6 (1H, m), 3.6-3.7 (1H, m), 6.39 (1H, dd, J = 3.4, 8.3 Hz), 6.65 (1H, dd, J = 3.2, 3.2 Hz), 6.72 (1H, d, J = 8.2, 12.7 Hz), 7.25 (1H, d, J = 3.2 Hz). 646 1H-NMR (CDCl3) ppm: 0.95 (1H, br), 1.15- 1.30 (26H, m), 1.32-1.49 (2H, m), 1.63-1.82 (4H, m), 1.93-2.08 (3H, m), 2.78 (1H, d, J = 11.6 Hz), 2.93 (1H, d, J = 11.6 Hz), 3.45-3.55 (1H, m), 3.6-3.7 (1H, m), 6.92 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 2.6, 9.4 Hz), 7.23- 7.28 (1H, m), 7.46 (1H, d, J = 9.4 Hz). 647 1H-NMR (CDCl3) ppm: 1.07-1.16 (19H, m), 1.17-1.32 (8H, m), 1.32-1.48 (2H, m), 1.61- 1.89 (7H, m), 2.8-2.9 (2H, m), 3.5-3.55 (1H, m), 3.55-3.65 (1H, m), 6.40 (1H, d, J = 3.4 Hz), 7.21 (1H, d, J = 3.4 Hz), 7.31 (1H, d, J = 2.7 Hz), 8.06 (1H, d, J = 2.7 Hz). 648 1H-NMR (CDCl3) ppm: 1.03-1.17 (19H, m), 1.19-1.36 (8H, m), 1.36-1.49 (2H, m), 1.63- 1.90 (6H, m), 1.95-2.11 (1H, m), 3.05 (1H, d, J = 12.5 Hz), 3.38 (1H, d, J = 12.5 Hz), 3.45- 3.55 (1H, m), 3.95-4.05 (1H, m), 6.33 (1H, d, J = 5.6 Hz), 6.54 (1H, d, J = 3.6 Hz), 7.10 (1H, d, J = 3.6 Hz), 7.98 (1H, d, J = 5.6 Hz). 649 1H-NMR (CDCl3) ppm: 1.1-1.18 (19H, m), 1.18-1.22 (4H, m), 1.34 (3H, s), 1.36-1.44 (2H, m), 1.61-1.83 (7H, m), 1.85-1.98 (1H, m), 2.81 (1H, d, J = 11.5 Hz), 3.07 (1H, d, J = 11.4 Hz), 3.6-3.65 (1H, m), 3.65-3.75 (1H, m), 6.30 (1H, dd, J = 3.0, 8.2 Hz), 6.86 (1H, dd, J = 8.2, 12.0 Hz), 8.24 (1H, d, J = 3.1 Hz).

(352) TABLE-US-00068 TABLE 71 absolute configuration Ex. No. R.sup.4 NMR Salt 650 1H-NMR (CDCl3) ppm: 1.03 (1H, br), 1.15- 1.34 (8H, m), 1.34-1.52 (2H, m), 1.62-1.90 (4H, m), 2.81 (1H, d, J = 11.8 Hz), 3.05 (1H, d, J = 11.8 Hz), 3.43-3.55 (1H, m), 3.69-3.81 (1H, m), 6.71 (1H, s), 6.92 (1H, d, J = 2.0, 9.0 Hz), 7.56 (1H, d, J = 8.8 Hz), 7.89 (1H, d, J = 0.9 Hz), 9.76 (1H, br). 651 1H-NMR (CDCl3) ppm: 0.95-1.25 (6H, m), 1.33 (3H, s), 1.37-1.47 (2H, m), 1.64-1.80 (3H, m), 1.88-2.00 (1H, m), 3.02 (1H, d, J = 11.8 Hz), 3.09 (1H, d, J = 11.8 Hz), 3.62-3.68 (1H, m), 3.83-3.92 (1H, m), 6.4-6.45 (1H, m), 6.97 (1H, d, J = 8.3 Hz), 7.23 (1H, dd, J = 7.7, 8.1 Hz), 8.11 (1H, d, J = 1.0 Hz), 10.05 (1H, br). 652 0 1H-NMR (CDCl3) ppm: 0.95 (1H, br), 1.15- 1.33 (8H, m), 1.33-1.50 (2H, m), 1.64-1.88 (4H, m), 2.80 (1H, d, J = 11.8 Hz), 3.03 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.65-3.75 (1H, m), 6.66 (1H, s), 6.95 (1H, dd, J = 2.1, 9.0 Hz), 7.06 (1H, dd, J = 0.8, 2.0 Hz), 7.46 (1H, d, J = 9.0 Hz), 8.22 (1H, bs). 653 1H-NMR (CDCl3) ppm: 0.93-1.13 (3H, m), 1.20 (3H, s), 1.27-1.45 (5H, m), 1.58-1.79 (3H, m), 1.79-1.94 (1H, m), 2.70 (1H, d, J = 11.3 Hz), 3.08 (1H, d, J = 11.3 Hz), 3.6-3.7 (2H, m), 6.35 (1H, dd, J = 3.8, 8.3 Hz), 6.61 (1H, dd, J = 3.3, 5.5 Hz), 6.76 (1H, dd, J = 8.3, 10.7 Hz), 7.18 (1H, dd, J = 2.8, 2.8 Hz), 8.33 (1H, br). 654 1H-NMR (CDCl3) ppm: 0.80-1.25 (6H, m), 1.28 (3H, s), 1.31-1.48 (2H, m), 1.63-1.82 (4H, m), 2.81 (1H, d, J = 11.6 Hz), 2.89 (1H, d, J = 11.6 Hz), 3.5-3.6 (1H, m), 3.6-3.7 (1H, m), 6.95 (1H, d, J = 2.1 Hz), 7.03 (1H, dd, J = 0.7, 2.0 Hz), 7.17 (1H, dd, J = 2.3, 9.1 Hz), 7.28 (1H, d, J = 9.0 Hz), 8.64 (1H, br). 655 1H-NMR (DMSO-d6) ppm: 1.0-1.25 (2H, m), 1.25-1.35 (7H, m), 1.45-1.9 (5H, m), 2.55-4.35 (6H, m), 6.27 (1H, dd, J = 1.9, 3.3 Hz), 6.49 (1H, s), 7.33 (1H, dd, J = 2.9, 2.9 Hz), 7.40 (1H, d, J = 2.5 Hz), 8.04 (1H, d, J = 2.6 Hz), 11.30 (1H, s). Fumarate 656 1H-NMR (CDCl3) ppm: 1.00 (1H, br), 1.18- 1.36 (7H, m), 1.36-1.52 (3H, m), 1.64-1.83 (3H, m), 1.98-2.13 (1H, m), 3.09 (1H, d, J = 12.6 Hz), 3.43 (1H, d, J = 12.5 Hz), 3.52 (1H, br), 4.0-4.1 (1H, m), 6.36 (1H, d, J = 5.7 Hz), 6.51 (1H, d, J = 3.6 Hz), 7.13 (1H, d, J = 3.6 Hz), 8.03 (1H, d = 5.7 Hz), 9.99 (1H, br). 657 1H-NMR (CDCl3) ppm: 1.03-1.17 (2H, m), 1.22 (3H, s), 1.33 (3H, s), 1.36-1.45 (2H, m), 1.62-1.79 (3H, m), 1.83-1.96 (1H, m), 2.83 (1H, d, J = 11.5 Hz), 3.05 (1H, d, J = 11.5 Hz), 3.65-3.7 (1H, m), 3.7-3.8 (1H, m), 6.28 (1H, dd, J = 3.3, 8.3 Hz), 6.91 (1H, dd, J = 8.3, 10.3 Hz), 8.12 (1H, d, J = 3.3 Hz), 10.26 (1H, br).

(353) TABLE-US-00069 TABLE 72 absolute configuration Ex. No. R.sup.4 NMR Salt 658 1H-NMR (CDCl3) ppm: 0.75-1.65 (11H, m), 1.65-1.9 (4H, m), 2.82 (1H, d, J = 11.7 Hz), 3.03 (1H, d, J = 11.7 Hz), 3.46-3.54 (1H, m), 3.71-3.79 (1H, m), 3.80 (3H, s), 6.51 (1H, d, J = 1.6 Hz), 6.96 (1H, dd, J = 2.1, 9.0 Hz), 7.02 (1H, s), 7.46 (1H, d, J = 9.0 Hz). 659 1H-NMR (CDCl3) ppm: 0.85-1.15 (3H, m), 1.20 (3H, s), 1.32 (3H, s), 1.35-1.45 (1H, m), 1.6-1.8 (4H, m), 1.85-2.0 (1H, m), 2.80 (1H, d, J = 11.5 Hz), 3.10 (1H, d, J = 11.6 Hz), 3.6-3.7 (1H, m), 3.7-3.8 (1H, m), 3.85 (3H, s), 6.52 (1H, d, J = 7.6 Hz), 6.89 (1H, d, J = 8.4 Hz) 7.20 (1H, s), 7.25-7.3 (1H, m). 660 1H-NMR (DMSO-d6) ppm: 1.0-1.25 (2H, m), 1.25-1.4 (7H, m), 1.45-1.9 (5H, m), 2.93 (2H, s), 3.38 (3H, br), 3.63 (1H, br), 3.70- 3.83 (4H, m), 6.28 (1H, d, J = 3.4 Hz), 6.53 (2H, s), 7.39 (1H, d, J = 3.3 Hz), 7.43 (1H, d, J = 2.6 Hz), 8.10 (1H, d, J = 2.6 Hz). Fumarate 661 00 1H-NMR (DMSO-d6) ppm: 1.15-1.4 (9H, m), 1.5-1.8 (4H, m), 1.95-2.15 (1H, m), 3.09 (1H, d, J = 12.9 Hz), 3.43 (1H, d, J = 12.8 Hz), 3.55-3.65 (1H, m), 3.73 (3H, s), 4.05-4.15 (1H, m), 6.41 (1H, d, J = 5.6 Hz), 6.49 (1H, d, J = 3.6 Hz), 6.55 (2H, s), 7.26 (1H, d, J = 3.6 Hz), 7.93 (1H, d, J = 5.6 Hz). Fumarate 662 01 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (2H, m), 1.30-1.42 (1H, m), 1.51 (3H, s), 1.54 (3H, s), 1.57-1.66 (1H, m), 1.69-1.98 (3H, m), 1.98-2.09 (1H, m), 2.99 (1H, d, J = 12.9 Hz), 3.26 (1H, d, J = 12.8 Hz), 3.9-4.0 (1H, m), 4.05-4.2 (4H, s), 6.39 (1H, dd, J = 3.0, 8.3 Hz), 7.05 (1H, dd, J = 8.2, 11.8 Hz), 8.14 (1H, br), 8.38 (1H, d, J = 2.3 Hz), 9.95 (1H, br). Hydrochloride 663 02 1H-NMR (DMSO-d6) ppm: 1.00-1.16 (2H, m), 1.34-1.44 (1H, m), 1.50 (3H, s), 1.52 (3H, s), 1.58-1.95 (4H, m), 1.98-2.09 (1H, m), 2.98 (1H, d, J = 13.0 Hz), 3.24 (1H, d, J = 13.0 Hz), 3.85-3.95 (1H, m), 3.95-4.1 (1H, m), 4.17 (3H, s), 6.24 (1H, dd, J = 3.2, 8.0 Hz), 6.85 (1H, dd, J = 8.0, 11.5 Hz), 7.95- 8.2 (1H, m), 8.74 (1H, d, J = 2.7 Hz), 9.75- 9.95 (1H, m). Hydrochloride 664 03 1H-NMR (DMSO-d6) ppm: 1.05-1.3 (2H, m), 1.3-1.45 (7H, m), 1.5-1.7 (2H, m), 1.7- 1.9 (3H, m), 2.97 (1H, d, J = 12.4 Hz), 3.17 (1H, d, J = 12.7 Hz), 3.72 (1H, br), 3.81 (3H, s), 3.9-4.0 (1H, m), 6.58 (6H, s), 6.98 (1H, d, J = 2.0 Hz), 7.14 (1H, dd, J = 2.2, 9.1 Hz), 7.49 (1H, d, J = 9.0 Hz), 8.10 (1H, s). 3 Fumarate 665 04 1H-NMR (DMSO-d6) ppm: 1.05-1.15 (1H, m), 1.15-1.35 (9H, m), 1.45-1.75 (3H, m), 1.75-1.9 (1H, m), 2.80 (1H, d, J = 11.9 Hz), 3.0-3.6 (4H, m), 3.77 (3H, s), 3.8-3.9 (1H, m), 6.51 (1H, s), 6.90 (1H, d, J = 1.8 Hz), 7.03 (1H, dd, J = 2.0, 8.9 Hz), 7.43 (1H, d, J = 8.8 Hz), 7.99 (1H, s). Fumarate

(354) TABLE-US-00070 TABLE 73 absolute configuration 05 Ex. No. R.sup.4 NMR Salt 666 06 1H-NMR (DMSO-d6) ppm: 1.00-1.25 (2H, m), 1.31-1.42 (1H, m), 1.46 (3H, s), 1.49 (3H, s), 1.58-1.69 (1H, m), 1.69-1.84 (2H, m), 1.84-2.05 (3H, m), 2.05-2.2 (1H, m), 2.70-2.92 (5H, m), 3.24 (1H, d, J = 13.0 Hz), 3.45-3.57 (1H, m), 3.80-3.93 (1H, m), 6.53 (1H, dd, J = 2.0, 11.6 Hz), 6.66-6.76 (1H, m), 7.9-8.2 (1H, m), 9.7-10.0 (1H, m). Hydrochloride 667 07 1H-NMR (DMSO-d6) ppm: 1.00-1.21 (2H, m), 1.29-1.41 (1H, m), 1.48 (6H, s), 1.55- 1.67 (1H, m), 1.67-2.06 (5H, m), 2.07-2.21 (1H, m), 2.70 (1H, d, J = 12.7 Hz), 2.78-3.00 (4H, m), 3.21-3.39 (2H, m), 3.78-3.89 (1H, m), 6.74 (1H, dd, J = 4.4, 8.6 Hz), 6.88 (1H, dd, J = 8.6, 8.6 Hz), 8.01 (1H, br), 9.74 (1H, br). Hydrochloride 668 08 1H-NMR (DMSO-d6) ppm: 1.10-1.24 (1H, m), 1.34-1.42 (1H, m), 1.45 (3H, s), 1.48 (3H, s), 1.58-2.03 (6H, m), 2.03-2.19 (1H, m), 2.72-2.95 (5H, m), 3.27 (1H, d, J = 12.9 Hz), 3.38-3.55 (1H, m), 3.79-3.95 (1H, m), 4.28-4.11 (1H, m), 6.72 (1H, d, J = 1.5 Hz), 6.94 (1H, s), 7.9-8.1 (1H, m), 9.6-9.8 (1H, m). Hydrochloride 669 09 1H-NMR (DMSO-d6) ppm: 1.20-1.48 (6H, m), 1.51 (3H, s), 1.63-1.93 (4H, m), 1.93- 2.10 (1H, m), 2.96 (1H, d, J = 13.4 Hz), 3.29 (1H, d, J = 14.0 Hz), 3.7-3.85 (1H, m), 3.9- 4.05 (1H, m), 6.70 (1H, dd, J = 2.5, 8.9 Hz), 7.12 (1H, d, J = 2.4 Hz), 7.23 (1H, d, J = 8.9 Hz), 8.15 (1H, br), 9.86 (1H, br). Hydrochloride 670 0 1H-NMR (DMSO-d6) ppm: 1.1-1.25 (9H, m), 1.25-1.4 (1H, m), 1.45-1.75 (4H, m), 1.9- 2.05 (1H, m), 2.92 (1H, d, J = 12.2 Hz), 3.06 (1H, d, J = 12.3 Hz), 3.1-3.63 (3H, m), 3.63- 3.70 (1H, m), 6.57 (2H, s), 6.71 (1H, d, J = 8.6 Hz), 6.75-6.81 (1H, m), 7.04 (1H, dd, J = 8.3, 8.3 Hz). Fumarate 671 1H-NMR (DMSO-d6) ppm: 1.15-1.31 (2H, m), 1.35-1.46 (4H, m), 1.50 (3H, s), 1.61- 1.87 (4H, m), 1.93-2.07 (1H, m), 2.92 (1H, d, J = 13.2 Hz), 3.11 (1H, d, J = 13.2 Hz), 3.7-3.8 (1H, m), 3.8-3.9 (1H, m), 5.88-5.95 (2H, m), 6.32 (1H, d, J = 2.4, 8.5 Hz), 6.71 (1H, d, J = 2.4 Hz), 6.76 (1H, d, J = 8.5 Hz), 7.9-8.15 (1H, m), 9.7-9.9 (1H, m). Hydrochloride

(355) TABLE-US-00071 TABLE 74 absolute configuration Ex. No. R.sup.4 NMR Salt 672 1H-NMR (CDCl3) ppm: 1.02-1.15 (19H, m), 1.15-1.28 (11H, m), 1.29-1.46 (2H, m), 1.60- 1.76 (4H, m), 2.67 (1H, d, J = 11.6 Hz), 2.83 (1H, d, J = 11.6 Hz), 3.4-3.55 (2H, m), 6.69- 6.74 (2H, m), 6.74-6.79 (2H, m). 673 1H-NMR (CDCl3) ppm: 1.11 (18H, d, J = 7.0 Hz), 1.16-1.33 (11H, m), 1.33-1.59 (3H, m), 1.65-1.78 (4H, m), 2.68 (1H, d, J = 11.8 Hz), 2.97 (1H, d, J = 11.9 Hz), 3.4-3.45 (1H, m), 3.55-3.6 (1H, m), 6.28 (1H, dd, J = 1.9, 7.6 Hz), 6.37 (1H, dd, J = 2.3, 2.3 Hz), 6.43 (1H, dd, J = 2.4, 7.8 Hz), 7.03 (1H, dd, J = 8.1, 8.1 Hz). 674 1H-NMR (CDCl3) ppm: 1.04-1.15 (19H, m), 1.15-1.30 (11H, m), 1.32-1.47 (2H, m), 1.47- 1.77 (4H, m), 2.70 (1H, d, J = 11.7 Hz), 2.92 (1H, d, J = 11.7 Hz), 3.41-3.48 (1H, m), 3.54- 3.63 (1H, m), 3.75 (3H, s), 4.78-4.88 (2H, m), 6.65 (1H, dd, J = 3.0, 8.7 Hz), 6.71 (1H, d, J = 8.8 Hz), 7.22 (1H, d, J = 2.9 Hz). 675 1H-NMR (CDCl3) ppm: 1.06-1.14 (18H, m), 1.15-1.29 (12H, m), 1.29-1.48 (2H, m), 1.58- 1.76 (4H, m), 2.65 (1H, d, J = 11.8 Hz), 2.83 (1H, d, J = 11.6 Hz), 3.35-3.45 (1H, m), 3.45- 3.55 (1H, m), 6.40-6.48 (1H, m), 6.55 (1H, dd, J = 2.9, 14.1 Hz), 6.79 (1H, dd, J = 9.4, 9.4 Hz). 676 1H-NMR (CDCl3) ppm: 1.11 (18H, d, J = 7.3 Hz), 1.16-1.21 (4H, m), 1.21-1.33 (7H, m), 1.34-1.47 (2H, m), 1.47-1.78 (5H, m), 2.66 (1H, d, J = 11.6 Hz), 2.81 (1H, d, J = 11.6 Hz), 3.4-3.55 (2H, m), 6.61 (1H, d, J = 3.0, 8.9 Hz), 6.78 (1H, d, J = 8.9 Hz), 6.81 (1H, d, J = 3.0 Hz). 677 1H-NMR (CDCl3) ppm: 1.06-1.11 (18H, m), 1.11-1.22 (7H, m), 1.23 (3H, s), 1.25-1.80 (8H, m), 2.71 (1H, d, J = 11.8 Hz), 3.01 (1H, d, J = 11.9 Hz), 3.4-3.5 (1H, m), 3.6-3.7 (1H, m), 4.73 (2H, s), 6.79-6.85 (2H, m), 7.18- 7.23 (2H, m), 678 1H-NMR (CDCl3) ppm: 1.05-1.12 (18H, m), 1.12-1.48 (13H, m), 1.48-1.82 (5H, m), 2.70 (1H, d, J = 11.9 Hz), 2.99 (1H, d, J = 12.0 Hz), 3.35-3.45 (1H, m), 3.55-3.65 (1H, m), 4.77 (2H, s), 6.47 (1H, dd, J = 2.4, 13.9 Hz), 6.61 (1H, dd, J = 2.4, 8.6 Hz), 7.32 (1H, dd, J = 8.8, 8.8 Hz). 679 0 1H-NMR (CDCl3) ppm: 1.03 (18H, d, J = 2.4 Hz), 1.13-1.27 (9H, m), 1.27-1.77 (6H, m), 2.67 (1H, d, J = 11.5 Hz), 2.80 (1H, d, J = 11.5 Hz), 3.4-3.55 (2H, m), 4.96 (2H, s), 6.42 (1H, d, J = 2.8 Hz), 6.70 (1H, dd, J = 2.9, 8.8 Hz), 6.80 (1H, d, J = 8.8 Hz).

(356) TABLE-US-00072 TABLE 75 absolute configuration Ex. No. R.sup.4 NMR Salt 680 1H-NMR (CDCl3) ppm: 1.02-1.30 (9H, m), 1.30-1.49 (2H, m), 1.50-1.83 (4H, m), 2.70 (1H, d, J = 10.4 Hz), 2.81 (1H, d, J = 11.4 Hz), 3.4-3.6 (2H, m), 6.75 (4H, bs). 681 1H-NMR (CDCl3) ppm: 1.16-1.30 (8H, m), 1.30-1.49 (3H, m), 1.60-1.83 (4H, m), 2.71 (1H, d, J = 12.0 Hz), 3.03 (1H, d, J = 12.0 Hz), 3.38-3.45 (1H, m), 3.56-3.68 (1H, m), 6.17- 6.23 (1H, m), 6.33 (1H, dd, J = 2.3, 2.3 Hz), 6.43 (1H, dd, J = 2.2, 8.3 Hz), 7.06 (1H, dd, J = 8.1, 8.1 Hz). 682 1H-NMR (DMSO-d6) ppm: 1.1-1.25 (2H, m), 1.3-1.4 (7H, m), 1.5-1.9 (5H, m), 2.87 (1H, d, J = 12.4 Hz), 2.97 (1H, d, J = 12.6 Hz), 3.63-3.78 (5H, m), 4.44 (2H, s), 6.54 (3H, s), 6.73 (1H, dd, J = 2.9, 8.8 Hz), 6.80 (1H, d, J = 8.8 Hz), 6.99 (1H, d, J = 2.8 Hz). 3/2 Fumarate 683 1H-NMR (CDCl3) ppm: 1.09-2.34 (16H, m), 2.81 (1H, d, J = 12.1 Hz), 2.85-3.1 (1H, m), 3.5-3.6 (1H, m), 3.6-3.75 (1H, m), 6.73 (1H, dd, J = 2.8, 8.9 Hz), 6.81 (1H, d, J = 2.8 Hz), 6.92 (1H, d, J = 8.8 Hz). 684 1H-NMR (CDCl3) ppm: 1.15-1.60 (12H, m), 1.61-1.83 (4H, m), 2.72 (1H, d, J = 12.0 Hz), 3.03 (1H, d, J = 11.9 Hz), 3.4-3.45 (1H, m), 3.6-3.7 (1H, m), 4.56 (2H, s), 6.80-6.86 (2H, m), 7.20-7.25 (2H, m). 685 1H-NMR (CDCl3) ppm: 0.92 (1H, br), 1.16- 1.36 (8H, m), 1.37-1.48 (2H, m), 1.57 (1H, br), 1.62-1.84 (4H, m), 2.71 (1H, d, J = 12.0 Hz), 3.02 (1H, d, J = 12.0H), 3.35-3.45 (1H, m), 3.55-3.65 (1H, m), 4.62 (2H, s), 6.51 (1H, dd, J = 2.5, 14.0 Hz), 6.59 (1H, dd, J = 2.5, 8.5 Hz), 7.19 (1H, dd, J = 8.8, 8.8 Hz). 686 1H-NMR (CDCl3) ppm: 0.92-1.02 (1H, m), 1.02-1.18 (7H, m), 1.19-1.32 (1H, m), 1.35- 1.66 (5H, m), 1.69-1.83 (1H, m), 2.60 (1H, d, J = 11.3 Hz), 2.69 (1H, d, J = 11.3 Hz), 3.32 (1H, br), 3.41-3.50 (1H, m), 4.43 (2H, d, J = 4.6 Hz), 4.88 (1H, t, J = 5.4 Hz), 6.55 (1H, dd, J = 2.9, 8.7 Hz), 6.60 (1H, d, J = 8.6 Hz), 6.83 (1H, d, J = 2.7 Hz), 8.55 (1H, s).

(357) TABLE-US-00073 TABLE 76 absolute configuration Ex. No. R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 687 OCH3 1H-NMR (DMSO-d6) 2 Hydrochloride ppm: 1.1-1.3 (2H, m), 1.35-1.45 (4H, m), 1.52 (3H, s), 1.6- 1.9 (4H, m), 1.95-2.1 (1H, m), 2.93 (1H, d, J = 13.1 Hz), 3.10 (1H, d, J = 13.0 Hz), 3.68 (3H, s), 3.7-3.9 (2H, m), 4.35-5.75 (1H, m), 6.75-6.85 (2H, m), 6.85-6.95 (2H, m), 8.11 (1H, br), 9.92 (1H, br). 688 CH3 Cl 1H-NMR (CDCl3) ppm: 0.93-1.1 (2H, m), 1.17 (3H, s), 1.31 (3H, s), 1.35- 1.43 (2H, m), 1.55- 1.75 (3H, m), 1.78- 1.93 (1H, m), 2.37 (3H, s), 2.42 (1H, d, J = 11.0 Hz), 2.83-2.91 (1H, m), 3.10 (1H, d, J = 11.0 Hz), 3.5-3.6 (1H, m), 6.79 (1H, dd, J = 2.1, 7.1 Hz), 6.99-7.09 (2H, m). 689 CH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.0-1.17 (2H, m), 1.3-1.43 (1H, m), 1.49 (3H, s), 1.52 (3H, s), 1.56-1.68 (1H, m), 1.68-1.87 (2H, m), 1.87-2.1 (2H, m), 2.30 (3H, s), 2.62 (1H, d, J = 12.6 Hz), 3.11-3.23 (1H, m), 3.25-3.45 (1H, m), 3.78-3.92 (1H, m), 6.92-7.04 (2H, m), 7.08-7.22 (2H, m), 8.03 (1H, br), 9.65-9.95 (1H, m). 690 CH3 1H-NMR (DMSO-d6) 2 Hydrochloride ppm: 1.18-1.35 (2H, m), 1.35-1.48 (4H, m), 1.52 (3H, s), 1.62-1.9 (4H, m), 1.98-2.04 (1H, m), 2.19 (3H, s), 2.91 (1H, d, J = 13.3 Hz), 3.25 (1H, d, J = 13.3 Hz), 3.7-3.8 (1H, m), 3.9-4.0 (1H, m), 4.1-4.45 (1H, m), 6.8- 6.87 (2H, m), 6.98- 7.07 (2H, m), 8.05- 8.25 (1H, m), 9.8- 10.05 (1H, m). 691 CH3 CH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 0.98-1.15 (2H, m), 1.3-1.42 (1H, m), 1.49 (3H, s), 1.52 (3H, s), 1.55-1.67 (1H, m), 1.67-1.83 (2H, m), 1.83-2.008 (2H, m), 2.20 (3H, s), 2.22 (3H, s), 2.59 (1H, d, J = 12.6 Hz), 3.05-3.15 (1H, m), 3.25-3.4 (1H, m), 3.82-3.96 (1H, m), 6.82 (1H, d, J = 7.8 Hz), 6.91 (1H, d, J = 7.4 Hz), 7.03 (1H, dd, J = 7.7, 7.7 Hz), 7.98 (1H, br), 9.65- 9.8 (1H, m). 692 CH3 Cl 1H-NMR (DMSO-d6) 2 Hydrochloride ppm: 1.22-1.47 (6H, m), 1.53 (3H, s), 1.63-1.93 (4H, m), 1.97-2.08 (1H, m), 2.27 (3H, s), 2.93 (1H, d, J = 13.6 Hz), 3.36 (1H, d, J = 13.5 Hz), 3.7-3.8 (1H, m), 3.8-4.1 (2H, m), 6.79 (1H, dd, J = 3.0, 8.9 Hz), 6.93 (1H, d, J = 2.9 Hz), 7.20 (1H, d, J = 8.8 Hz), 8.1-8.3 (1H, m), 9.85-10.05 (1H, m). 693 CH3 F 1H-NMR (DMSO-d6) 2 Hydrochloride ppm: 1.16-1.33 (2H, m), 1.36-1.45 (4H, m), 1.52 (3H, s), 1.62-1.9 (4H, m), 2.0- 2.08 (1H, m), 2.18 (3H, d, J = 1.7 Hz), 2.93 (1H, d, J = 13.3 Hz), 3.21 (1H, d, J = 13.2 Hz), 3.7-3.8 (1H, m), 3.9-4.0 (1H, m), 4.15-4.55 (1H, m), 6.72-6.8 (1H, m), 6.81-6.89 (1H, m), 6.97 (1H, dd, J = 9.1, 9.1 Hz), 8.05-8.25 (1H, m), 9.85-10.1 (1H, m). 694 CH3 F 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.0-1.2 (2H, m), 1.3-1.45 (1H, m), 1.49 (3H, s), 1.51 (3H, s), 1.56-1.84 (3H, m), 1.84-2.06 (2H, m), 2.20 (3H, d, J = 2.2 Hz), 2.67 (1H, d, J = 12.7 Hz), 3.15- 3.25 (1H, m), 3.29- 3.42 (1H, m), 3.85- 4.0 (1H, m), 6.83 (1H, d, J = 8.0 Hz), 6.89 (1H, dd, J = 8.8, 8.8 Hz), 7.16 (1H, dd, J = 7.9, 15.3 Hz), 8.02 (1H, br), 9.72 (1H, br). 695 Cl 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.25-1.46 (6H, m), 1.52 (3H, s), 1.63-1.95 (4H, m), 1.95-2.1 (1H, m), 2.95 (1H, d, J = 13.7 Hz), 3.47 (1H, d, J = 13.6 Hz), 3.7-3.8 (1H, m), 4.0-4.1 (1H, m), 6.77 (1H, dd, J = 1.4, 7.8 Hz), 6.90 (1H, d, J = 2.2, 8.4 Hz), 6.96-7.01 (1H, m), 7.21 (1H, dd, J = 8.1, 8.1 Hz), 8.17 (1H, br), 9.85 (1H, br). 696 CH3 OCH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.0-1.2 (2H, m), 1.3-1.4 (1H, m), 1.48 (3H, s), 1.51 (3H, s), 1.55-1.65 (1H, m), 1.65-1.85 (2H, m), 1.85-2.05 (2H, m), 2.13 (3H, s), 2.62 (1H, d, J = 12.6 Hz), 3.1-3.2 (1H, m), 3.3-3.4 (1H, m), 3.76 (3H, s), 3.8-3.9 (1H, m), 6.61 (1H, d, J = 7.9 Hz), 6.72 (1H, d, J = 8.1 Hz), 7.10 (1H, dd, J = 8.1, 8.1 Hz), 8.01 (1H, br), 9.71 (1H, br). 697 Cl CH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.24-1.47 (6H, m), 1.51 (3H, s), 1.63-1.91 (4H, m), 1.91-2.08 (1H, m), 2.20 (3H, s), 2.91 (1H, d, J = 13.5 Hz), 3.23-3.42 (1H, m), 3.66-3.80 (1H, m), 3.94-4.08 (1H, m), 6.84 (1H, dd, J = 2.6, 8.5 Hz), 6.97 (1H, d, J = 2.6 Hz), 7.16 (1H, d, J = 8.6 Hz), 8.12 (1H, br), 9.82 (1H, br). 698 F CH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.25-1.45 (6H, m), 1.51 (3H, s), 1.65-1.9 (4H, m), 2.0- 2.05 (1H, m), 2.10 (3H, s), 2.91 (1H, d, J = 13.6 Hz), 3.3-3.45 (1H, m), 3.7-3.8 (1H, m), 3.95-4.05 (1H, m), 6.67 (1H, dd, J = 2.5, 8.5 Hz), 6.74 (1H, dd, J = 2.4, 13.5 Hz), 7.08 (1H, dd, J = 8.9, 8.9 Hz), 8.0-8.3 (1H, m), 9.75-10.0 (1H, m). 699 OCHF2 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.21-1.35 (2H, m), 1.35-1.48 (4H, m), 1.53 (3H, s), 1.63-1.95 (4H, m), 1.98-2.12 (1H, m), 2.94 (1H, d, J = 13.4 Hz), 3.32 (1H, d, J = 13.3 Hz), 3.7-3.8 (1H, m), 3.9-4.05 (1H, m), 6.85-7.26 (5H, m), 8.20 (1H, br), 9.99 (1H, br). 700 OCF3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.25-1.49 (6H, m), 1.49-1.57 (3H, m), 1.65-1.95 (4H, m), 1.95-2.09 (1H, m), 2.96 (1H, d, J = 13.6 Hz), 3.39-3.48 (1H, m), 3.71-3.83 (1H, m), 3.98-4.09 (1H, m), 6.98-7.05 (2H, m), 7.16-7.24 (2H, m), 8.16 (1H, br), 9.65-10.1 (1H, m). 701 Cl CN 1H-NMR (DMSO-d6) Fumarate ppm: 1.10 (3H, s), 1.15-1.25 (4H, m), 1.25-1.45 (2H, m), 1.45-1.7 (4H, m), 1.85-2.0 (1H, m), 2.76 (1H, d, J = 12.8 Hz), 2.85-3.85 (4H, m), 3.85-3.95 (1H, m), 6.56 (1H, s), 6.94 (1H, dd, J = 2.5, 9.1 Hz), 7.09 (1H, d, J = 2.4 Hz), 7.59 (1H, d, J = 9.0 Hz). 702 F OCF3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.25-1.5 (6H, m), 1.52 (3H, s), 1.65-2.1 (5H, m), 2.97 (1H, d, J = 13.8 Hz), 3.54 (1H, d, J = 13.6 Hz), 3.65-3.8 (1H, m), 4.0-4.15 (1H, m), 6.81 (1H, dd, J = 2.2, 9.3 Hz), 7.05 (1H, dd, J = 2.9, 14.4 Hz), 7.34 (1H, dd, J = 9.0, 9.0 Hz), 8.24 (1H, br), 9.92 (1H, br). 703 F OCHF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.10-1.37 (9H, m), 1.44-1.75 (4H, m), 1.75-1.90 (1H, m), 2.68 (1H, d, J = 12.4 Hz), 3.15 (1H, d, J = 12.4 Hz), 3.25- 3.45 (1H, m), 3.7-3.8 (1H, m), 6.51 (1H, m), 6.67 (1H, d, J = 2.1, 9.1 Hz), 6.81-7.24 (3H, m) 704 Cl OCHF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.07-1.36 (9H, m), 1.43-1.58 (1H, m), 1.58-1.72 (3H, m), 1.73-1.89 (1H, m), 2.67 (1H, d, J = 12.2 Hz), 3.0-3.7 (4H, m), 3.7-3.8 (1H, m), 6.52 (1H, s), 6.82- 7.24 (4H, m). 705 CHF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.15-1.41 (9H, m), 1.48-1.92 (5H, m), 2.75 (1H, d, J = 12.7 Hz), 2.8-4.4 (6H, m), 6.46 (1H, d, J = 7.8 Hz), 6.54 (2H, s), 6.62 (1H, s), 6.76 (1H, dd, J = 2.1, 8.5 Hz), 7.0-7.4 (2H, m). 706 OCHF2 F 1H-NMR (DMSO-d6) Fumarate ppm: 0.97-1.36 (9H, m), 1.43-1.73 (4H, m), 1.73-1.87 (1H, m), 2.67 (1H, d, J = 12.1 Hz), 2.95-3.8 (5H, m), 6.52 (1H, s), 6.7-6.8 (2H, m), 7.0-7.4 (2H, m). 707 OCHF2 Cl 1H-NMR (DMSO-d6) Fumarate ppm: 1.11-1.37 (9H, m), 1.45-1.74 (4H, m), 1.77-1.91 (1H, m), 2.69 (1H, d, J = 12.3 Hz), 2.75-4.2 (5H, m), 6.52 (1H, s), 6.73-6.83 (2H, m), 7.03-7.43 (2H, m). 708 CN OCHF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.06-1.21 (7H, m), 1.21-1.36 (2H, m), 1.41-1.70 (4H, m), 1.74-1.89 (1H, m), 2.68 (1H, d, J = 12.3 Hz), 2.9-3.75 (4H, m), 3.75-3.85 (1H, m), 6.54 (1H, s), 6.99-7.14 (4H, m). 709 OCHF2 OCHF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.1-1.4 (9H, m), 1.45-1.75 (4H, m), 1.75-1.9 (1H, m), 2.69 (1H, d, J = 12.2 Hz), 2.8-4.3 (5H, m), 6.52 (1H, s), 6.71-7.38 (5H, m). 710 F OCHF2 F 1H-NMR (DMSO-d6) Fumarate ppm: 1.08-1.22 (7H, m), 1.25-1.40 (2H, m), 1.42-1.72 (4H, m), 1.76-1.92 (1H, m), 2.66 (1H, d, J = 12.5 Hz), 2.8-4.35 (5H, m), 6.53 (1H, s), 6.66-6.76 (2H, m), 7.05 (1H, t, J = 72.9 Hz). 711 OCH2CHF2 1H-NMR (DMSO-d6) 2 Hydrochloride ppm: 1.15-1.31 (2H, m), 1.32-1.49 (4H, m), 1.52 (3H, s), 1.62-1.89 (4H m), 1.98-2.08 (1H, m), 2.93 (1H, d, J = 13.1 Hz), 3.16 (1H, d, J = 13.2 Hz), 3.7-3.8 (1H, m), 3.80-4.27 (4H, m), 6.18-6.50 (1H, m), 6.90 (4H, s), 8.0-8.25 (1H, m), 9.8-10.1 (1H, m). 712 F OCH2CF2 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.20-1.46 (6H, m), 1.51 (3H, s), 1.63-1.89 (4H m), 1.92-2.08 (1H, m), 2.91 (1H, d, J = 13.4 Hz), 3.29 (1H, d, J = 12.8 Hz), 3.67- 3.79 (1H, m), 3.88- 4.01 (1H, m), 4.20- 4.33 (2H, m), 6.18- 6.52 (1H, m), 6.68 (1H, dd, J = 1.8, 9.1 Hz), 6.91 (1H, dd, J = 2.9, 14.7 Hz), 7.10 (1H, dd, J = 9.5, 9.5 Hz), 8.0-8.2 (1H, m), 9.75-9.95 (1H, m). 713 CH3 OCHCF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.06-1.16 (1H, m), 1.16-1.37 (8H, m), 1.45-1.88 (5H, m), 2.17 (3H, s), 2.69 (1H, d, J = 12.0 Hz), 3.04 (1H, d, J = 12.0 Hz), 3.1-3.9 (4H, m), 6.50 (1H, s), 6.71 (1H, dd, J = 3.0, 8.9 Hz), 6.75-7.16 (3H, m). 714 OCH3 OCHCF2 1H-NMR (DMSO-d6) Fumarate ppm: 1.08-1.18 (1H, m), 1.18-1.27 (7H, m), 1.27-1.38 (1H, m), 1.44-1.60 (1H, m), 1.60-1.74 (3H, m), 1.74-1.88 (1H, m), 2.71 (1H, d, J = 12.1 Hz), 3.08 (1H, d, J = 12.2 Hz), 3.15- 3.85 (7H, m), 6.40 (1H, dd, J = 2.7, 8.9 Hz), 6.50 (1H, s), 6.57 (1H, d, J = 2.6 Hz), 6.62-7.02 (2H, m). 715 OCHCF2 1H-NMR (DMSO-d6) ppm: 0.94-1.14 (1H, m), 1.14-1.15 (1H, m), 1.18 (3H, s), 1.26 (3H, s), 1.28- 1.43 (2H, m), 1.48 (1H, br), 1.61-1.73 (3H, m), 1.76-1.90 (1H, m), 2.49 (1H, d, J = 1 1.2 Hz), 3.05 (1H, d, J = 11.2 Hz), 3.45-3.6 (2H, m), 6.55 (1H, dd, J = 70.2, 81.4 Hz), 6.91 (1H, dd, J = 1.4, 8.0 Hz), 6.93-6.99 (1H, m), 7.07-7.18 (2H, m)

(358) TABLE-US-00074 TABLE 77 absolute configuration 0 Ex. No. R.sup.4 NMR Salt 716 1H-NMR (DMSO-d6) ppm: 1.05-1.25 (2H, m), 1.35-1.45 (1H, m), 1.47 (3H, s), 1.50 (3H, s), 1.6-2.05 (5H, m), 2.15 (3H, d, J = 0.7 Hz), 2.70 (1H, d, J = 12.8 Hz), 3.20 (1H, d, J = 12.9 Hz), 3.25-3.4 (1H, m), 3.8-3.9 (1H, m), 6.77 (1H, d, J = 3.2 Hz), 7.09 (1H, d, J = 1.0, 3.3 Hz), 7.9-8.1 (1H, m), 9.6-9.75 (1H, m). 717 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (2H, m), 1.3-1.45 (1H, m), 1.52 (3H, s), 1.56 (3H, s), 1.6-1.7 (1H, m), 1.7-2.1 (4H, m), 2.87 (1H, d, J = 12.8 Hz), 3.36 (1H, d, J = 13.1 Hz), 3.65-3.75 (1H, m), 4.1-4.2 (1H, m), 7.06 (1H, s), 7.35-7.45 (2H, m) 7.9-8.0 (2H, m), 8.0-8.15 (1H, m), 9.6-9.8 (1H, m). Hydro- chlo- ride

(359) TABLE-US-00075 TABLE 78 absolute configuration Ex. No. R.sup.4 NMR Salt 718 1H-NMR(CDCl3) ppm: 1.08-1.15 (18H, m), 1.19-1.34 (12H, m), 1.35-1.48 (2H, m), 1.64-1.85 (4H, m), 2.82 (1H, d, J = 11.6 Hz), 3.04 (1H, d, J = 11.7 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 6.95 (1H, d, J = 2.2 Hz), 7.03 (1H, dd, J = 2.5, 8.8 Hz), 7.10 (1H, d, J = 2.4 Hz), 7.23 (1H, d, J = 2.5, 9.1 Hz), 7.51 (1H, d, J = 8.8 Hz), 7.55 (1H, d, J = 9.1 Hz). 719 1H-NMR (CDCl3) ppm: 1.13 (18H, d, J = 7.3 Hz), 1.18-1.36 (12H, m), 1.36-1.65 (2H, m), 1.65-1.87 (4H, m), 2.83 (1H, d, J = 11.9 Hz), 3.12 (1H, d, J = 11.9 Hz), 3.45-3.55 (1H, m), 3.75-3.85 (1H, m), 6.82 (1H, d, J = 2.3 Hz), 6.86 (1H, dd, J = 2.4, 8.7 Hz), 7.02 (1H, d, J = 2.3 Hz), 7.10 (1H, dd, J = 2.4, 9.0 Hz), 7.53 (1H, d, J = 8.7 Hz), 7.59 (1H, d, J = 9.0 Hz). 720 1H-NMR (CDCl3) ppm: 1.04-1.12 (18H, m), 1.12-1.32 (12H, m), 1.32-1.64 (2H, m), 1.65-1.86 (4H, m), 2.82 (1H, d, J = 11.8 Hz), 3.08 (1H, d, J = 11.8 Hz), 3.47-3.53 (1H, m), 3.73-3.81 (1H, m), 3.88 (3H, s), 5.17 (1H, d, J = 11.0 Hz), 5.24 (1H, d, J = 11.0 Hz), 6.94 (1H, d, J = 2.5 Hz), 7.16 (1H, d, J = 9.0 Hz), 7.31 (1H, dd, J = 2.5, 9.4 Hz), 7.58 (1H, d, J = 9.0 Hz), 8.12 (1H, d, J = 9.4 Hz). 721 1H-NMR (CDCl3) ppm: 1.14 (18H, d, J = 6.7 Hz), 1.19-1.33 (13H, m), 1.33-1.65 (1H, m), 1.65-1.84 (4H, m), 2.83 (1H, d, J = 11.6 Hz), 3.04 (1H, d, J = 11.6 Hz), 3.5-3.6 (1H, m), 3.7-3.8 (1H, m), 3.87 (3H, s), 4.93 (2H, d, J = 0.9 Hz), 6.96 (1H, s), 6.99 (1H, d, J = 2.2 Hz), 7.21 (1H, dd, J = 2.4, 9.0 Hz), 7.59 (1H, d, J = 9.0 Hz), 7.77 (1H, s).

(360) TABLE-US-00076 TABLE 79 absolute configuration Ex. No. R.sup.4 NMR Salt 722 1H-NMR (CDCl3) ppm: 1.14-1.51 (11H, m), 1.65-1.85 (4H, m), 2.83 (1H, d, J = 11.7 Hz), 3.05 (1H, d, J = 11.8 Hz), 3.52-3.57 (1H, m), 3.69-3.79 (1H, m), 6.97 (1H, d, J = 2.3 Hz), 6.99-7.06 (2H, m), 7.22-7.28 (1H, m), 7.52-7.58 (2H, m). 723 0 1H-NMR (CDCl3) ppm: 1.18-1.36 (9H, m), 1.35-1.51 (2H, m), 1.66-1.86 (4H, m), 2.84 (1H, d, J = 11.9 Hz), 3.13 (1H, d, J = 12.0 Hz), 3.45-3.55 (1H, m), 3.75-3.85 (1H, m), 6.8-6.85 (2H, m), 6.94 (1H, d, J = 2.4 Hz), 7.10 (1H, d, J = 2.4, 9.1 Hz), 7.57 (1H, d, J = 8.7 Hz), 7.60 (1H, d, J = 9.0 Hz). 724 1H-NMR (DMSO-d6) ppm: 1.1-1.2 (1H, m), 1.2-1.4 (8H, m), 1.5-1.9 (5H, m), 2.86 (1H, d, J = 12.2 Hz), 3.20 (1H, d, J = 12.5 Hz), 3.58 (1H, br), 3.85 (3H, s), 3.9- 4.0 (1H, m), 4.85 (2H, s), 6.54 (2H, s), 7.05 (1H, d, J = 2.4 Hz), 7.28 (1H, d, J = 9.1 Hz), 7.39 (1H, dd, J = 2.5, 9.5 Hz), 7.66 (1H, d, J = 9.0H), 7.97 (1H, d, J = 9.4 Hz). Fuma- rate 725 1H-NMR (CDCl3) ppm: 0.97 (1H, br), 1.15-1.35 (8H, m), 1.35-1.5 (2H, m), 1.65- 1.85 (4H, m), 2.42 (1H, t, J = 6.5 Hz), 2.82 (1H, d, J = 11.8 Hz), 3.05 (1H, d, J = 11.7H), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.94 (3H, s), 4.79 (2H, d, J = 5.9 Hz), 6.98 (1H, d, J = 2.4 Hz), 7.02 (1H, s), 7.21-7.28 (1H, m), 7.54 (1H, s), 7.60 (1H, d, J = 9.0 Hz).

(361) TABLE-US-00077 TABLE 80 absolute configuration Ex. No. R.sup.4 NMR Salt 726 1H-NMR (DMSO-d6) ppm: 0.9-1.05 (1H, m), 1.05-1.2 (1H, m), 1.3-1.45 (1H, m), 1.52 (3H, s), 1.55-1.65 (4H, m), 1.65-1.85 (2H, m), 1.85-2.05 (2H, m), 2.73 (1H, d, J = 12.5 Hz), 3.25-3.6 (2H, m), 3.94 (3H, s), 4.15-4.3 (1H, m), 6.88 (1H, d, J = 8.2 Hz), 7.06 (1H, d, J = 8.0 Hz), 7.5-7.55 (1H, m), 7.55-7.6 (1H, m), 7.96 (1H, br), 8.16 (1H, dd, J = 1.0, 8.3 Hz), 8.24 (1H, d, J = 8.1 Hz), 9.4-9.6 (1H, m). Hydro- chloride 727 1H-NMR (DMSO-d6) ppm: 0.85-1.0 (1H, m), 1.0-1.15 (1H, m), 1.3-1.4 (1H, m), 1.5- 1.65 (7H, m), 1.65-1.85 (2H, m), 1.85-2.1 (2H, m), 2.59 (3H, s), 2.76 (1H, d, J = 12.5 Hz), 3.3-3.45 (1H, m), 3.51 (1H, d, J = 12.5 Hz), 4.15-4.3 (1H, m), 7.02 (1H, d, J = 7.5 Hz), 7.28 (1H, d, J = 7.4 Hz), 7.5-7.65 (2H, m), 7.95-8.15 (2H, m), 8.25-8.35 (1H, m), 9.6-9.8 (1H, m). Hydro- chloride 728 1H-NMR (DMSO-d6) ppm: 1.23-1.54 (6H, m), 1.58 (3H, s), 1.64-2.02 (4H, m), 2.02- 2.15 (1H, m), 3.07 (1H, d, J = 13.4 Hz), 3.50 (1H, d, J = 13.4 Hz), 3.75-3.9 (1H, m), 3.9-4.53 (2H, m), 7.18 (1H, d, J = 2.2 Hz), 7.22-7.32 (1H, m), 7.32-7.46 (2H, m), 7.65- 7.82 (3H, m), 8.26 (1H, br), 10.02 (1H, br). 2 Hydro- chloride 729 1H-NMR (CDCl3) ppm: 0.83-0.99 (1H, m), 1.021.13 (1H, m), 1.27 (3H, s), 1.32- 1.42 (2H, m), 1.46 (3H, s), 1.54-1.71 (2H, m), 1.71-1.81 (1H, m), 1.85-1.99 (1H, m), 2.69 (1H, d, J = 11.1 Hz), 3.3-3.45 (2H, m), 3.75-3.85 (1H, m), 7.15 (1H, s), 7.5-7.55 (2H, m), 7.6-7.7 (2H, m), 7.7-7.8 (1H, m), 8.3-8.4 (1H, m), 8.55-8.65 (1H, m), 8.65- 8.75 (1H, m). 730 1H-NMR (CDCl3) ppm: 0.9-1.65 (11H, m), 1.65-1.9 (4H, m), 2.84 (1H, d, J = 12.0 Hz), 3.13 (1H, d, J = 11.9 Hz), 3.50 (1H, bs), 3.75-3.85 (1H, m), 3.89 (3H, s), 6.89 (1H, dd, J = 2.5, 8.8 Hz), 6.92 (1H, d, J = 2.4 Hz), 6.97 (1H, d, J = 2.4 Hz), 7.11 (1H, dd, J = 2.5, 9.0 Hz), 7.57 (1H, d, J = 8.8 Hz), 7.60 (1H, d, J = 9.0 Hz). 731 1H-NMR (DMSO-d6) ppm: 1.3-1.5 (6H, m), 1.55 (3H, s), 1.65-2.05 (5H, m), 3.08 (1H, d, J = 13.6 Hz), 3.62 (1H, d, J = 13.6 Hz), 3.8-3.9 (1H, m), 4.2-4.3 (1H, m), 7.32 (1H, d, J = 2.1 Hz), 7.50 (1H, dd, J = 1.6, 8.4 Hz), 7.63 (1H, dd, J = 2.5, 9.2 Hz), 7.85-8.0 (2H, m), 8.11-8.2 (1H, m), 8.26 (1H, s), 9.6-9.75 (1H, m). Hydro- chloride 732 0 1H-NMR (DMSO-d6) ppm: 1.32-1.54 (6H, m), 1.57 (3H, s), 1.66-2.13 (5H, m), 3.10 (1H, d, J = 13.9 Hz), 3.72 (1H, d, J = 13.7Hz), 3.75-3.9 (1H, m), 4.25-4.35 (1H, m), 7.29 (1H, d, J = 2.2 Hz), 7.5-7.65 (2H, m), 7.81 (1H, d, J = 8.6 Hz), 7.91 (1H, d, J = 9.2 Hz), 8.15-8.45 (2H, m), 9.92 (1H, br). Hydro- chloride 733 1H-NMR (DMSO) ppm: 1.0-1.35 (9H, m), 1.4-1.6 (2H, m), 1.6-1.7 (3H, m), 1.8-1.95 (1H, m), 2.72 (1H, d, J = 12.3 Hz), 3.12 (1H, d, J = 11.1 Hz), 3.3-3.4 (1H, m), 3.8- 3.9 (1H, m), 3.92 (3H, s), 7.09 (1H, d, J = 1.8 Hz), 7.39 (1H, d, J = 9.2 Hz), 7.49 (1H, dd, J = 2.4, 9.5 Hz), 7.71 (1H, d, J = 9.0 Hz), 7.89 (1H, d, J = 9.4 Hz). 734 1H-NMR (CDCl3) ppm: 1.00 (1H, br), 1.19-1.37 (8H, m), 1.38-1.51 (2H, m), 1.67- 1.79 (3H, m), 1.79-1.93 (1H, m), 2.90 (1H, d, J = 11.8 Hz), 3.18 (1H, d, J = 11.9 Hz), 3.53 (1H, br), 3.8-3.9 (1H, m), 7.05 (1H, d, J = 2.1 Hz), 7.3-7.45 (3H, m), 7.8-7.95 (3H, m), 8.15 (1H, s), 8.25 (1H, s). 735 1H-NMR (DMSO-d6) ppm: 1.15-1.25 (1H, m), 1.25-1.4 (8H, m), 1.5-1.95 (5H, m), 2.88 (1H, d, J = 12.6 Hz), 3.31 (1H, d, J = 12.4Hz), 3.54 (1H, br), 3.95-4.05 (1H, m), 6.54 (2H, s), 7.13 (1H, d, J = 2.1 Hz), 7.34 (1H, dd, J = 2.2, 8.7 Hz), 7.44 (1H, dd, J = 2.4, 9.2 Hz), 7.67-7.76 (2H, m), 7.81 (1H, d, J = 2.1 Hz). Fumarate 736 1H-NMR (CDCl3) ppm: 1.09 (1H, br), 1.15-1.35 (8H, m), 1.35-1.5 (2H, m), 1.65- 1.85 (4H, m), 2.50 (3H, s), 2.82 (1H, d, J = 11.6 Hz), 3.07 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.90 (3H, s), 6.96 (1H, d, J = 2.5 Hz), 7.18 (1H, d, J = 9.0 Hz), 7.30 (1H, dd, J = 2.6, 9.4 Hz), 7.51 (1H, d, J = 9.0 Hz), 7.81 (1H, d, J = 9.3 Hz). 737 1H-NMR (DMSO-d6) ppm: 1.06-1.19 (1H, m), 1.19-1.39 (8H, m), 1.47-1.80 (4H, m), 1.80-1.96 (1H, m), 2.83 (1H, d, J = 12.2 Hz), 2.9-4.4 (5H, m), 6.51 (1H, s), 7.05-7.45 (4H, m), 7.49 (1H, d, J = 2.4 Hz), 7.7-7.8 (2H, m). 1/2 Fumarate 738 1H-NMR (DMSO-d6) ppm: 1.23-1.54 (6H, m), 1.60 (3H, s), 1.66-2.06 (4H, m), 2.06- 2.20 (1H, m), 3.07 (1H, d, J = 13.4 Hz), 3.45 (1H, d, J = 13.9 Hz), 3.75-3.9 (1H, m), 3.95 (3H, s), 4.1-4.2 (1H, m), 4.77 (1H, br), 7.25 (1H, d, J = 2.2 Hz), 7.46 (1H, s), 7.58 (1H, dd, J =2.4, 9.2 Hz), 7.81 (1H, d, J = 9.2 Hz), 8.23 (1H, s), 8.25-8.4 (1H, m), 10.18 (1H, br). 2 Hydro- chloride 739 1H-NMR (DMSO-d6) ppm: 1.27-1.50 (6H, m), 1.58 (3H, s), 1.65-2.13 (5H, m), 3.06 (1H, d, J = 13.6 Hz), 3.56 (1H, d, J = 13.6 Hz), 3.73-3.87 (1H, m), 4.14-4.26 (1H, m), 7.05 (1H, d, J = 1.8 Hz), 7.28-7.38 (2H, m), 7.43-7.52 (1H, m), 7.75 (1H, d, J = 8.5 Hz), 7.84 (1H, d, J = 8.2 Hz), 8.15-8.4 (1H, m), 9.9-10.1 (1H, m). Hydro- chloride 740 1H-NMR (DMSO-d6) ppm: 1.28-1.50 (6H, m), 1.57 (3H, s), 1.66-2.00 (4H, m), 2.00- 2.18 (1H, m), 3.08 (1H, d, J = 13.5 Hz), 3.56 (1H, d, J =13.5 Hz), 3.75-3.9 (1H, m), 3.95-4.1 (1H, m), 7.23 (1H, d, J = 2.0 Hz), 7.36-7.45 (1H, m), 7.45-7.54 (1H, m), 7.65 (1H, d, J = 2.4 Hz), 7.78 (1H, d, J = 8.1 Hz), 7.97 (1H, d, J = 8.4 Hz), 8.1-8.35 (1H, m), 9.8-10.1 (1H, m). Hydro- chloride 741 1H-NMR (DMSO-d6) ppm: 1.06-1.17 (1H, m), 1.17-1.39 (8H, m), 1.46-1.79 (4H, m), 1.79-1.92 (1H, m), 2.82 (1H, d, J = 12.1 Hz), 2.9-4.2 (5H, m), 4.30-4.41 (2H, m), 6.27-6.59 (2H, m), 7.06 (1H, d, J = 2.1 Hz), 7.10 (1H, dd, J = 2.6, 8.9 Hz), 7.26 (1H, d, J = 2.5 Hz), 7.36 (1H, dd, J = 2.4, 9.2 Hz), 7.60-7.68 (2H, m). 1/2 Fumarate

(362) TABLE-US-00078 TABLE 81 absolute configuration 0 Ex. No. R.sup.4 NMR Salt 742 1H-NMR (DMSO-d6) ppm: 1.0-1.15 (2H, m), 1.3-1.45 (1H, m), 1.48 (3H, s), 1.50 (3H, s), 1.55-1.65 (1H, m), 1.65-1.8 (2H, m), 1.8-2.0 (2H, m), 2.25-2.35 (1H, m), 2.4-2.5 (1H, m), 2.6-2.75 (2H, m), 2.95-3.1 (2H, m), 3.21 (3H, s), 3.3-3.5 (1H, m), 3.78 (3H, s), 3.85-3.95 (1H, m), 6.78 (1H, d, J = 8.9 Hz), 6.93 (1H, d, J = 8.9 Hz), 7.97 (1H, br), 9.59 (1H, br). Hydro- chloride 743 1H-NMR (DMSO-d6) ppm: 1.08-1.37 (9H, m), 1.42 (6H, s), 1.48-1.83 (5H, m), 2.74 (1H, d, J = 12.2 Hz), 2.94 (1H, d, J = 12.3 Hz), 3.51 (1H, br), 3.6-3.75 (1H, m), 4.73 (2H, s), 6.53 (2H, s), 6.57 (1H, d, J = 2.6 Hz), 6.65 (1H, d, J = 8.9 Hz), 6.75 (1H, dd, J = 2.8, 9.0 Hz). Fumarate

(363) TABLE-US-00079 TABLE 82 absolute configuration Ex. No. R.sup.4 NMR Salt 744 1H-NMR (CDCl3) ppm: 0.94-1.09 (3H, m), 1.20 (3H, s), 1.34 (3H, s), 1.36-1.44 (2H, m), 1.45-1.79 (3H, m), 1.81-1.94 (1H, m), 2.55-2.65 (4H, m), 3.15 (1H, d, J = 11.2 Hz), 3.4-3.5 (1H, m), 3.65-3.7 (1H, m), 6.74 (1H, dd, J = 0.6, 7.6 Hz), 7.05 (1H, s), 7.13 (1H, dd, J = 7.8, 7.8 Hz), 7.38 (1H, d, J = 8.0 Hz). 745 1H-NMR (DMSO-d6) ppm: 1.1-1.2 (1H, m), 1.2-1.4 (8H, m), 1.45-1.75 (4H, m), 1.75-1.9 (1H, m), 2.47 (3H, d, J = 1.2 Hz), 2.6-2.7 (6H, m), 6.49 (1H, s), 6.90 (1H, s), 6.99 (1H, dd, J = 2.3, 8.8 Hz), 7.25 (1H, d, J = 2.1 Hz), 7.48 (1H, d, J = 8.8 Hz). 1/2 Fumarate 746 1H-NMR (DMSO-d6) ppm: 1.1-1.4 (9H, m), 1.5-1.95 (5H, m), 2.31 (3H, d, J = 1.2 Hz), 2.6-5.0 (7H, m), 6.52 (2H, s), 7.01 (1H, d, J = 1.2 Hz), 7.11 (1H, dd, J = 2.3, 8.9 Hz), 7.34 (1H, d, J = 2.2 Hz), 7.55 (1H, d, J = 8.8 Hz). 1/2 Fumarate 747 1H-NMR (DMSO-d6) ppm: 0.93-1.10 (2H, m), 1.28-1.42 (1H, m), 1.51-1.66 (7H, m), 1.70-2.00 (3H, m), 2.00-2.18 (1H, m), 2.69 (3H, s), 2.80 (1H, d, J = 12.5 Hz), 3.2-3.3 (1H, m), 3.48 (1H, d, J = 12.6 Hz), 3.85-3.95 (1H, m), 7.02 (1H, d, J = 7.5 Hz), 7.26 (1H, d, J = 7.8, 7.8 Hz), 7.36 (1H, d, J = 0.6 Hz), 7.69 (1H, d, J = 7.6 Hz), 7.95-8.15 (1H, m), 9.95-10.1 (1H, m). Hydrochloride 748 1H-NMR (CDCl3) ppm: 0.92-1.08 (3H, m), 1.20 (3H, s), 1.32-1.43 (5H, m), 1.45- 1.78 (3H, m), 1.81-1.94 (1H, m), 2.57 (1H, d, J = 11.1 Hz), 3.14 (1H, d, J = 11.1 Hz), 3.33-3.41 (1H, m), 3.63-3.70 (1H, m), 6.71 (1H, dd, J = 4.1, 8.4 Hz), 6.92 (1H, dd, J = 8.9, 8.9 Hz), 7.41 (1H, d, J = 5.4 Hz), 7.46 (1H, dd, J = 3.7, 5.4 Hz). 749 1H-NMR (CDCl3) ppm: 0.92-1.08 (3H, m), 1.20 (3H, s), 1.29-1.42 (5H, m), 1.45- 1.78 (3H, m), 1.82-1.96 (1H, m), 2.61 (1H, d, J = 11.2 Hz), 3.15 (1H, d, J = 11.1 Hz), 3.42-3.50 (1H, m), 3.64-3.71 (1H, m), 6.74 (1H, d, J = 8.2 Hz), 7.21 (1H, d, J = 8.2 Hz), 7.43 (1H, d, J = 5.5 Hz), 7.47 (1H, d, J = 5.5 Hz). 750 0 1H-NMR (CDCl3) ppm: 0.9-1.1 (2H, m), 1.20 (3H, s), 1.3-1.45 (5H, m), 1.45-1.8 (4H, m), 1.8-1.95 (1H, m), 2.56 (1H, d, J = 11.1 Hz), 3.14 (1H, d, J = 11.1 Hz), 3.3-3.4 (1H, m), 3.6-3.7 (1H, m), 3.96 (3H, s), 6.66 (1H, d, J = 8.2 Hz), 6.74 (1H, d, J = 8.2 Hz), 7.39 (1H, d, J = 5.4 Hz), 7.45 (1H, d, J = 5.4 Hz). 751 1H-NMR (CDCl3) ppm: 0.95-1.1 (2H, m), 1.22 (3H, s), 1.3-1.45 (5H, m), 1.45-1.85 (4H, m), 1.85-2.0 (1H, m), 2.65 (1H, d, J = 11.2 Hz), 3.17 (1H, d, J = 11.2 Hz), 3.45-3.55 (1H, m), 3.7-3.8 (1H, m), 3.96 (3H, s), 6.77-6.82 (1H, m), 7.33 (1H, dd, J = 7.9, 7.9 Hz), 7.45 (1H, d, J = 8.1 Hz), 8.14 (1H, d, J = 0.5 Hz). 752 1H-NMR (CDCl3) ppm: 0.93 (1H, br), 1.16-1.33 (8H, m), 1.33-1.49 (2H, m), 1.64- 1.85 (4H, m), 2.80 (1H, d, J = 11.6 Hz), 2.97 (1H, d, J = 11.7 Hz), 3.48 (1H, br), 3.6-3.7 (1H, m), 7.04 (1H, d, J = 2.1 Hz), 7.10 (1H, d, J = 2.2 Hz), 7.20 (1H, d, J = 5.4 Hz), 7.41 (1H, d, J = 5.5 Hz). 753 1H-NMR (DMSO-d6) ppm: 0.94-1.14 (2H, m), 1.29-1.44 (1H, m), 1.51 (3H, s), 1.53 (3H, s), 1.58-2.07 (5H, m), 2.84 (1H, d, J = 12.9 Hz), 3.41(1H, d, J = 13.0 Hz), 3.6-3.7 (1H, m), 4.15-4.25 (1H, m), 7.11 (1H, dd, J = 6.5, 12.6 Hz), 7.77 (1H, dd, J = 3.8, 5.4 Hz), 7.84 (1H, d, J = 5.4 Hz), 8.04 (1H, br), 9.81 (1H, br). Hydrochloride 754 1H-NMR (DMSO-d6) ppm: 1.38-1.57 (5H, m), 1.64 (3H, s), 1.70-2.02 (4H, m), 2.03- 2.14 (1H, m), 2.37-2.54 (1H, m), 3.2-3.5 (2H, m), 3.55 (1H, d, J = 15.0 Hz), 3.9-4.0 (1H, m), 4.23 (1H, d, J = 15.3 Hz), 4.6-4.75 (1H, m), 7.27 (1H, d, J = 7.2 Hz), 7.67 (1H, d, J = 5.7 Hz), 8.45-8.6 (2H, m), 8.88 (1H, br), 10.33 (1H, m), 14.95 (1H, br). 2 Hydrochloride 755 1H-NMR (DMSO-d6) ppm: 1.0-1.19 (2H, m), 1.31-1.46 (1H, m), 1.51 (3H, s), 1.52 (3H, s), 1.60-1.89 (3H, m), 1.93-2.08 (2H, m), 3.00 (1H, d, J = 12.9 Hz), 3.46 (1H, d, J = 13.0 Hz), 3.90-4.01 (1H, m), 3.95-4.08 (1H, m), 6.96 (1H, dd, J = 2.1, 11.0 Hz), 7.41 (1H, dd, J = 2.2, 9.1 Hz), 7.46 (1H, d, J = 5.4 Hz), 7.86 (1H, d, J = 5.4 Hz), 8.16 (1H, br), 9.78 (1H, br). Hydrochloride

(364) TABLE-US-00080 TABLE 83 absolute configuration Ex. No. R.sup.4 NMR Salt 756 1H-NMR (CDCl3) ppm: 1.02-1.17 (3H, m), 1.20 (3H, s), 1.31 (3H, s), 1.34-1.46 (2H, m), 1.47-1.79 (3H, m), 1.81-1.95 (1H, m), 2.45 (3H, d, J = 1.0 Hz), 2.80 (1H, d, J = 11.5 Hz), 3.05 (1H, d, J = 11.5 Hz), 3.55-3.65 (2H, m), 6.39 (1H, dd, J = 1.0, 1.0 Hz), 6.56 (1H, dd, J = 0.8, 7.7 Hz), 6.95-7.05 (1H, m), 7.06 (1H, dd, J = 7.9, 7.9 Hz). 757 1H-NMR (DMSO-d6) ppm: 1.17-1.37 (2H, m), 1.37-1.52 (4H, m), 1.56 (3H, s), 1.61- 1.73 (1H, m), 1.73-1.99 (3H, m), 2.00-2.15 (1H, m), 2.37 (3H, d, J = 0.9 Hz), 3.00 (1H, d, J = 13.3 Hz), 3.28 (1H, d, J = 13.2 Hz), 3.7-3.85 (1H, m), 3.95-4.1 (1H, m), 4.92 (1H, br), 6.40 (1H, d, J = 0.8 Hz), 6.89 (1H, dd, J = 2.1, 8.6 Hz), 7.05 (1H, d, J = 1.5 Hz), 7.33 (1H, d, J = 8.5 Hz), 8.15-8.35 (1H, m), 10.0-10.2 (1H, m). 2 Hydrochloride 758 1H-NMR (DMSO-d6) ppm: 1.01-1.19 (2H, m), 1.33-1.44 (1H, m), 1.48 (3H, s), 1.51 (3H, s), 1.59-2.07 (5H, m), 3.01 (1H, d, J = 13.0 Hz), 3.28 (1H, d, J = 13.1 Hz), 3.75-3.9 (1H, m), 4.0-4.15 (1H, m), 6.83 (1H, dd, J = 5.9, 13.5 Hz), 7.36 (1H, dd, J = 2.6, 2.6 Hz), 8.0-8.2 (2H, m), 9.7-9.9 (1H, m). Hydrochloride 759 0 1H-NMR (DMSO-d6) ppm: 1.0-1.2 (2H, m), 1.34-1.44 (1H, m), 1.50 (3H, s), 1.53 (3H, s), 1.60-2.06 (5H, m), 3.05 (1H, d, J = 12.8 Hz), 3.27 (1H, d, J = 13.0 Hz), 3.84 (3H, s), 3.88-4.00 (2H, m), 6.66 (1H, d, J = 8.5 Hz), 6.75 (1H, d, J = 8.5 Hz), 6.93 (1H, J = 2.2 Hz), 7.92 (1H, d, J = 2.2 Hz), 8.0- 8.25 (1H, m), 9.55-9.8 (1H, m). Hydrochloride 760 1H-NMR (CDC13) ppm: 0.99-1.27 (5H, m), 1.28 (3H, s), 1.33-1.47 (2H, m), 1.48- 1.84 (5H, m), 2.77-2.90 (2H, m), 3.45-3.55 (1H, m), 3.55-3.65 (1H, m), 4.01 (3H, s), 6.51 (1H, d, J = 2.0 Hz), 6.58 (1H, d, J = 2.1 Hz), 6.63 (1H, d, J = 2.1 Hz), 7.53 (1H, d, J = 2.0 Hz). 761 1H-NMR (DMSO-d6) ppm: 1.05-1.25 (2H, m), 1.35-1.45 (1H, m), 1.48 (3H, s), 1.52 (3H, s), 1.6-2.05 (5H, m), 3.13 (1H, d, J = 13.2 Hz), 3.28 (1H, d, J = 13.5 Hz), 3.9-4.0 (1H, m), 4.0-4.1 (1H, m), 6.63 (1H, dd, J = 2.1, 12.3 Hz), 7.09 (1H, dd, J = 1.3, 8.7 Hz), 7.22 (1H, dd, J = 0.7, 2.2 Hz), 7.96 (1H, d, J = 2.3 Hz), 8.0-8.2 (1H, m), 9.6-9.9 (1H, m). Hydrochloride 762 1H-NMR (DMSO-d6) ppm: 1.16-1.34 (2H, m), 1.35-1.45 (1H, m), 1.47 (3H, s), 1.54 (3H, s), 1.66-1.89 (3H, m), 1.92-2.11 (2H, m), 3.25 (1H, d, J = 13.6 Hz), 3.45 (1H, d, J = 13.4 Hz), 3.83-4.02 (1H, m), 4.20-4.38 (1H, m), 6.68 (1H, dd, J = 2.0, 12.2 Hz), 6.87-7.05 (2H, m), 8.02 (1H, d, J = 2.1 Hz), 8.24 (1H, br), 9.7-10.0 (1H, m). Hydrochloride 763 1H-NMR (DMSO-d6) ppm: 1.27-1.47 (6H, m), 1.53 (3H, s), 1.61-1.96 (4H, m), 1.97- 2.09 (1H, m), 3.00 (1H, d, J = 13.6 Hz), 3.45 (1H, d, J = 13.5 Hz), 3.71-3.81 (1H, m), 4.05-4.15 (1H, m), 6.81-6.93 (2H, m), 6.98- 7.04 (1H, m), 7.83 (1H, d, J = 2.2 Hz), 8.1- 8.3 (1H, m), 9.8-10.0 (1H, m). Hydrochloride 764 1H-NMR (DMSO-d6) ppm: 1.18-1.48 (6H, m), 1.53 (3H, s), 1.62-1.93 (4H, m), 1.95- 2.13 (1H, m), 3.00 (1H, d, J = 13.3 Hz), 3.30 (1H, d, J = 13.2 Hz), 3.7-3.85 (1H, m), 3.95- 4.1 (1H, m), 4.83 (1H, br), 6.91 (1H, dd, J = 2.2, 3.0 Hz), 6.94 (1H, d, J 2.1 Hz), 7.01 (1H, dd, J = 2.1, 14.2 Hz), 7.99 (1H, d, J = 2.1 Hz), 8.12 (1H, br), 9.86 (1H, br). 2 Hydrochloride 765 1H-NMR (DMSO-d6) ppm: 1.21-1.37 (2H, m), 1.37-1.47 (4H, m), 1.52 (3H, s), 1.62- 1.90 (4H, m), 1.95-2.08 (1H, m), 3.02 (1H, d, J = 13.2 Hz), 3.29 (1H, d, J = 13.2 Hz)' 3.75-3.9 (1H, m), 3.95-4.1 (1H, m), 6.92 (1H, d, J = 2.2 Hz), 7.12 (1H, d, J = 2.2 Hz), 7.16 (1H, d, J = 2.2 Hz), 8.01 (1H, d, J = 2.1 Hz), 8.06 (1H, br), 9.74 (1H, br). Hydrochloride 766 1H-NMR (DMSO-d6) ppm: 1.19-1.36 (2H, m), 1.38-1.48 (4H, m), 1.52 (3H, s), 1.62- 1.89 (4H, m), 1.93-2.06 (1H, m), 3.03 (1H, d, J = 13.3 Hz), 3.25-3.4 (1H, m), 3.75-3.9 (1H, m), 4.0-4.1 (1H, m), 7.22 (1H, d, J = 2.4 Hz), 7.37 (1H, dd, J = 2.5, 9.3 Hz), 7.62 (1H, d, J = 9.2 Hz), 7.95 (1H, d, J = 0.7 Hz), 8.06 (1H, br), 9.64 (1H, br). Hydrochloride 767 1H-NMR (DMSO-d6) ppm: 1.15-1.29 (8H, m), 1.29-1.40 (2H, m), 1.48-1.80 (4H, m), 1.80-1.96 (1H, m), 2.83 (1H, d, J = 12.8 Hz), 2.9-3.85 (4H, m), 3.9-4.0 (1H, m), 6.55 (2H, s), 7.09 (1H, s), 7.13 (1H, dd, J = 2.1, 8.9 Hz), 7.56 (1H, d, J = 8.9 Hz), 7.89 (1H, d, J = 0.6 Hz). Fumarate 768 1H-NMR (DMSO-d6) ppm: 0.85-1.1 (2H, m), 1.2-1.35 (7H, m), 1.4-1.8 (4H, m), 1.85-2.05 (1H, m) 2.78 (1H, d, J = 11.8 Hz), 2.85-4.5 (5H, m), 6.5 (1H, s), 6.58 (1H, d, J = 8.6 Hz), 7.0-7.4 (3H, m), 7.99 (1H, d, J = 2.2 Hz). 1/2 Fumarate

(365) TABLE-US-00081 TABLE 84 absolute configuration 0 Ex. No. R.sup.4 NMR Salt 769 H-NMR (CDCl3) ppm: 1.11-1.18 (20H, m), 1.22 (3H, s), 1.26-1.36 (4H, m), 1.37- 1.49 (2H, m), 1.64-1.87 (7H, m), 2.82 (1H, d, J = 11.8 Hz), 3.02 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.6-3.7 (1H, m), 6.82 (1H, s), 6.86 (1H, dd, J = 2.0, 8.9 Hz), 7.54 (1H, d, J = 8.8 Hz), 8.04 (1H, d, J = 0.8 Hz). 770 1H-NMR (CDCl3) ppm: 1.11-1.19 (19H, m), 1.21 (3H, s), 1.23-1.31 (2H, m), 1.35 (3H, s), 1.37-1.46 (2H, m), 1.62-1.85 (6H, m), 1.95-2.04 (1H, m), 3.03 (1H, d, J = 11.9 Hz), 3.09 (1H, d, J = 12.0 Hz), 3.55- 3.65 (1H, m), 3.8-3.9 (1H, m), 6.41 (1H, d, J = 7.5 Hz), 7.05 (1H, d, J = 8.4 Hz), 7.16 (1H, dd, J = 7.6, 8.3 Hz), 8.26 (1H, d, J = 0.8 Hz). 771 1H-NMR (CDCl3) ppm: 1.17-1.23 (21H, m), 1.25-1.33 (5H, m), 1.33-1.50 (3H, m), 1.62-1.90 (4H, m), 1.93-2.05 (3H, m), 2.82 (1H, d, J = 11.8 Hz), 3.00 (1H, d, J = 11.8 Hz), 3.45-3.50 (1H, m), 3.55-3.65 (1H, m), 6.88-6.95 (2H, m), 7.28 (1H, s), 7.41- 7.48 (1H, m). 772 1H-NMR (CDCl3) ppm: 0.93-1.17 (21H, m), 1.19 (3H, s), 1.23-1.44 (5H, m), 1.58- 1.78 (6H, m), 1.78-1.93 (1H, m), 2.67 (1H, d, J = 11.2 Hz), 3.09 (1H, d, J = 11.2 Hz), 3.5- 3.6 (1H, m), 3.6-3.7 (1H, m), 6.39 (1H, dd, J = 3.4, 8.3 Hz), 6.65 (1H, dd, J = 3.2, 3.2 Hz), 6.72 (1H, d, J = 8.2, 12.7 Hz), 7.25 (1H, d, J = 3.2 Hz). 773 1H-NMR (CDCl3) ppm: 1.12-1.29 (27H, m), 1.30-1.48 (2H, m), 1.62-1.82 (4H, m), 1.93-2.07 (3H, m), 2.78 (1H, d, J = 11.6 Hz), 2.93 (1H, d, J = 11.6 Hz), 3.45-3.55 (1H, m), 3.6-3.7 (1H, m), 6.92 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 2.5, 9.4 Hz), 7.24 (1H, s), 7.46 (1H ,d, J = 9.4 Hz). 774 1H-NMR (CDCl3) ppm: 1.09-1.16 (19H, m), 1.20 (3H, s), 1.23-1.32 (5H, m), 1.33- 1.48 (2H, m), 1.61-1.90 (7H, m), 2.81-2.91 (2H, m), 3.49-3.55 (1H, m), 3.55-3.63 (1H, m), 6.40 (1H, d, J = 3.4 Hz), 7.21 (1H, d, J = 3.4 Hz), 7.31 (1H, d, J = 2.8 Hz), 8.06 (1H, d, J = 2.7 Hz). 775 1H-NMR (CDCl3) ppm: 1.07-1.17 (19H, m), 1.21 (3H, s), 1.23-1.35 (5H, m), 1.37- 1.49 (2H, m), 1.63-1.90 (6H, m), 1.96-2.09 (1H, m), 3.05 (1H, d, J = 12.6 Hz), 3.38 (1H, d, J = 12.5 Hz), 3.48-3.54 (1H, m), 3.94-4.02 (1H, m), 6.33 (1H, d, J = 5.6 Hz), 6.54 (1H, d, J = 3.6 Hz), 7.10 (1H, d, J = 3.6 Hz), 7.98 (1H, d, J = 5.5 Hz). 776 1H-NMR (CDCl3) ppm: 1.1-1.18 (19H, m), 1.18-1.22 (4H, m), 1.34 (3H, s), 1.36- 1.44 (2H, m), 1.61-1.84 (7H, m), 1.86-1.98 (1H, m), 2.81 (1H, d, J = 11.4 Hz), 3.07 (1H, d, J = 11.4 Hz), 3.6-3.65 (1H, m), 3.65- 3.75 (1H, m), 6.30 (1H, dd, J = 3.0, 8.2 Hz), 6.86 (1H, dd, J = 8.2, 12.0 Hz), 8.24 (1H, d, J = 3.1 Hz).

(366) TABLE-US-00082 TABLE 85 absolute configuration Ex. No. R.sup.4 NMR Salt 777 00 1H-NMR (CDCl3) ppm: 1.07 ( 1H, br), 1.16-1.33 (8H, m), 1.35-1.50 (2H, m), 1.64- 1.88 (4H, m), 2.81 (1H, d, J = 11.8 Hz), 3.05 (1H, d, J = 11.8 Hz), 3.46-3.53 (1H, m), 3.68-3.79 (1H, m), 6.71 (1H, s), 6.92 (1H, d, J = 2.0, 9.0 Hz), 7.5-7.6 (1H, m), 7.89 (1H, d, J = 0.9 Hz), 9.7 (1H, br). 778 01 1H-NMR (CDCl3) ppm: 0.94-1.24 ( 6H, m), 1.33 (3H, s), 1.37-1.47 (2H, m), 1.63- 1.80 (3H, m), 1.88-2.02 (1H, m), 3.02 (1H, d, J = 11.8 Hz), 3.09 (1H, d, J = 11.9 Hz), 3.62-3.68 (1H, m), 3.83-3.92 (1H, m), 6.43 (1H, d, J = 7.6 Hz), 6.97 (1H, d, J = 8.3 Hz), 7.23 (1H, dd, J = 7.7, 8.1 Hz), 8.10 (1H, d, J = 0.9 Hz), 9.96 (1H, br). 779 02 1H-NMR (CDCl3) ppm: 0.95 (1H, br), 1.15-1.35 (8H, m), 1.35-1.52 (2H, m), 1.52- 1.90 (4H, m), 2.81 (1H, d, J = 11.9 Hz), 3.03 (1H, d, J = 11.8 Hz), 3.45-3.55 (1H, m), 3.65-3.8 (1H, m), 6.66 (1H, s), 6.95 (1H, dd, J = 2.1, 9.0 Hz), 7.06 (1H, dd, J = 0.8, 2.0 Hz), 7.46 (1H, d, J = 9.0 Hz), 8.23 (1H, bs). 780 03 1H-NMR (CDCl3) ppm: 0.95-1.11 (3H, m), 1.20 (3H, s), 1.28-1.44 (5H, m), 1.59- 1.79 (3H, m), 1.79-1.93 (1H, m), 2.70 (1H, d, J = 11.3 Hz), 3.08 (1H, d, J = 11.3 Hz), 3.6- 3.7 (2H, m), 6.35 (1H, dd, J = 3.8, 8.3 Hz), 6.61 (1H, dd, J = 3.2, 5.6 Hz), 6.76 (1H, dd, J = 8.3, 10.7 Hz ), 7.17 (1H, dd, J = 2.8, 2.8 Hz), 8.39 (1H, br). 781 04 1H-NMR (CDCl3) ppm: 1.01 ( 1H, br), 1.10-1.26 (5H, m), 1.28 (3H, s), 1.31-1.48 (2H, m), 1.61-1.83 (4H, m), 2.81 (1H, d, J = 11.5 Hz), 2.89 (1H, d, J = 11.5 Hz), 3.5-3.6 (1H, m), 3.6-3.7 (1H, m), 6.95 (1H, d, J = 2.1 Hz), 7.04 (1H, dd, J = 0.8, 2.0 Hz), 7.17 (1H, dd, J = 2.3, 9.1 Hz), 7.28 (1H, d, J = 9.1 Hz), 8.68 (1H, br). 782 05 1H-NMR (DMSO-d6) ppm: 1.00-1.37 (9H, m), 1.47-1.9 (5H, m), 2.90 (2H, s), 2.95- 4.35 (4H, m), 6.27 (1H, dd, J = 1.9, 3.3 Hz), 6.49 (1H, s), 7.34 (1H, dd, J = 2.9, 2.9 Hz), 7.40 (1H, d, J = 2.5 Hz), 8.04 (1H, d, J = 2.6 Hz), 11.30 (1H, s). 1/2 Fumarate 783 06 1H-NMR (CDCl3) ppm: 0.81-1.37 (8H, m), 1.37-1.51 (3H, m), 1.65-1.83 (3H, m), 1.98-2.13 (1H, m), 3.09 (1H, d, J = 12.6 Hz), 3.4-3.5 (1H, m), 3.5-3.55 (1H, m), 4.0-4.1 (1H, m), 6.36 (1H, d, J = 5.7 Hz), 6.50 (1H, d, J = 3.6 Hz), 7.1-7.2 (1H, m), 8.0-8.1 (1H, m), 9.7-10.6 (1H, m). 784 07 1H-NMR (CDCl3) ppm: 1.02-1.17 (2H, m), 1.22 (3H, s), 1.34 (3H, s), 1.36-1.45 (2H, m), 1.62-1.80 (3H, m), 1.83-1.96 (1H, m), 2.84 (1H, d, J = 11.5 Hz), 3.05 (1H, d, J = 11.5 Hz), 3.65-3.7 (1H, m), 3.7-3.8 (1H, m), 6.28 (1H, dd, J = 3.3, 8.3 Hz), 6.91 (1H, dd, J = 8.2, 10.4 Hz), 8.12 (1H, d, J = 3.4 Hz), 10.38 (1H, br).

(367) TABLE-US-00083 TABLE 86 absolute configuration 08 Ex. No. R.sup.4 NMR Salt 785 09 1H-NMR (CDCl3) ppm: 1.15-1.32 (9H, m), 1.33-1.50 (2H, m), 1.64-1.88 (4H, m), 2.82 (1H, d, J = 11.7Hz), 3.03 (1H, d, J = 11.7 Hz), 3.46-3.54 (1H, m), 3.71-3.79 (1H, m), 3.80 (3H, s), 6.51 (1H, d, J = 1.7 Hz), 6.96 (1H, dd, J = 2.1, 9.0 Hz), 7.02 (1H, s), 7.46 (1H, d, J = 9.0 Hz). 786 0 1H-NMR (DMSO-d6 ) ppm: 1.0-1.25 (2H, m), 1.25-1.4 (7H, m), 1.45-1.9 (5H, m), 2.94 (2H, s), 3.36 (3H, br), 3.66 (1H, br), 3.7-3.8 (4H, m), 6.29 (1H, d, J = 3.3 Hz), 6.54 (2H, s), 7.39 (1H, d, J = 3.3 Hz), 7.43 (1H, d, J = 2.2 Hz), 8.10 (1H, d, J = 2. 5Hz). Fumarate 787 1H-NMR (DMSO-d6 ) ppm: 1.15-1.4 (9H, m), 1.5-1.8 (4H, m), 2.0-2.15 (1H, m), 3.09 (1H, d, J = 12.9 Hz), 3.43 (1H, d, J = 12.4 Hz), 3.55-3.65 (1H, m), 3.73 (3H, s), 4.05-4.15 (1H, m), 6.41 (1H, d, J = 5.6 Hz), 6.49 (1H, d, J = 3.6 Hz), 6.55 (2H, s), 7.26 (1H, d, J = 3.6 Hz), 7.93 (1H, d, J = 5.6 Hz). Fumarate 788 1H-NMR (DMSO-d6 ) ppm: 0.97-1.13 (2H, m), 1.33-1.44 (1H, m), 1.51 (3H, s), 1.53 (3H, s), 1.58-1.67 (1H, m), 1.67-1.96 (3H, m), 1.96-2.07 (1H, m), 3.00 (1H, d, J = 12.9 Hz), 3.26 (1H, d, J = 13.0 Hz), 3.85-4.0 (1H, m), 4.05-4.2 ( 4H, m), 6.40 (1H, dd, J = 3.0, 8.3 Hz), 7.05 (1H, dd, J = 8.2, 11.8 Hz), 8.0-8.2 (1H, m), 8.38 (1H, d, J = 2.3 Hz), 9.65-9.9 (1H, m). Hydrochloride 789 1H-NMR (DMSO-d6 ) ppm: 1.00-1.16 (2H, m), 1.34-1.44 (1H, m), 1.50 (3H, s), 1.53 (3H, s), 1.58-1.96 (4H, m), 1.98-2.09 (1H, m), 2.98 (1H, d, J = 12.9 Hz), 3.24 (1H, d, J = 13.0 Hz), 3.85-3.95 (1H, m), 3.95-4.08 (1H, m), 4.17 (3H, s), 6.24 (1H, dd, J = 3.2, 8.0 Hz), 6.85 (1H, dd, J = 8.0, 11.5 Hz), 7.95-8.2 (1H, m), 8.74 (1H, d, J = 2.8 Hz), 9.7-10.0 (1H, m). Hydrochloride

(368) TABLE-US-00084 TABLE 87 absolute configuration Ex. No. R.sup.4 NMR Salt 790 1H-NMR (DMSO-d6) ppm: 1.01-1.25 (2H, m), 1.32-1.42 (1H, m), 1.46 (3H, s), 1.48 (3H, s), 1.58-2.03 (6H, m), 2.05-2.18 (1H, m), 2.70-2.93 (5H, m), 3.24 (1H, d, J = 12.9 Hz), 3.45-3.57 (1H, m), 3.81-3.93 (1H, m), 6.53 (1H, d, J = 11.4 Hz), 6.70 (1H, d, J = 8.4 Hz), 8.02 (1H, br), 9.72 (1H, br). Hydrochloride 791 1H-NMR (DMSO-d6) ppm: 0.90-1.21 (2H, m), 1.28-1.41 (1H, m), 1.48 (6H, s), 1.57- 1.67 (1H, m), 1.67-2.06 (5H, m), 2.08-2.21 (1H, m), 2.70 (1H, d, J = 12.4 Hz), 2.78-3.00 (4H, m), 3.22-3.42 (2H, m), 3.77-3.92 (1H, m), 6.74 (1H, dd, J = 4.3, 8.6 Hz), 6.88 (1H, dd, J = 8.6, 8.6 Hz), 8.01 (1H, br), 9.73 (1H, br). Hydrochloride 792 1H-NMR (CDCl3) ppm: 0.75-1.15 (3H, m), 1.17 (3H, s), 1.27 (3H, s), 1.3-1.45 (2H, m), 1.45-1.75 (3H, m), 1.75-1.95 (1H, m), 1.95-2.1 (1H, m), 2.1-2.25 (1H, m), 2.52 (1H, d, J = 11.2 Hz), 2.85-3.05 (5H, m), 3.1-3.2 (1H, m), 3.45-3.55 (1H, m), 6.58 (1H, d, J = 8.4 Hz), 7.03 (1H, d, J = 8.4 Hz). 793 1H-NMR (DMSO-d6) ppm: 1.11-1.24 (1H, m), 1.34-1.42 (1H, m), 1.45 (3H, s), 1.47 (3H, s), 1.59-2.03 (6H, m), 2.05-2.17 (1H, m), 2.7-2.95 (5H, m), 3.27 (1H, d, J = 12.9 Hz), 3.38-3.55 (1H, m), 3.79-3.95 (1H, m), 4.28-4.11 (1H, m), 6.72 (1H, d, J = 1.5 Hz), 6.94 (1H, s), 7.9-8.1 (1H, m), 9.6- Hydrochloride 9.8 (1H, m). 794 1H-NMR (DMSO-d6) ppm: 1.20-1.48 (6H, m), 1.52 (3H, s), 1.62-1.93 (4H, m), 1.96- 2.12 (1H, m), 2.97 (1H, d, J = 13.4 Hz), 3.29 (1H, d, J = 13.4 Hz), 3.7-3.85 (1H, m), 3.9- 4.05 (1H, m), 6.70 (1H, dd, J = 2.4, 8.9 Hz), Hydrochloride 7.12 (1H, d, J = 2.4 Hz), 7.23 (1H, d, J = 8.9 Hz), 8.18 (1H, br), 9.94 (1H, br). 795 0 1H-NMR (DMSO-d6) ppm: 1.1-1.25 (9H, m), 1.25-1.35 (1H, m), 1.45-1.75 (4H, m), 1.9-2.05 (1H, m), 2.94 (1H, d, J = 12.2 Hz), 3.07 (1H, d, J = 12.3 Hz), 3.11-3.62 (3H, m), 3.63-3.71 (1H, m), 6.57 (2H, s), 6.72 (1H, d, J = 8.0 Hz), 6.75-6.81 (1H, m), 7.04 (1H, dd, J = 8.3, 8.3 Hz). Fumarate 796 1H-NMR (CDCl3) ppm: 0.65-1.3 (9H, m), 1.3-1.95 (6H, m), 2.69 (1H, d, J = 11.5 Hz), 2.79 (1H, d, J = 11.6 Hz), 3.4-3.55 (2H, m), 5.84-5.90 (2H, m), 6.25 (1H, dd, J = 11.6 Hz), 6.51 (1H, d, J = 2.4 Hz), 6.69 (1H, d, J = 8.5 Hz).

(369) TABLE-US-00085 TABLE 88 absolute configuration Ex. No. R.sup.4 NMR Salt 797 1H-NMR (CDCl3) ppm: 1.01-1.13 (19H, m), 1.14-1.28 (11H, m), 1.31-1.46 (2H, m), 1.60-1.76 (4H, m), 2.67 (1H, d, J = 11.6 Hz), 2.83 (1H, d, J = 11.5 Hz), 3.4-3.55 (2H, m), 6.69-6.74 (2H, m), 6.74-6.80 (2H, m). 798 1H-NMR (CDCl3) ppm: 1.07-1.16 (19H, m), 1.16-1.33 (11H, m), 1.33-1.47 (2H, m), 1.62-1.80 (4H, m), 2.68 (1H, d, J = 12.0 Hz), 2.97 (1H, d, J = 11.9 Hz), 3.4-3.45 (1H, m), 3.55-3.6 (1H, m), 6.25-6.35 (1H, m), 6.37 (1H, dd, J = 2.4, 7.8 Hz), 6.43 (1H, dd, J = 1.9, 8.3 Hz), 7.03 (1H, dd, J = 8.1, 8.1 Hz). 799 1H-NMR (CDCl3) ppm: 1.07-1.14 (19H, m), 1.14-1.29 (11H, m), 1.29-1.47 (2H, m), 1.59-1.77 (4H, m), 2.70 (1H, d, J = 11.7 Hz), 2.92 (1H, d, J = 11.7 Hz), 3.4-3.5 (1H, m), 3.55-3.65 (1H, m), 3.75 (3H, s), 4.78-4.89 (2H, m), 6.65 (1H, dd, J = 3.1, 8.8 Hz), 6.71 (1H, d, J = 8.8 Hz), 7.22 (1H, d, J = 3.0 Hz). 800 1H-NMR (CDCl3) ppm: 1.06-1.13 (18H, m), 1.14-1.29 (12H, m), 1.32-1.48 (2H, m), 1.48-1.76 (4H, m), 2.65 (1H, d, J = 11.8 Hz), 2.83 (1H, d, J = 11.6 Hz), 3.35-3.45 (1H, m), 3.45-3.55 (1H, m), 6.39-6.48 (1H, m), 6.55 (1H, dd, J = 2.9, 14.1 Hz), 6.79 (1H, dd, J = 9.4, 9.4 Hz). 801 1H-NMR (CDCl3) ppm: 1.11 (18H, d, J = 7.2 Hz), 1.15-1.21 (4H, m), 1.21-1.33 (7H, m), 1.34-1.47 (2H, m), 1.47-1.77 (5H, m), 2.66 (1H, d, J = 11.5 Hz), 2.81 (1H, d, J = 11.6 Hz), 3.4-3.55 (2H, m), 6.61 (1H, d, J = 3.0, 8.9 Hz), 6.78 (1H, d, J = 8.9 Hz), 6.81 (1H, d, J = 3.0 Hz). 802 1H-NMR (CDCl3) ppm: 1.04-1.11 (18H, m), 1.11-1.22 (7H, m), 1.23 (3H, s), 1.26- 1.49 (4H, m), 1.64-1.79 (4H, m), 2.71 (1H, d, J = 11.9 Hz), 3.01 (1H, d, J = 11.9 Hz), 3.4-3.5 (1H, m), 3.6-3.7 (1H, m), 4.73 (2H, s), 6.79-6.86 (2H, m), 7.18-7.23 (2H, m), 803 1H-NMR (CDCl3) ppm: 1.03-1.12 (18H, m), 1.12-1.48 (13H, m), 1.50-1.82 (5H, m), 2.70 (1H, d, J = 12.0 Hz), 2.99 (1H, d, J = 12.0 Hz), 3.35-3.45 (1H, m), 3.55-3.65 (1H, m), 4.77 (2H, s), 6.47 (1H, dd, J = 2.4, 14.0 Hz), 6.61 (1H, dd, J = 2.4, 8.6 Hz), 7.32 (1H, dd, J = 8.8, 8.8 Hz). 804 0 1H-NMR (CDCl3) ppm: 1.03 (18H, d, J = 2.4 Hz), 1.13-1.27 (9H, m), 1.27-1.77 (6H, m), 2.67 (1H, d, J = 11.6 Hz), 2.80 (1H, d, J = 11.5 Hz), 3.4-3.55 (2H, m), 4.96 (2H, s), 6.42 (1H, d, J = 2.9 Hz), 6.70 (1H, dd, J = 2.9, 8.8 Hz), 6.80 (1H, d, J = 8.8 Hz).

(370) TABLE-US-00086 TABLE 89 absolute configuration Ex. No. R.sup.4 NMR Salt 805 1H-NMR (CDCl3) ppm: 1.00-1.48 (11H, m), 1.54-1.87 (4H, m), 2.70 (1H, d, J = 10.4 Hz), 2.81 (1H, d, J = 11.5 Hz), 3.3-3.65 (2H, m), 6.75 (4H, bs). 806 1H-NMR (CDCl3) ppm: 1.14-1.49 (11H, m), 1.60-1.83 (4H, m), 2.71 (1H, d, J = 12.1 Hz), 3.03 (1H, d, J = 12.0 Hz), 3.37-3.44 (1H, m), 3.56-3.67 (1H, m), 6.16-6.23 (1H, m), 6.33 (1H, dd, J = 2.3, 2.3 Hz), 6.43 (1H, dd, J = 2.1, 8.4 Hz), 7.06 (1H, dd, J = 8.1, 8.1 Hz). 807 1H-NMR (DMSO-d6) ppm: 1.0-1.25 (2H, m), 1.25-1.4 (7H, m), 1.4-1.85 (5H, m), 2.78 (1H, d, J = 12.3 Hz), 2.90 (1H, d, J = 12.1 Hz), 2.95-4.1 (9H, m), 4.44 (2H, s), 6.50 (2H, s), 6.71 (1H, dd, J = 2.8, 8.8 Hz), Fumarate 6.79 (1H, d, J = 8.9 Hz), 6.97 (1H, d, J = 2.7 Hz). 808 1H-NMR (CDCl3) ppm: 1.10-1.27 (9H, m), 1.31-1.48 (1H, m), 1.49-2.01 (6H, m), 2.68 (1H, d, J = 11.5 Hz), 2.78 (1H, d, J = 11.5 Hz), 3.4-3.55 (2H, m), 6.73 (1H, dd, J = 2.8, 8.9 Hz), 6.78 (1H, d, J = 2.8 Hz), 6.89 (1H, d, J = 8.9 Hz). 809 1H-NMR (CDCl3) ppm: 1.17-1.61 (12H, m), 1.62-1.83 (4H, m), 2.72 (1H, d, J = 11.9 Hz), 3.03 (1H, d, J = 11.9 Hz), 3.4-3.45 (1H, m), 3.6-3.7 (1H, m), 4.56 (2H, s), 6.80-6.86 (2H, m), 7.20-7.25 (2H, m). 810 1H-NMR (CDCl3) ppm: 0.91 (1H, br), 1.17-1.48 (10H, m), 1.56 (1H, br), 1.62-1.84 (4H, m), 2.71 (1H, d, J = 12.1 Hz), 3.02 (1H, d, J = 12.0H), 3.35-3.45 (1H, m), 3.55- 3.65 (1H, m), 4.62 (2H, d, J = 3.2 Hz), 6.51 (1H, dd, J = 2.5, 14.0 Hz), 6.59 (1H, dd, J = 2.5, 8.5 Hz), 7.19 (1H, dd, J = 8.8, 8.8 Hz). 811 1H-NMR (CDCl3) ppm: 0.92-1.02 (1H, m), 1.02-1.13 (4H, m), 1.15 (3H, s), 1.21- 1.30 (1H, m), 1.35-1.65 (5H, m), 1.69-1.83 (1H, m), 2.60 (1H, d, J = 11.3 Hz), 2.69 (1H, d, J = 11.3 Hz), 3.32 (1H, br), 3.41-3.49 (1H, m), 4.43 (2H, d, J = 4.6 Hz), 4.88 (1H, t, J = 5.4 Hz), 6.55 (1H, dd, J = 2.8, 8.7 Hz), 6.60 (1H, d, J = 8.6 Hz), 6.83 (1H, d, J = 2.7 Hz), 8.55 (1H, s).

(371) TABLE-US-00087 TABLE 90 absolute configuration Ex. No. R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 812 OCH3 1H-NMR (DMSO-d6) 2 ppm: 1.1-1.3 (2H, m), Hydrochloride 1.35-1.45 (4H, m), 1.52 (3H, s), 1.6-1.9 (4H, m), 1.95-2.1 (1H, m), 2.93 (1H, d, J = 13.1 Hz), 3.11 (1H, d, J = 13.0 Hz), 3.68 (3H, s), 3.7-3.9 (2H, m), 4.35-5.35 (1H, m), 6.75-6.85 (2H, m), 6.85-6.95 (2H, m), 8.09 (1H, br), 9.90 (1H, br). 813 CH3 Cl 1H-NMR (CDCl3) ppm: 0.93-1.09 (3H, m), 1.16 (3H, s), 1.23- 1.34 (4H, m), 1.34-1.44 (2H, m), 1.44-1.75 (2H, m), 1.79-1.92 (1H, m), 2.37 (3H, s), 2.41 (1H, d, J = 11.0 Hz), 2.83-2.91 (1H, m), 3.10 (1H, d, J = 11.1 Hz), 3.51-3.57 (1H, m), 6.79 (1H, dd, J = 2.1, 7.1 Hz), 6.99-7.08 (2H, m). 814 CH3 1H-NMR (CDCl3) Hydrochloride ppm: 0.78-1.13 (3H, m), 1.16 (3H, s), 1.28- 1.42 (5H, m), 1.54-1.76 (4H, m), 1.81-1.95 (1H, m), 2.34 (3H, s), 2.43 (1H, d, J = 11.1 Hz), 2.87-2.96 (1H, m), 3.13 (1H, d, J = 11.1 Hz), 3.47-3.58 (1H, m), 6.88 (1H, dd, J = 1.0, 7.9 Hz), 6.91-6.97 (1H, m), 7.07- 7.15 (1H, m), 7.17 (1H, dd, J = 0.7, 7.5 Hz). 815 CH3 1H-NMR (DMSO-d6) 2 ppm: 1.16-1.33 (2H, Hydrochloride m), 1.34-1.48 (4H, m), 1.49-1.56 (3H, m), 1.61- 1.93 (4H, m), 1.97-2.11 (1H, m), 2.19 (3H, s), 2.91 (1H, d, J = 13.2 Hz), 3.19-3.32 (1H, m), 3.68- 3.80 (1H, m), 3.87-3.99 (1H, m), 4.35-6.4 (1H, m), 6.83 (2H, d, J = 8.4 Hz), 7.02 (2H, d, J = 8.1 Hz), 8.0-8.35 (1H, m), 9.8-10.2 (1H, m). 816 CH3 CH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 0.96-1.18 (2H, m), 1.28-1.45 (1H, m), 1.49 (3H, s), 1.52 (3H, s), 1.56-1.67 (1H, m), 1.67-1.83 (2H, m), 1.83- 2.10 (2H, m), 2.20 (3H, s), 2.22 (3H, s), 2.59 (1H, d, J = 12.6 Hz), 3.0- 3.15 (1H, m), 3.25-3.4 (1H, m), 3.8-3.95 (1H, m), 6.82 (1H, d, J = 7.8 Hz), 6.90 (1H, d, J = 7.4 Hz), 7.03 (1H, dd, J = 7.7, 7.7 Hz), 8.02 (1H, br), 9.65-9.9 (1H, m). 817 CH3 Cl 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.21-1.49 (6H, m), 1.53 (3H, s), 1.63- 1.96 (4H, m), 1.96-2.16 (1H, m), 2.26 (3H, s), 2.93 (1H, d, J = 13.5 Hz), 3.36 (1H, d, J = 13.4 Hz), 3.65-3.8 (1H, m), 3.95- 4.05 (1H, ), 4.43 (1H, br), 6.79 1H, dd, J = 2.9, 8.8 Hz), 6.93 (1H, d, J = 2.8 Hz), 7.20 (1H, d, J = 8.8 Hz), 8.1-8.4 (1H, m), 9.8-10.2 (1H, m). 818 CH3 F 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.16-1.35 (2H, m), 1.35-1.48 (4H, m), 1.52 (3H, s), 1.62-1.95 (4H, m), 1.95-2.14 (1H, m), 2.18 (3H, d, J = 1.6 Hz), 2.93 (1H, d, J = 13.2 Hz), 3.21 (1H, d, J = 13.1 Hz), 3.7-3.8 (1H, m), 3.85-4.0 (1H, m), 4.05-5.8 (1H, m), 6.71- 6.81 (1H, m), 6.85 (1H, dd, J = 2.9, 6.6 Hz), 6.97 (1H, dd, J = 9.1, 9.1 Hz), 8.05-8.3 (1H, m), 9.85- 10.2 (1H, m). 819 CH3 F 1H-NMR (DMSO-d6) Hydrochloride ppm: 0.98-1.20 (2H, m), 1.3-1.43 (1H, m), 1.50 (3H, s), 1.51 (3H, s), 1.56-1.69 (1H, m), 1.69-1.87 (2H, m), 1.87- 2.08 (2H, m), 2.20 (3H, d, J = 2.3 Hz), 2.67 (1H, d, J = 12.6 Hz), 3.15-3.25 (1H, m), 3.36 (1H, d, J = 12.8 Hz), 3.8-4.0 (1H, m), 6.83 (1H, d, J = 8.0 Hz), 6.89 (1H, dd, J = 8.8, 8.8 Hz), 7.16 (1H, dd, J = 7.9, 15.2 Hz), 8.08 (1H, br), 9.7-10.0 (1H, m). 820 F CH3 1H-NMR (DMSO-d6) Fumarate ppm: 1.14-1.41 (9H, m), 1.50-1.90 (5H, m), 2.09 (3H, d, J = 0.8 Hz), 2.78 (1H, d, J = 12.8 Hz), 3.19 (1H, d, J = 12.8 Hz), 3.5-3.6 (1H, m), 3.8-3.9 (1H, m), 6.52 (2H, s), 6.60-6.71 (2H, m), 7.05 (1H, dd, J = 8.9, 8.9 Hz). 821 Cl CH3 1H-NMR (DMSO-d6) Fumarate ppm: 1.15-1.40 (9H, m), 1.5-1.9 (5H, m), 2.19 (3H, d, J = 0.8 Hz), 2.78 (1H, d, J = 12.7 Hz), 3.18 (1H, d, J = 12.7 Hz), 3.5-3.6 (1H, m), 3.8-3.9 (1H, m), 6.54 (2H, s), 6.80 (1H, dd, J = 2.6, 8.5 Hz), 6.90 (1H, d, J = 2.6 Hz), 7.13 (1H, d, J = 8.5 Hz). 822 Cl 1H-NMR (DMSO-d6) ppm: 1.12-1.21 (4H, Fumarate m), 1.22 (3H, s), 1.24- 1.37 (2H, m), 1.45-1.77 (4H, m), 1.77-1.92 (1H, m), 2.72 (1H, d, J = 12.5 Hz), 3.18 (1H, d, J = 12.4 Hz), 3.40 (1H, brs), 3.75-3.85 (1H, m), 6.50 (1H, s), 6.67 (1H, dd, J = 1.6, 7.7 Hz), 6.8-6.9 (2H, m), 7.16 (1H, dd, J = 8.1, 8.1 Hz). 823 CH3 OCH3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.0-1.17 (2H, m), 1.29-1.43 (1H, m), 1.48 (3H, s), 1.51 (3H, s), 1.56-2.05 (5H, m), 2.12 (3H, s), 2.62 (1H, d, J = 12.6 Hz), 3.05-3.2 (1H m), 3.3-3.4 (1H, m), 3.76 (3H, s), 3.85-3.95 (1H, m), 6.61 (1H, d, J = 7.9 Hz), 6.72 (1H, d, J = 8.2 Hz), 7.10 (1H, dd, J = 8.1, 8.1 Hz), 7.99 (1H, br), 9.5-9.8 (1H, m). 824 OCHF2 1H-NMR (DMSO-d6) 2 ppm: 1.21-1.36 (2H, Hydrochloride m), 1.36-1.46 (4H, m), 1.52 (3H, s), 1.63-1.92 (4H, m), 1.93-2.09 (1H, m), 2.94 (1H, d, J = 13.4 Hz), 3.33 (1H, d, J = 13.3 Hz), 3.5-4.4 (2H, m), 6.84-7.26 (5H, m), 8.13 (1H, br), 9.84 (1H, br). 825 OCF3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.26-1.48 (6H, m), 1.50 (3H, s), 1.63- 1.92 (4H, m), 1.92-2.06 (1H, m), 2.96 (1H, d, J = 13.6 Hz), 3.44 (1H, d, J = 13.5 Hz), 3.72-3.83 (1H, m), 3.98-4.09 (1H, m), 6.96-7.07 (2H, m), 7.15- 7.27 (2H, m), 8.08 (1H, br), 9.67 (1H, br). 826 Cl CN 1H-NMR (DMSO-d6) ppm: 1.10 (3H, s), Fumarate 1.15-1.25 (4H, m), 1.25- 1.45 (2H, m), 1.45-1.75 (4H, m), 1.85-2.0 (1H, m), 2.75 (1H, d, J = 13.0 Hz), 2.9-3.85 (4H, m), 3.85-3.95 (1H, m), 6.56 (1H, s), 6.94 (1H, dd, J = 2.5, 9.1 Hz), 7.09 (1H, d, J = 2.4 Hz), 7.59 (1H, d, J = 9.0 Hz). 827 F OCF3 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.28-1.46 (6H, m), 1.51 (3H ,s), 1.63- 2.10 (5H, m), 2.97 (1H, d, J = 13.8 Hz), 3.54 (1H, d, J = 13.8 Hz) 3.65-3.8 (1H, m), 4.0-4.15 (1H, m), 6.81 (1H, dd, J = 2.2, 9.2 Hz), 7.05 (1H, dd, J = 2.9, 14.4 Hz), 7.34 (1H, dd, J = 9.2, 9.2 Hz), 8.22 (1H, br), 9.89 (1H, br). 828 F OCHF2 1H-NMR (DMSO-d6) 1/2 ppm: 1.09-1.37 (9H, Fumarate m), 1.44-1.73 (4H, m), 1.75-1.90 (1H, m), 2.66 (1H, d, J = 12.1 Hz), 3.0- 3.7 (4H, m), 3.7-3.8 (1H, m), 6.52 (1H, m), 6.67 (1H, d, J = 2.1, 9.3 Hz), 6.80-7.22 (3H, m) 829 Cl OCHF2 1H-NMR (DMSO-d6) ppm: 1.08-1.37 (9H, Fumarate m), 1.43-1.59 (1H, m), 1.59-1.74 (3H, m), 1.75- 1.90 (1H, m), 2.69 (1H, d, J = 12.3 Hz), 2.8-4.2 (5H, m), 6.52 (1H, s), 6.82-7.25 (4H, m). 830 OCHF2 1H-NMR (DMSO-d6) 1/2 ppm: 1.13-1.41 (9H, Fumarate m), 1.46-1.93 (5H, m), 2.75 (1H, d, J = 12.5 Hz), 2.8-4.4 (6H, m), 6.46 (1H, d, J = 8.1 Hz), 6.54 (2H, s), 6.62 (1H, s), 6.76 (1H, dd, J = 8.4 Hz), 7.0-7.4 (2H, m). 831 OCHF2 F 1H-NMR (DMSO-d6) ppm: 1.02-1.36 (9H, Fumarate m), 1.44-1.59 (1H, m), 1.59-1.74 (3H, m) 1.74- 1.87 (1H, m), 2.65-4.5 (6H, m), 6.52 (1H, s), 6.7-6.8 (2H, m), 7.0-7.4 (2H, m). 832 OCHF2 Cl 1H-NMR (DMSO-d6) ppm: 1.10-1.38 (9H, Fumarate m), 1.44-1.74 (4H, m), 1.76-1.91 (1H, m), 2.69 (1H, d, J = 12.3 Hz), 2.75-4.2 (5H, m), 6.53 (1H, s), 6.75-6.85 (2H, m), 7.05-7.45 (2H, m). 833 CN OCHF2 1H-NMR (DMSO-d6) ppm: 1.06-1.23 (7H, Fumarate m), 1.23-1.37 (2H, m), 1.43-1.74 (4H, m), 1.75- 1.89 (1H, m), 2.69 (1H, d, J = 12.4 Hz), 2.9-3.75 (4H, m), 3.75-3.85 (1H, m), 6.53 (1H, s), 7.00- 7.41 (4H, m). 834 OCHF2 OCHF2 1H-NMR (DMSO-d6) ppm: 1.1-1.4 (9H, m), Fumarate 1.44-1.76 (4H, m), 1.76- 1.90 (1H, m), 2.69 (1H, d, J = 12.2 Hz), 2.8-4.25 (5H, m), 6.52 (1H, s), 6.71-7.36 (5H, m). 835 F OCHF2 F 1H-NMR (DMSO-d6) ppm: 1.08-1.23 (7H, Fumarate m), 1.24-1.40 (2H, m), 1.43-1.73 (4H, m), 1.76- 1.91 (1H, m), 2.67 (1H, d, J = 12.5 Hz), 2.8-4.2 (5H, m), 6.53 (1H, s), 6.67-6.77 (2H, m), 7.05 (1H, t, J = 72.9 Hz). 836 OCH2CHF2 1H-NMR (DMSO-d6) 2 ppm: 1.13-1.31 (2H, Hydrochloride m), 1.32-1.47 (4H, m), 1.53 (3H, s), 1.61-1.90 (4H, m), 1.97-2.12 (1H, m), 2.93 (1H, d, J = 13.1 Hz), 3.15 (1H, d, J = 13.1 Hz), 3.69-3.81 (1H, m), 3.83-3.93 (1H, m), 4.10-4.46 (3H, m), 6.12- 6.53 (1H, m), 6.90 (4H, s), 8.0-8.25 (1H, m), 9.9-10.1 (1H, m). 837 F OCH2CHF2 1H-NMR (DMSO-d6) Hydrochloride ppm: 1.20-1.46 (6H, m), 1.51 (3H, s), 1.63- 1.91 (4H, m), 1.93-2.10 (1H, m), 2.91 (1H, d, J = 13.4 Hz), 3.29 (1H, d, J = 13.2 Hz), 3.67-3.80 (1H, m), 3.89-4.01 (1H, m), 4.20-4.35 (2H, m), 6.18- 6.51 (1H, m), 6.68 (1H, dd, J = 1.8, 9.1 Hz), 6.91 (1H, dd, J = 2.9, 14.7 Hz), 7.10 (1H, dd, J = 9.5, 9.5 Hz), 8.05-8.2 (1H, m), 9.75-9.95 (1H, m). 838 CH3 OCHF2 1H-NMR (DMSO-d6) 1/2 ppm: 1.06-1.15 (1H, Fumarate m), 1.15-1.38 (8H, m), 1.42-1.88 (5H, m), 2.17 (3H, s), 2.68 (1H, d, J = 11.9 Hz), 3.04 (1H, d, J = 12.1 Hz), 3.1-3.9 (4H, m), 6.50 (1H, s), 6.71 (1H, dd, J = 2.9, 8.9 Hz), 6.75-7.16 (3H, m). 839 OCH3 OCHF2 1H-NMR (DMSO-d6) ppm: 1.10-1.39 (9H, Fumarate m), 1.45-1.90 (5H, m), 2.72 (1H, d, J = 12.2 Hz), 2.95-4.1 (8H, m), 6.40 (1H, dd, J = 2.8, 8.9 Hz), 6.50 (1H, s), 6.57 (1H, d, J = 2.7 Hz), 6.63-7.03 (2H, m). 840 OCHF2 1H-NMR (DMSO-d6) ppm: 0.94-1.14 (1H, m), 1.14-1.17 (1H, m), 1.18 (3H, s), 1.26 (3H, s), 1.29-1.55 (3H, m), 1.59-1.73 (3H, m), 1.76- 1.90 (1H, m), 2.49 (1H, d, J = 11.2 Hz), 3.04 (1H, d, J = 11.2 Hz), 3.5-3.6 (2H, m), 6.55 (1H, dd, J = 70.2, 81.4 Hz), 6.91 (1H, dd, J = 1.4, 8.0 Hz), 6.93-6.99 (1H, m), 7.07- 7.18 (2H, m)

(372) TABLE-US-00088 TABLE 91 absolute configuration 0 Ex. No. R.sup.4 NMR Salt 841 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (2H, m), 1.35-1.45 (1H, m), 1.51 (3H, s), 1.56 (3H, s), 1.6-2.05 (5H, m), 2.87 (1H, d, J = 12.8 Hz), 3.3-3.4 (1H, m), 3.65-3.75 (1H, m), 4.1-4.2 (1H, m), 7.05 (1H, s), 7.35-7.45 (2H, m), 7.9-8.1 (3H, m), 9.5-9.7 (1H, m). Hydrochloride 842 1H-NMR (CDCl3) ppm: 0.89-1.18 (5H, m), 1.25-1.74 (9H, m), 1.74-1.86 (1H, m), 2.19 (3H, d, J = 0.9 Hz), 2.52 (1H, d, J = 11.2 Hz), 2.93 (1H, d, J = 11.2 Hz), 3.03-3.10 (1H, m), 3.47-3.52 (1H, m), 6.35 (1H, d, J = 3.3 Hz), 6.84-6.88 (1H, m).

(373) TABLE-US-00089 TABLE 92 relative configuration Ex. No. R.sup.4 NMR Salt 843 1H-NMR (CDCL3) ppm 0.97-1.09 (1H, m), 1.23-1.38 (2H, m), 1.62-1.68 (3H, m), 1.63 (3H, s), 1.68 (3H, s), 1.92-2.05 (1H, m), 2.29- 2.36 (1H, m), 2.73 (1H, d, J = 12.4 Hz), 2.94- 3.03 (1H, m), 3.11-3.22 (1H, m), 3.28 (1H, d, Hydrochloride J = 12.4 Hz), 7.02 (1H, dd, J = 8.5, 2.4 Hz), 7.25 (1H, d, J = 2.4 Hz), 7.39 (1H, d, J = 8.5 Hz), 9.50 (1H, brs), 9.78 (1H, brs) 844 1H-NMR (DMSO-d6) ppm: 1.00-1.98 (13H, m), 1.98-2.28 (1H, br), 2.65-3.90 (4H, br), 4.18 (3H, s), 6.70-7.95 (3H, m), 8.22-8.60 (1H, br), 8.80-11.33 (3H, brm). 2 Hydrochloride

(374) TABLE-US-00090 TABLE 93 absolute configuration Ex. No. R.sup.4 NMR Salt 845 1H-NMR (CDCl3) ppm: 1.03-1.17 (23H, m), 1.17-1.41 (6H, m), 1.43 (3H, s), 1.59-1.68 (1H, m), 1.68-1.80 (3H, m), 2.32-2.40 (1H, m), 2.68 (1H, d, J = 11.3 Hz), 2.78-2.85 (1H, m), 2.88 (1H, d, J = 11.3 Hz), 7.08 (1H, dd, J = 2.4, 8.8 Hz), 7.16 (1H, d, J = 2.4 Hz), 7.22 (1H, dd, J = 2.1, 8.7 Hz), 7.37 (1H, d, J = 1.8 Hz), 7.57-7.64 (2H, m). 846 1H-NMR (CDCl3) ppm: 0.82-1.17 (23H, m), 1.20-1.46 (9H, m), 1.60-1.70 (1H, m), 1.70- 1.85 (3H, m), 2.35-2.45 (1H, m), 2.69 (1H, d, J = 11.3 Hz), 2.77-2.86 (1H, m), 2.91 (1H, d, J = 11.3 Hz), 7.02 (1H, dd, J = 2.4, 8.8 Hz), 7.09-7.15 (2H, m), 7.27 (1H, d, J = 1.9 Hz), 7.60-7.68 (2H, m). 847 1H-NMR (CDCl3) ppm : 0.97-1.41 (29H, m), 1.43 (3H, s), 1.60-1.70 (1H, m), 1.70-1.80 (3H, m), 2.35-2.43 (1H, m), 2.69 (1H, d, J = 11.3 Hz), 2.78-2.87 (1H, m), 2.89 (1H, d, J = 11.3 Hz), 7.11 (1H, d, J =8.9 Hz), 7.34 (1H, dd, J = 2.1, 9.0 Hz), 7.37 (1H, d, J = 1.9 Hz), 7.53 (1H, d, J = 8.9 Hz), 8.10 (1H, d, J = 8.9 Hz). 848 0 1H-NMR (CDCl3) ppm: 0.74-1.42 (29H, m), 1.44 (3H, s), 1.58-1.83 (4H, m), 2.35-2.43 (1H, m), 2.68 (1H, d, J = 11.3 Hz), 2.78-2.87 (1H, m), 2.91 (1H, d, J = 11.3 Hz), 3.91 (3H, s), 5.19-5.27 (2H, m), 7.21 (1H, d, J = 9.1 Hz), 7.29 (1H, d, J = 2.2, 9.1 Hz), 7.37 (1H, d, J = 2.1 Hz), 7.69 (1H, d, J = 9.0 Hz), 8.16 (1H, d, J = 9.1 Hz). 849 1H-NMR (CDCl3) ppm: 0.96-1.19 (23H, m), 1.19-1.42 (6H, m), 1.44 (3H, s), 1.57-1.78 (4H, m), 2.32-2.41 (1H, m), 2.71 (1H, d, J = 11.3 Hz), 2.77-2.86 (1H, m), 2.87 (1H, d, J = 11.3 Hz), 3.89 (3H, s), 4.94 (2H, d, J = 1.1 Hz), 7.02 (1H, s), 7.22 (1H, dd, J = 2.0, 8.6 Hz), 7.44 (1H, d, J = 1.8 Hz), 7.64 (1H, d, J = 8.6 Hz), 7.88 (1H, s).

(375) TABLE-US-00091 TABLE 94 absolute configuration Ex. No. R.sup.4 NMR Salt 850 1H-NMR (DMSO-d6) ppm: 0.88-1.03 (4H, m), 1.11-1.37 (6H, m), 1.45-1.68 (5H, m), 2.26-2.35 (1H, m), 2.58 (1H, d, J = 10.9 Hz), 2.62-2.70 (1H, m), 2.73 (1H, d, J = 10.9 Hz), 7.02 (1H, dd, J = 2.4, 8.7 Hz), 7.05 (1H, d, J = 2.4 Hz), 7.16 (1H, dd, J = 2.1, 8.7 Hz), 7.37 (1H, d, J = 1.8 Hz), 7.58 (1H, d, J = 8.8 Hz), 7.67 (1H, d, J = 8.9 Hz), 9.57 (1H, brs). 851 1H-NMR (DMSO-d6) ppm: 0.88-1.02 (4H, m), 1.10-1.37 (6H, m), 1.44-1.74 (5H, m), 2.32-2.41 (1H, m), 2.60 (1H, d, J = 11.1 Hz), 2.63-2.72 (1H, m), 2.80 (1H, d, J = 11.1 Hz), 6.94 (1H, dd, J = 2.4, 8.8 Hz), 7.00 (1H, dd, J = 2.0, 8.8 Hz), 7.02 (1H, d, J = 2.4 Hz), 7.21 (1H, d, J = 1.8 Hz), 7.64 (2H, d, J = 8.7 Hz), 9.63 (1H, s). 852 1H-NMR (DMSO-d6) ppm: 0.90-1.08 (4H, m), 1.15-1.40 (6H, m), 1.51-1.73 (4H, m), 2.35-2.47 (1H, m), 2.65 (1H, d, J = 11.2 H), 2.70-2.85 (2H, m), 2.90-3.75 (1H, br), 7.23 (1H, d, J = 8.9 Hz), 7.34 (1H, dd, J = 2.1, 9.0 Hz), 7.46 (1H, d, J = 2.0 Hz), 7.70 (1H, d, J = 8.9 Hz), 7.92 (1H, d, J = 9.0 Hz), 9.05-11.25 (1H, br). 853 1H-NMR (DMSO-d6) ppm: 0.95-1.10 (4H, m), 1.17-1.40 (6H, m), 1.56-1.80 (4H, m), 2.49-2.60 (1H, m), 2.73-2.87 (2H, m), 2.92 (1H, d, J = 11.5 Hz), 3.18-3.46 (1H, br), 7.10- 7.18 (2H, m), 7.50 (1H, d, J = 2.0 Hz), 7.67 (1H, d, J = 8.8 Hz), 7.75 (1H, d, J = 8.7 Hz), 9.95-10.75 (1H, br). 854 1H-NMR (DMSO-d6) ppm: 0.90-1.07 (4H, m), 1.13-1.37 (6H, m), 1.47-1.70 (5H, m), 2.30-2.40 (1H, m), 2.61 (1H, d, J = 11.0 Hz), 2.65-2.74 (1H, m), 2.77 (1H, d, J = 11.0 Hz), 3.88 (3H, s), 4.82 (1H, t, J = 5.1 Hz), 4.89 (2H, d, J = 5.1 Hz), 7.27 (1H, dd, J = 2.1, 9.1 Hz), 7.35 (1H, d, J = 9.1 Hz), 7.42 (1H, d, J = 2.1 Hz), 7.80 (1H, d, J = 9.1 Hz), 8.03 (1H, d, J = 9.1 Hz). 855 1H-NMR (DMSO-d6) ppm: 0.95-1.10 (1H, m), 1.10-1.50 (9H, m), 1.53-1.73 (3H, m), 1.77-1.87 (1H, m), 2.58-2.70 (1H, m), 2.85 (2H, s), 2.89-3.00 (1H, m), 3.87 (3H, s), 4.61 (2H, s), 6.46 (1H, s), 7.20 (1H, dd, J = 2.0, 8.7 Fumarate Hz), 7.22 (1H, s), 7.46 (1H, d, J = 1.6 Hz), 7.73 (1H, d, J = 8.7 Hz), 7.79 (1H, s).

(376) TABLE-US-00092 TABLE 95 absolute configuration Ex. No. R.sup.4 NMR Salt 856 0 1H-NMR (CDCl3) ppm: 0.91-1.05 (1H, m), 1.08 (3H, s), 1.12-1.62 (9H, m), 1.68-1.78 (2H, m), 2.42-2.50 (1H, m), 2.62 (1H, d, J = 11.3 Hz), 2.75 (1H, d, J = 11.3 Hz), 2.91-3.00 (1H, m), 3.98 (3H, s), 6.78 (1H, d, J = 8.1 Hz), 7.20 (1H, d, J = 8.1 Hz), 7.43-7.54 (2H, m), 8.21-8.26 (1H, m), 8.50-8.54 (1H, m). 857 1H-NMR (DMSO-d6) ppm : 0.93-1.22 (2H, m), 1.26-1.44 (5H, m), 1.44-1.54 (1H, m), 1.56-1.77 (5H, m), 1.99-2.08 (1H, m), 2.62 (3H, s), 2.76 (1H, d, J = 12.4 Hz), 2.98-3.08 (2H, m), 3.33-3.50 (1H, m), 7.28 (1H, d, J = 7.5 Hz), 7.38 (1H, d, J = 7.5 Hz), 7.54-7.61 (2H, m), 7.97-8.03 (1H, m), 8.43-8.52 (1H, m), 9.10-9.25 (1H, br), 9.62-9.77 (1H, br). Hydrochloride 858 1H-NMR (DMSO-d6) ppm: 1.00-1.30 (2H, m), 1.30-1.45 (4H, m), 1.45-1.62 (2H, m), 1.62-1.81 (5H, m), 2.00-2.13 (1H, m), 2.91 (1H, d, J = 12.6 Hz), 3.05-3.20 (2H, m), 3.41- 3.57 (1H, m), 3.75-4.30 (1H, br), 7.61-7.77 (5H, m), 7.98-8.05 (1H, m), 8.54-8.61 (1H, m), 8.77-8.88 (2H, m), 9.19-9.35 (1H, m), 9.669.81 (1H, m). 2 Hydrochloride 859 1H-NMR (DMSO-d6) ppm : 0.90-1.45 (6H, m), 1.53-1.80 (7H, m), 1.97-2.12 (1H, m), 2.83-3.40 (4H, m), 3.86 (3H, s), 7.05-7.25 (2H, m), 7.32 (1H, d, J = 2.4 Hz), 7.42-7.68 (1H, br), 7.75-7.87 (2H, m), 8.25-9.55 (2H, br), 2 Hydrochloride 9.55-10.02 (1H, br). 860 1H-NMR (DMSO-d6) ppm: 0.85-1.00 (1H, m), 1.10-1.70 (12H, m), 1.75-1.86 (1H, m), 2.65-2.80 (3H, m), 2.99-3.10 (1H, m), 3.25- 3.43 (4H, m), 6.46 (1H, s), 7.20-7.34 (3H, m), 7.45 (1H, dd, J = 7.0, 8.2 Hz), 7.88 (1H, d, J = 8.2 Hz), 8.07-9.40 (1H, br). Fumarate 861 1H-NMR (DMSO-d6) ppm: 1.04-1.43 (6H, m), 1.54-1.80 (7H, m), 1.97-2.10 (1H, m), 2.86-3.07 (2H, m), 3.07-3.30 (2H, m), 3.98 (3H, s), 7.43 (1H, d, J = 9.1 Hz), 7.55 (1H, d, J = 9.2 Hz), 7.66 (1H, brs), 7.95 (1H, d, J = 9.1 Hz), 8.04 (1H, d, J = 9.1 Hz), 8.11-8.95 (1H, br), 9.08-9.35 (1H, m), 9.60-9.86 (1H, m). 2 Hydrochloride 862 1H-NMR (CDCl3) ppm: 0.84-0.97 (1H, br), 1.03-1.17 (4H, m), 1.22-1.46 (6H, m), 1.61- 1.74 (1H, m), 1.74-1.88 (3H, m), 2.45-2.55 (1H, m), 2.76 (1H, d, J = 11.5 Hz), 2.82-2.90 (1H, m), 2.98 (1H, d, J = 11.5 Hz), 7.38-7.43 (2H, m), 7.50 (1H, dd, J = 1.6, 8.4 Hz), 7.77- 7.86 (2H, m), 8.12 (1H, s). 863 1H-NMR (DMSO-d6) ppm: 1.05-1.43 (6H, m), 1.54-1.80 (7H, m), 1.98-2.10 (1H, m), 2.90-3.32 (4H, m), 3.95 (3H, s), 6.91 (1H, d, J = 7.2 Hz), 7.24-7.36 (1H, br), 7.38-7.49 (2H, m), 7.50-7.68 (1H, br), 8.11 (1H, d, J = 8.9 Hz), 9.00-9.45 (1H, br), 9.55-9.98 (1H, br), 10.50-12.10 (1H, br). 2 Hydrochloride 864 1H-NMR (DMSO-d6) ppm: 1.10-1.47 (6H, m), 1.54-1.80 (7H, m), 2.01-2.14 (1H, m), 2.95-3.37 (4H, m), 4.00 (3H, s), 7.30 (1H, d, J = 8.3 Hz), 7.51 (1H, d, J = 9.1 Hz), 7.73 (1H, brs), 7.95 (2H, d, J = 9.1 Hz), 9.39 (1H, brs), 9.90 (1H, brs), 11.80 (1H, brs). 2 Hydrochloride 865 1H-NMR (DMSO-d6) ppm: 1.03-1.44 (6H, m), 1.53-1.79 (7H, m), 1.97-2.09 (1H, m), 2.92-3.06 (2H, m), 3.06-3.16 (1H, m), 3.16- 3.30 (1H, m), 6.24-7.14 (1H, m), 7.36 (1H, dd, J = 2.1, 8.8 Hz), 7.49 (1H, dd, J = 2.1, 8.8 Hz), 2 Hydrochloride 7.64 (1H, brs), 7.88 (1H, d, J = 8.8 Hz), 7.94 (1H, d, J = 8.8 Hz), 8.00 (1H, d, J = 2.1 Hz), 9.10-9.39 (1H, brs), 9.63-9.87 (1H, brs). 866 0 1H-NMR (CDCl3) ppm: 0.75-1.19 (5H, m), 1.24-1.43 (3H, m), 1.45 (3H, s), 1.64-1.73 (1H, m), 1.73-1.82 (2H, m), 1.90-2.00 (1H, m), 2.45-2.54 (1H, m), 2.72 (1H, d, J = 11.5 Hz), 2.83-2.92 (1H, m), 3.02 (1H, d, J = 11.5 Hz), 7.26 (1H, dd, J = 2.1, 9.0 Hz), 7.37-7.47 (2H, m), 7.50 (1H, brs), 7.91 (1H, d, J = 9.0 Hz), 7.94-7.99 (2H, m), 8.30 (1H, s), 8.34 (1H, s). 867 1H-NMR (DMSO-d6) ppm: 1.15-1.45 (6H, m), 1.53-1.80 (7H, m), 1.97-2.10 (1H, m), 2.94-3.09 (2H, m), 3.09-3.18 (1H, m), 3.18- 3.31 (1H, m), 4.00-4.62 (1H, br), 7.16 (0.25H, s), 7.32-7.40 (2.5H, m), 7.53 (0.25H, s), 7.61- 2 Hydrochloride 7.72 (2H, m), 7.90 (1H, d, J = 8.8 Hz), 7.98 (1H, d, J = 9.0 Hz).9.10-9.45 (1H, br), 9.61- 9.90 (1H, br). 868 1H-NMR (DMSO-d6) ppm: 1.05-1.47 (6H, m), 1.55-1.80 (7H, m), 1.99-2.10 (1H, m), 2.41-3.05 (2H, m), 3.05-3.16 (1H, m), 3.16- 3.30 (1H, m), 3.75-4.60 (4H, m), 7.45 (1H, dd, J = 2.0, 8.8 Hz), 7.57 (1H, s), 7.67 (1H, s), 3 Hydrochloride 7.90 (1H, d, J = 8.9 Hz), 8.48 (1H, s), 9.10- 9.40 (1H, br), 9.61-9.90 (1H, br). 869 1H-NMR (DMSO-d6) ppm: 1.05-1.45 (6H, m), 1.54-1.80 (7H, m), 1.96-2.07 (1H, m), 2.93-3.04 (1H, m), 3.04-3.16 (2H, m), 3.18- 3.32 1H, m), 4.23-4.51 (1H, br), 7.46-7.50 (1H, m), 7.58-7.67 (3H, m), 7.97-8.04 (1H, m), 8.08-8.14 (1H, m), 9.03-9.25 (1H, br), 9.51- 9.75 (1H, br). 2 Hydrochloride 870 1H-NMR (DMSO-d6) ppm: 1.08-1.45 (6H, m), 1.52-1.80 (7H, m), 1.99-2.10 (1H, m), 2.96-3.17 (3H, m), 3.17-3.30 (1H, m), 4.45- 4.55 (1H, br), 7.16 (1H, dd, J = 1.7, 12.3 Hz), 7.48 (1H, s), 7.51-7.64 (2H, m), 7.98 (2H, d, J = 8.2 Hz), 9.15-9.36 (1H, br), 9.70-9.90 (1H, br). 2 Hydrochloride 871 1H-NMR (CDCl3) ppm: 1.00-1.15 (4H, m), 1.15-1.52 (7H, m), 1.57-1.68 (1H, m), 1.68- 1.79 (3H, m), 2.34-2.42 (1H, m), 2.69 (1H, d, J = 11.3 Hz), 2.77-2.86 (1H, m), 2.88 (1H, d, J = 11.3 Hz), 4.28 (2H, dt, J = 4.1, 13.1 Hz), 6.15 (1H, tt, J = 4.1, 55.2 Hz), 7.10 (1H, d, J = 2.5 Hz), 7.14 (1H, dd, J = 2.6, 8.9 Hz), 7.27 (1H, dd, J = 2.1, 8.7 Hz), 7.41 (1H, d, J = 2.0 Hz), 7.63-7.72 (2H, m). 872 1H-NMR (CDCl3) ppm: 1.00-1.15 (4H, m), 1.20-1.70 (8H, m), 1.70-1.88 (3H, m), 2.39- 2.48 (1H, m), 2.70 (1H, d, J = 11.4 Hz), 2.80- 2.89 (1H, m), 2.93 (1H, d, J = 11.4 Hz), 4.29 (2H, dt, J = 4.2, 13.1 Hz), 6.15 (1H, tt, J = 4.1, 55.2 Hz), 7.03-7.11 (2H, m), 7.16 (1H, dd, J = 2.1, 8.7 Hz), 7.33 (1H, d, J = 2.0 Hz), 7.65- 7.74 (2H, m). 873 1H-NMR (DMSO-d6) ppm: 0.90-1.06 (1H, m), 1.06-1.64 (12H, m), 1.63-1.74 (1H, m), 1.80-1.83 (1H, m), 2.50-2.62 (1H, m), 2.71 (1H, d, J = 11.9 Hz), 2.86 (1H, d, J = 11.9 Hz), 2.92-3.02 (1H, m), 4.78 (2H, s), 6.48 (2H, s), 6.73 (1H, d, J = 8.6 Hz), 6.83 (1H, d, J = 2.2 Fumarate Hz), 6.91 (1H, dd, J = 2.3, 8.6 Hz). 9.52-11.33 (1H, br), 9.37-11.61 (1H, br).

(377) TABLE-US-00093 TABLE 96 absolute configuration Ex. No. R.sup.4 NMR Salt 874 1H-NMR (DMSO-d6) ppm: 0.96-1.10 (1H, m), 1.10-1.25 (1H, m), 1.26-1.41 (4H, m), 1.47-1.78 (7H, m), 1.94-2.05 (1H, m), 2.56 (3H, s), 2.84 (1H, d, J = 12.4 Hz), 2.90-3.02 (2H, m), 3.23-3.35 (1H, m), 7.15 (1H, d, J = 7.6 Hz), 7.22-7.33 (2H, m), 7.68 (1H, d, J = Hydrochloride 7.9 Hz), 8.91-9.09 (1H, brm), 9.54-9.70 (1H, brm). 875 0 1H-NMR (DMSO-d6) ppm: (80 C.): 1.03- 1.46 (6H, m), 1.51-1.78 (7H, m), 2.01-2.11 (1H, m), 2.53 (3H, s), 2.88 (1H, d, J = 12.4 Hz), 2.97-3.08 (1H, m), 3.10-3.25 (2H, m), 7.05 (1H, s), 7.13 (1H, d, J = 8.4 Hz), 7.60- Hydrochloride 7.68 (2H, m), 9.20 (1H, brs), 9.70 (1H, brs). 876 1H-NMR (DMSO-d6) ppm: 0.95-1.40 (6H, m), 1.40-1.78 (7H, m), 1.95-2.05 (1H, m), 2.85 (1H, d, J = 12.5 Hz), 2.90-3.00 (1H, m), 3.03 (1H, d, J = 12.5 Hz), 3.28-3.44 (1H, m), 7.26 (2H, d, J = 7.0 Hz), 7.64 (1H, dd, J = 4.0, 5.2 Hz), 7.86 (1H, d, J = 5.4 Hz), 9.07 (1H, brs), 9.64 (1H, brs). Hydrochloride 877 1H-NMR (DMSO-d6) ppm: 0.97-1.45 (6H, m), 1.45-1.80 (7H, m), 1.94-2.09 (1H, m), 2.88 (1H, d, J = 12.5 Hz), 2.93-3.05 (2H, m), 3.26- 3.45 (1H, m), 7.28 (1H, d, J = 8.2 Hz), 7.50 (1H, d, J = 8.2 Hz), 7.64 (1H, d, J = 5.4 Hz), 7.88 (1H, d, J = 5.4 Hz), 9.06 (1H, brs), 9.59 (1H, brs). Hydrochloride 878 1H-NMR (DMSO-d6) ppm: 0.90-1.79 (13H, m), 1.35-2.06 (1H, m), 2.75-3.05 (4H, m), 3.94 (3H, s), 6.94 (1H, d, J = 7.9 Hz), 7.18 (1H, d, J = 7.9 Hz), 7.55 (1H, d, J = 5.4 Hz), 7.71 (1H, d, J = 5.4 Hz), 8.80 (1H, brs), 9.31 (1H, brs). Hydrochloride

(378) TABLE-US-00094 TABLE 97 absolute configuration Ex. No. R.sup.4 NMR Salt 879 1H-NMR (DMSO-d6) ppm: 0.97-1.10 (1H, m), 1.10-1.41 (5H, m), 1.50-1.78 (7H, m), 1.94-2.05 (1H, m), 2.44 (3H, s), 2.75-3.09 (3H, m), 3.09-3.30 (1H, m), 6.58 (1H, brs), 6.98 (1H, d, J = 7.2 Hz), 7.19 (1H, t, J = 7.8 Hz), 7.31 (1H, d, J = 7.8 Hz), 9.00 (1H, brs), Hydrochloride 9.59 (1H, brs). 880 1H-NMR (DMSO-d6) ppm: 1.00-1.43 (6H, m), 1.44-1.78 (7H, m), 1.90-2.07 (1H, m), 2.42 (3H, d, J = 0.9 Hz), 2.75-3.30 (4H, m), 3.48- 4.50 (1H, br), 6.54 (1H, s), 7.04 (1H, brs), 7.30 (1H, brs), 7.48 (1H, d, J = 8.6 Hz), 9.11 2 Hydrochloride (1H, brs), 9.70 (1H, brs). 881 1H-NMR (DMSO-d6) ppm: 0.99-1.15 (1H, m), 1.15-1.42 (5H, m), 1.47-1.77 (7H, m), 1.93-2.05 (1H, m), 2.75-3.18 (3H, m), 3.27 (1H, brs), 7.08 (1H, brs), 7.22 (1H, brs), 8.14 (1H, s), 9.00 (1H, brs), 9.67 (1H, brs). Hydrochloride 882 1H-NMR (CDCl3) ppm: 0.75-1.14 (5H, m), 1.14-1.40 (3H, m), 1.42 (3H, s), 1.56-1.68 (2H, m), 1.68-1.79 (2H, m), 2.20-2.30 (1H, m), 2.65 (1H, d, J = 11.1 Hz), 2.74-2.85 (2H, m), 3.99 (3H, s), 6.61 (1H, d, J = 1.7 Hz), 6.70 (1H, d, J = 2.1 Hz), 6.95 (1H, d, J = 1.7 Hz), 7.59 (1H, d, J = 2.1 Hz). 883 1H-NMR (DMSO-d6) ppm: 1.01-1.42 (6H, m), 1.49-1.68 (6H, m), 1.68-1.78 (1H, m), 1.95-2.05 (1H, m), 2.80-2.95 (2H, m), 3.01- 3.10 (1H, m), 3.10-3.24 (1H, m), 6.50-7.80 (4H, m), 8.10 (1H, d, J = 2.1 Hz), 9.13 (1H, brs), 9.71 (1H, brs). 2 Hydrochloride 884 0 1H-NMR (DMSO-d6) ppm: 1.00-1.41 (6H, m), 1.45-1.67 (6H, m), 1.67-1.77 (1H, m), 1.92-2.03 (1H, m), 2.80-2.94 (2H, m), 3.01- 3.10 (1H, m), 3.10-3.25 (1H, m), 3.65-4.00 (1H, br), 7.05 (1H, d, J = 2.1 Hz), 7.18 (1H, d, J = 1.7 Hz), 7.43 (1H, d, J = 1.7 Hz), 8.12 (1H, d, J = 2.1 Hz), 9.10 (1H, brs), 9.60 (1H, brs). 2 Hydrochloride 885 1H-NMR (DMSO-d6) ppm: 0.92-1.07 (1H, m), 1.07-1.88 (13H, m), 2.60-3.01 (3H, m), 3.10-4.92 (2H, br), 6.45 (3H, s), 7.35 (1H, dd, J = 2.1, 8.9 Hz), 7.54 (1H, d, J = 2.0 Hz), 7.68 (1H, d, J = 8.9 Hz), 8.04 (1H, d, J = 0.8 Hz). Fumarate 886 1H-NMR (CDCl3) ppm: 0.96-1.12 (4H, m), 1.16-1.44 (6H, m), 1.55-1.80 (5H, m), 2.20- 2.30 (1H, m), 2.62 (1H, d, J = 11.2 Hz), 2.75- 2.85 (2H, m), 7.04 (1H, dd, J = 1.8, 11.8 Hz), 7.15 (1H, d, J = 1.8 Hz), 7.42 (1H, d, J = 2.5 Hz). 887 1H-NMR (CDCl3) ppm: 0.96-1.15 (4H, m), 1.15-1.39 (3H, m), 1.42 (3H, s), 1.55-1.69 (3H, m), 1.69-1.80 (2H, m), 2.23-2.34 (1H, m), 2.65 (1H, d, J = 11.1 Hz), 2.75-2.85 (2H, m), 4.01 (3H, s), 6.76 (1H, d, J = 1.7 Hz), 6.97 (1H, d, J = 1.7 Hz), 7.38 (1H, s). 888 1H-NMR (DMSO-d6) ppm: 0.99-1.42 (7H, m), 1.50-1.78 (7H, m), 1.72-2.05 (1H, m), 2.75-3.11 (3H, m), 3.16-3.40 (1H, br), 4.95- 6.80 (1H, br), 6.95-7.11 (2H, m), 7.12-7.21 (1.25H, m), 7.33 (0.5H, s), 7.51 (0.25H, s), 8.08 (1H, brs), 9.05 (1H, brs), 9.64 (1H, brs). 2 Hydrochloride 889 1H-NMR (CDCl3) ppm: 0.99-1.12 (4H, m), 1.20-1.43 (7H, m), 1.62-1.83 (4H, m), 2.34- 2.42 (1H, m), 2.70 (1H, d, J = 11.5 Hz), 2.76- 2.85 (1H, m), 2.91 (1H, d, J = 11.5 Hz), 3.92 (3H, s), 6.45 (1H, d, J = 1.4 Hz), 6.80-6.83 (1H, m), 7.45 (1H, d, J = 0.9 Hz). 890 1H-NMR (CDCl3) ppm: 1.01-1.15 (4H, m), 1.20-1.45 (7H, m), 1.67-1.90 (4H, m), 2.44- 2.53 (1H, m), 2.77-2.87 (2H, m), 2.98 (1H, d, J = 11.9 Hz), 6.74 (1H, dd, J = 1.6, 11.5 Hz), 6.90-6.94 (1H, m), 7.43 (1H, d, J = 0.9 Hz).

(379) TABLE-US-00095 TABLE 98 absolute configuration Ex. No. R.sup.4 NMR Salt 891 1H-NMR (CDCl3) ppm: 0.83-1.43 (26H, m), 1.52 (3H, s), 1.55-1.91 (7H, m), 2.34-2.61 (2H, m), 2.80-3.00 (2H, m), 6.69-6.84 (3H, m), 7.24 (1H, d, J = 3.2 Hz). 892 1H-NMR (CDCl3) ppm: 0.76-1.40 (26H, m), 1.52 (3H, s), 1.56-1.95 (7H, m), 2.36-2.64 (2H, m), 2.80-3.01 (2H, m), 3.88 (3H, s), 6.54 (1H, d, J = 8.1 Hz), 6.69 (1H, d, J = 3.1 Hz), 6.73 (1H, d, J = 8.1 Hz), 7.24 (1H, d, J = 3.1 Hz). 893 00 1H-NMR (CDCl3) ppm: 0.98-1.17 (23H, m), 1.17-1.40 (3H, m), 1.42 (3H, s), 1.55-1.66 (2H, m), 1.66-1.76 (2H, m), 1.84 (3H, quint, J = 7.5 Hz), 2.27-2.38 (1H, m), 2.72 (1H, d, J = 11.2 Hz), 2.77-2.85 (2H, m), 6.47 (1H, d, J = 3.4 Hz), 7.27 (1H, d, J = 3.4 Hz), 7.61 (1H, d, J = 2.4 Hz), 8.06 (1H, d, J = 2.4 Hz). 894 01 1H-NMR (CDCl3) ppm: 0.90-1.40 (26H, m), 1.43 (3H, s), 1.59-1.80 (4H, m), 1.95-2.06 (3H, m), 2.30-2.39 (1H, m), 2.58 (1H, d, J = 11.3 Hz), 2.79-2.89 (2H, m), 6.98 (1H, d, J = 1.5, 8.5 Hz), 7.31 (1H, s), 7.34 (1H, d, J = 0.6 Hz), 7.52 (1H, d, J = 8.5 Hz).

(380) TABLE-US-00096 TABLE 99 absolute configuration 02 Ex. No. R.sup.4 NMR Salt 895 03 1H-NMR (DMSO-d6) ppm: 0.77-0.92 (1H, m), 0.95 (3H, s), 1.08-1.35 (3H, m), 1.40 (3H, s), 1.47-1.58 (2H, m), 1.58-1.82 (3H, m), 2.27- 2.48 (2H, m), 2.60-2.85 (2H, m), 6.47 (1H, brs), 6.58-6.65 (1H, m), 6.81 (1H, dd, J = 8.3, 10.9 Hz), 7.30 (1H, t, J = 2.6 Hz), 11.47 (1H, s). 896 04 1H-NMR (CDCl3) ppm: 0.77-0.99 (4H, m), 1.08-1.90 (11H, m), 2.21-2.46 (2H, m), 2.58- 2.85 (2H, m), 3.86 (3H, s), 6.38 (1H, brs), 6.47-6.63 (2H, m), 7.13 (1H, t, J = 2.6 Hz), 11.07 (1H, s). 897 05 1H-NMR (DMSO-d6) ppm: 0.91-1.08 (1H, m), 1.08-1.60 (11H, m), 1.61-1.72 (1H, m), 1.78-1.90 (1H, m), 2.60-2.71 (1H, m), 2.75 (1H, d, J = 11.7 Hz), 2.90-3.05 (2H, m), 6.39 (1H, dd, J = 1.8, 3.4 Hz), 6.47 (1H, s), 7.42- 7.49 (1H, m), 7.73 (1H, d, J = 2.0 Hz), 7.98 (1H, d, J = 2.2 Hz), 8.18-10.97 (2H, br), 11.59 (1H, s). Fumarate 898 06 1H-NMR (DMSO-d6) ppm: 0.81-1.02 (4H, m), 1.10-1.36 (6H, n), 1.36-2.05 (5H, m), 2.25- 2.35 (1H, m), 2.57 (1H, d, J = 11.0 Hz), 2.62- 2.70 (1H, m), 2.75 (1H, d, J = 11.0 Hz), 6.91 (1H, dd, J = 1.7, 8.6 Hz), 7.03 (1H, s), 7.27 (1H, d, J = 0.6 Hz), 7.55 (1H, d, J = 8.6 Hz) 11.93-12.33 (1H, br).

(381) TABLE-US-00097 TABLE 100 absolute configuration 07 Ex. No. R.sup.4 NMR Salt 899 08 1H-NMR (CDCl3) ppm: 0.75-1.13 (5H, m), 1.25-1.45 (3H, m), 1.48 (3H, s), 1.62-1.85 (3H, m), 2.08-2.19 (1H, m), 2.66-2.78 (2H, m), 2.85-2.94 (1H, m), 3.27 (1H, d, J = 11.9 Hz), 3.85 (3H, s), 6.46 (1H, d, J = 3.5 Hz), 6.63 (1H, d, J = 5.4 Hz), 7.06 (1H, d, J = 3.5 Hz), 8.20 (1H, d, J = 5.4 Hz). 900 09 1H-NMR (DMSO-d6) ppm: 0.91-1.62 (11H, m), 1.62-1.84 (2H, m), 1.82-1.95 (1H, m), 2.65-2.83 (2H, m), 2.99-3.10 (2H, m), 3.79 (3H, s), 6.41 (1H, d, J = 3.4 Hz), 6.48 (2H, s), 7.50 (1H, d, J = 3.4 Hz), 7.76 (1H, d, J = 2.2 Hz), 8.04 (1H, d, J = 2.2 Hz), 8.35-11.00 (2H, br) Fumarate

(382) TABLE-US-00098 TABLE 101 absolute configuration 0 Ex. No. R.sup.4 NMR Salt 901 1H-NMR (DMSO-d6) ppm: 0.86-1.01 (1H, m), 1.12-1.40 (5H, m), 1.51-1.76 (7H, m), 1.72- 2.10 (3H, m), 2.67-2.81 (2H, m), 2.81-3.00 (5H, m), 3.05-3.20 (1H, m), 6.65-7.10 (2H, m), 7.21 (1H, d, J = 8.4 Hz), 9.03-9.20 (1H, m), 9.59-9.77 (1H, m). 2 Hydrochloride 902 1H-NMR (DMSO-d6) ppm: 0.88-1.04 (1H, m), 1.15-1.41 (5H, m), 1.48-1.80 (7H, m), 1.90-2.10 (3H, m), 2.65-3.05 (7H, m), 3.05- 3.22 (1H, m), 4.90-6.25 (1H, br), 6.94 (1H, s), 7.11 (1H, s), 9.21 (1H, brs), 9.70 (1H, brs). 2 Hydrochloride 903 1H-NMR (DMSO-d6) ppm: 0.93-1.22 (2H, m), 1.22-1.43 (4H, m), 1.43-1.79 (7H, m), 1.90-2.10 (1H, m), 2.58-3.40 (6H, m), 4.52 (2H, t, J = 8.6 Hz), 5.30-6.20 (1H, br), 6.50- 7.45 (3H, m), 8.65-9.38 (1H, br), 9.38-9.92 (1H, br). 2 Hydrochloride 904 1H-NMR (DMSO-d6) ppm: 0.96-1.13 (1H, m), 1.13-1.42 (5H, m), 1.49-1.66 (6H, m), 1.66-1.77 (1H, m), 1.93-2.05 (1H, m), 2.74- 2.90 (2H, m), 2.98 (1H, d, J = 12.5 Hz), 3.08- 3.20 (1H, m), 4.35-4.68 (1H, br), 6.95 (1H, dd, J = 2.0, 8.6 Hz), 7.26 (1H, d, J = 2.0 Hz), 7.36 (1H, d, J = 8.6 Hz), 8.98-9.20 (1H, br), 9.60- 9.85 (1H, br). 2 Hydrochloride

(383) TABLE-US-00099 TABLE 102 absolute configuration Ex. No. R.sup.4 NMR Salt 905 1H-NMR (CDCl3) ppm: 0.75-1.04 (2H, m) 1.04-1.13 (21H, m), 1.15-1.37 (6H, m), 1.38 (3H, s), 1.52-1.75 (4H, m), 2.12-2.20 (1H, m), 2.58 (1H, d, J = 11.1 Hz), 2.69-2.78 (2H, m), 6.76-6.81 (2H, m), 6.92-6.97 (2H, m). 906 1H-NMR (CDCl3) ppm: 0.88-1.14 (23H, m), 1.16-1.37 (6H, m), 1.38 (3H, s), 1.60-1.77 (4H, m), 2.20-2.29 (1H, m), 2.57 (1H, d, J = 11.3 Hz), 2.72-2.82 (2H, m), 6.60-6.65 (2H, m), 6.65-6.70 (1H, m), 7.07-7.14 (1H, m). 907 1H-NMR (CDCl3) ppm: 0.75-1.15 (23H, m), 1.17-1.40 (9H, m), 1.52-1.75 (4H, m), 2.10- 2.17 (1H, m), 2.55 (1H, d, J = 11.1 Hz), 2.70- 2.77 (2H, m), 6.69-6.74 (1H, m), 6.78-6.87 (2H, m). 908 1H-NMR (CDCl3) ppm: 0.81-1.38 (29H, m), 1.39 (3H, s), 1.58-1.76 (4H, m), 2.23-2.32 (1H, m), 2.61 (1H, d, J = 11.2 Hz), 2.72-2.82 (2H, m), 4.79 (2H, s), 7.02-7.08 (2H, m), 7.24- 7.30 (2H, m). 909 0 1H-NMR (CDCl3) ppm: 0.75-1.35 (29H, m), 1.37 (3H, s), 1.62-1.78 (4H, m), 2.22-2.30 (1H, m), 2.60 (1H, d, J = 11.4 Hz), 2.71-2.85 (2H, m), 5.30 (2H, s), 6.72 (1H, dd, J = 2.0, 12.0 Hz), 6.86 (1H, J = 2.0, 8.2 Hz), 7.44 (1H, t, J = 8.4 Hz). 910 1H-NMR (CDCl3) ppm: 0.75-1.39 (32H, m), 1.53-1.75 (4H, m), 2.10-2.17 (1H, m), 2.56 (1H, d, J = 11.1 Hz), 2.68-2.77 (2H, m), 6.80 (1H, d, J = 8.6 Hz), 6.84 (1H, dd, J = 2.4, 8.6 Hz), 7.08 (1H, d, J = 2.4 Hz). 911 1H-NMR (CDCl3) ppm: 0.85-1.09 (23H, m), 1.09-1.36 (3H, m), 1.37 (3H, s), 1.50-1.75 (4H, m), 2.11-2.19 (1H, m), 2.57 (1H, d, J = 11.1 Hz), 2.67-2.77 (2H, m), 4.95 (2H, s), 6.67 (1H, d, J = 2.5 Hz), 6.82 (1H, d, J = 8.5 Hz), 6.91 (1H, dd, J = 2.5, 8.5 Hz).

(384) TABLE-US-00100 TABLE 103 absolute configuration Ex. No. R.sup.4 NMR Salt 912 1H-NMR (CDCl3) ppm: 0.92-1.06 (1H, m), 1.09 (3H, s), 1.12-1.37 (3H, m), 1.40 (3H, s), 1.55-1.66 (2H, m), 1.66-1.78 (2H, m), 2.15- 2.25 (1H, m), 2.57-2.65 (1H, m), 2.69-2.83 (2H, m), 3.15-4.30 (2H, br), 6.72-6.79 (2H, m), 6.95-7.01 (2H, m). 913 1H-NMR (DMSO-d6) ppm: 0.82-1.00 (4H, m), 1.09-1.35 (6H, m), 1.40-1.52 (1H, m), 1.52-1.70 (4H, m), 2.12-2.25 (1H, m), 2.45- 2.55 (1H, m), 2.55-2.65 (1H, m), 2.66 (1H, d, J = 11.0 Hz), 6.40-6.51 (3H, m), 7.00-7.10 (1H, m), 9.21 (1H, s). 914 1H-NMR (DMSO-d6) ppm: 0.90-1.05 (1H, m), 1.05-1.38 (5H, m), 1.38-1.62 (6H, m), 1.64-1.74 (1H, m), 1.82-1.94 (1H, m), 2.53- 2.62 (1H, m), 2.70 (1H, d, J = 12.0 Hz), 2.86 (1H, d, J = 12.0 Hz), 2.95-3.06 (1H, m), 3.74 (3H, s), 4.45 (2H, s), 4.65-5.60 (1H, br), 6.46 (1H, s), 6.87 (1H, d, J = 8.6 Hz), 6.94 (1H, dd, J = 2.5, 8.6 Hz), 7.15 (1H, d, J = 2.2 Hz), 8.59-10.40 (1H, br). Fumarate 915 1H-NMR (DMSO-d6) ppm: 0.82-0.99 (4H, m), 1.05-1.32 (6H, m), 1.41-1.50 (1H, m), 1.50-1.65 (3H, m), 2.05-2.14 (1H, m), 2.47 (1H, d, J = 10.8 Hz), 2.53-2.62 (2H, m), 2.95- 3.65 (1H, br), 6.67-6.72 (1H, m), 6.79-6.87 (2H, m), 8.65-10.50 (1H, m). 916 1H-NMR (CDCl3) ppm: 0.85-1.10 (5H, m), 1.15-1.42 (6H, m), 1.56-2.05 (5H, m), 2.25- 2.15 (1H, m), 2.56-2.65 (1H, m), 2.72-2.84 (2H, m), 4.64 (2H, s), 7.04-7.10 (2H, m), 7.25- 7.32 (2H, m). 917 1H-NMR (CDCl3) ppm: 0.95-1.44 (11H, m), 1.44-2.20 (5H, m), 2.25-2.35 (1H, m), 2.61 (1H, d, J = 11.4 Hz), 2.72-2.86 (2H, m), 4.69 (2H, s), 6.75 (1H, dd, J = 2.0, 12.1 Hz), 6.83 (1H, dd, J = 2.0, 8.1 Hz), 7.29 (1H, t, J = 8.4 Hz). 918 0 1H-NMR (CDCl3) ppm: 0.90-1.11 (4H, m), 1.14-1.42 (6H, m), 1.53-1.77 (4H, m), 2.12- 2.21 (1H, m), 2.57 (1H, d, J = 11.2 Hz), 2.67- 2.80 (2H, m), 2.81-3.38 (2H, br), 6.89-6.97 (2H, m), 7.07 (1H, dd, J = 0.5.1.9 Hz). 919 1H-NMR (DMSO-d6) ppm: 0.78-0.93 (1H, m), 0.95 (3H, s), 1.04-1.32 (6H, m), 1.37-1.66 (5H, m), 2.05-2.14 (1H, m), 2.45-2.62 (3H, m), 4.43 (2H, s), 4.65-5.20 (1H, br), 6.65 (1H, d, J = 8.4 Hz), 6.74 (1H, dd, J = 2.5, 8.4 Hz), 7.03 (1H, d, J = 2.5 Hz), 8.81-9.28 (1H, br).

(385) TABLE-US-00101 TABLE 104 absolute configuration Ex. No. R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 920 CH3 1H-NMR (DMSO-d6) ppm: 0.88-1.03 (1H, m), 1.10-1.25 (1H, m), 1.25- 1.40 (4H, m), 1.45-1.66 (6H, m), 1.67-1.89 (1H, m), 1.92-2.03 (1H, m), 2.26 (3H, m), 2.65 (1H, d, J = 12.5 Hz), 2.80 (1H, d, J = 12.5 Hz), 2.88-3.00 (1H, m), 3.15-3.28 (1H, m), 7.06-7.17 (2H, m), 7.19-7.26 (2H, m), 9.04 (1H, brs), 9.58 (1H, brs). Hydrochloride 921 CH3 CH3 1H-NMR (DMSO-d6) ppm: 0.87-1.02 (1H, m), 1.10-1.24 (1H, m), 1.24- 1.40 (4H, m), 1.40-1.64 (6H, m), 1.67-1.77 (1H, m), 1.95-2.04 (1H, m), 2.21 (3H, s), 2.22 (3H, s), 2.59 (1H, d, J = 12.5 Hz), 2.82 (1H, d, J = 12.5 Hz), 2.86-2.95 (1H, m), 3.15- 3.37 (1H, m), 6.97-7.03 (2H, m), 7.07-1.15 (1H, m), 9.11 (1H, brs), 9.65 (1H, brs). Hydrochloride 922 F CN 1H-NMR (DMSO-d6) ppm: 1.22-1.65 (10H, m), 1.65-1.84 (2H, m), 1.90-2.00 (1H, m), 2.10- 2.20 (1H, m), 3.38-3.61 (4H, m), 3.78 (1H, d, J = 14.5 Hz), 6.83 (1H, dd, J = 2.3, 8.9 Hz), 6.97 (1H, dd, J = 2.0, 13.7 Hz), 7.65 (1H, t, J = 8.5 Hz), 8.93-9.15 (1H, m), 9.51- 9.71 (1H, m). 2 Hydrochloride 923 OCF3 1H-NMR (DMSO-d6) ppm: 1.00-1.15 (1H, m), 1.15-1.41 (5H, m), 1.50- 1.67 (6H, m), 1.67-1.77 (1H, m), 1.95-2.05 (1H, m), 2.81-2.95 (2H, m), 3.01 (1H, d, J = 12.5 Hz), 3.11-3.25 (1H, m), 5.42- 6.30 (1H, br), 7.20-7.27 (2H, m), 7.31-7.37 (2H, m), 9.02-9.20 (1H, brm), 9.60-9.80 (1H, brm). 2 Hydrochloride 924 OCF3 1H-NMR (DMSO-d6) ppm: 1.04-1.20 (1H, m), 1.20-1.41 (5H, m), 1.49- 1.78 (7H, m), 1.96-2.06 (1H, m), 2.85-3.11 (3H, m), 3.15-3.28 (1H, m), 5.10-6.60 (1H, br), 7.00- 7.15 (1H, m), 7.22-7.29 (1H, m), 7.47-7.54 (1H, m), 9.09 (1H, brs), 9.71 (1H, brs). 2 Hydrochloride 925 OCHF2 1H-NMR (DMSO-d6) ppm: 0.98-1.11 (1H, m), 1.11-1.25 (1H, m), 1.25- 1.40 (4H, m), 1.48-1.65 (6H, m), 1.65-1.76 (1H, m), 1.92-2.03 (1H, m), 2.75-2.90 (2H, m), 2.99 (1H, d, J = 12.8 Hz), 3.10-3.23 (1H, m), 4.85- 5.90 (1H, br), 7.01 (0.25H, s), 7.13-7.22 (4.5H, m), 7.38 (0.25H, s), 9.06 (1H, brs), 9.63 (1H, brs). 2 Hydrochloride 926 Cl OCHF2 1H-NMR (DMSO-d6) ppm: 1.02-1.42 (6H,m), 1.50-1.66 (6H, m), 1.66- 1.77 (1H, m), 1.95-2.05 (1H, m), 2.81-2.94 (2H, m), 3.02 (1H, d, J = 12.5 Hz), 3.10-3.23 (1H, m), 3.88-4.25 (1H, br), 7.15 (1H, dd, J = 2.6, 8.8 Hz), 7.24 (1H, t, J = 73.3 Hz), 7.32 (1H, d, J = 2.6 Hz), 7.34 (1H, d, J = 8.8 Hz), 9.05-9.22 (1H, m), 9.62- 9.80 (1H, m). 2 Hydrochloride 927 OCHF2 1H-NMR (DMSO-d6) ppm: 1.02-1.16 (1H, m), 1.16-1.41 (5H, m), 1.50- 1.67 (6H, m), 1.67-1.78 (1H, m), 1.96-2.06 (1H, m), 2.84-2.97 (2H, m), 3.04 (1H, d, J = 12.5 Hz), 3.11-3.25 (1H, m), 6.89 (1H, s), 6.96 (1H, dd, J = 2.1, 8.1 Hz), 7.00 (1H, d, J = 8.1 Hz), 7.27 (1H, t, J = 74.1 Hz), 7.39 (1H, t, J = 8.1 Hz), 8.30-9.30 (2H, br), 9.69-9.89 (1H, br). 2 Hydrochloride 928 OCHF2 Cl 1H-NMR (DMSO-d6) ppm: 1.04-1.40 (6H, m), 1.50-1.69 (6H, m), 1.69- 1.79 (1H, m), 1.92-2.04 (1H, m), 2.78-2.89 (1H, m), 2.89-3.06 (2H, m), 3.15-3.27 (1H, m), 7.01- 7.08 (2H, m), 7.32 (1H, t, J = 73,3 Hz), 7.54 (1H, d, J = 8.4 Hz), 8.81-9.11 (1H, m), 9.40-9.69 (1H, m). Hydrochloride 929 OCHF2 F 1H-NMR (DMSO-d6) ppm: 1.00-1.40 (6H, m), 1.47-1.65 (6H, m), 1.67- 1.77 (1H. m), 1.90-2.00 (1H, m), 2.70-2.80 (1H, m), 2.87 (1H, d, J = 12.5 Hz), 2.96 (1H, d, J = 12.5 Hz), 3.10-3.24 (1H, m), 7.02-7.11 (2.25H, m), 7.27 (0.5H, s), 7.37 (1H, dd, J = 8.8, 10.5 Hz), 7.46 (0.25H, s), 8.80-9.00 (1H, br), 9.39-9.58 (1H, br). Hydrochloride 930 CN OCHF2 1H-NMR (DMSO-d6) ppm: 1.03-1.15 (1H, m), 1.17-1.41 (5H, m), 1.48- 1.82 (7H, m), 1.93-2.05 (1H, m), 2.82-2.91 (1H, m), 2.94 (1H, d, J = 12.7 Hz), 3.01 (1H, d, J = 12.7 Hz), 3.08-3.25 (1H, m), 4.00-4.60 (1H, br), 7.39 (1H, t, J = 72.6 Hz), 7.42 (1H, d, J = 8.9 Hz), 7.51 (1H, dd, J = 2.7, 9.0 Hz), 7.69 (1H, d, J = 2.7 Hz), 8.90-9.10 (1H, br), 9.40- 9.65 (1H, br). 2 Hydrochloride 931 F OCHF2 F 1H-NMR (DMSO-d6) ppm: 1.08-1.42 (6H, m), 1.42-1.80 (7H, m), 1.96- 2.07 (1H, m), 2.90-3.00 (1H, m), 3.05 (1H, d, J = 13.0 Hz), 3.10 (1H, d, J = 13.0 Hz), 3.17-3.29 (1H, m), 3.55-3.85 (1H, br), 6.97-7.06 (2.25H, m), 7.19 (0.5H, s). 7.37 (0.25H, s), 8.90-9.07 (1H, br), 9.51-9.70 (1H, br). 2 Hydrochloride 932 OCH2CHF2 1H-NMR (DMSO-d6) ppm: 0.98-1.80 (13H, m), 1.91-2.14 (1H, m), 2.61-3.50 (4H, m), 4.20- 4.40 (2H, m), 4.61-6.20 (1H, br), 6.39 (1H, tt, J = 3.4, 54.5 Hz), 6.85-7.65 (4H, brm), 8.84-10.20 (2H, br). 2 Hydrochloride 933 F OCH2CHF2 1H-NMR (CDCl3) ppm: 0.95-1.09 (4H, m), 1.15- 1.44 (7H, m), 1.57-1.78 (4H, m), 2.13-2.22 (1H, m), 2.56 (1H, d, J = 11.1 Hz), 2.70-2.79 (2H, m), 4.21 (2H, dt, J = 4.2, 13.1 Hz), 6.08 (1H, tt, J = 4.2, 55.1 Hz), 6.77-6.83 (1H. m), 6.84-6.95 (2H, m). 934 Cl OCH2CHF2 1H-NMR (CDCl3) ppm: 0.93-1.10 (4H, m), 1.15- 1.41 (7H, m), 1.53-1.77 (4H, m), 2.14-2.23 (1H, m), 2.57 (1H, d, J = 11.0 Hz), 2.68-2.79 (2H, m), 4.20 (2H, dt, J = 4.2, 13.0 Hz), 6.12 (1H, tt, J = 4.2, 55.1 Hz), 6.87 (1H,d, J = 8.7 Hz), 6.96 (1H, dd, J = 2.5, 8.7 Hz), 7.13 (1H, d, J = 2.5 Hz). 935 CH3 OCHF2 1H-NMR (DMSO-d6) ppm: 0.96-1.10 (1H, m), 1.12-1.40 (5H, m), 1.47- 1.63 (6H, m), 1.67-1.76 (1H, m), 1.90-2.01 (1H, m), 2.21 (3H, m), 2.70- 2.87 (2H, m), 2.96 (1H, d, J = 12.1 Hz), 3.07-3.22 (1H, m), 4.40-6.50 (1H, br), 6.94 (0.25H, s), 6.97- 7.03 (1H, m), 7.03-7.08 (1H, m), 7.09-7.15 (1.5H, m), 7.31 (0.25H, s), 9.01 (1H, brs), 9.56 (1H, brs). 2 Hydrochloride 936 OCH3 OCHF2 1H-NMR (DMSO-d6) ppm: 1.02-1.40 (6H, m), 1.50-1.79 (7H, m), 1.96- 2.06 (1H, m), 2.78-2.95 (2H, m), 2.98-3.22 (2H, m), 3.82 (3H, s), 6.75 (1H, d, J = 7.8 Hz), 6.80- 6.93 (1.25H, m), 7.01 (0.5H. s), 7.11-7.21 (1.25H, m), 7.21-7.75 (1H, br), 9.14 (1H, brs), 9.77 (1H, brs). 2 Hydrochloride

(386) TABLE-US-00102 TABLE 105 absolute configuration Ex. No. R.sup.4 NMR Salt 937 1H-NMR (DMSO-d6) ppm: 1.15-1.60 (10H, m), 1.60-1.86 (2H, m), 1.95-2.15 (2H, m), 2.47 (3H, s), 3.37 (1H, d, J = 14.2 Hz), 3.41-3.66 (2H, m), 3.88 (1H, d, J = 14.2 Hz), 5.32-7.05 (1.5H, br), 7.18 (1H, d, J = 9.2 Hz), 7.36 (1H, d, J = 9.2 Hz), 7.45-9.40 (1.5 H, br). Oxalate

(387) TABLE-US-00103 TABLE 106 absolute configuration Ex. No. R.sup.4 NMR Salt 938 1H-NMR (CDCl3) ppm: 0.98-1.17 (23H, m), 1.17-1.40 (6H, m), 1.43 (3H, s), 1.59-1.68 (1H, m), 1.68-1.80 (3H, m), 2.32-2.41 (1H, m), 2.68 (1H, d, J = 11.3 Hz), 2.77-2.85 (1H, m), 2.88 (1H, d, J = 11.3 Hz), 7.08 (1H, dd, J = 2.4, 8.8 Hz), 7.16 (1H, d, J = 2.4 Hz), 7.22 (1H, dd, J = 2.1, 8.7 Hz), 7.37 (1H, d, J = 1.8 Hz), 7.57-7.64 (2H, m). 939 1H-NMR (CDCl3) ppm: 0.82-1.18 (23H, m), 1.20-1.40 (6H, m), 1.43 (3H, s), 1.59-1.70 (1H, m), 1.70-1.85 (3H, m), 2.35-2.45 (1H, m), 2.69 (1H, d, J = 11.3 Hz), 2.77-2.86 (1H, m), 2.91 (1H, d, J = 11.3 Hz), 7.02 (1H, dd, J = 2.4, 8.8 Hz), 7.09-7.15 (2H, m), 7.27 (1H, d, J = 1.9 Hz), 7.61-7.68 (2H, m). 940 1H-NMR (CDCl3) ppm: 0.97-1.41 (29H, m), 1.43 (3H, s), 1.59-1.70 (1H, m), 1.70-1.80 (3H, m), 2.34-2.44 (1H, m), 2.69 (1H, d, J = 11.3 Hz), 2.78-2.87 (1H, m), 2.89 (1H, d, J = 11.3 Hz), 7.11 (1H, d, J = 8.9 Hz), 7.34 (1H, dd, J = 2.1, 9.0 Hz), 7.37 (1H, d, J = 1.9 Hz), 7.53 (1H, d, J = 8.9 Hz), 8.10 (1H, d, J = 8.9 Hz). 941 1H-NMR (CDCl3) ppm :0.75-1.42 (29H, m), 1.44 (3H, s), 1.58-1.83 (4H, m), 2.34-2.42 (1H, m), 2.68 (1H, d, J = 11.3 Hz), 2.78-2.87 (1H, m), 2.91 (1H, d, J = 11.3 Hz), 3.91 (3H, s), 5.19-5.27 (2H, m), 7.21 (1H, d, J = 9.1 Hz), 7.29 (1H, d, J = 2.2, 9.1 Hz), 7.37 (1H, d, J = 2.1 Hz), 7.69 (1H, d, J = 9.0 Hz), 8.16 (1H, d, J = 9.1 Hz). 942 0 1H-NMR (CDCl3) ppm: 0.95-1.18 (23H, m), 1.18-1.40 (6H, m), 1.44 (3H, s), 1.57-1.77 (4H, m), 2.33-2.41 (1H, m), 2.71 (1H, d, J = 11.2 Hz), 2.77-2.85 (1H, m), 2.87 (1H, d, J = 11.2 Hz), 3.89 (3H, s), 4.94 (2H, d, J = 1.0 Hz), 7.02 (1H, s), 7.22 (1H, dd, J = 2.0, 8.6 Hz), 7.43 (1H, d, J = 1.8 Hz), 7.64 (1H, d, J = 8.6 Hz), 7.88 (1H, s).

(388) TABLE-US-00104 TABLE 107 absolute configuration Ex. No. R.sup.4 NMR Salt 943 1H-NMR (DMSO-d6) ppm: 0.88-1.03 (4H, m), 1.10-1.37 (6H, m), 1.45-1.68 (5H, m), 2.25-2.36 (1H, m), 2.58 (1H, d, J = 10.9 Hz), 2.62-2.71 (1H, m), 2.73 (1H, d, J = 10.9 Hz), 7.02 (1H, dd, J = 2.4, 8.7 Hz), 7.05 (1H, d, J = 2.4 Hz), 7.16 (1H, dd, J = 2.1, 8.7 Hz), 7.37 (1H, d, J = 1.8 Hz), 7.58 (1H, d, J = 8.8 Hz), 7.67 (1H, d, J = 8.8 Hz), 9.57 (1H, brs). 944 1H-NMR (DMSO-d6) ppm: 0.88-1.04 (4H, m), 1.12-1.37 (6H, m), 1.45-1.74 (5H, m), 2.32-2.41 (1H, m), 2.60 (1H, d, J = 11.1 Hz), 2.63-2.72 (1H, m), 2.80 (1H, d, J = 11.1 Hz), 6.94 (1H, dd, J = 2.4, 8.8 Hz). 6.97-7.04 (2H, m), 7.21 (1H, d, J = 1.8 Hz), 7.64 (2H, d, J = 8.8 Hz). 9.62 (1H, s). 945 1H-NMR (DMSO-d6) ppm: 0.90-1.10 (4H, m), 1.15-1.40 (6H, m), 1.51-1.75 (4H, m), 2.35-2.48 (1H, m), 2.60-2.88 (3H, m), 2.96- 3.88 (1H, br), 7.23 (1H, d, J = 8.9 Hz), 7.34 (1H, dd, J = 2.1, 9.0 Hz), 7.47 (1H, d, J = 2.0 Hz), 7.70 (1H, d, J = 8.9 Hz), 7.92 (1H, d, J = 9.0 Hz), 8.92-11.38 (1H, br). 946 1H-NMR (DMSO-d6) ppm: 0.93-1.12 (4H, m), 1.15-1.41 (6H, m), 1.54-1.80 (4H, m), 2.48-2.60 (1H, m), 2.70-2.87 (2H, m), 2.92 (1H, d, J = 11.5 Hz), 3.03-4.36 (1H, br), 7.08- 7.18 (2H, m), 7.50 (1H, d, J = 2.0 Hz), 7.67 (1H, d, J = 8.8 Hz), 7.75 (1H, d, J = 8.7 Hz), 8.89-11.11 (1H, br). 947 1H-NMR (DMSO-d6) ppm: 0.90-1.05 (4H, m), 1.13-1.37 (6H, m), 1.47-1.70 (5H, m), 2.30-2.39 (1H, m), 2.61 (1H, d, J = 11.0 Hz), 2.64-2.73 (1H, m), 2.78 (1H, d, J = 11.0 Hz), 3.88 (3H, s), 4.81 (1H, t, J = 5.2 Hz), 4.88 (2H, d, J = 5.2 Hz), 7.27 (1H, dd, J = 2.2, 9.1 Hz), 7.35 (1H, d, J = 9.1 Hz), 7.42 (1H, d, J = 2.1 Hz), 7.80 (1H, d, J = 9.1 Hz), 8.03 (1H, d, J = 9.1 Hz). 948 1H-NMR (DMSO-d6) ppm : 0.95-1.10 (1H, m), 1.10-1.50 (9H, m), 1.53-1.73 (3H, m), 1.77-1.87 (1H, m), 2.58-2.70 (1H, m), 2.85 (2H, s), 2.89-3.00 (1H, m), 3.87 (3H, s), 4,61 (2H, s), 6.46 (1H, s), 7.20 (1H, dd, J = 2.0, 8.7 Hz), 7.22 (1H, s), 7.46 (1H, d, J = 1.6 Hz), 7.73 (1H, d, J = 8.7 Hz), 7.79 (1H, s). 1/2 Fumarate

(389) TABLE-US-00105 TABLE 108 absolute configuration Ex. No. R.sup.4 NMR Salt 949 1H-NMR (CDCl3) ppm: 0.91-1.05 (1H, m), 1.08 (3H, s), 1.12-1.62 (9H, m), 1.68-1.78 (2H, m), 2.42-2.50 (1H, m), 2.62 (1H, d, J = 11.3 Hz), 2.75 (1H, d, J = 11.3 Hz), 2.91-3.00 (1H, m), 3.98 (3H, s), 6.78 (1H, d, J = 8.1 Hz), 7.20 (1H, d, J = 8.1 Hz), 7.43-7.54 (2H, m), 8.21-8.26 (1H, m), 8.50-8.54 (1H, m). 950 0 1H-NMR (DMSO-d6) ppm: 0.93-1.22 (2H, m), 1.26-1.44 (5H, m), 1.44-1.54 (1H, m), 1.56-1.77 (5H, m), 1.99-2.08 (1H, m), 2.62 (3H, s), 2.76 (1H, d, J = 12.4 Hz), 2.98-3.08 (2H, m), 3.33-3.50 (1H, m), 7.28 (1H, d, J = 7.5 Hz), 7.38 (1H, d, J = 7.5 Hz), 7.54-7.61 (2H, m), 7.97-8.03 (1H, m), 8.43-8.52 (1H, m), 9.10-9.25 (1H, br), 9.62-9.77 (1H, br). Hydrochloride 951 1H-NMR (DMSO-d6) ppm: 1.00-1.30 (2H, m), 1.30-1.45 (4H, m), 1.45-1.65 (2H, m), 1.65-1.85 (5H, m), 2.00-2.13 (1H, m), 2.91 (1H, d, J = 12.6 Hz), 3.05-3.20 (2H, m), 3.41- 3.57 (1H, m), 3.93-4.29 (1H, br), 7.61-7.77 (5H, m), 7.98-8.05 (1H, m), 8.55-8.61 (1H, m), 8.77-8.88 (2H, m), 9.19-9.35 (1H, m), 9.669.81 (1H, m). 2 Hydrochloride 952 1H-NMR (DMSO-d6) ppm: 0.96-1.45 (6H, m), 1.55-1.80 (7H, m), 2.00-2.12 (1H, m), 2.85-3.40 (4H, m), 3.87 (3H, s), 7.05-7.26 (2H, m), 7.32 (1H, d, J = 2.5 Hz), 7.42-7.73 (1H, br), 7.73-7.90 (2H, m), 8.75-9.60 (2H, br), 9.60-10.15 (1H, br). 2 Hydrochloride 953 1H-NMR (DMSO-d6) ppm: 0.85-1.00 (1H, m), 1.10-1.70 (12H, m), 1.75-1.87 (1H, m), 2.62-2.81 (3H, m), 2.98-3.12 (1H, m), 3.20- 3.45 (4H, m), 6.46 (1H, s), 7.15-7.35 (3H, m), 7.35-7.52 (1H, m), 7.88 (1H, d, J = 8.1 Hz), 8.05-9.35 (1H, br). 1/2 Fumarate 954 1H-NMR (DMSO-d6) ppm: 1.05-1.45 (6H, m), 1.55-1.80 (7H, m), 1.99-2.10 (1H, m), 2.91-3.08 (2H, m), 3.08-3.30 (2H, m), 3.98 (3H, s), 7.44 (1H, d, J = 9.0 Hz), 7.56 (1H, d, J = 9.2 Hz), 7.67 (1H, brs), 7.96 (1H, d, J = 9.1 Hz), 8.05 (1H, d, J = 9.1 Hz), 8.15-9.10 (1H, br), 9.17-9.40 (1H, m), 9.69-9.89 (1H, m). 2 Hydrochloride 955 1H-NMR (CDCl3) ppm: 0.80-0.98 (1H, br), 1.03-1.17 (4H, m), 1.22-1.47 (6H, m), 1.63- 1.74 (1H, m), 1.74-1.89 (3H, m), 2.45-2.55 (1H, m), 2.76 (1H, d, J = 11.5 Hz), 2.81-2.90 (1H, m), 2.98 (1H, d, J = 11.5 Hz), 7.38-7.44 (2H, m), 7.49 (1H, dd, J = 1.6, 8.4 Hz), 7.76- 7.81 (1H, m), 7.83 (1H, d, J = 8.4 Hz), 8.12 (1H, s). 956 1H-NMR (DMSO-d6) ppm: 1.12-1.45 (6H, m), 1.55-1.90 (7H, m), 2.00-2.14 (1H, m), 3.08-3.40 (4H, m), 4.52-5.08 (1H, br), 7.45 (1H, dd, J = 2.0, 8.9 Hz), 7.64 (1H, d, J = 1.7 Hz), 7.73 (1H, dd, J = 1.6, 8.5 Hz), 8.00 (1H, d, J = 8.9 Hz), 8.04 (1H, d, J = 8.6 Hz), 8.49 (1H, s), 9.10-9.25 (1H, br), 9.60-9.75 (1H, br). 2 Hydrochloride 957 1H-NMR (DMSO-d6) ppm: 1.03-1.45 (6H, m), 1.50-1.80 (7H, m), 1.98-2.10 (1H, m), 2.90-3.30 (4H, m), 3.95 (3H, s), 6.91 (1H, d, J = 7.1 Hz), 7.23-7.34 (1H, br), 7.38-7.49 (2H, m), 7.48-7.65 (1H, br), 8.10 (1H, d, J = 8.9 Hz), 9.10-9.36 (1H, br), 9.60-9.88 (1H, br), 10.00-11.50 (1H, br). 2 Hydrochloride 958 1H-NMR (DMSO-d6) ppm: 1.10-1.48 (6H, m), 1.55-1.80 (7H, m), 1.981-2.10 (1H, m), 2.95-3.10 (2H, m ), 3.10-3.21 (1H, m), 3.21- 3.85 (1H, m), 3.99 (3H, s), 7.26 (1H, dd, J = 1.5, 8.7 Hz), 7.50 (1H, d, J = 9.1 Hz), 7.66 (1H, brs), 7.93 (2H, d, J = 9.1 Hz), 9.20 (1H, brs), 9.72 (1H, brs), 9.89-10.70 (1H, brs). 2 Hydrochloride 959 1H-NMR (DMSO-d6) ppm: 1.10-1.43 (6H, m), 1.56-1.80 (7H, m), 1.99-2.09 (1H, m), 2.95-3.06 (2H, m), 3.11 (1H, d, J = 12.5 Hz), 3.17-3.30 (1H, m), 6.05-7.25 (1H, br), 7.36 (1H, dd, J = 1.9, 8.8 Hz), 7.49 (1H, dd, J = 2.1, 8.8 Hz), 7.64 (1H, brs), 7.88 (1H, d, J = 8.9 Hz), 7.94 (1H, d, J = 8.9 Hz), 8.00 (1H, d, J = 1.8 Hz), 9.15-9.34 (1H, br), 9.69-9.85 (1H, br). 2 Hydrochloride 960 0 1H-NMR (CDCl3) ppm: 0.75-1.19 (5H, m), 1.24-1.44 (3H, m), 1.41 (3H, s), 1.59-1.73 (1H, m), 1.73-1.82 (2H, m), 1.90-2.00 (1H, m), 2.45-2.54 (1H, m), 2.73 (1H, d, J = 11.5 Hz), 2.81-2.92 (1H, m), 3.02 (1H, d, J = 11.5 Hz), 7.26 (1H, dd, J = 2.1, 9.0 Hz), 7.38-7.47 (2H, m), 7.51 (1H, d, J = 1.3 Hz), 7.91 (1H, d, J = 9.1 Hz), 7.94-7.99 (2H, m), 8.30 (1H, s), 8.34 (1H, s). 961 1H-NMR (DMSO-d6) ppm: 1.15-1.48 (6H, m), 1.55-1.80 (7H, m), 1.95-2.09 (1H, m), 2.91-3.05 (2H, m), 3.05-3.16 (1H, m), 3.16- 3.30 (1H, m), 3.70-4.4.10 (1H, br), 7.16 (0.25H, s), 7.32-7.40 (2.5H, m), 7.53 (0.25H, s), 7.62-7.70 (2H, m), 7.90 (1H, d, J = 8.8 Hz), 7.98 (1H, d, J = 9.0 Hz).9.05-9.25 (1H, br), 9.54-9.78 (1H, br). 2 Hydrochloride 962 1H-NMR (DMSO-d6) ppm: 1.05-1.50 (6H, m), 1.55-1.80 (7H, m), 1.97-2.10 (1H, m), 2.40-3.05 (2H, m), 3.05-3.16 (1H, m), 3.16- 3.31 (1H, m), 3.65-4.25 (4H, m), 7.44 (1H, dd, J = 2.0, 8.8 Hz), 7.56 (1H, s), 7.65 (1H, s), 7.89 (1H, d, J = 8.8 Hz), 8.47 (1H, s), 9.05- 9.35 (1H, br), 9.53-9.84 (1H, br). 2 Hydrochloride 963 1H-NMR (DMSO-d6) ppm: 1.08-1.46 (6H, m), 1.54-1.80 (7H, m), 1.97-2.08 (1H, m), 2.95-3.17 (3H, m), 3.17-3.31 1H, m), 4.65- 4.45 (1H, br), 7.46-7.50 (1H, m), 7.57-7.67 (3H, m), 7.97-8.04 (1H, m), 8.07-8.15 (1H, m), 9.13-9.35 (1H, br), 9.62-9.80 (1H, br). 2 Hydrochloride 964 1H-NMR (DMSO-d6) ppm: 1.08-1.47 (6H, m), 1.53-1.82 (7H, m), 1.98-2.09 (1H, m), 2.93-3.17 (3H, m), 3.17-3.30 (1H, m), 4.30- 4.85 (1H, br), 7.15 (1H, dd, J = 1.6, 12.4 Hz), 7.47 (1H, d, J = 1.3 Hz), 7.51-7.64 (2H, m), 7.97 (2H, d, J = 8.2 Hz), 9.10-9.30 (1H, br), 9.67-9.85 (1H, br). 2 Hydrochloride 965 1H-NMR (CDCl3) ppm: 1.00-1.15 (4H, m), 1.17-1.52 (7H, m), 1.58-1.68 (1H, m), 1.68- 1.79 (3H, m), 2.34-2.42 (1H, m), 2.69 (1H, d, J = 11.3 Hz), 2.77-2.86 (1H, m), 2.88 (1H, d, J = 11.3 Hz), 4.28 (2H, dt, J = 4.1, 13.1 Hz), 6.15 (1H, tt, J = 4.1, 55.2 Hz), 7.10 (1H, d, J = 2.5 Hz), 7.14 (1H, dd, J = 2.6, 8.9 Hz), 7.27 (1H, dd, J = 2.1, 8.7 Hz), 7.41 (1H, d, J = 2.0 Hz), 7.63-7.72 (2H, m). 966 1H-NMR (CDCl3) ppm: 1.00-1.15 (4H, m), 1.20-1.70 (8H, m), 1.70-1.88 (3H, m), 2.39- 2.48 (1H, m), 2.70 (1H, d, J = 11.4 Hz), 2.79- 2.88 (1H, m), 2.93 (1H, d, J = 11.4 Hz), 4.29 (2H, dt, J = 4.2, 13.1 Hz), 6.15 (1H, tt, J = 4.1, 55.2 Hz), 7.03-7.11 (2H, m), 7.16 (1H, dd, J = 2.1, 8.6 Hz), 7.33 (1H, d, J = 2.0 Hz), 7.65- 7.74 (2H, m). 967 1H-NMR (DMSO-d6) ppm: 0.91-1.05 (1H, m), 1.07-1.36 (5H, m), 1.36-1.63 (12H, m), 1.63-1.74 (1H, m), 1.80-1.83 (1H, m), 2.50- 2.62 (1H, m), 2.71 (1H, d, J = 12.0 Hz), 2.86 (1H, d, J = 12.0 Hz), 2.92-3.02 (1H, m), 4.78 (2H, s), 6.48 (2H, s), 6.73 (1H, d, J = 8.6 Hz), 6.83 (1H, d, J = 2.3 Hz), 6.91 (1H, dd, J = 2.3, 8.6 Hz). 9.52-11.33 (1H, br). Fumarate

(390) TABLE-US-00106 TABLE 109 absolute configuration Example R.sup.4 NMR Salt 968 1H-NMR (DMSO-d6) ppm: 0.96-1.10 (1H, m), 1.10-1.25 (1H, m), 1.25-1.41 (4H, m), 1.47-1.78 (7H, m), 1.94-2.05 (1H, m), 2.56 (3H, s), 2.84 (1H, d, J = 12.4 Hz), 2.90-3.02 (2H, m), 3.23-3.35 (1H, m), 7.15 (1H, d, J = 7.6 Hz), 7.22-7.33 (2H, m), 7.68 (1H, d, J = 7.9 Hz), 8.91-9.09 (1H, brm), 9.54-9.70 (1H, brm). Hydrochloride 969 0 1H-NMR (DMSO-d6) ppm (80 C): 1.03- 1.46 (6H, m), 1.50-1.79 (7H, m), 2.02-2.12 (1H, m), 2.53 (3H, s), 2.88 (1H, d, J = 12.4 Hz), 3.02-3.12 (1H, m), 3.12-3.27 (2H, m), 7.05 (1H, s), 7.13 (1H, d, J = 8.6 Hz), 7.62- 7.68 (2H, m), 9.25 (1H, brs), 9.75 (1H, brs). Hydrochloride 970 1H-NMR (DMSO-d6) ppm: 0.95-1.41 (6H, m), 1.40-1.76 (7H, m), 1.96-2.05 (1H, m), 2.84 (1H, d, J = 12.4 Hz), 2.93-3.01 (1H, m), 3.04 (1H, d, J = 12.4 Hz), 3.28-3.44 (1H, m), 7.25 (2H, d, J = 7.0 Hz), 7.64 (1H, dd, J = 4.0, 5.3 Hz), 7.86 (1H, d, J = 5.3 Hz), 9.04-9.19 (1H, brm), 9.63-9.75 (1H, brm). Hydrochloride 971 1H-NMR (DMSO-d6) ppm: 0.97-1.43 (6H, m), 1.45-1.78 (7H, m), 1.96-2.06 (1H, m), 2.87 (1H, d, J = 12.4 Hz), 2.94-3.06 (2H, m), 3.26- 3.43 (1H, m), 7.28 (1H, d, J = 8.1 Hz), 7.50 (1H, d, J = 8.1 Hz), 7.64 (1H, d, J = 5.4 Hz), 7.88 (1H, d, J = 5.4 Hz), 9.12 (1H, brs), 9.66 (1H, brs). Hydrochloride 972 1H-NMR (DMSO-d6) ppm: 0.92-1.80 (13H, m), 1.36-2.05 (1H, m), 2.75-3.05 (4H, m), 3.94 (3H, s), 6.94 (1H, d, J = 7.9 Hz), 7.18 (1H, d, J = 7.9 Hz), 7.55 (1H, d, J = 5.4 Hz), 7.71 (1H, d, J = 5.4 Hz), 8.81 (1H, brs), 9.31 (1H, brs). Hydrochloride 973 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (1H, m), 1.15-1.3 (1H, m), 1.3-1.45 (5H, m), 1.5- 1.7 (6H, m), 1.7, 1.8 (1H, m), 1.9-2.0 (1H m), 2.85-3.1 (3H, m), 3.2-3.4 (1H, m), 7.24 (1H, d, J = 7.2 Hz), 7.42 (1H, dd, J = 7.7, 7.7 Hz), 7.70-7.77 (2H, m), 8.84 (1H, br), 9.28 (1H, br). Hydrochloride

(391) TABLE-US-00107 TABLE 110 absolute configuration Example R.sup.4 NMR Salt 974 1H-NMR (DMSO-d6) ppm: 0.97-1.10 (1H, m), 1.10-1.41 (5H, m), 1.50-1.78 (7H, m), 1.94-2.05 (1H, m), 2.44 (3H, s), 2.75-3.09 (3H, m), 3.09-3.30 (1H, m), 6.58 (1H, brs), 6.98 (1H, d, J = 7.2 Hz), 7.19 (1H, t, J = 7.8 Hz), 7.31 (1H, d, J = 7.8 Hz), 9.00 (1H, brs), 9.59 (1H, brs). Hydrochloride 975 1H-NMR (DMSO-d6) ppm: 1.00-1.44 (6H, m), 1.44-1.79 (7H, m), 1.95-2.08 (1H, m), 2.42 (3H, d, J = 0.9 Hz), 2.78-3.30 (4H, m), 3.78- 4.64 (1H, br), 6.55 (1H, s), 7.04 (1H, brs), 7.32 (1H, brs), 7.48 (1H, d, J = 8.6 Hz), 8.91- 9.35 (1H, br), 9.54-9.90 (1H, br). 2 Hydrochloride 976 1H-NMR (DMSO-d6) ppm: 1.00-1.14 (1H, m), 1.14-1.42 (5H, m), 1.43-1.77 (7H, m), 1.93-2.03 (1H, m), 2.72-3.12 (3H, m), 3.27 (1H, brs), 7.08 (1H, brs), 7.24 (1H, brs), 8.14 (1H, s), 8.95 (1H, brs), 9.57 (1H, brs). Hydrochloride 977 1H-NMR (CDCl3) ppm: 0.86-1.13 (5H, m), 1.13-1.40 (3H, m), 1.42 (3H, s), 1.57-1.68 (2H, m), 1.68-1.79 (2H, m), 2.20-2.30 (1H, m), 2.65 (1H, d, J = 11.1 Hz), 2.74-2.85 (2H, m), 3.99 (3H, s), 6.61 (1H, d, J = 1.8 Hz), 6.70 (1H, d, J = 2.1 Hz), 6.95 (1H, d, J = 1.8 Hz), 7.59 (1H, d, J = 2.1 Hz). 978 0 1H-NMR (DMSO-d6) ppm: 1.02-1.42 (6H, m), 1.49-1.78 (7H, m), 1.96-2.06 (1H, m), 2.82-2.97 (2H, m), 3.04-3.25 (2H, m), 6.55- 7.25 (3H, m), 7.30 (1H, s), 8.11 (1H, d, J = 2.1 Hz), 9.11-9.30 (1H, m), 9.70-9.86 (1H, m). 2 Hydrochloride 979 1H-NMR (DMSO-d6) ppm: 1.00-1.40 (6H, m), 1.45-1.78 (7H, m), 1.95-2.05 (1H, m), 2.82-2.95 (2H, m), 3.02-3.24 (2H, m), 3.78- 4.47 (1H, br), 7.05 (1H, d, J = 2.2 Hz), 7.19 (1H, d, J = 1.7 Hz), 7.44 (1H, d, J = 1.7 Hz), 8.12 (1H, d, J = 2.2 Hz), 9.15 (1H, brs), 9.66 (1H, brs). 2 Hydrochloride 980 1H-NMR (DMSO-d6) ppm: 0.90-1.05 (1H, m), 1.12-1.84 (13H, m), 2.55-2.95 (4H, m), 3.10-4.75 (2H, br), 6.43 (3H, s), 7.34 (1H, dd, J = 2.1, 8.9 Hz), 7.53 (1H, d, J = 2.0 Hz), 7.68 (1H, d, J = 8.9 Hz), 8.03 (1H, d, J = 0.8 Hz). Fumarate 981 1H-NMR (CDCl3) ppm: 0.96-1.15 (4H, m), 1.15-1.45 (6H, m), 1.48-1.80 (5H, m), 2.21- 2.30 (1H, m), 2.62 (1H, d, J = 11.1 Hz), 2.75- 2.85 (2H, m), 7.04 (1H, dd, J = 1.8, 11.8 Hz), 7.15 (1H, d, J = 1.8 Hz), 7.42 (1H, d, J = 2.5 Hz). 982 1H-NMR (CDCl3) ppm: 0.96-1.15 (4H, m), 1.15-1.40 (3H, m), 1.42 (3H, s), 1.55-1.70 (3H, m), 1.70-1.80 (2H, m), 2.23-2.35 (1H, m), 2.66 (1H, d, J = 11.1 Hz), 2.75-2.86 (2H, m), 4.01 (3H, s), 6.76 (1H, d, J = 1.7 Hz), 6.97 (1H, d, J = 1.7 Hz), 7.38 (1H, s). 983 1H-NMR (DMSO-d6) ppm: 0.99-1.42 (6H, m), 1.50-1.78 (7H, m), 1.72-2.05 (1H, m), 2.75-3.11 (3H, m), 3.16-3.40 (1H, br), 4.95- 6.80 (1H, br), 6.95-7.11 (2H, m), 7.12-7.21 (1.25H, m), 7.33 (0.5H, s), 7.51 (0.25H, s), 8.08 (1H, brs), 9.05 (1H, brs), 9.64 (1H, brs). 2 Hydrochloride 984 1H-NMR (CDC13) ppm: 0.99-1.12 (4H, m), 1.20-1.43 (7H, m), 1.62-1.83 (4H, m), 2.34- 2.42 (1H, m), 2.70 (1H, d, J = 11.5 Hz), 2.76- 2.85 (1H, m), 2.91 (1H, d, J = 11.5 Hz), 3.92 (3H, s), 6.45 (1H, d, J = 1.4 Hz), 6.80-6.83 (1H, m), 7.45 (1H, d, J = 0.9 Hz). 985 1H-NMR (CDCl3) ppm: 1.01-1.15 (4H, m), 1.20-1.45 (7H, m), 1.67-1.90 (4H, m), 2.44- 2.53 (1H, m), 2.77-2.87 (2H, m), 2.98 (1H, d, J = 11.9 Hz), 6.74 (1H, dd, J = 1.6, 11.5 Hz), 6.90-6.94 (1H, m), 7.43 (1H, d, J = 0.9 Hz).

(392) TABLE-US-00108 TABLE 111 absolute configuration Example R.sup.4 NMR Salt 986 1H-NMR (CDCl3) ppm: 0.83-1.44 (26H, m), 1.52 (3H, s), 1.55-1.90 (7H, m), 2.36-2.62 (2H, m), 2.80-3.00 (2H, m), 6.69-6.84 (3H, m), 7.24 (1H, d, J = 3.2 Hz). 987 0 1H-NMR (CDCl3) ppm: 0.80-1.38 (26H, m), 1.42 (3H, s), 1.58-1.77 (4H, m), 2.01 (3H, sextet, J = 7.5 Hz), 2.25-2.34 (1H, m), 2.65 (1H, d, J = 11.2 Hz.), 2.75-2.85 (2H, m), 7.11 (1H, dd, J = 2.1, 9.1 Hz), 7.32 (1H, d, J = 2.1 Hz), 7.33 (1H, d, J = 0.5 Hz), 7.50 (1H, d, J = 9.1 Hz). 988 1H-NMR (CDCl3) ppm: 0.76-1.40 (26H, m), 1.52 (3H, s), 1.56-1.94 (7H, m), 2.35-2.64 (2H, m), 2.79-3.01 (2H, m), 3.88 (3H, s), 6.54 (1H, d, J = 8.1 Hz), 6.69 (1H, d, J = 3.1 Hz), 6.74 (1H, d, J = 8.1 Hz), 7.24 (1H, d, J = 3.2 Hz). 989 1H-NMR (CDCl3) ppm: 0.95-1.20 (22H, m), 1.20-1.45 (3H, m), 1.52 (3H, s), 1.62-1.90 (7H, m), 2.10-2.20 (1H, m), 2.57-2.68 (2H, m), 2.83-2.95 (1H, m), 3.26 (1H, d, J = 11.7 Hz), 6.55 (1H, d, J = 3.5 Hz), 6.63 (1H, d, J = 5.2 Hz), 7.18 (1H, d, J = 3.5 Hz), 8.12 (1H, d, J = 5.2 Hz). 990 1H-NMR (CDCl3) ppm: 0.96-1.17 (23H, m), 1.17-1.40 (3H, m), 1.42 (3H, s), 1.55-1.66 (2H, m), 1.66-1.76 (2H, m), 1.84 (3H, quint, J = 7.5 Hz), 2.28-2.37 (1H, m), 2.72 (1H, d, J = 11.2 Hz), 2.76-2.85 (2H, m), 6.47 (1H, d, J = 3.4 Hz), 7.27 (1H, d, J = 3.4 Hz), 7.61 (1H, d, J = 2.4 Hz), 8.06 (1H, d, J = 2.4 Hz). 991 1H-NMR (CDCl3) ppm: 0.89-1.40 (26H, m), 1.43 (3H, s), 1.60-1.80 (4H, m), 1.95-2.07 (3H, m), 2.30-2.40 (1H, m), 2.58 (1H, d, J = 11.3 Hz), 2.80-2.90 (2H, m), 6.98 (1H, d, J = 1.6, 8.5 Hz), 7.31 (1H, s), 7.34 (1H, d, J = 0.6 Hz), 7.52 (1H, d, J = 8.5 Hz).

(393) TABLE-US-00109 TABLE 112 absolute configuration Example R.sup.4 NMR Salt 992 1H-NMR (DMSO-d6) ppm: 0.77-0.92 (1H, m), 0.95 (3H, s), 1.09-1.35 (3H, m), 1.40 (3H, s), 1.46-1.57 (2H, m), 1.58-1.83 (3H, m), 2.29- 2.47 (2H, m), 2.60-2.85 (2H, m), 6.47 (1H, brs), 6.58-6.65 (1H, m), 6.81 (1H, dd, J = 8.3, 11.0 Hz), 7.30 (1H, t, J = 2.7 Hz), 11.47 (1H, s). 993 1H-NMR (DMSO-d6) ppm: 0.83-1.00 (4H, m), 1.08-1.34 (6H, m), 1.41-1.67 (5H, m), 2.19-2.27 (1H, m), 2.55 (1H, d, J = 10.8 Hz), 2.59-2.69 (2H, m), 7.11 (1H, dd, J = 1.8, 8.8 Hz), 7.26 (1H, d, J = 0.8 Hz), 7.32 (1H, d, J = 1.8 Hz), 7.32 (1H, d, J = 8.8 Hz), 12.25 (1H, brs). 994 1H-NMR (CDCl3) ppm: 0.75-0.99 (4H, m), 1.08-1.90 (11H, m), 2.20-2.45 (2H, m), 2.58- 2.86 (2H, m), 3.86 (3H, s), 6.38 (1H, brs), 6.47-6.66 (2H, m), 7.13 (1H, t, J = 2.5 Hz), 11.07 (1H, s). 995 1H-NMR (DMSO-d6) ppm: 0.95-1.09 (1H, m), 1.21 (3H, s), 1.25-1.65 (7H, m), 1.69-1.79 (1H, m), 1.86-2.03 (2H, m), 2.88 (1H, d, J = 12.4 Hz), 2.96-3.21 (3H, m), 6.39 (1H, d, J = 2.6 Hz), 6.49 (2H, s), 6.72 (1H, d, J = 5.3 Hz), 7.33-7.38 (1H, m), 8.09 (1H, d, J = 5.3 Hz), 8.35-11.15 (1H, br), 11.58 (1H, s). Fumarate 996 00 1H-NMR (DMSO-d6) ppm: 0.95-1.10 (1H, m), 1.10-1.23 (1H, m), 1.23-1.38 (4H, m), 1.38-1.60 (6H, m), 1.63-1.75 (1H, m), 1.84- 1.95 (1H, m), 2.72-2.85 (2H, m), 3.00-3.13 (2H, m), 6.38-6.43 (1H, m), 6.50 (1H, s), 7.43- 7.48 (1H, m), 7.75 (1H, d, J = 1.9 Hz), 7.99 (1H, d, J = 2.2 Hz), 8.35-11.30 (2H, br), 11.61 (1H, s). Fumarate 997 01 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (4H, m), 1.10-1.36 (6H, m), 1.35-2.10 (5H, m), 2.25-2.35 (1H, m), 2.56 (1H, d, J = 11.0 Hz), 2.62-2.70 (1H, m), 2.75 (1H, d, J = 11.0 Hz), 6.91 (1H, dd, J = 1.2, 8.6 Hz), 7.02 (1H, s), 7.27 (1H, s), 7.55 (1H, d, J = 8.6 Hz) 11.93- 12.33 (1H, br).

(394) TABLE-US-00110 TABLE 113 absolute configuration 02 Example R.sup.4 NMR Salt 998 03 1H-NMR (CDCl3) ppm: 0.72-1.19 (5H, m), 1.25-1.45 (3H, m), 1.48 (3H, s), 1.65-1.82 (3H, m), 2.08-2.20 (1H, m), 2.65-2.80 (2H, m), 2.80- 2.95 (1H, m), 3.27 (1H, d, J = 11.9 Hz), 3.85 (3H, s), 6.45 (1H, d, J = 3.5 Hz), 6.63 (1H, d, J = 5.3 Hz), 7.06 (1H, d, J = 3.5 Hz), 8.20 (1H, d, J = 5.3 Hz). 999 04 1H-NMR (DMSO-d6) ppm: 0.95-1.60 (11H, m), 1.60-1.83 (2H, m), 1.83-1.95 (1H, m), 2.65- 2.83 (2H, m), 3.00-3.10 (2H, m), 3.79 (3H, s), 6.41 (1H, d, J = 3.4 Hz), 6.48 (2H, s), 7.50 (1H, d, J = 3.4 Hz), 7.77 (1H, d, J = 2.2 Hz), 8.04 (1H, d, J = 2.2 Hz), 8.35-10.85 (2H, br). Fumarate

(395) TABLE-US-00111 TABLE 114 absolute configuration 05 Example R.sup.4 NMR Salt 1000 06 1H-NMR (DMSO-d6) ppm: 0.87-1.00 (1H, m), 1.15-1.40 (5H, m), 1.50-1.78 (7H, m), 1.90- 2.11 (3H, m), 2.65-2.80 (2H, m), 2.80-3.05 (5H, m), 3.09-3.25 (1H, m), 3.48 (1H, brs), 6.99 (1H, d, J = 8.3 Hz), 7.21 (1H, d, J = 8.3 Hz), 8.90- 9.10 (1H, m), 9.40-9.64 (1H, m). 2 Hydrochloride 1001 07 1H-NMR (DMSO-d6) ppm: 0.89-1.04 (1H, m), 1.20-1.40 (5H, m), 1.46-1.78 (7H, m), 1.88- 2.09 (3H, m), 2.64-3.00 (7H, m), 3.05-3.25 (1H, m), 3.25-3.50 (1H, br), 6.96 (1H, s), 7.12 (1H, s), 8.70-9.10 (1H, brs), 9.15-9.55 (1H, brs). 2 Hydrochloride 1002 08 1H-NMR (DMSO-d6) ppm: 0.90-1.21 (2H, m), 1.22-1.43 (4H, m), 1.43-1.80 (7H, m), 1.90- 2.10 (1H, m), 2.58-3.40 (6H, m), 4.52 (2H, t, J = 8.6 Hz), 5.35-6.40 (1H, br), 6.55-7.60 (3H, m), 8.60-10.20 (2H, br). 2 Hydrochloride 1003 09 1H-NMR (DMSO-d6) ppm: 0.98-1.13 (1H, m), 1.13-1.40 (5H, m), 1.47-1.65 (6H, m), 1.65- 1.77 (1H, m), 1.91-2.06 (1H, m), 2.74-2.90 (2H, m), 2.99 (1H, d, J = 12.5 Hz), 3.08-3.21 (1H, m), 4.05-5.00 (1H, br), 6.95 (1H, dd, J = 2.0, 8.6 Hz), 7.26 (1H, d, J = 2.0 Hz), 7.36 (1H, d, J = 8.6 Hz), 8.94-9.20 (1H, br), 9.55-9.85 (1H, br). 2 Hydrochloride

(396) TABLE-US-00112 TABLE 115 absolute configuration 0 Example R.sup.4 NMR Salt 1004 1H-NMR (CDCl3) ppm: 0.78-1.04 (2H, m), 1.04-1.14 (21H, m), 1.15-1.35 (6H, m), 1.38 (3H, s), 1.51-1.75 (4H, m), 2.12-2.20 (1H, m), 2.58 (1H, d, J = 11.1 Hz), 2.69-2.78 (2H, m), 6.76-6.81 (2H, m), 6.92-6.97 (2H, m). 1005 1H-NMR (CDCl3) ppm: 0.85-1.15 (23H, m), 1.15-1.37 (6H, m), 1.38 (3H, s), 1.60-1.77 (4H, m), 2.20-2.29 (1H, m), 2.58 (1H, d, J = 11.3 Hz), 2.72-2.82 (2H, m), 6.60-6.65 (2H, m), 6.65-6.70 (1H, m), 7.07-7.13 (1H, m). 1006 1H-NMR (CDCl3) ppm: 0.75-1.13 (23H, m), 1.13-1.39 (9H, m), 1.50-1.75 (4H, m), 2.08- 2.18 (1H, m), 2.55 (1H, d, J = 11.2 Hz), 2.69- 2.78 (2H, m), 6.68-6.74 (1H, m), 6.77-6.86 (2H, m). 1007 1H-NMR (CDCl3) ppm: 0.92-1.38 (29H, m), 1.39 (3H, s), 1.58-1.76 (4H, m), 2.23-2.31 (1H, m), 2.61 (1H, d, J = 11.3 Hz), 2.71-2.82 (2H, m), 4.79 (2H, s), 7.02-7.08 (2H, m), 7.22-7.31 (2H, m). 1008 1H-NMR (CDCl3) ppm: 0.72-1.35 (29H, m), 1.36 (3H, s), 1.60-1.78 (4H, m), 2.21-2.30 (1H, m), 2.60 (1H, d, J = 12.1 Hz), 2.71-2.84 (2H, m), 5.30 (2H, s), 6.72 (1H, dd, J = 2.0, 12.0 Hz), 6.86 (1H, J = 2.0, 8.2 Hz), 7.44 (1H, t, J = 8.4 Hz). 1009 1H-NMR (CDCl3) ppm: 0.72-1.39 (32H, m), 1.52-1.75 (4H, m), 2.08-2.18 (1H, m), 2.56 (1H, d, J = 11.1 Hz), 2.67-2.77 (2H, m), 6.80 (1H, d, J = 8.6 Hz), 6.84 (1H, dd, J = 2.4, 8.6 Hz), 7.08 (1H, d, J = 2.4 Hz). 1010 1H-NMR (CDCl3) ppm: 0.86-1.09 (23H, m), 1.09-1.36 (3H, m), 1.37 (3H, s), 1.50-1.75 (4H, m), 2.11-2.19 (1H, m), 2.57 (1H, d, J = 11.1 Hz), 2.67-2.77 (2H, m), 4.95 (2H, s), 6.67 (1H, d, J = 2.5 Hz), 6.82 (1H, d, J = 8.5 Hz), 6.91 (1H, dd, J = 2.5, 8.5 Hz).

(397) TABLE-US-00113 TABLE 116 absolute configuration Example R.sup.4 NMR Salt 1011 1H-NMR (CDCl3) ppm: 0.92-1.06 (1H, m), 1.09 (3H, s), 1.12-1.39 (3H, m), 1.41 (3H, s), 1.55-1.66 (2H, m), 1.66-1.79 (2H, m), 2.17- 2.25 (1H, m), 2.61 (1H, d, J = 11.3 Hz), 2.70- 2.83 (2H, m), 3.53-4.70 (2H, br), 6.73-6.79 (2H, m), 6.94-7.01 (2H, m). 1012 0 1H-NMR (DMSO-d6) ppm: 0.82-1.00 (4H, m), 1.09-1.35 (6H, m), 1.40-1.52 (1H, m), 1.52- 1.70 (4H, m), 2.15-2.25 (1H, m), 2.44-2.55 (1H, m), 2.55-2.64 (1H, m), 2.66 (1H, d, J = 12.2 Hz), 6.39-6.51 (3H, m), 6.99-7.09 (1H, m), 9.21 (1H, s). 1013 1H-NMR (DMSO-d6) ppm: 0.90-1.03 (1H, m), 1.05-1.53 (10H, m), 1.53-1.62 (1H, m), 1.62-1.74 (1H, m), 1.80-1.90 (1H, m), 2.48- 2.59 (1H, m), 2.68 (1H, J = 11.8 Hz), 2.84 (1H, d, J = 11.8 Hz), 2.90-3.01 (1H, m), 3.74 (3H, s), 4.45 (2H, s), 6.45 (1H, s), 6.86 (1H, d, J = 8.6 Hz), 6.94 (1H, dd, J = 2.5, 8.6 Hz), 7.15 (1H, d, J = 2.5 Hz), 8.10-10.15 (1H, br). Fumarate 1014 1H-NMR (DMSO-d6) ppm: 0.83-1.00 (4H, m), 1.05-1.31 (6H, m), 1.40-1.51 (1H, m), 1.51- 1.65 (3H, m), 2.05-2.14 (1H, m), 2.47 (1H, d, J = 10.8 Hz), 2.53-2.62 (2H, m), 3.10-3.60 (1H, br), 6.67-6.73 (1H, m), 6.79-6.87 (2H, m), 9.00- 10.10 (1H, m). 1015 1H-NMR (CDCl3) ppm: 0.84-1.12 (5H, m), 1.16-1.45 (6H, m), 1.59-2.14 (5H, m), 2.25- 2.35 (1H, m), 2.56-2.65 (1H, m), 2.72-2.85 (2H, m), 4.64 (2H, m), 7.07 (2H, dd, J = 1.3, 8.1 Hz), 7.29 (2H, d, J = 8.1 Hz). 1016 1H-NMR (CDCl3) ppm: 0.95-1.44 (11H, m), 1.44-2.22 (5H, m), 2.26-2.35 (1H, m), 2.62 (1H, d, J = 11.4 Hz), 2.72-2.87 (2H, m), 4.69 (2H, s), 6.75 (1H, dd, J = 2.0, 12.0 Hz), 6.81 (1H, dd, J = 2.0, 8.1 Hz), 7.29 (1H, t, J = 8.4 Hz). 1017 1H-NMR (CDCl3) ppm: 0.89-1.12 (4H, m), 1.14-1.43 (6H, m), 1.53-1.77 (4H, m), 2.12- 2.21 (1H, m), 2.57 (1H, d, J = 11.2 Hz), 2.67- 2.80 (2H, m), 2.80-3.30 (2H, br), 6.89-6.96 (2H, m), 7.05-7.09 (1H, m). 1018 1H-NMR (DMSO-d6) ppm: 0.78-0.94 (1H, m), 0.95 (3H, s), 1.04-1.32 (6H, m), 1.39-1.66 (5H, m), 2.05-2.15 (1H, m), 2.45-2.62 (3H, m), 4.43 (2H, s), 4.70-5.15 (1H, br), 6.65 (1H, d, J = 8.4 Hz), 6.74 (1H, dd, J = 2.5, 8.4 Hz), 7.03 (1H, d, J = 2.5 Hz), 8.80-9.30 (1H, br).

(398) TABLE-US-00114 TABLE 117 absolute configuration Example R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR Salt 1019 CH3 H H H H 1H-NMR (DMSO- Hydrochloride d6) ppm: 0.88- 1.03 (1H, m), 1.10- 1.25 (1H, m), 1.25- 1.40 (4H, m), 1.45- 1.66 (6H, m), 1.67- 1.89 (1H, m), 1.92- 2.03 (1H, m), 2.26 (3H, m), 2.65 (1H, d, J = 12.5 Hz), 2.80 (1H, d, J = 12.5 Hz), 2.88-3.00 (1H, m), 3.15-3.28 (1H, m), 7.06-7.17 (2H, m), 7.19-7.26 (2H, m), 9.04 (1H, brs), 9.58 (1H, brs). 1020 CH3 CH3 H H H 1H-NMR (DMSO- Hydrochloride d6) ppm: 0.89- 1.02 (1H, m), 1.09- 1.23 (1H, m), 1.24- 1.40 (4H, m), 1.40- 1.66 (6H, m), 1.67- 1.76 (1H, m), 1.93- 2.02 (1H, m), 2.21 (3H, s), 2.22 (3H, s), 2.60 (1H, d, J = 12.5 Hz), 2.76-2.95 (2H, m), 3.15-3.35 (1H, m), 6.97-7.03 (2H, m), 7.07-1.15 (1H, m), 9.07 (1H, brs), 9.61 (1H, brs). 1021 H F CN H H 1H-NMR (DMSO- Fumarate d6) ppm: 1.21- 1.65 (10H, m), 1.65- 1.84 (2H, m), 1.90- 2.00 (1H, m), 2.10- 2.20 (1H, m), 3.38- 3.61 (3H, m), 3.78 (1H, d, J = 14.5 Hz), 6.83 (1H, dd, J = 2.3, 8.9 Hz), 6.97 (1H, dd, J = 2.0, 13.7 Hz), 7.65 (1H, t, J = 8.5 Hz), 8.93- 9.15 (1H, m), 9.51- 9.71 (1H, m). 1022 H H OCF3 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.00- 1.15 (1H, m), 1.15- 1.40 (5H, m), 1.50- 1.67 (6H, m), 1.67- 1.77 (1H, m), 1.95- 2.05 (1H, m), 2.80- 2.95 (2H, m), 3.01 (1H, d, J = 12.4 Hz), 3.11-3.25 (1H, m), 5.15-5.32 (1H, br), 7.20-7.27 (2H, m), 7.31-7.37 (2H, m), 9.10 (1H, brs), 9.68 (1H, brm). 1023 H F OCF3 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.04- 1.20 (1H, m), 1.20- 1.41 (5H, m), 1.479- 1.78 (7H, m), 1.97- 2.07 (1H, m), 2.86- 3.11 (3H, m), 3.15- 3.27 (1H, m), 4.45- 6.85 (1H, br), 7.00- 7.16 (1H, m), 7.22- 7.29 (1H, m), 7.46- 7.55 (1H, m), 9.12 (1H, brs), 9.77 (1H, brs). 1024 H H OCHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 0.98- 1.40 (6H, m), 1.49- 1.77 (7H, m), 1.95- 2.06 (1H, m), 2.76- 2.95 (2H, m), 3.03 (1H, d, J = 12.3 Hz), 3.10-3.23 (1H, m), 6.20-6.90 (1H, br), 7.01 (0.25H, s), 7.13-7.23 (4.5H, m), 7.38 (0.25H, s), 9.17 (1H, brs), 9.74 (1H, brm). 1025 H F OCHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.03-1.40 (6H, m), 1.50-1.67 (6H, m), 1.67-1.77 (1H, m), 1.96-2.05 (1H, m), 2.81-2.95 (2H, m), 3.02 (1H, d, J = 12.5 Hz), 3.10- 3.23 (1H, m), 3.88- 4.20 (1H, br), 6.96- 7.01 (1H, m), 7.02 (0.25H, s), 7.17 (1H, dd, J = 2.5, 12.1 Hz), 7.20 (0.5H, s) 7.33 (1H, t, J = 8.9 Hz), 7.39 (0.25H, s), 9.08-9.22 (1H, m), 9.70-9.88 (1H, m). 1026 H Cl OCHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.02- 1.15 (1H, m), 1.15- 1.41 (5H, m), 1.50- 1.67 (6H, m), 1.67- 1.78 (1H, m), 1.93- 2.04 (1H, m), 2.78- 2.95 (2H, m), 2.95- 3.06 (1H, m), 3.10- 3.25 (1H, m), 3.50- 4.05 (1H, br), 7.15 (1H, dd, J = 2.5, 8.8 Hz), 7.24 (1H, t, J = 73.3 Hz), 7.32 (1H, d, J = 2.5 Hz), 7.34 (1H, d, J = 8.8 Hz), 8.90-9.20 (1H, br), 9.44-9.75 (1H, br). 1027 H OCHF2 H H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.01- 1.15 (1H, m), 1.15- 1.42 (5H, m), 1.50- 1.68 (6H, m), 1.68- 1.78 (1H, m), 1.96- 2.06 (1H, m), 2.83- 2.96 (2H, m), 3.03 (1H, d, J = 12.7 Hz), 3.10-3.25 (1H, m), 6.89 (1H, s), 6.96 (1H, dd, J = 2.1, 8.1 Hz), 7.00 (1H, d, J = 8.1 Hz), 7.27 (1H, t, J = 74.1 Hz), 7.39 (1H, t, J = 8.1 Hz), 7.85-8.90 (1H, br), 9.00-9.25 (1H, br), 9.65-9.85 (1H, br). 1028 H OCHF2 Cl H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.02- 1.41 (6H, m), 1.49- 1.80 (7H, m), 1.91- 2.07 (1H, m), 2.78- 2.90 (1H, m), 2.90- 3.05 (2H, m), 3.10- 3.27 (1H, m), 3.90- 4.65 (1H, br), 7.01- 7.08 (2H, m), 7.32 (1H, t, J = 73.3 Hz), 7.54 (1H, d, J = 8.4 Hz), 8.85-9.10 (1H, m), 9.39-9.70 (1H, m). 1029 H OCHF2 F H H 1H-NMR (DMSO- Hydrochloride d6) ppm: 1.00- 1.40 (6H, m), 1.47- 1.65 (6H, m), 1.67- 1.77 (1H, m), 1.90- 2.00 (1H, m), 2.70- 2.80 (1H, m), 2.87 (1H, d, J = 12.5 Hz), 2.96 (1H, d, J = 12.5 Hz), 3.10-3.24 (1H, m), 7.02-7.11 (2.25H, m), 7.27 (0.5H, s), 7.37 (1H, dd, J = 8.8, 10.5 Hz), 7.46 (0.25H, s), 8.80-9.00 (1H, br), 9.39-9.58 (1H, br). 1030 H CN OCHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.02- 1.15 (1H, m), 1.17- 1.40 (5H, m), 1.48- 1.81 (7H, m), 1.93- 2.07 (1H, m), 2.82- 2.91 (1H, m), 2.94 (1H, d, J = 12.6 Hz), 3.01 (1H, d, J = 12.6 Hz), 3.08-3.25 (1H, m), 3.70-4.20 (1H, br), 7.39 (1H, t, J = 72.6 Hz), 7.42 (1H, d, J = 8.9 Hz), 7.51 (1H, dd, J = 2.7, 9.0 Hz), 7.69 (1H, d, J = 2.7 Hz), 8.90-9.10 (1H, br), 9.35-9.70 (1H, br). 1031 H F OCHF2 F H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.08- 1.40 (6H, m), 1.43- 1.80 (7H, m), 1.95- 2.07 (1H, m), 2.88- 2.99 (1H, m), 3.05 (1H, d, J = 13.1 Hz), 3.09 (1H, d, J = 13.1 Hz), 3.17-3.30 (1H, m), 3.48-3.70 (1H, br), 6.97-7.06 (2.25H, m), 7.19 (0.5H, s), 7.37 (0.25H, s), 8.81-9.04 (1H, br), 9.45-9.65 (1H, br). 1032 H H OCH2CHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 0.98- 1.85 (13H, m), 1.90- 2.20 (1H, m), 2.60- 3.80 (4H, m), 4.20- 4.40 (2H, m), 4.40- 5.40 (1H, br), 6.38 (1H, tt, J = 3.4, 54.5 Hz), 6.85-7.70 (4H, brm), 8.84-10.40 (2H, br). 1033 H F OCH2CHF2 H H 1H-NMR (CDCl3) ppm: 0.94-1.11 (4H, m), 1.14-1.41 (7H, m), 1.57-1.78 (4H, m), 2.13-2.22 (1H, m), 2.56 (1H, d, J = 11.1 Hz), 2.70- 2.79 (2H, m), 4.21 (2H, dt, J = 4.2, 13.1 Hz), 6.08 (1H, tt, J = 4.2, 55.1 Hz), 6.77- 6.83 (1H, m), 6.83- 6.95 (2H, m). 1034 H Cl OCH2CHF2 H H 1H-NMR (CDCl3) ppm: 0.93-1.11 (4H, m), 1.15-1.41 (7H, m), 1.55-1.77 (4H, m), 2.14-2.23 (1H, m), 2.57 (1H, d, J = 11.0 Hz), 2.68- 2.78 (2H, m), 4.20 (2H, dt, J = 4.2, 13.0 Hz), 6.12 (1H, tt, J = 4.2, 55.1 Hz), 6.87 (1H, d, J = 8.7 Hz), 6.96 (1H, dd, J = 2.5, 8.7 Hz), 7.13 (1H, d, J = 2.5 Hz). 1035 H CH3 OCHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 0.97- 1.10 (1H, m), 1.12- 1.40 (5H, m), 1.47- 1.63 (6H, m), 1.67- 1.76 (1H, m), 1.90- 2.01 (1H, m), 2.20 (3H, m), 2.70-2.80 (1H, m), 2.83 (1H, d, J = 12.3 Hz), 2.95 (1H, d, J = 12.3 Hz), 3.08-3.22 (1H, m), 4.60-5.40 (1H, br), 6.94 (0.25H, s), 6.99 (1H, dd, J = 2.5, 8.5 Hz), 7.05 (1H, d, J = 2.5 Hz), 7.09-7.15 (1.5H, m), 7.31 (0.25H, s), 8.85-9.01 (1H, m), 9.40-9.55 (1H, m). 1036 H OCH3 OCHF2 H H 1H-NMR (DMSO- 2 Hydrochloride d6) ppm: 1.00- 1.40 (6H, m), 1.50- 1.80 (7H, m), 1.95- 2.06 (1H, m), 2.75- 2.94 (2H, m), 2.96- 3.07 (1H, m), 3.09- 3.22 (1H, m), 3.82 (3H, s), 6.08-6.65 (1H, br), 6.73 (1H, d, J = 8.2 Hz), 6.80- 6.89 (1.25H, m), 7.01 (0.5H, s), 7.14 (1H, d, J = 8.4 Hz), 7.19 (0.25H, s), 9.09 (1H, brs), 9.72 (1H, brs).

(399) TABLE-US-00115 TABLE 118 absolute configuration Example R.sup.4 NMR Salt 1037 1H-NMR (DMSO-d6) ppm: 1.1-1.35 (3H, m), 1.4-1.55 (1H, m), 1.55-1.95 (8H, m), 1.95-2.05 (2H, m), 2.68 (1H, d, J = 11.9 Hz), 2.8-4.0 (5H, m), 6.55 (1H, s), 6.85-6.95 (2H, m), 7.14-7.22 (2H, m). Fumarate 1038 0 1H-NMR (CDCl3) ppm: 0.95-1.15 (2H, m), 1.3-1.4 (1H, m), 1.4-2.1 (11H, m), 2.25-2.4 (1H, m), 3.04 (1H, d, J = 11.1 Hz), 3.17 (1H, d, J = 10.9 Hz), 3.41 (1H, br), 3.45-3.58 (1H, m), 6.54 (1H, dd, J = 3.3, 8.4 Hz), 6.82 (1H, dd, J = 2.5, 2.5 Hz), 6.91 (1H, dd, J = 8.6, 10.4 Hz), 7.59 (1H, d, J = 2.1 Hz). 1039 1H-NMR (DMSO-d6) ppm: 0.95-1.5 (3H, m), 1.5-1.7 (2H, m), 1.7-2.3 (6H, m), 2.3-2.7 (3H, m), 3.0-3.4 (1H, m), 3.59 (2H, br), 3.73 (1H, br), 7.07 (1H, br), 7.3-7.45 (1H, m), 7.48 (1H, d, J = 5.4 Hz), 7.64 (1H, br), 7.75 (1H, d, J = 5.4 Hz), 8.75-10.3 (2H, m). Hydrochloride

(400) TABLE-US-00116 TABLE 119 absolute configuration Ex. No. R.sup.4 NMR Salt 1040 1H-NMR (DMSO-d6) ppm: 1.1-1.35 (3H, m), 1.4-1.55 (1H, m), 1.55-1.95 (8H, m), 1.95-2.05 (2H, m), 2.68 (1H, d, J = 11.9 Hz), 2.8-4.0 (5H, m), 6.55 (1H, s), 6.85-6.95 (2H, m), 7.14-7.22 (2H, m). Fumarate 1041 1H-NMR (CDCl3) ppm: 0.95-1.1 (2H, m), 1.3-1.4 (1H, m), 1.4-2.1 (11H, m), 2.25-2.4 (1H, m), 3.01 (1H, d, J = 11.0 Hz), 3.17 (1H, d, J = 11.1 Hz), 3.40 (1H, br), 3.45-3.5 (1H, m), 3.97 (3H, s), 6.58 (1H, d, J = 8.4 Hz), 6.70 (1H, d, J = 8.4 Hz), 6.80 (1H, d, J = 2.1 Hz), 7.58 (1H, d, J = 2.1 Hz). 1042 1H-NMR (CDCl3) ppm: 0.95-1.15 (2H, m), 1.3-1.4 (1H, m), 1.4-2.1 (11H, m), 2.25-2.4 (1H, m), 3.04 (1H, d, J = 11.1 Hz), 3.17 (1H, d, J = 10.9 Hz), 3.41 (1H, br), 3.45-3.58 (1H, m), 6.54 (1H, dd, J = 3.3, 8.4 Hz), 6.82 (1H, dd, J = 2.5, 2.5 Hz), 6.91 (1H, dd, J = 8.6, 10.4 Hz), 7.59 (1H, d, J = 2.1 Hz). 1043 1H-NMR (DMSO-d6) ppm: 0.95-1.5 (3H, m), 1.5-1.7 (2H, m), 1.7-2.3 (6H, m), 2.3-2.7 (3H, m), 3.0-3.4 (1H, m), 3.59 (2H, br), 3.73 (1H, br), 7.07 (1H, br), 7.3-7.45 (1H, m), 7.48 (1H, d, J = 5.4 Hz), 7.64 (1H, br), 7.75 (1H, d, J = 5.4 Hz), 8.75-10.3 (2H, m). Hydrochloride

(401) TABLE-US-00117 TABLE 120 relative configuration Ex. No. R.sup.4 NMR Salt 1044 1H-NMR (CDCl3) ppm: 0.90-2.30 (10H, m), 2.36-3.40 (7H, m), 3.50-3.70 (1H, m), 7.30- 7.55 (3H, m), 7.55-7.75 (1H, m), 7.75-7.90 (3H, m), 9.75-10.40 (2H, br). 2 Hydrochloride

(402) TABLE-US-00118 TABLE 121 absolute configuration Ex. No. R.sup.4 NMR Salt 1045 0 1H-NMR (DMSO-d6) ppm: 0.85-1.0 (1H, m), 1.12-1.40 (2H, m), 1.42-1.63 (3H, m), 1.65-1.78 (1H, m), 1.84-1.97 (3H, m), 1.97- 2.06 (1H, m). 2.24-2.38 (2H, m), 2.39-2.49 (1H, m), 2.73-2.93 (2H, m), 3.03 (1H, d, J = 12.5 Hz), 3.23 (1H, d, J = 12.5 Hz), 3.6 (1H, br), 7.15-7.25 (2H, m), 7.37-7.46 (2H, m), 9.37 (1H, br), 9.87 (1H, br). 2 Hydrochloride 1046 1H-NMR (CDCl3) ppm: 0.95-1.1 (1H, m), 1.15-1.45 (3H, m), 1.45-1.95 (10H, m), 2.45- 2.7 (3H, m), 2.80 (1H, dd, J = 1.7, 11.2 Hz), 3.19 (1H, d, J = 11.1 Hz), 3.91 (3H, s), 7.08- 7.15 (2H, m), 7.29 (1H, dd, J = 2.1, 8.7 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.63-7.71 (2H, m). 1047 1H-NMR (DMSO-d6) ppm: 0.85-1.1 (1H, m), 1.1-1.45 (2H, m), 1.45-1.65 (3H, m), 1.65-1.8 (1H, m), 1.8-2.0 (3H, m), 2.0-2.15 (1H, m), 2.25-2.65 (3H, m), 2.85-3.35 (2H, m), 3.6-4.35 (3H, m), 6.9-7.2 (2H, m), 7.31 (1H, dd, J = 8.0, 8.0 Hz), 7.46 (1H, d, J = 8.2 Hz), 8.00 (1H, d, J = 1.6 Hz), 9.3-10.3 (2H, m). 2 Hydrochloride 1048 1H-NMR (DMSO-d6) ppm: 0.8-1.0 (1H, m), 1.1-1.6 (5H, m), 1.6-2.0 (5H, m), 2.1-2.5 (3H, m), 2.75-2.95 (2H, m), 2.95-3.13 (1H, m), 3.17 (1H, d, J = 12.6 Hz), 6.56 (4H, s), 6.99-7.14 (2H, m), 7.20 (1H, dd, J = 8.6, 10.7 Hz), 8.09 (1H, d, J = 2.0 Hz), 11.4 (5H, br). 2 Fumarate

(403) TABLE-US-00119 TABLE 122 absolute configuration Ex. No. R.sup.4 NMR Salt 1049 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (1H, m), 1.1-1.4 (2H, m), 1.4-1.65 (3H, m), 1.65- 1.8 (1H, m), 1.8-2.0 (3H, m), 2.0-2.1 (1H, m), 2.25-2.4 (2H, m), 2.4-2.6 (1H, m), 2.75- 2.95 (2H, m), 3.0-3.1 (1H, m), 3.23 (1H, d, J = 12.6 Hz), 3.5-4.0 (1H, m), 7.15-7.25 (2H, m), 7.35-7.45 (2H, m), 9.3-9.6 (1H, m), 9.85-10.1 (1H, m). 2 Hydrochloride 1050 1H-NMR (CDCl3) ppm: 0.95-1.1 (1H, m), 1.1-1.45 (3H, m), 1.45-1.95 (10H, m), 2.45- 2.7 (3H, m), 2.80 (1H, dd, J = 1.7, 11.2 Hz), 3.19 (1H, d, J = 11.2 Hz), 3.91 (3H, s), 7.07- 7.15 (2H, m), 7.29 (1H, dd, J = 2.1, 8.7 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.63-7.71 (2H, m). 1051 1H-NMR (DMSO-d6) ppm: 0.85-1.1 (1H, m), 1.1-1.4 (2H, m), 1.4-1.65 (3H, m), 1.65- 1.8 (1H, m), 1.8-2.0 (3H, m), 2.0-2.15 (1H, m), 2.25-2.65 (3H, m), 2.8-3.45 (2H, m), 3.5-4.25 (3H, m), 6.9-7.2 (2H, m), 7.31 (1H, dd, J = 8.0, 8.0 Hz), 7.46 (1H, d, J = 8.2 Hz), 8.00 (1H, d, J = 1.8 Hz), 9.3-10.3 (2H, m). 2 Hydrochloride 1052 1H-NMR (DMSO-d6) ppm: 0.8-0.95 (1H, m), 1.1-1.4 (3H, m), 1.45-1.6 (2H, m), 1.6- 1.7 (1H, m), 1.7-1.9 (4H, m), 2.0-2.15 (1H, m), 2.15-2.3 (1H, m), 2.35-2.5 (1H, m), 2.65-2.85 (2H, m), 2.85-3.0 (1H, m), 3.13 (1H, d, J = 11.7 Hz), 6.53 (3H, s), 7.0-7.1 (2H, m), 7.18 (1H, dd, J = 8.6, 10.8 Hz), 8.07 (1H, d, J = 2.1 Hz), 10.3 (4H, br). 1.5 Fumarate

(404) TABLE-US-00120 TABLE 123 relative configuration Ex. No. R.sup.4 NMR Salt 1053 0 1H-NMR (CDCl3) ppm: 1.14-1.29 (1H, m), 1.29-1.38 (1H, m), 1.38-1.58 (3H, m), 1.62- 1.86 (4H, m), 2.95-3.05 (2H, m), 3.1-3.25 (3H, m), 3.6-3.7 (1H, m), 6.74-6.82 (2H, m), 7.14-7.21 (2H, m). 1054 1H-NMR (CDCl3) ppm: 1.14-1.36 (2H, m), 1.37-1.65 (3H, m), 1.65-1.77 (2H, m), 1.77- 1.91 (2H, m), 3.01-3.17 (2H, m), 3.19-3.28 (3H, m), 3.75-3.83 (1H, m), 3.88 (3H, s), 6.97-7.11 (3H, m), 7.23-7.30 (1H, m), 7.57 (1H, d, J = 8.8 Hz), 7.62 (1H, d, J = 9.0 Hz). 1055 1H-NMR (DMSO-d6) ppm: 0.97-1.14 (2H, m), 1.32-1.43 (1H, m), 1.43-1.67 (2H, m), 1.68-2.03 (3H, m), 3.01-3.14 (2H, m), 3.25- 3.43 (2H, m), 3.55-3.64 (1H, m), 3.66-3.77 (1H, m), 6.55 (4H, s), 6.68 (1H, br), 7.10 (1H, dd, J = 8.7, 10.7 Hz), 7.22 (1H, br), 8.05 (1H, d, J = 2.2 Hz), 11.27 (5H, br). 2 Fumarate 1056 1H-NMR (DMSO-d6) ppm: 0.95-1.15 (2H, m), 1.28-1.40 (1H, m), 1.43-1.72 (3H, m), 1.94 (2H, br), 2.90-3.12 (2H, m), 3.19-3.30 (1H, m), 3.34-3.57 (2H, m), 3.70-3.87 (1H, br), 6.53 (2H, s), 7.00 (1H, br), 7.34 (1H, dd, J = 7.7, 7.7 Hz), 7.45 (1H, d, J = 5.4 Hz), 7.5-7.65 (1H, m), 7.72 (1H, d, J = 5.4 Hz), 10.5 (3H, br). Fumarate 1057 1H-NMR (CDCl3) ppm: 0.96-1.18 (2H, m), 1.33-1.72 (5H, m), 1.72-1.91 (1H, m), 1.92- 2.07 (1H, m), 2.82-2.92 (1H, m), 3.03-3.17 (1H, m), 3.17-3.27 (1H, m), 3.38 (1H, br), 3.42-3.52 (1H, m), 3.52-3.61 (1H, m), 6.85 (1H, d, J = 7.6 Hz), 7.21-7.28 (1H, m), 7.37 (1H, d, J = 5.5 Hz), 7.40-7.47 (1H, m), 7.52 (1H, d, J = 8.0 Hz). 1058 1H-NMR (DMSO-d6) ppm: 1.26-1.42 (2H, m), 1.42-1.63 (2H, m), 1.63-1.91 (3H, m), 1.91-2.04 (1H, m), 3.01-3.18 (2H, m), 3.24- 3.42 (1H, m), 3.47-3.55 (1H, m), 3.55-3.65 (1H, m), 4.06-4.19 (1H, m), 6.95 (1H, dd, J = 2.9, 9.0 Hz), 7.18 (1H, d, J = 2.9 Hz), 7.43 (1H, d, J = 9.0 Hz), 9.00 (1H, br), 9.62 (1H, br). Hydrochloride 1059 1H-NMR (DMSO-d6) ppm: 0.9-1.15 (2H, m), 1.25-1.4 (1H, m), 1.4-1.7 (3H, m), 1.91 (2H, br), 2.82-2.92 (1H, m), 2.97-3.10 (1H, m), 3.15-3.60 (7H, m), 6.52 (2H, s), 6.94 (1H, br), 7.15 (1H, dd, J = 8.9, 8.9 Hz), 7.59 (1H, br), 7.83 (1H, d, J = 5.3 Hz). Fumarate 1060 1H-NMR (DMSO-d6) ppm: 1.0-1.15 (2H, m), 1.28-1.40 (1H, m), 1.4-1.65 (2H, m), 1.65-1.77 (1H, m), 1.78-1.98 (2H, m), 2.95- 3.15 (2H, m), 3.15-3.25 (1H, m), 3.25-3.4 (1H, m), 3.43 (1H, br), 3.7-3.8 (1H, m), 6.53 (2H, s), 6.68 (1H, d, J = 8.5 Hz), 7.19 (1H, bs), 7.26 (1H, d, J = 8.4 Hz), 8.04 (1H, d, J = 2.2 Hz). Fumarate 1061 1H-NMR (DMSO-d6) ppm: 1.17-1.32 (2H, m), 1.34-1.56 (2H, m), 1.59-1.85 (3H, m), 1.86-1.96 (1H, m), 2.95-3.14 (2H, m), 3.23- 3.40 (3H, m), 3.90-3.99 (1H, m), 6.51 (2H, s), 7.13 (1H, dd, J = 2.3, 8.9 Hz), 7.27-7.34 (2H, m), 7.66 (1H, d, J = 5.4 Hz), 7.80 (1H, d, J = 8.9 Hz). Fumarate 1062 1H-NMR (DMSO-d6) ppm: 1.16-1.40 (3H, m), 1.40-1.55 (1H, m), 1.57-1.73 (2H, m), 1.73-1.87 (2H, m), 2.85-3.03 (3H, m), 3.04- 3.83 (4H, m), 3.85-3.93 (1H, m), 6.49 (1H, s), 7.09 (1H, dd, J = 2.2, 8.9 Hz), 7.25 (1H, d, J = 5.3 Hz), 7.35-7.41 (2H, m), 7.67 (1H, d, J = 8.8 Hz). Fumarate

(405) TABLE-US-00121 TABLE 124 absolute configuration 0 Ex. No. R.sup.4 NMR Salt 1063 1H-NMR (CDCl3) ppm: 1.23-1.43 (3H m), 1.44-1.57 (1H, m), 1.58-1.72 (1H, m), 1.74- 1.84 (1H, m), 2.08-2.27 (2H, m), 2.33-2.42 (1H, m), 2.72-2.79 (1H, m), 2.86-2.93 (1H, m), 2.97 (1H, d, J = 13.2 Hz), 3.14-3.25 (2H, m), 3.81-3.90 (4H, m), 4.22 (1H, d, J = 13.1 Hz), 6.97 (1H, bs), 7.02-7.09 (2H, m), 7.22-7.30 (2H, m), 7.31-7.38 (2H, m), 7.38- 7.43 (2H, m), 7.55 (1H, d, J = 8.7 Hz), 7.61 (1H, d, J = 9.0 Hz). 1064 1H-NMR (CDCl3) ppm: 1.0-1.2 (2H, m), 1.2-1.4 (1H, m), 1.4-1.9 (3H, m), 2.0-2.5 (3H, m), 2.75-3.2 (4H, m), 3.38 (1H, br), 3.60 (1H, br), 3.96 (3H, s), 4.19 (1H, br), 6.54 (1H, br), 6.68 (1H, d, J = 8.2 Hz), 6.82 (1H, br), 7.22-7.29 (1H, m), 7.29-7.38 (2H, m), 7.38-7.44 (2H, m), 7.58 (1H, d, J = 2.2 Hz).

(406) TABLE-US-00122 TABLE 125 absolute configuration Ex. No. R.sup.4 NMR Salt 1065 1H-NMR (CDCl3) ppm: 1.15-1.56 (5H, m), 1.65-1.76 (2H, m), 1.76-1.90 (2H, m), 3.01- 3.18 (2H, m), 3.20-3.28 (3H, m), 3.76-3.83 (1H, m), 3.88 (3H, s), 7.01 (1H, d, J = 2.4 Hz), 7.04 (1H, d, J = 2.5 Hz), 7.07 (1H, dd, J = 2.6, 8.8 Hz), 7.25 (1H, dd, J = 2.5, 9.0 Hz), 7.57 (1H, d, J = 8.8 Hz), 7.62 (1H, d, J = 9.0 Hz). 1066 1H-NMR (DMSO-d6) ppm: 0.93-1.22 (2H, m), 1.33-1.47 (1H, m), 1.47-1.70 (1H, m), 1.70-1.94 (2H, m), 1.94-2.19 (1H, m), 2.88- 3.22 (2H, m), 3.27-3.48 (2H, m), 3.59-3.78 (2H, m), 3.88 (3H, s), 6.69 (1H, br), 6.82 (1H, d, J = 8.3 Hz), 7.13 (1H, d, J = 1.9 Hz), 7.95 (1H, d, J = 2.1 Hz), 8.5 (1H, br), 9.00 (1H, br), 9.68 (1H, br). 2 Hydrochloride

(407) TABLE-US-00123 TABLE 126 absolute configuration Ex. No. R.sup.4 NMR Salt 1067 1H-NMR (CDCl3) ppm: 1.22-1.43 (3H m), 1.45-1.56 (1H, m), 1.58-1.72 (1H, m), 1.74- 1.84 (1H, m), 2.08-2.27 (2H, m), 2.32-2.42 (1H, m), 2.73-2.79 (1H, m), 2.86-2.93 (1H, m), 2.97 (1H, d, J = 13.1 Hz), 3.14-3.25 (2H, m), 3.8-3.9 (4H, m), 4.22 (1H, d, J = 13.2 Hz), 6.97 (1H, bs), 7.02-7.09 (2H, m), 7.22-7.30 (2H, m), 7.31-7.37 (2H, m), 7.37- 7.43 (2H, m), 7.55 (1H, d, J = 8.7 Hz), 7.61 (1H, d, J = 9.0 Hz). 1068 1H-NMR (CDCl3) ppm: 1.0-1.2 (2H, m), 1.2-1.4 (1H, m), 1.4-1.85 (3H, m), 2.05-2.5 (3H, m), 2.65-3.15 (4H, m), 3.2-3.5 (1H, m), 3.60 (1H, br), 3.96 (3H, s), 4.05-4.4 (1H, m), 6.54 (1H, br), 6.68 (1H, d, J = 8.2 Hz), 6.82 (1H, br), 7.22-7.29 (1H, m), 7.29-7.38 (2H, m), 7.38-7.44 (2H, m), 7.58 (1H, d, J = 2.2 Hz).

(408) TABLE-US-00124 TABLE 127 absolute configuration Ex. No. R.sup.4 NMR Salt 1069 0 1H-NMR (CDCl3) ppm: 1.15-1.56 (5H, m), 1.65-1.76 (2H, m), 1.76-1.89 (2H, m), 3.00- 3.20 (2H, m), 3.20-3.28 (3H, m), 3.76-3.83 (1H, m), 3.88 (3H, s), 7.01 (1H, d, J = 2.4 Hz), 7.04 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 2.6, 8.8 Hz), 7.26 (1H, dd, J = 2.5, 9.0 Hz), 7.57 (1H, d, J = 8.8 Hz), 7.62 (1H, d, J = 9.0 Hz). 1070 1H-NMR (DMSO-d6) ppm: 0.94-1.19 (2H, m), 1.35-1.47 (1H, m), 1.47-1.70 (1H, m), 1.70-1.91 (2H, m), 1.91-2.18 (1H, m), 3.0- 3.25 (2H, m), 3.25-3.55 (2H, m), 3.6-3.8 (2H, m), 3.88 (3H, s), 6.69 (1H, br), 6.82 (1H, d, J = 8.4 Hz), 7.13 (1H, d, J = 2.2 Hz), 7.95 (1H, d, J = 2.1 Hz), 8.90 (1H, br), 9.56 (1H, br). Hydrochloride

(409) TABLE-US-00125 TABLE 128 absolute configuration Ex. No. R.sup.4 NMR Salt 1071 1H-NMR (CDCl3) ppm: 0.96-1.19 (19H, m), 1.19-1.41 (6H, m), 1.50-1.67 (2H, m), 1.67- 1.82 (3H, m), 2.48-2.65 (2H, m), 2.94-3.09 (2H, m), 3.09-3.25 (2H, m), 7.09 (1H, dd, J = 2.4, 8.9 Hz), 7.17 (1H, d, J = 2.4 Hz), 7.28 (1H, dd, J = 2.1, 11.0 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.59-7.66 (2H, m). 1072 1H-NMR (CDCl3) ppm: 0.95-1.09 (1H, m), 1.14 (18H, d, J = 7.5 Hz), 1.20-1.45 (3H, m), 1.48-1.85 (8H, m), 2.58-2.74 (2H, m), 2.90- 3.00 (1H, m), 3.00-3.08 (1H, m), 3.17-3.30 (2H, m), 6.74 (1H, dd, J = 0.7, 3.2 Hz), 6.85 (1H, d, J = 7.3 Hz), 7.03-7.10 (1H, m), 7.17 (1H, d, J = 3.2 Hz), 7.26 (1H, d, J = 8.3 Hz). 1073 1H-NMR (CDCl3) ppm: 0.95-1.09 (1H, m), 1.09-1.42 (21H, m), 1.53-1.80 (8H, m), 2.41- 2.50 (1H, m), 2.54-2.64 (1H, m), 2.95-3.10 (3H, m), 3.13-3.23 (1H, m), 6.56 (1H, d, J = 0.4, 3.1 Hz), 6.97 (1H, dd, J = 2.1, 8.8 Hz), 7.23 (1H, d, J = 3.1 Hz), 7.37-7.44 (2H, m). 1074 1H-NMR (CDCl3) ppm: 0.94-1.06 (1H, m), 1.05-1.25 (19H, m), 1.25-1.45 (2H, m), 1.53- 1.80 (8H, m), 2.42-2.50 (1H, m), 2.55-2.65 (1H, m), 2.90-3.00 (1H, m), 3.00-3.13 (2H, m), 3.16- 3.25 (1H, m), 6.56 (1H, dd, J = 0.7, 3.2 Hz), 6.97 (1H, dd, J = 1.7, 8.3 Hz), 7.20 (1H, d, J = 3.2 Hz), 7.32 (1H, s), 7.52 (1H, d, J = 8.3 Hz).

(410) TABLE-US-00126 TABLE 129 absolute configuration Ex. No. R.sup.4 NMR Salt 1075 1H-NMR (CDCl3) ppm: 0.95-1.09 (1H, m), 1.20-1.55 (4H, m), 1.55-1.63 (1H, m), 1.66- 1.86 (3H, m), 2.59-2.77 (2H, m), 2.81-3.01 (1H, m), 3.01-3.09 (1H, m), 3.18-3.30 (2H, m), 6.66- 6.71 (1H, m), 6.87 (1H, dd, J = 1.1, 7.2 Hz), 7.10-7.21 (3H, m), 8.25 (1H, brs). 1076 1H-NMR (CDCl3) ppm: 0.96-1.10 (1H, m), 1.10-1.43 (3H, m), 1.43-1.65 (3H, m), 1.65- 1.84 (2H, m), 2.42-2.53 (1H, m), 2.53-2.66 (1H, m), 2.97-3.12 (3H, m), 3.15-3.26 (1H, m), 6.51 (1H, dd, J = 1.0, 2.1 Hz), 7.06 (1H, dd, J = 2.0, 8.6 Hz), 7.17-7.23 (1H, m), 7.32 (1H, d, J = 8.6 Hz), 7.44 (1H, d, J = 2.0 Hz), 8.36 (1H, brs). 1077 0 1H-NMR (DMSO-d6) ppm: 0.81-0.96 (1H, m), 1.06-1.35 (3H, m), 1.43-1.57 (2H, m), 1.58- 1.74 (2H, m), 2.01 (1H, brs), 2.30-2.41 (2H, m), 2.75-2.97 (4H, m), 6.31-6.37 (1H, m), 6.80 (1H, dd, J = 1.8, 8.4 Hz), 7.10 (1H, s), 7.25 (1H, t, J = 2.7 Hz), 7.41 (1H, d, J = 8.4 Hz), 10.89 (1H, s). 1078 1H-NMR (DMSO-d6) ppm: 0.85-0.98 (1H, m), 1.12-1.35 (3H, m), 1.48-1.73 (4H, m), 2.17 (1H, brs), 2.32-2.50 (2H, m), 2.76-3.01 (4H, m), 6.99-7.08 (2H, m), 7.20 (1H, dd, J = 2.1, 8.7 Hz), 7.41 (1H, d, J = 1.8 Hz), 7.58 (1H, d, J = 8.8 Hz), 7.67 (1H, d, J = 8.8 Hz), 9.56 (1H, brs).

(411) TABLE-US-00127 TABLE 130 absolute configuration Ex. No. R.sup.4 NMR Salt 1079 1H-NMR (CDCl3) ppm: 1.00-1.14 (1H, m), 1.20-1.45 (3H, m), 1.45-1.60 (1H, m), 1.60- 1.68 (1H, m), 1.68-1.85 (3H, m), 2.53-2.66 (2H, m), 2.95-3.10 (2H, m), 3.15-3.26 (2H, m), 7.33 (1H, dd, J = 2.1, 8.8 Hz), 7.37-7.47 (2H, m), 7.51 (1H, d, J = 2.1 Hz), 7.74-7.82 (3H, m). 1080 1H-NMR (CDCl3) ppm: 0.98-1.12 (1H, m), 1.17-1.82 (8H, m), 2.48-2.64 (2H, m), 2.95- 3.25 (4H, m), 3.90 (3H, s), 7.08-7.14 (2H, m), 7.31 (1H, dd, J = 2.1, 8.7 Hz), 7.47 (1H, d, J = 2.0 Hz), 7.63-7.70 (2H, m). 1081 1H-NMR (CDCl3) ppm: 0.97-1.10 (1H, m), 1.15-1.69 (6H, m), 1.69-1.84 (2H, m), 2.45- 2.54 (1H, m), 2.54-2.65 (1H, m), 2.93-3.13 (3H, m), 3.13-3.25 (1H, m), 7.19 (1H, dd, J = 2.0, 8.6 Hz), 5.27 (1H, d, J = 5.4 Hz), 7.42 (1H, d, J = 5.4 Hz), 7.59 (1H, d, J = 2.0 Hz), 7.79 (1H, d, J = 8.6 Hz). 1082 1H-NMR (DMSO-d6) ppm: 0.95-1.22 (2H, m), 1.22-1.37 (1H, m), 1.39-1.51 (1H, m), 1.51- 1.68 (2H, m), 1.68-1.78 (1H, m), 1.99-2.11 (1H, m), 2.92-3.75 (6H, brm), 4.30-5.75 (1H, br), 7.00-7.30 (2H, m), 7.30-7.52 (1H, m), 8.15 (1H, s), 9.45-10.25 (2H, brm). 2 Hydrochloride 1083 1H-NMR (DMSO-d6) ppm: 0.90-1.05 (1H, m), 1.10-1.38 (2H, m), 1.49-1.66 (3H, m), 1.67- 1.78 (1H, m), 1.96-2.08 (1H, m), 2.94-3.10 (1H, m), 3.10-3.42 (5H, m), 3.53-4.15 (1H, br), 7.08 (1H, d, J = 8.3 Hz), 7.21 (1H, brs), 7.40 (1H, d, J = 8.3 Hz), 8.12 (1H, d, J = 2.1 Hz), 9.51 (2H, brs). 2HC 1084 1H-NMR (DMSO-d6) ppm: 1.10-1.52 (4H, m), 1.52-1.69 (2H, m), 1.69-1.81 (1H, m), 2.03- 2.22 (1H, m), 3.20-4.30 6H, m), 7.05 (1H, s), 7.25-7.70 (1H, m), 7.70-8.05 (2H, m), 8.14 (1H, s), 9.60-10.47 (2H, m). (1H not found) 2HC 1085 1H-NMR (CDCl3) ppm: 1.00-1.13 (1H, m), 1.19-1.45 (3H, m), 1.58-1.90 (5H, m), 2.52- 2.65 (2H, m), 2.95-3.25 (4H, m), 7.22 (1H, dt, J = 2.5, 8.8 Hz), 7.36 (1H, dd, J = 2.0, 8.8 Hz), 7.40 (1H, dd, J = 2.5, 9.9 Hz), 7.51 (1H, d, J = 2.0 Hz), 7.69-7.78 (2H, m). 1086 0 1H-NMR (DMSO-d6) ppm: 0.79-0.97 (1H, m), 1.05-1.56 (4H, m), 1.56-1.72 (2H, m), 1.77- 1.90 (1H, m), 2.62-2.75 (1H, m), 2.79-3.19 (5H, m), 3.19-3.70 (1H, br), 3.75 (3H, s), 6.37-6.56 (2H, m), 6.78 (1H, d, J = 7.2 Hz), 7.30-7.14 (1H, m), 7.14-7.33 (2H, m). Fumarate 1087 1H-NMR (DMSO-d6) ppm: 0.86-1.00 (1H, m), 1.04-1.47 (4H, m), 1.47-1.57 (1H, m), 1.61- 1.71 (1H, m), 1.77-1.86 (1H, m), 2.55-2.72 (2H, m), 2.92-3.16 (4H, m), 3.75 (3H, s), 5.25-6.25 (1H, br), 6.35 (1H, dd, J = 0.4, 3.0 Hz), 6.96 (1H, dd, J = 1.9, 8.6 Hz), 7.25-7.33 (2H, m), 7.35 (1H, d, J = 8.6 Hz). (2H not found) Oxalate 1088 1H-NMR (CDCl3) ppm: 0.95-1.11 (1H, m), 1.11-1.42 (3H, m), 1.53-1.82 (5H, m), 2.45-2.55 (1H, m), 2.55-2.64 (1H, m), 2.98-3.12 (3H, m), 3.15-3.25 (1H, m), 3.75 (3H, s), 6.43 (1H, dd, J = 0.8, 3.1 Hz), 6.98-7.03 (2H, m), 7.12-7.15 (1H, m), 7.53 (1H, d, J = 8.4 Hz). 1089 1H-NMR (DMSO-d6) ppm: 0.87-1.02 (1H, m), 1.08-1.50 (4H, m), 1.50-1.60 (1H, m), 1.62- 1.72 (1H, m), 1.75-1.86 (1H, m), 2.57-2.76 (2H, m), 2.92-3.16 (4H, m), 3.20-4.38 (1H, br), 6.91 (1H, s), 7.09 (1H, dd, J = 1.9, 8.5 Hz), 7.41 (1H, d, J = 1.9 Hz), 7.52 (1H, d, J = 8.5 Hz), 7.97 (1H, d, J = 1.8 Hz). (2H not found) Oxalate

(412) TABLE-US-00128 TABLE 131 absolute configuration Ex. No. R.sup.4 NMR Salt 1090 1H-NMR (CDCl3) ppm: 0.99-1.18 (19H, m), 1.20-1.41 (6H, m), 1.49-1.68 (2H, m), 1.68- 1.82 (3H, m), 2.49-2.64 (2H, m), 2.94-3.10 (2H, m), 3.10-3.25 (2H, m), 7.09 (1H, dd, J = 2.4, 8.8 Hz), 7.17 (1H, d, J = 2.4 Hz), 7.28 (1H, dd, J = 2.1, 11.0 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.59-7.66 (2H, m). 1091 1H-NMR (CDCl3) ppm: 0.93-1.10 (1H, m), 1.14 (18H, d, J = 7.5 Hz), 1.20-1.45 (3H, m), 1.49-1.85 (8H, m), 2.58-2.74 (2H, m), 2.90- 3.00 (1H, m), 3.00-3.08 (1H, m), 3.17-3.30 (2H, m), 6.74 (1H, dd, J = 0.7, 3.2 Hz), 6.85 (1H, d, J = 7.3 Hz), 7.03-7.10 (1H, m), 7.17 (1H, d, J = 3.2 Hz), 7.26 (1H, d, J = 8.3 Hz). 1092 1H-NMR (CDCl3) ppm: 0.95-1.10 (1H, m), 1.10-1.41 (21H, m), 1.53-1.80 (8H, m), 2.41- 2.50 (1H, m), 2.53-2.62 (1H, m), 2.95-3.10 (3H, m), 3.13-3.23 (1H, m), 6.56 (1H, d, J = 0.4, 3.1 Hz), 6.97 (1H, dd, J = 2.1, 8.8 Hz), 7.23 (1H, d, J = 3.1 Hz), 7.37-7.44 (2H, m). 1093 1H-NMR (CDCl3) ppm: 0.94-1.06 (1H, m), 1.05-1.25 (19H, m), 1.25-1.45 (2H, m), 1.53- 1.80 (8H, m), 2.42-2.50 (1H, m), 2.55-2.65 (1H, m), 2.90-3.00 (1H, m), 3.00-3.13 (2H, m), 3.16- 3.25 (1H, m), 6.56 (1H, dd, J = 0.7, 3.2 Hz), 6.97 (1H, dd, J = 1.7, 8.3 Hz), 7.20 (1H, d, J = 3.2 Hz), 7.32 (1H, s), 7.52 (1H, d, J = 8.3 Hz).

(413) TABLE-US-00129 TABLE 132 absolute configuration Ex. No. R.sup.4 NMR Salt 1094 000 1H-NMR (CDCl3) ppm: 0.95-1.09 (1H, m), 1.18-1.55 (4H, m), 1.55-1.63 (1H, m), 1.66- 1.85 (3H, m), 2.59-2.77 (2H, m), 2.81-3.01 (1H, m), 3.01-3.09 (1H, m), 3.18-3.30 (2H, m), 6.67- 6.71 (1H, m), 6.87 (1H, dd, J = 1.1, 7.2 Hz), 7.10-7.20 (3H, m), 8.15-8.47 (1H, br). 1095 001 1H-NMR (CDCl3) ppm: 0.96-1.10 (1H, m), 1.11-1.43 (3H, m), 1.52-1.84 (5H, m), 2.42-2.52 (1H, m), 2.54-2.64 (1H, m), 2.97-3.10 (3H, m), 3.14-3.25 (1H, m), 6.51 (1H, dd, J = 1.0, 2.1 Hz), 7.06 (1H, dd, J = 2.0, 8.6 Hz), 7.17-7.23 (1H, m), 7.32 (1H, d, J = 8.6 Hz), 7.44 (1H, d, J = 2.0 Hz), 8.20 (1H, brs). 1096 002 1H-NMR (DMSO-d6) ppm: 0.81-0.95 (1H, m), 1.05-1.35 (3H, m), 1.41-1.57 (2H, m), 1.58- 1.74 (2H, m), 2.05 (1H, brs), 2.30-2.41 (2H, m), 2.75-2.97 (4H, m), 6.30-6.38 (1H, m), 6.80 (1H, dd, J = 1.8, 8.4 Hz), 7.10 (1H, s), 7.25 (1H, t, J = 2.7 Hz), 7.41 (1H, d, J = 8.4 Hz), 10.89 (1H, s). 1097 003 1H-NMR (DMSO-d6) ppm: 0.85-0.99 (1H, m), 1.12-1.36 (3H, m), 1.48-1.76 (4H, m), 2.17 (1H, brs), 2.31-2.50 (2H, m), 2.76-3.01 (4H, m), 6.99-7.08 (2H, m), 7.20 (1H, dd, J = 2.0, 8.7 Hz), 7.41 (1H, d, J = 1.6 Hz), 7.58 (1H, d, J = 8.8 Hz), 7.67 (1H, d, J = 8.8 Hz), 9.57 (1H, brs).

(414) TABLE-US-00130 TABLE 133 absolute configuration 004 Ex. No. R.sup.4 NMR Salt 1098 005 1H-NMR (CDCl3) ppm: 1.00-1.14 (1H, m), 1.20-1.45 (3H, m), 1.45-1.68 (2H, m), 1.68- 1.85 (3H, m), 2.53-2.66 (2H, m), 2.95-3.10 (2H, m), 3.15-3.26 (2H, m), 7.33 (1H, dd, J = 2.1, 8.8 Hz), 7.37-7.47 (2H, m), 7.51 (1H, d, J = 2.1 Hz), 7.74-7.82 (3H, m). 1099 006 1H-NMR (CDCl3) ppm: 0.98-1.12 (1H, m), 1.17-1.45 (3H, m), 1.45-1.85 (5H, m), 2.49- 2.64 (2H, m), 2.95-3.25 (4H, m), 3.90 (3H, s), 7.08-7.14 (2H, m), 7.31 (1H, dd, J = 2.1, 8.7 Hz), 7.47 (1H, d, J = 2.0 Hz), 7.63-7.70 (2H, m). 1100 007 1H-NMR (CDCl3) ppm: 0.97-1.10 (1H, m), 1.15-1.69 (6H, m), 1.69-1.84 (2H, m), 2.45- 2.54 (1H, m), 2.54-2.63 (1H, m), 2.93-3.13 (3H, m), 3.13-3.25 (1H, m), 7.19 (1H, dd, J = 2.0, 8.6 Hz), 5.27 (1H, d, J = 5.4 Hz), 7.42 (1H, d, J = 5.4 Hz), 7.59 (1H, d, J = 2.0 Hz), 7.79 (1H, d, J = 8.6 Hz). 1101 008 1H-NMR (DMSO-d6) ppm: 0.91-1.10 (1H, m), 1.10-1.37 (2H, m), 1.41-1.66 (3H, m), 1.66- 1.79 (1H, m), 1.06-2.09 (1H, m), 2.95-3.55 (6H, m), 3.70-4.95 (1H, br), 7.00-7.17 (1H, m), 7.17- 7.40 (2H, m), 8.08-8.19 (1H, m), 9.33-9.90 (2H, m). 2 Hydrochloride 1102 009 1H-NMR (DMSO-d6) ppm: 0.92-1.09 (1H, m), 1.10-1.39 (2H, m), 1.47-1.68 (3H, m), 1.68- 1.78 (1H, m), 1.99-2.09 (1H, m), 2.94-3.14 (1H, br), 3.14-3.50 (5H, brm), 4.05-5.03 (1H, br), 7.08-7.19 (1H, m), 7.25-7.36 (1H, m), 7.41 (1H, d, J = 8.2 Hz), 8.14 (1H, d, J = 1.6 Hz), 9.70 (2H, brs). 2 Hydrochloride 1103 010 1H-NMR (DMSO-d6) ppm: 1.12-1.51 (4H, m), 1.53-1.68 (2H, m), 1.69-1.79 (1H, m), 2.07- 2.19 (1H, m), 3.20-4.27 6H, m), 7.04 (1H, s), 7.30-7.65 (1H, m), 7.65-8.05 (2H, m), 8.13 (1H, s), 9.65-10.40 (2H, m). (1H not found) 2 Hydrochloride 1104 011 1H-NMR (CDCl3) ppm: 1.00-1.13 (1H, m), 1.18-1.45 (3H, m), 1.58-1.90 (5H, m), 2.52- 2.65 (2H, m), 2.95-3.11 (2H, m), 3.11-3.25 (2H, m), 7.22 (1H, dt, J = 2.5, 8.8 Hz), 7.36 (1H, dd, J = 2.0, 8.8 Hz), 7.40 (1H, dd, J = 2.5, 9.9 Hz), 7.51 (1H, d, J = 2.0 Hz), 7.69-7.78 (2H, m). 1105 012 1H-NMR (DMSO-d6) ppm: 0.80-0.96 (1H, m), 1.05-1.56 (4H, m), 1.56-1.72 (2H, m), 1.77- 1.90 (1H, m), 2.62-2.75 (1H, m), 2.77-2.90 (1H, m), 2.90-3.19 (4H, m), 3.19-3.70 (1H, br), 3.75 (3H, s), 6.37-6.54 (2H, m), 6.78 (1H, d, J = 7.3 Hz), 7.30-7.14 (1H, m), 7.14-7.31 (2H, m). Fumarate 1106 013 1H-NMR (DMSO-d6) ppm: 0.86-1.00 (1H, m), 1.04-1.47 (4H, m), 1.47-1.57 (1H, m), 1.61- 1.70 (1H, m), 1.77-1.87 (1H, m), 2.55-2.72 (2H, m), 2.90-3.16 (4H, m), 3.75 (3H, s), 5.25-6.25 (1H, br), 6.35 (1H, d, J = 2.9 Hz), 6.96 (1H, dd, J = 1.7, 8.6 Hz), 7.25-7.33 (2H, m), 7.35 (1H, d, J = 8.6 Hz). (2H not found) Oxalate 1107 014 1H-NMR (CDCl3) ppm: 0.96-1.10 (1H, m), 1.10-1.44 (3H, m), 1.48-1.82 (5H, m), 2.45- 2.55 (1H, m), 2.55-2.64 (1H, m), 2.98-3.12 (3H, m), 3.15-3.25 (1H, m), 3.75 (3H, s), 6.43 (1H, dd, J = 0.8, 3.1 Hz), 6.98-7.03 (2H, m), 7.12- 7.15 (1H, m), 7.53 (1H, d, J = 8.5 Hz). 1108 015 1H-NMR (DMSO-d6) ppm: 0.87-1.02 (1H, m), 1.08-1.50 (4H, m), 1.50-1.60 (1H, m), 1.62- 1.72 (1H, m), 1.75-1.86 (1H, m), 2.54-2.76 (2H, m), 2.92-3.17 (4H, m), 3.20-5.40 (1H, br), 6.91 (1H, d, J = 1.2 Hz), 7.10 (1H, dd, J = 1.9, 8.6 Hz), 7.41 (1H, d, J = 1.9 Hz), 7.52 (1H, d, J = 8.6 Hz), 7.97 (1H, d, J = 2.0 Hz). (2H not found) Oxalate

(415) TABLE-US-00131 TABLE 134 relative configuration 016 Ex. No. R.sup.4 NMR Salt 1109 017 1H-NMR (DMSO-d6) ppm: 1.22-1.52 (6H, m), 1.56-1.97 (4H, m), 2.00-2.18 (1H, m), 2.75- 2.95 (1H, m), 3.20-3.40 (1H, m), 3.40-3.60 (2H, m), 3.96-4.10 (1H, m), 4.20-4.57 (1H, br), 6.91-7.01 (2H, m), 7.19-7.31 (2H, m), 8.69 (1H, brs), 10.11 (1H, brs). 2 Hydrochloride 1110 018 1H-NMR (CDCl3) ppm: 1.15-1.33 (6H, m), 1.48-1.58 (2H, m), 1.66-1.85 (4H, m), 2.68 (1H, t, J = 11.8 Hz), 3.02-3.12 (1H, m). 3.23 (1H, dd, J = 3.3, 11.4 Hz), 3.29-3.24 (1H, m), 3.76 (1H, td, J = 3.3, 11.4 Hz), 3.88 (3H, s), 7.00 (1H, d, J = 2.3 Hz), 7.02-7.30 (2H, m), 7.22-7.29 (1H, m), 7.57 (1H, d, J = 8.8 Hz), 7.61 (1H, d, J = 9.0 Hz). 1111 019 1H-NMR (DMSO-d6) ppm: 1.17-1.36 (2H, m), 1.36-1.51 (4H, m), 1.62-2.00 (4H, m), 2.06- 2.17 (1H, m), 2.94-3.05 (1H, m), 3.30-3.50 (1H, m), 3.50-3.64 (2H, m), 4.04-4.13 (1H, m). 4.59- 5.50 (1H, br), 7.17 (1H, d, J = 8.9 Hz), 7.31 (1H, d, J = 5.4 Hz), 7.38 (1H, brs), 7.62 (1H, d, J = 5.4 Hz), 7.83 (1H, d, J = 8.9 Hz), 8.68 (1H, brs), 10.12 (1H, brs). 2 Hydrochloride 1112 020 1H-NMR (DMSO-d6) ppm: 0.99-1.17 (2H, m), 1.30-1.49 (4H, m), 1.55-1.75 (2H, m), 1.75-1.98 (2H, m), 1.98-2.13 (1H, m), 3.12- 3.28 (2H, m), 3.28-3.50 (1H, m), 3.67-3.85 (2H, m), 6.67 (1H, dd, J = 3.4, 8.6 Hz), 7.10 (1H, dd, J = 8.6. 10.7 Hz), 7.28 (1H, dd, J = 2.6, 2.6 Hz), 8.07 (1H, d, J = 2.2 Hz ), 8.43 (1H, br), 9.94 (1H, br). Hydrochloride 1113 021 1H-NMR (DMSO-d6) ppm: 1.03-1.21 (2H, m), 1.37-1.48 (4H, m), 1.58-1.85 (3H, m), 1.95-2.14 (2H, m), 3.23 (1H, d, J = 10.6 Hz), 3.36-3.55 (2H, m), 3.64-3.76 (1H, m), 3.85- 3.96 (1H, m), 7.01 (1H, d, J = 7.6 Hz), 7.34 (1H, dd, J = 7.7, 7.7 Hz ), 7.46 (1H, d, J = 5.4 Hz), 7.57-7.62 (1H, m), 7.75 (1H, d, J = 5.4 Hz), 8.35-8.6 (1H, m), 9.82 (1H, br). Hydrochloride

(416) TABLE-US-00132 TABLE 134 absolute configuration 022 Ex. No. R.sup.4 NMR Salt 1114 023 1H-NMR (CDCl3) ppm: 0.95-1.10 (4H, m), 1.13 (18H, d, J = 7.3 Hz), 1.19-1.47 (7H, m), 1.59-1.67 (1H, m), 1.70-1.84 (3H, m), 2.45- 2.53 (1H, m), 2.57 (1H, dd, J = 10.3, 11.0 Hz), 2.62-2.70 (1H, m), 3.12 (1H, dd, J = 2.7, 11.2 Hz), 3.16-3.24 (1H, m), 7.09 (1H, dd, J = 2.4, 8.9 Hz), 7.17 (1H, d, J = 2.4 Hz), 7.27 (1H, dd, J = 2.1, 8.7 Hz), 7.44 (1H, d, J = 2.0 Hz), 7.59- 7.65 (2H, m). 1115 024 1H-NMR (CDCl3) ppm: 0.94-1.12 (4H, m), 1.15-1.46 (4H, m), 1.57-1.68 (2H, m), 1.68- 1.85 (11H, m), 2.42-2.51 (1H, m), 2.59-2.70 (2H, m), 3.10 (1H, dd, J = 2.7, 11.2 Hz), 3.15- 3.25 (1H, m), 7.29 (1H, dd, J = 2.2, 8.6 Hz), 7.30-7.37 (1H, m), 7.42-7.49 (1H, m), 7.76 (1H, d, J = 2.1 Hz), 7.93 (1H, d, J = 7.2 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.29 (1H, d, J = 8.3 Hz).

(417) TABLE-US-00133 TABLE 135 absolute configuration 025 Ex. No. R.sup.4 NMR Salt 1116 026 1H-NMR (DMSO-d6) ppm: 0.85-0.99 (4H, m), 1.13-1.35 (3H, m), 1.49-1.75 (4H, m), 1.99 (1H, brs), 2.32-2.50 (3H, m), 2.92-3.02 (2H, m), 7.00-7.09 (2H, m), 7.19 (1H, dd, J = 2.1, 8.7 Hz), 7.41 (1H, d, J = 1.8 Hz), 7.58 (1H, d, J = 8.8 Hz), 7.66 (1H, d, J = 8.8 Hz), 9.56 (1H, brs). 1117 027 1H-NMR (DMSO-d6) ppm: 1.10-1.57 (7H, m), 1.57-1.71 (2H, m), 1.71-1.82 (1H, m), 2.11- 2.22 (1H, m), 3.00-3.40 (6H, m), 7.22 (1H, t, J = 7.4 Hz), 7.35-7.85 (4H, m), 8.09 (1H, d, J = 7.8 Hz), 8.37 (1H, brs), 9.96 (2H, brs), 11.61 (1H, brs). 2 Hydrochloride

(418) TABLE-US-00134 TABLE 136 absolute configuration 028 Ex. No. R.sup.4 NMR Salt 1118 029 . 1H-NMR (CDCl3) ppm: 0.98-1.11 (4H, m), 1.17-1.58 (4H, m), 1.58-1.85 (4H, m), 2.44- 2.53 (1H, m), 2.56-2.70 (2H, m), 3.12 (1H, dd, J = 2.8, 11.2 Hz), 3.15-3.25 (1H, m), 3.90 (3H, s), 7.08-7.16 (2H, m), 7.30 (1H, dd, J = 2.0, 8.7 Hz), 7.46 (1H, d, J = 2.0 Hz), 7.65 (1H, d, J = 4.8 Hz), 7.67 (1H, d, J = 4.9 Hz). 1119 030 1H-NMR (DMSO-d6) ppm: 0.95-1.05 (1H, m), 1.11 (3H, d, J = 6.3Hz ), 1.15-1.5 (3H, m), 1.5-1.6 (1H, m), 1.65-1.75 (2H, m), 1.85-1.95 (1H, m), 2.65-2.85 (3H, m), 2.85- 4.35 (4H, m ), 6.50 (1H, s), 7.33 (1H, dd, J = 2.1, 8.7 Hz), 7.4-7.5 (2H, m), 7.57 (1H, d, J = 1.8 Hz), 7.8-7.9 (3H, m). Fumarate 1120 031 1H-NMR (CDCl3) ppm: 0.98-1.12 (4H, m), 1.18-1.48 (4H, m), 1.58-1.69 (1H, m), 1.69- 1.85 (3H, m), 2.46-2.54 (1H, m), 2.57 (1H, dd, J = 10.2, 11.0 Hz), 2.62-2.70 (1H, m), 3.10- 3.25 (2H, m), 7.22 (1H, dt, J = 2.6, 8.8 Hz), 7.35 (1H, dd, J = 1.8, 8.7 Hz), 7.40 (1H, dd, J = 2.5, 9.9 Hz), 7.50 (1H, d, J = 1.9 Hz), 7.68-7.77 (2H, m).________________

(419) TABLE-US-00135 TABLE 137 absolute configuration 032 Ex. No. R.sup.4 NMR Salt 1121 033 1H-NMR (CDCl3) ppm: 0.97-1.17 (4H, m), 1.17-1.49 (4H, m), 1.53-1.89 (4H, m), 2.42- 2.55 (1H, m), 2.55-2.71 (2H, m), 3.08 (1H, dd, J = 2.8, 11.3 Hz), 3.13-3.26 (1H, m), 7.19 (1H, dd, J = 2.0, 8.6 Hz), 7.27 (1H, d, J = 5.4 Hz), 7.42 (1H, d. J = 5.4 Hz), 7.58 (1H, d, J = 2.0 Hz), 7.78 (1H, d, J = 8.6 Hz). 1122 034 1H-NMR (CDCl3) ppm: 0.85-1.02 (1H, m), 1.05 (3H, d, J = 6.4 Hz), 1.17-1.54 (4H, m), 1,54-1.63 (1H, m), 1.63-1.83 (3H, m), 2.40- 2.55 (1H, m), 2.55-2.65 (1H, m), 2.65-2.74 (1H, m), 3.10 (1H, dd, J = 2.8, 11.4 Hz), 3.15-3.26 (1H, m), 7.12 (1H, dd, J = 0.7, 7.6 Hz), 7.30 (1H, t, J = 7.8 Hz), 7.35 (1H, d, J = 5.5 Hz), 7.57 (1H, d, J = 5.5 Hz), 7.64 (1H, d, J = 8.0 Hz). 1123 035 1H-NMR (DMSO-d6) ppm: 0.90-1.04 (1H, m), 1.12 (3H, d, J = 6.4 Hz), 1.17-1.35 (2H, m), 1.35-1.49 (1H, m), 1.50-1.62 (1H, m), 1.64- 1.74 (1H, m), 1.84-1.94 (1H, m), 2.65-2.84 (3H, m), 3.10 (1H, dd, J = 2.9, 11.7 Hz), 3.21-3.34 (1H, m), 4.30-6.30 (1.5H, br), 6.49 (1.5H, s), 7.18 (1H, dd, J = 1.7, 8.4 Hz), 7.39 (1H, d, J = 5.4 Hz), 7.67 (1H, d, J = 5.4 Hz). 7.75 (1H, d, J = 17 Hz), 7.81 (1H, d, J = 8 4 Hz)._____ Fumarate

(420) TABLE-US-00136 TABLE 138 absolute configuration 036 Ex. No. R.sup.4 NMR Salt 1124 037 1H-NMR (DMSO-d6) ppm at 80 C.: 0.96- 1.38 (6H, m), 1.40-1.50 (1H, m), 1.50-1.80 (3H, m), 2.06-2.17 (1H, m), 3.01-3.20 (2H, m), 3.27- 3.40 (2H, m), 3.50-3.65 (1H, m), 5.90-6.39 (1H, br), 7.05-7.22 (2H, m), 7.32 (1H, brs), 8.03 (1H, d, J = 2.0 Hz), 9.64 (1H, brs), 9.81 (1H, brs). 2 Hydrochloride 1125 038 1H-NMR (DMSO-d6) ppm: 0.85-1.00 (1H, m), 1.05-1.38 (5H, m), 1.38-1.75 (4H, m), 1.87- 2.00 (1H, m), 2.65-3.00 (3H, m), 3.12 (1H, dd, J = 2.8, 11.9 Hz), 3.30-3.47 (1H, m), 6.53 (2H, s), 7.04 (1H, d. J = 8.3 Hz), 7.14 (1H, brs), 7.37 (1H, d, J = 8.3 Hz), 8.08 (1H, d, J = 2.2 Hz). (3H, not found) Fumarate 1126 039 1H-NMR (DMSO-d6) ppm at 80 C.: 1.02- 1.38 (6H, m), 1.38-1.50 (1H, m), 1.50-1.79 (3H, m), 2.05-2.16 (2H, m), 3.10-3.29 (2H, m), 3.29- 3.57 (2H, br), 3.57-3.73 (1H, br), 3.94 (3H, s), 4.30-4.25 (1H, br), 6.91 (1H, d. J = 8.4 Hz), 7.16 (1H, brs), 7.31 (1H, brs), 7.93 (1H, s), 9.72 (1H, brs). 2 Hydrochloride 1127 040 1H-NMR (DMSO-d6) ppm at 80 C.: 1.03- 1.38 (6H, m), 1.40-1.79 (4H, m), 2.06-2.18 (1H, m), 2.45 (3H, s), 3.12-3.31 (2H, m), 3.31-3.56 (2H, m), 3.56-3.77 (1H, m), 5.39-6.13 (1H, br), 7.08-7.21 (2H, m), 7.21-7.40 (1H, m), 7.95 (1H, d, J = 2.0 Hz), 9.79 (2H, brs). 2 Hydrochloride 1128 041 1H-NMR (DMSO-d6) ppm at 80 C.: 1.02- 1.39 (6H, m), 1.45-1.80 (4H, m), 2.08-2.18 (1H, m), 3.10-3.30 (2H, m), 3.32-3.55 (2H, m), 3.55- 3.74 (1H, m), 5.50-6.15 (1H, br), 7.16-7.25 (1H, m), 7.25-7.36 (2H, m), 7.47 (1H, d, J = 8.2 Hz), 7.94 (1H, d, J = 2.0 Hz), 9.55-10.05 (2H, brm). 2 Hydrochloride 1129 042 1H-NMR (DMSO-d6) ppm: 0.89-1.03 (1H, m), 1.08-1.35 (5H, m), 1.35-1.60 (3H, m), 1.63- 1.73 (1H, m), 1.84-1.96 (1H, m), 2.62-2.85 (3H, m), 3.08 (1H, dd, J = 2.8, 11.8 Hz), 3.22-3.35 (1H, m), 6.50 (2H, s), 6.91 (1H, dd, J = 0.9, 2.1 Hz), 7.07 (1H, dd, J = 1.7, 8.3 Hz), 7.36 (1H, s), 7.58 (1H, d, J = 8.2 Hz), 7.95 (1H, d, J = 2.2 Hz). (3H not found) Fumarate 1130 043 1H-NMR (DMSO-d6) ppm: 1.09-1.55 (7H, m), 1.55-1.80 (3H, m), 2.10-2.22 (1H, m), 3.35- 4.13 (5H, m), 4.13-5.22 (1H, br), 7.12 (1H, s), 7.60 (1H, brs), 7.81 (1H, s), 7.98 (1H, brs), 8.15 (1H, s), 10.09 (2H, brs). 2 Hydrochloride 1131 044 1H-NMR (DMSO-d6) ppm: 0.90-1.06 (1H, m), 1.15-1.38 (5H, m), 1.47-1.67 (3H, m), 1.67- 1.80 (1H, m), 1.99-2.11 (1H, m), 2.80-3.30 (4H, m), 3.40-3.60 (1H, m), 4.40-5.10 (1H, br), 7.13- 7.38 (2H, m), 8.15 (1H, d, J = 2.0 Hz), 9.05- 9.58 (1H, br), 9.70-9.95 (1H, br). 2 Hydrochloride

(421) TABLE-US-00137 TABLE 139 absolute configuration 045 Ex. No. R.sup.4 NMR Salt 1132 046 1H-NMR (CDCl3) ppm: 0.94-1.10 (4H, m), 1.13-1.65 (6H, m), 1.65-1.83 (2H, m), 2.37- 2.47 (1H, m), 2.55-2.69 (2H, m), 3.05 (1H, dd, J = 2.8, 11.2 Hz), 3.12-3.23 (1H, m), 3.77 (3H, s), 6.42 (1H, d, J = 0.7, 3.1 Hz), 7.03 (1H, d, J = 3.1 Hz), 7.08 (1H, d, J = 2.0, 8.6 Hz), 7.22- 7 30 (1H, m), 7.41 (1H, d, J = 18 Hz). 1133 047 1H-NMR (DMSO-d6) ppm: 0.90-1.05 (1H, m), 1.09-1.35 (5H, m), 1.39-1.60 (3H, m), 1.64- 1.76 (1H, m), 1.88-2.00 (1H, m), 2.68-2.79 (1H, m), 2.79-2.94 (2H, m), 3.01-3.11 (1H, m), 3.28- 3.40 (1H, m), 3.75 (3H, s), 6.36 (1H, d, J = 0.6, 3.1 Hz), 6.51 (2H, s), 6.87 (1H, d, J = 1.7, 8.4 Hz), 7.18 (1H, s), 7.27 (1H, d, J = 3.1 Hz), 7.47 (1H, d, J = 8.3 Hz). (3H not found) Fumarate 1134 048 1H-NMR (CDCl3) ppm: 0.82-0.92 (1H, m), 0.94 (3H, d, J = 6.3 Hz), 1.06-1.34 (4H, m), 1.38-1.58 (2H, m), 1.59-1.75 (2H, m), 2.28- 2.37 (1H, m), 2.37-2.49 (2H, m), 2.89 (1H, dd, J = 2.6, 10.8 Hz), 2.94-3.04 (1H, m), 3.86 (3H, s), 7.21 (1H, dd, J = 1.9, 8.9 Hz), 7.31 (1H, s), 7.36 (1H, d, J = 1.7 Hz), 7.51 (1H, d, J = 8.9 Hz). 1135 049 1H-NMR (DMSO-d6) ppm: 0.82-0.96 (1H, m), 1.01-1.35 (5H, m), 1.35-1.85 (4H, m), 1.85- 1.96 (1H, m), 2.53-3.05 (3H, m), 3.05-3.23 (1H, m), 3.23-3.40 (1H, m), 3.76 (3H, s), 6.39-6.57 (3H, m), 6.79 (1H, d, J = 8.0 Hz), 7.09 (1H, t, J = 7.8 Hz), 7.17-7.28 (2H, m). (3H not found) Fumarate 1136 050 1H-NMR (DMSO-d6) ppm: 0.93-1.10 (1H, m), 1.10-1.35 (5H, m), 1.41-1.59 (3H, m), 1.64- 1.78 (1H, m), 1.91-2.04 (1H, m), 2.75-3.04 (3H, m), 3.11 (1H, dd, J = 2.0, 12.0 Hz), 3.32-3.46 (1H, m), 3.85 (3H, s), 6.53 (2H, s), 7.15-7.23 (1H, m), 7.29 (1H, dd, J = 1.9. 8.6 Hz), 7.42- 7.49 (1H, m), 7.53 (1H, d, J = 8.6 Hz), 7.56 (1H, d, J = 8.3 Hz), 7.94 (1H, d, J = 1.8 Hz), 8.15 (1H, d, J = 7.7 Hz). (3H, not found) Fumarate

(422) TABLE-US-00138 TABLE 140 absolute configuration 051 Ex. No. R.sup.4 NMR Salt 1137 052 1H-NMR (CDCl3) ppm: 0.88-1.08 (4H, m), 1.15-1.57 (4H, m), 1.60-1.68 (2H, m), 1.68-1.80 (2H, m), 2.31-2.39 (1H, m), 2.46 (1H, dd, J = 10.4, 11.0 Hz), 2.55-2.63 (1H, m), 3.00 (1H, dd, J = 2.8, 11.2 Hz), 3.07-3.18 (1H, m), 7.03- 7.09 (2H, m), 7.23-7.29 (2H, m). 1138 053 1H-NMR (CDCl3) ppm: 0.98-1.10 (4H, m), 1.20-1.46 (4H, m), 1.65-1.90 (4H, m), 2.46- 2.67 (3H, m), 3.10-3.25 (2H, m), 6.98 (1H, dd, J = 2.1, 8.5 Hz), 7.12 (1H, d, J = 2.1 Hz), 7.54 (1H, d, J = 8.5 Hz) 1139 054 1H-NMR (DMSO-d6) ppm: 0.89-1.03 (1H, m), 1.11 (3H, d, J = 6.4 Hz), 1.17-1.34 (2H, m), 1.34-1.47 (1H, m), 1.51-1.74 (3H, m), 1.82- 1.94 (1H, m), 2.64-2.74 (2H, m), 2.74-2.84 (1H, m), 3.14 (1H, dd, J = 3.0, 11.9 Hz), 3.20-3.33 (1H, m), 6.51 (2H, s), 6.97-7.04 (1H, m), 7.19 (1H, dd, J = 2.4, 11.3 Hz), 7.50 (1H, t, J = 8.7 Hz), 8.90-11.40 (2H, br). (1H not found) Fumarate 1140 055 1H-NMR (DMSO-d6) ppm: 0.89-1.03 (1H, m), 1.10 (3H, d, J = 6.4 Hz), 1.14-1.45 (3H, m), 1.48-1.62 (2H, m), 1.65-1.73 (1H, m), 1.82- 1.92 (1H, m), 2.58-2.81 (3H, m), 3.05 (1H, dd, J = 3.0, 11.7 Hz), 3.19-3.30 (1H, m), 6.51 (2H, s), 7.11-7.18 (1H, m), 7.31-7.41 (2H, m), 9.00- 11.60 (2H, br). (1H not found) Fumarate

(423) TABLE-US-00139 TABLE 141 absolute configuration 056 Ex. No. R.sup.4 NMR Salt 1141 057 1H-NMR (CDCl3) ppm: 0.96-1.10 (4H, m), 1.13 (18H, d, J = 7.3 Hz), 1.19-1.50 (7H, m), 1.58-1.67 (1H, m), 1.68-1.84 (3H, m), 2.45- 2.53 (1H, m), 2.57 (1H, dd, J = 10.3, 11.0 Hz), 2.62-2.70 (1H, m), 3.12 (1H, dd, J = 2.7, 11.2 Hz), 3.15-3.24 (1H, m), 7.09 (1H, dd, J = 2.4, 8.9 Hz), 7.17 (1H, d, J = 2.4 Hz), 7.27 (1H, dd, J = 2.1, 8.7 Hz), 7.44 (1H, d, J = 2.0 Hz), 7.59- 7.65 (2H, m). 1142 058 1H-NMR (CDCl3) ppm: 0.94-1.12 (4H, m), 1.15-1.46 (4H, m), 1.57-1.68 (2H, m), 1.68- 1.85 (11H, m), 2.42-2.51 (1H, m), 2.59-2.70 (2H, m), 3.10 (1H, dd, J = 2.7, 11.2 Hz), 3.15- 3.25 (1H, m), 7.29 (1H, dd, J = 2.2, 8.6 Hz), 7.30-7.37 (1H, m), 7.42-7.49 (1H, m), 7.76 (1H, d, J = 2.1 Hz), 7.93 (1H, d, J = 7.2 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.29 (1H, d, J = 8.3 Hz).

(424) TABLE-US-00140 TABLE 142 absolute configuration 059 Ex. No. R.sup.4 NMR Salt 1143 060 1H-NMR (DMSO-d6) ppm: 0.83-1.00 (4H, m), 1.12-1.35 (3H, m), 1.48-1.75 (4H, m), 1.99 (1H, brs), 2.31-2.50 (3H, m), 2.92-3.03 (2H, m), 6.99-7.09 (2H, m), 7.19 (1H, dd, J = 2.0, 8.7 Hz), 7.41 (1H, d, J = 1.7 Hz), 7.58 (1H, d, J = 8.8 Hz), 7.66 (1H, d, J = 8.8 Hz), 9.57 (1H, brs). 1144 061 1H-NMR (DMSO-d6) ppm: 1.10-1.57 (7H, m), 1.57-1.71 (2H, m), 1.71-1.82 (1H, m), 2.11- 2.22 (1H, m), 3.00-3.40 (6H, m), 7.22 (1H, t, J = 7.4 Hz). 7.35-7.85 (4H. m). 8.09 (1H, d, J = 7.8 Hz). 8.37 (1H, brs), 9.96 (2H, brs), 11.61 (1H, brs). 2 Hydrochloride

(425) TABLE-US-00141 TABLE 143 absolute configuration 062 Ex. No. R.sup.4 NMR Salt 1145 063 1H-NMR (CDCl3) ppm: 0.98-1.12 (4H, m), 1.18-1.58 (4H, m), 1.58-1.85 (4H, m), 2.45- 2.53 (1H, m), 2.56-2.70 (2H, m), 3.12 (1H, dd, J = 2.8, 11.2 Hz), 3.16-3.25 (1H, m), 3.90 (3H, s), 7.08-7.16 (2H, m), 7.30 (1H, dd, J = 2.01, 8.7 Hz), 7.46 (1H, d, J = 2.0 Hz), 7.65 (1H, d, J = 4.9 Hz), 7.67 (1H, d, J = 4.9 Hz). 1146 064 1H-NMR (DMSO-d6) ppm: 0.92-1.06 (1H, m), 1.11 (3H, d, J = 6.4 Hz), 1.16-1.51 ( 3H, m), 1.52-1.64 (1H, m), 1.64-1.78 (2H, m), 1.82-1.94 (1H, m), 2.65-2.85 (3H, m), 2.85- 4.2 (4H, m), 6.50 (1H, s), 7.33 (1H, dd, J = 2.1, 8.7 Hz ), 7.39-7.51 (2H, m), 7.56 (1H, d, J = 1.9 Hz), 7.80-7.89 (3H, m). Fumarate 1147 065 1H-NMR (CDCl3) ppm: 0.98-1.12 (4H, m), 1.18-1.48 (4H, m), 1.60-1.69 (1H, m), 1.69- 1.85 (3H, m), 2.46-2.54 (1H, m), 2.57 (1H, dd, J = 10.2, 11.0 Hz), 2.62-2.71 (1H, m), 3.10- 3.25 (2H, m), 7.22 (1H, dt, J = 2.6, 8.8 Hz), 7.35 (1H, dd, J = 1.8. 8.7 Hz), 7.40 (1H, dd, J = 2.5, 9.9 Hz), 7.50 (1H, d, J = 1.9 Hz), 7.68-7.77 (2H, m).

(426) TABLE-US-00142 TABLE 144 absolute configuration 066 Ex. No. R.sup.4 NMR Salt 1148 067 1H-NMR (CDCl3) ppm: 0.97-1.17 (4H, m), 1.17-1.89 (8H, m), 2.41-2.50 (1H, m), 2.53- 2.69 (2H, m), 3.08 (1H, dd, J = 2.8, 11.2 Hz), 3.13-3.22 (1H, m), 7.18 (1H, dd, J = 2.0, 8.5 Hz), 7.27 (1H, d, J = 5.4 Hz), 7.42 (1H, d, J = 5.4 Hz), 7.58 (1H, d, J = 2.0 Hz), 7.78 (1H, d, J = 8 5 Hz). 1149 068 1H-NMR (CDCI3) ppm: 0.86-1.02 (1H, m), 1.05 (3H, d, J = 6.4 Hz), 1.17-1.54 (4H, m), 1.54-1.63 (1H, m), 1.63-1.83 (3H, m), 2.39- 2.55 (1H, m), 2.55-2.65 (1H, m), 2.65-2.74 (1H, m), 3.10 (1H, dd, J = 2 8. 11.4 Hz). 3.15-3.26 (1H, m), 7.12 (1H, dd, J = 0.7, 7.6 Hz), 7.30 (1H, t, J = 7.8 Hz), 7.35 (1H, d, J = 5.5 Hz), 7.57 (1H, d, J = 5.5 Hz), 7.64 (1H, d, J = 8.0 Hz). 1150 069 1H-NMR (DMS0-d6) ppm: 0.90-1.04 (1H, m), 1.10-1.35 (5H, m), 1.35-1.62 (2H, m), 1.64- 1.74 (1H, m), 1.84-1.95 (1H, m), 2.65-2.84 (3H, m), 3.11 (1H, dd, J = 2.8, 11.8 Hz), 3.21-3.35 (1H, m), 6.49 (1.5H, s), 7.19 (1H, dd, J = 1.8, 8.5 Hz), 7.39 (1H, d, J = 5.4 Hz), 7.68 (1H, d, J = 5.4 Hz), 7.75 (1H, d, J = 1.8 Hz), 7.81 (1H, d, J = 8.5 Hz), 7.50-9.40 (1H, br). Fumarate

(427) TABLE-US-00143 TABLE 145 absolute configuration 070 Ex. No. R.sup.4 NMR Salt 1151 071 1H-NMR (DMSO-d6) ppm at 80 C.: 0.96- 1.39 (6H, m), 1.40-1.50 (1H, m), 1.50-1.80 (3H, m), 2.05-2.15 (1H, m), 2.98-3.20 (2H, m), 3.20- 3.40 (2H, m), 3.42-3.64 (1H, m), 5.23-6.05 (1H, br), 7.05-7.21 (2H, m), 7.30 (1H, brs), 8.03 (1H, s), 9.56 (1H, brs), 9.77 (1H, brs). 2 Hydrochloride 1152 072 1H-NMR (DMSO-d6) ppm: 0.85-1.00 (1H, m), 1.05-1.38 (5H, m), 1.38-1.75 (4H, m), 1.87- 2.00 (1H, m), 2.65-3.00 (3H, m), 3.12 (1H, dd, J = 2.8, 11.9 Hz), 3.30-3.47 (1H, m), 6.53 (2H, s), 7.04 (1H, d. J = 8.3 Hz), 7.14 (1H, brs), 7.37 (1H, d, J = 8 3 Hz), 8 08 (1H, d, J = 2.2 Hz). (3H, not found) Fumarate 1153 073 1H-NMR (DMSO-d6) ppm at 80 C.: 1.00- 1.38 (6H, m), 1.38-1.50 (1H, m), 1.50-1.79 (3H, m), 2.05-2.14 (2H, m), 3.09-3.25 (2H, m), 3.25- 3.50 (2H, br), 3.54-3.70 (1H, br), 3.94 (3H, s), 4.35-5.05 (1H, br), 6.90 (1H, d, J = 8.4 Hz), 7.07-7.20 (1H, m), 7.27 (1H, brs), 7.92 (1H, d, J = 18 Hz), 9.68 (1H, brs). 2 Hydrochloride 1154 074 1H-NMR (DMSO-d6) ppm at 80 C.: 1.05- 1.38 (6H, m), 1.38-1.52 (1H, m), 1.52-1.62 (1H, m), 1.62-1.79 (2H, m), 2.09-2.18 (1H, m), 2.46 (3H, s), 3.17-3.37 (2H, m), 3.37-3.66 (2H, m), 3.66-3.75 (1H, m), 6.25-7.10 (1H, br), 7.14 (1H, d, J = 7.8 Hz), 7.19-7.30 (1H, m), 7.40 (1H, brs), 7.97 (1H, d, J = 2.1 Hz), 9.88 (2H, brs). 2 Hydrochloride 1155 075 1H-NMR (DMSO-d6) ppm at 80 C.: 1.00- 1.38 (6H, m), 1.45-1.80 (4H, m), 2.08-2.18 (1H, m), 3.06-3.27 (2H, m), 3.27-3.49 (2H, m), 3.53- 3.70 (1H, m), 4.94-5.68 (1H, br), 7.13-7.22 (1H, m), 7.25-7.35 (2H, m), 7.45 (1H, d, J = 8.2 Hz), 7.93 (1H, d, J = 1.5 Hz), 9.45-10.00 (2H, brm). 2 Hydrochloride 1156 076 1H-NMR (DMSO-d6) ppm: 0.89-1.03 (1H, m), 1.05-1.35 (5H, m), 1.35-1.61 (3H, m), 1.61- 1.75 (1H, m), 1.82-1.96 (1H, m), 2.62-2.86 (3H, m), 3.08 (1H, d, J = 11.6 Hz), 3.21-3.36 (1H, m), 6.50 (2H, s), 6.91 (1H, d, J = 2.0 Hz), 7.07 (1H, dd, J = 1.3, 8.3 Hz), 7.36 (1H, s), 7.58 (1H, d, J = 8.2 Hz), 7.95 (1H, d, J = 2.2 Hz). (3H not found) Fumarate 1157 077 1H-NMR (DMSO-d6) ppm: 1.09-1.55 (7H, m), 1.55-1.80 (3H, m), 2.10-2.22 (1H, m), 3.30- 4.10 (5H, m), 4.10-5.20 (1H, br), 7.11 (1H, s), 7.58 (1H, brs), 7.80 (1H, s), 7.97 (1H, brs), 8.15 (1H, s), 10.06 (2H, brs). 2 Hydrochloride 1158 078 1H-NMR (DMSO-d6) ppm : 0.90-1.10 (1H, m), 1.15-1.38 (5H, m), 1.47-1.69 (3H, m), 1.69- 1.80 (1H, m), 2.00-2.11 (1H, m), 2.80-3.40 (4H, m), 3.40-3.60 (1H, m), 5.35-6.36 (1H, br), 7.13- 7.44 (2H, m), 8.15 (1H, d, J = 2.0 Hz), 9.08- 9.66 (1H, br), 9.66-10.08 (1H, br). 2 Hydrochloride

(428) TABLE-US-00144 TABLE 146 absolute configuration 079 Ex No. R.sup.4 NMR Salt 1159 080 1H-NMR (CDCl3) ppm: 0.95-1.10 (4H, m), 1.10-1.54 (4H, m), 1.54-1.65 (2H, m), 1.65- 1.83 (2H, m), 2.37-2.47 (1H, m), 2.55-2.69 (2H, m), 3.05 (1H, dd, J = 2.8, 11.2 Hz), 3.12-3.23 (1H, m), 3.77 (3H, s), 6.42 (1H, d, J = 0.7, 3.1 Hz), 7.03 (1H, d, J = 3.1 Hz), 7.08 (1H, d, J = 2.0, 8.6 Hz), 7.22-7.30 (1H, m), 7.41 (1H, d, J = 1.8 Hz). 1160 081 1H-NMR (DMSO-d6) ppm: 0.90-1.05 (1H, m), 1.09-1.35 (5H, m), 1.39-1.60 (3H, m), 1.64- 1.75 (1H, m), 1.88-2.00 (1H, m), 2.67-2.95 (3H, m), 3.07 (1H, dd, J = 2.8, 12.0 Hz), 3.28-3.40 (1H, m), 3.75 (3H, s), 6.36 (1H, d, J = 0.6, 3.0 Hz), 6.51 (2H, s), 6.87 (1H, d, J = 1.6, 8.4 Hz), 7.18 (1H, s), 7.27 (1H, d, J = 3.0 Hz), 7.47 (1H, d, J = 8.3 Hz). (3H not found) Fumarate 1161 082 1H-NMR (CDCl3) ppm: 0.82-0.92 (1H, m), 0.94 (3H, d, J = 6.3 Hz), 1.06-1.34 (4H, m), 1.38-1.58 (2H, m), 1.59-1.75 (2H, m), 2.28- 2.37 (1H, m), 2.37-2.49 (2H, m), 2.89 (1H, dd, J = 2.6, 10.8 Hz), 2.94-3.04 (1H, m), 3.86 (3H, s), 7.21 (1H, dd, J = 1.9, 8.9 Hz), 7.31 (1H, s), 7.36 (1H, d, J = 1.7 Hz), 7.51 (1H, d, J = 8.9 Hz). 1162 083 1H-NMR (DMSO-d6) ppm: 0.80-0.99 (1H, m), 1.00-1.35 (5H, m), 1.35-1.98 (5H, m), 2.53- 3.25 (4H, m), 3.23-3.40 (1H, m), 3.76 (3H, s), 6.40-6.58 (3H, m), 6.79 (1H, d, J = 8.0 Hz), 7.09 (1H, t, J = 7.8 Hz), 7.17-7.28 (2H, m). (3H not found) Fumarate 1163 084 1H-NMR (DMSO-d6) ppm: 0.93-1.08 (1H, m), 1.10-1.35 (5H, m), 1.401-1.60 (3H, m), 1.64-1.75 (1H, m), 1.90-2.03 (1H, m), 2.72- 3.00 (3H, m), 3.11 (1H, dd, J = 2.0, 12.0 Hz), 3.32-3.43 (1H, m), 3.85 (3H, s), 6.52 (2H, s), 7.15-7.23 (1H, m), 7.29 (1H, dd, J = 1.9, 8.6 Hz), 7.43-7.49 (1H, m), 7.53 (1H, d, J = 8.6 Hz), 7.56 (1H, d, J = 8.2 Hz), 7.94 (1H, d, J = 1.8 Hz), 8.14 (1H, d, J = 7.7 Hz). (3H, not found) Fumarate

(429) TABLE-US-00145 TABLE 147 absolute configuration 085 Ex. No. R.sup.4 NMR Salt 1164 086 1H-NMR (CDCl3) ppm: 0.88-1.08 (4H, m), 1.15-1.42 (4H, m), 1.42-1.60 (1H, br), 1.60- 1.69 (2H, m), 1.69-1.82 (2H, m), 2.31-2.39 (1H, m), 2.46 (1H, dd, J = 10.4, 11.0 Hz), 2.55-2.63 (1H, m), 3.00 (1H, dd, J = 2.8, 11.2 Hz), 3.07- 3.18 (1H, m), 7.02-7.09 (2H, m). 7.23-7.29 (2H, m). 1165 087 1H-NMR (CDl3) ppm: 0.98-1.10 (4H, m), 1.22-1.46 (4H, m), 1.65-1.90 (4H, m), 2.46- 2.67 (3H, m), 3.10-3.25 (2H, m), 6.98 (1H, dd, J = 2.1, 8.6 Hz), 7.12 (1H, d, J = 2.1 Hz), 7.54 (1H, d, J = 8.6 Hz) 1166 088 1H-NMR (DMSO-d6) ppm: 0.90-1.03 (1H, m), 1.12 (3H ,d, J = 6.4 Hz), 1.17-1.34 (2H, m), 1.34-1.48 (1H, m), 1.52-1.74 (3H, m), 1.84- 1.94 (1H, m), 2.65-2.75 (2H, m), 2.74-2.84 (1H, m), 3.14 (1H, dd, J = 3.0, 11.9 Hz), 3.22-3.34 (1H, m), 6.51 (2H, s), 6.97-7.04 (1H, m), 7.19 (1H, dd, J = 2.4, 11.3 Hz), 7.51 (1H, t, J = 8.6 Hz), 8.60-11.75 (2H, br). (1H not found) Fumarate 1167 089 1H-NMR (DMSO-d6) ppm: 0.88-1.02 (1H, m), 1.11 (3H, d, J = 6.4 Hz), 1.14-1.45 (3H, m), 1.48-1.62 (2H, m), 1.65-1.73 (1H, m), 1.82- I.92 (1H, m), 2.60-2.81 (3H, m), 3.05 (1H, dd, J = 3.0, 11.8 Hz), 3.19-3.30 (1H, m), 6.51 (2H, s), 7.11-7.18 (1H, m), 7.30-7.41 (2H, m), 8.85- 11.65 (2H, br). (1H not found) Fumarate

(430) TABLE-US-00146 TABLE 148 absolute configuration 090 Example R.sup.4 NMR Salt 1855 091 1H-NMR (DMSO-d6) ppm: 0.8-1.0 (4H, m), 1.1-1.6 (7H, m), 1.6-1.7 (1H, m), 1.8-1.9 (1H, m), 2.5-2.75 (3H, m), 2.85-3.9 (5H, m), 6.5-6.55 (2H, m), 7.1-7.2 (2H, m), 7.3- 7.4 (2H, m). Fumarate 1169 092 1H-NMR (CDCl3) ppm: 0.94 (3H, t, J = 7.5 Hz), 0.95-1.1 (1H, m), 1.15-1.5 (5H, m), 1.5-1.85 (5H, m), 2.46-2.69 (3H, m), 2.91- 3.01 (1H, m), 3.18 (1H, dd, J = 2.7, 11.2 Hz), 3.91 (3H, s), 7.08-7.14 (2H, m), 7.31 (1H, dd, J = 2.1, 8.7 Hz), 7.47 (1H, d, J = 2.0 Hz), 7.64-7.71 (2H, m). 1170 093 1H-NMR (DMSO-d6) ppm: 0.82-1.03 (4H, m), 1.09-1.36 (2H, m), 1.41-1.59 (4H, m), 1.59-1.75 (2H, m), 1.92-2.06 (1H, m), 2.71- 3.07 (3H, m), 3.10-3.20 (1H, m), 3.20-3.32 (1H, m), 6.56 (4H, s), 6.97-7.26 (3H, m), 11.5 (5H, m). 2 Fumarate 1171 094 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (4H, m), 1.1-1.4 (2H, m), 1.45-1.65 (4H, m), 1.65-1.85 (2H, m), 2.05-2.15 (1H, m), 2.85- 3.22 (3H, m), 3.22-3.38 (2H, m), 4.09 (1H, br), 7.24 (1H, d, J = 7.5 Hz), 7.35-7.5 (2H, m), 7.7-7.8 (2H, m), 9.15-9.35 (1H, m), 9.35-9.55 (1H, m). 2 Hydrochloride 1172 095 1H-NMR (CDCl3) ppm: 0.95 (3H, t, J = 7.5 Hz), 0.98-1.09 (1H, m), 1.14-1.50 (5H, m), 1.55-1.85 (5H, m), 2.44-2.53 (1H, m), 2.55-2.68 (2H, m), 2.91-3.00 (1H, m), 3.15 (1H, dd, J = 2.7, 11.1 Hz), 7.20 (1H, dd, J = 2.0, 8.6 Hz), 7.27 (1H, dd, J = 0.5, 5.4 Hz), 7.43 (1H, d, J = 5.4 Hz), 7.59 (1H, d, J = 2.0 Hz), 7.79 (1H, d, J = 8.6 Hz). 1173 096 1H-NMR (DMSO-d6) ppm: 0.85-1.05 (4H, m), 1.15-1.35 (2H, m), 1.35-1.5 (2H, m), 1.5-1.6 (3H, m), 1.65-1.75 (1H, m), 1.85- 1.95 (1H, m), 2.65-2.85 (3H, m), 3.05-3.2 (2H, m), 3.6 (3H, br), 6.51 (2H, s), 7.19 (1H, dd, J = 1.9, 8.5 Hz), 7.39 (1H, dd, J = 0.5, 5.4 Hz), 7.68 (1H, d, J = 5.4 Hz), 7.76 (1H, d, J = 1.8 Hz), 7.81 (1H, d, J = 8.5 Hz). Fumarate

(431) TABLE-US-00147 TABLE 149 absolute configuration 097 Example R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 MS(M + 1) 1174 H 098 H H H 327 1175 H H 099 H H 317 1176 H 00 H H H 327 1177 H 01 H H H 314 1178 H 02 H H H 328 1179 H 03 H H H 310 1180 H H 04 H H 344 1181 H 05 H H H 357 1182 H 06 H H H 344 1183 H H 07 H H 328 1184 H H 08 H H 342 1185 H 09 H H H 323 1186 H 0 H H H 328 1187 H H H H 330 1188 H Cl H H 385 1189 H H H H 351 1190 H H H H 342 1191 OCH3 OCH3 H H H 305 1192 H H O(CH2)2CH3 H H 303 1193 H H H H 343 1194 F H OCH3 H H 293 1195 Cl H H CF3 H 347 1196 Cl H H H H 297 1197 H OCH3 H H 381 1198 OCH3 H Cl H H 309 1199 F Cl H H H 297 1200 CH3 H OCH3 Cl H 323 1201 H OCH3 H H 381 1202 H H H H 311 1203 H H H H 342 1204 H H 0 H H 357 1205 H H OCH(CH3)2 H H 303 1206 H H H H 312 1207 OCH2CH3 H H H H 289 1208 H H H H 337 1209 Cl CF3 H H H 347 1210 H H CH2CH(CH3)2 H H 301 1211 CN H Cl H H 304 1212 H H H H 330 1213 H H H H 310

(432) TABLE-US-00148 TABLE 150 absolute configuration Example R.sup.4 MS(M + 1) 1214 296 1215 299 1216 296 1217 301 1218 0 338 1219 330 1220 303 1221 330 1222 296 1223 314 1224 299 1225 327 1226 316 1227 342 1228 0 315 1229 299 1230 314 1231 313

(433) TABLE-US-00149 TABLE 151 absolute configuration Example R.sup.4 MS(M + 1) 1232 277 1233 260 1234 316 1235 329 1236 315 1237 0 326 1238 322 1239 331 1240 280 1241 264 1242 276 1243 280 1244 246 1245 247 1246 323 1247 0 296 1248 260 1249 286 1250 302 1251 276 1252 332 1253 297 1254 314 1255 252 1256 261 1257 0 372 1258 330 1259 373 1260 326 1261 326 1262 277 1263 302 1264 297 1265 264 1266 271 1267 0 264 1268 246 1269 296 1270 322 1271 247 1272 276 1273 264 1274 247 1275 330 1276 280 1277 0 261 1278 297 1279 302 1280 266 1281 328 1282 263 1283 266

(434) TABLE-US-00150 TABLE 152 absolute configuration Example R.sup.4 MS(M + 1) 1284 315 1285 282 1286 00 245 1287 01 261 1288 02 277 1289 03 312 1290 04 274 1291 05 299 1292 06 281 1293 07 277 1294 08 337 1295 09 317 1296 0 261 1297 279 1298 267 1299 267 1300 275 1301 297 1302 283 1303 263 1304 249 1305 279 1306 0 285 1307 279 1308 279 1309 282 1310 275 1311 273 1312 296 1313 297 1314 297 1315 265 1316 0 259 1317 275 1318 299 1319 319 1320 271 1321 288 1322 277 1323 231 1324 249 1325 271 1326 0 288 1327 270 1328 309 1329 263 1330 296 1331 311 1332 333 1333 313 1334 328 1335 297 1336 0 286 1337 313 1338 371 1339 288 1340 323 1341 306

(435) TABLE-US-00151 TABLE 153 absolute configuration Example. R.sup.4 MS(M + 1) 1342 315 1343 282 1344 245 1345 0 261 1346 277 1347 312 1348 274 1349 299 1350 333 1351 245 1352 281 1353 299 1354 277 1355 0 337 1356 317 1357 261 1358 267 1359 267 1360 275 1361 297 1362 283 1363 263 1364 249 1365 0 279 1366 285 1367 279 1368 279 1369 282 1370 275 1371 273 1372 296 1373 297 1374 297 1375 0 265 1376 259 1377 275 1378 299 1379 319 1380 271 1381 288 1382 231 1383 249 1384 271 1385 00 288 1386 01 270 1387 02 263 1388 03 282 1389 04 337 1390 05 311 1391 06 333 1392 07 313 1393 08 328 1394 09 297 1395 0 286 1396 313 1397 282 1398 371 1399 288 1400 323 1401 306

(436) TABLE-US-00152 TABLE 154 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1402 307 1403 325 1404 0 309 1405 316 1406 309 1407 296 1408 321 1409 297 1410 341 1411 357 1412 331 1413 347 1414 0 331 1415 311 1416 333 1417 325 1418 335 1419 347 1420 297 1421 321 1422 314 1423 323 1424 0 332 1425 315 1426 331

(437) TABLE-US-00153 TABLE 155 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1427 307 1428 325 1429 309 1430 316 1431 309 1432 296 1433 0 321 1434 297 1435 341 1436 357 1437 331 1438 347 1439 331 1440 311 1441 333 1442 325 1443 0 335 1444 347 1445 297 1446 321 1447 314 1448 323 1449 332 1450 315 1451 331

(438) TABLE-US-00154 TABLE 156 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1452 0 307 1453 325 1454 309 1455 316 1456 313 1457 309 1458 296 1459 321 1460 297 1461 341 1462 0 357 1463 331 1464 347 1465 331 1466 327 1467 311 1468 333 1469 325 1470 335 1471 347 1472 0 321 1473 314 1474 323 1475 332 1476 315 1477 331

(439) TABLE-US-00155 TABLE 157 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1478 307 1479 325 1480 309 1481 00 316 1482 01 313 1483 02 309 1484 03 296 1485 04 321 1486 05 297 1487 06 341 1488 07 357 1489 08 331 1490 09 347 1491 0 331 1492 327 1493 311 1494 333 1495 325 1496 335 1497 347 1498 321 1499 314 1500 323 1501 0 332 1502 315 1503 331

(440) TABLE-US-00156 TABLE 158 relative configuration Ex. No. R.sup.4 MS(M + 1) 1504 281 1505 299 1506 283 1507 290 1508 283 1509 270 1510 0 295 1511 271 1512 315 1513 331 1514 305 1515 321 1516 305 1517 301 1518 285 1519 307 1520 0 299 1521 309 1522 321 1523 271 1524 295 1525 288 1526 297 1527 306 1528 289 1529 305

(441) TABLE-US-00157 TABLE 159 absolute configuration 0 Ex. No. R.sup.4 MS(M + 1) 1530 299 1531 270 1532 295 1533 271 1534 315 1535 331 1536 305 1537 321 1538 321 1539 0 295 1540 288 1541 306 1542 289 1543 305

(442) TABLE-US-00158 TABLE 160 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1544 281 1545 299 1546 270 1547 295 1548 0 271 1549 315 1550 331 1551 305 1552 321 1553 305 1554 321 1555 295 1556 288 1557 306 1558 0 289 1559 305

(443) TABLE-US-00159 TABLE 161 relative configuration Ex. No. R.sup.4 MS(M + 1) 1560 275 1561 291

(444) TABLE-US-00160 TABLE 162 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1562 267 1563 285 1564 269 1565 276 1566 0 251 1567 273 1568 269 1569 256 1570 281 1571 257 1572 301 1573 317 1574 275 1575 291 1576 00 307 1577 01 291 1578 02 271 1579 03 293 1580 04 285 1581 05 295 1582 06 307 1583 07 257 1584 08 281 1585 09 274 1586 0 283 1587 292

(445) TABLE-US-00161 TABLE 163 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1588 267 1589 285 1590 269 1591 276 1592 251 1593 273 1594 269 1595 0 256 1596 281 1597 257 1598 301 1599 317 1600 275 1601 291 1602 307 1603 291 1604 271 1605 0 293 1606 285 1607 295 1608 307 1609 257 1610 281 1611 274 1612 283 1613 292

(446) TABLE-US-00162 TABLE 164 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1614 0 285 1615 269 1616 276 1617 269 1618 281 1619 257 1620 301 1621 317 1622 291 1623 307 1624 0 287 1625 271 1626 293 1627 295 1628 307 1629 257 1630 281 1631 274 1632 292 1633 275 1634 0 291

(447) TABLE-US-00163 TABLE 165 absolute configuration Ex. No. R.sup.4 MS(M + 1) 1635 285 1636 269 1637 276 1638 269 1639 281 1640 257 1641 301 1642 317 1643 0 291 1644 307 1645 287 1646 271 1647 293 1648 295 1649 307 1650 257 1651 281 1652 274 1653 0 283 1654 292 1655 275 1656 291

(448) Pharmacological Study 1

(449) Measurement of Serotonin (5-HT) Uptake Inhibitory Activity of Test Compound Using Rat Brain Synaptosome

(450) Male Wistar rats were decapitated, and their brains were removed and dissected to remove the frontal cortex. The separated frontal cortex was placed in a 20-fold weight of a 0.32 molarity (M) sucrose solution and homogenized with a potter homogenizer. The homogenate was centrifuged at 1000 g at 4 C. for 10 minutes, and the supernatant was further centrifuged at 20000 g at 4 C. for 20 minutes. The pellet was suspended in an incubation buffer (20 mM HEPES buffer (pH 7.4) containing 10 mM glucose, 145 mM sodium chloride, 4.5 mM potassium chloride, 1.2 mM magnesium chloride, and 1.5 mM calcium chloride). The suspension was used as a crude synaptosome fraction.

(451) Uptake reaction was performed using each well of a 96-well round-bottom plate and a 200 l volume in total of a solution containing pargyline (final concentration: 10 M) and ascorbic acid (final concentration: 0.2 mg/ml).

(452) Specifically, a solvent, unlabeled 5-HT, and serially diluted test compounds were separately added to the wells, and the synaptosome fraction was added in an amount 1/10 of the final volume to each well and preincubated at 37 C. for 10 minutes. Then, a tritium-labeled 5-HT solution (final concentration: 8 nM) was added thereto to initiate uptake reaction at 37 C. 10 minutes later, the uptake reaction was terminated by suction filtration through a 96-well glass fiber filter plate. Furthermore, the filter was washed with a cold saline and then sufficiently dried. MicroScint-O (PerkinElmer Co., Ltd.) was added thereto, and the residual radioactivity on the filter was measured.

(453) An uptake value obtained by the addition of only the solvent was defined as 100%, and an uptake value (nonspecific uptake value) obtained by the addition of the unlabeled 5-HT (final concentration: 10 M) was defined as 0%. A 50% inhibitory concentration was calculated from the test compound concentrations and inhibitory activities thereat. The results are shown in Table 60.

(454) TABLE-US-00164 TABLE 60 Test compound 50% Inhibitory concentration (nM) Compound of Example 2 7.1 Compound of Example 7 1.0 Compound of Example 8 2.4 Compound of Example 10 6.2 Compound of Example 13 5.1 Compound of Example 15 12.5 Compound of Example 27 5.8 Compound of Example 33 2.6 Compound of Example 72 2.6 Compound of Example 77 0.8 Compound of Example 85 7.2 Compound of Example 106 9.7 Compound of Example 112 7.1 Compound of Example 118 13.7 Compound of Example 120 9.2 Compound of Example 124 8.5 Compound of Example 125 4.7 Compound of Example 130 5.3 Compound of Example 131 6.1 Compound of Example 132 8.8 Compound of Example 136 1.3 Compound of Example 150 5.4 Compound of Example 165 12.0 Compound of Example 186 5.2 Compound of Example 187 5.8 Compound of Example 188 6.0 Compound of Example 191 3.2 Compound of Example 192 2.9 Compound of Example 193 3.4 Compound of Example 196 4.4 Compound of Example 233 7.4 Compound of Example 246 6.8 Compound of Example 247 42.8 Compound of Example 273 44.0 Compound of Example 276 7.2 Compound of Example 281 5.8 Compound of Example 285 19.7 Compound of Example 288 56.1 Compound of Example 300 89.1 Compound of Example 307 19.3 Compound of Example 322 9.6 Compound of Example 344 6.8 Compound of Example 346 10.0 Compound of Example 348 6.4 Compound of Example 405 6.4 Compound of Example 409 35.6 Compound of Example 466 3.8 Compound of Example 577 5.2 Compound of Example 579 4.5 Compound of Example 580 2.5 Compound of Example 582 4.1 Compound of Example 586 5.2 Compound of Example 587 0.9 Compound of Example 593 4.9 Compound of Example 610 4.6 Compound of Example 621 7.0 Compound of Example 641 2.2 Compound of Example 654 1.5 Compound of Example 717 4.2 Compound of Example 778 87.5 Compound of Example 780 6.5 Compound of Example 781 6.2 Compound of Example 791 1.4 Compound of Example 805 42.6 Compound of Example 841 28.1 Compound of Example 850 7.3

(455) Pharmacological Study 2

(456) Measurement of Norepinephrine (NE) Uptake Inhibitory Activity of Test Compound Using Rat Brain Synaptosome

(457) Male Wistar rats were decapitated, and their brains were removed and dissected to remove the hippocampus. The separated hippocampus was placed in a 20-fold weight of a 0.32 molarity (M) sucrose solution and homogenized with a potter homogenizer. The homogenate was centrifuged at 1000 g at 4 C. for 10 minutes, and the supernatant was further centrifuged at 20000 g at 4 C. for 20 minutes. The pellet was suspended in an incubation buffer (20 mM HEPES buffer (pH 7.4) containing 10 mM glucose, 145 mM sodium chloride, 4.5 mM potassium chloride, 1.2 mM magnesium chloride, and 1.5 mM calcium chloride). The suspension was used as a crude synaptosome fraction.

(458) Uptake reaction was performed using each well of a 96-well round-bottom plate and a 200 l volume in total of a solution containing pargyline (final concentration: 10 M) and ascorbic acid (final concentration: 0.2 mg/ml).

(459) Specifically, a solvent, unlabeled NE, and serially diluted test compounds were separately added to the wells, and the synaptosome fraction was added in an amount 1/10 of the final volume to each well and preincubated at 37 C. for 10 minutes. Then, a tritium-labeled NE solution (final concentration: 12 nM) was added thereto to initiate uptake reaction at 37 C. Ten minutes later, the uptake reaction was terminated by suction filtration through a 96-well glass fiber filter plate. Furthermore, the filter was washed with a cold saline and then sufficiently dried. MicroScint-O (PerkinElmer Co., Ltd.) was added thereto, and the residual radioactivity on the filter was measured.

(460) An uptake value obtained by the addition of only the solvent was defined as 100%, and an uptake value (nonspecific uptake value) obtained by the addition of the unlabeled NE (final concentration: 10 M) was defined as 0%. A 50% inhibitory concentration was calculated from the test compound concentrations and inhibitory activities thereat. The results are shown in Table 61.

(461) TABLE-US-00165 TABLE 61 Test compound 50% Inhibitory concentration (nM) Compound of Example 2 4.6 Compound of Example 7 9.5 Compound of Example 8 60.9 Compound of Example 10 8.8 Compound of Example 13 14.3 Compound of Example 15 11.0 Compound of Example 27 0.9 Compound of Example 33 0.7 Compound of Example 72 1.0 Compound of Example 77 3.9 Compound of Example 85 4.9 Compound of Example 106 37.2 Compound of Example 112 87.3 Compound of Example 118 3.7 Compound of Example 120 9.2 Compound of Example 124 0.8 Compound of Example 125 1.9 Compound of Example 130 0.5 Compound of Example 131 0.7 Compound of Example 132 3.1 Compound of Example 136 0.5 Compound of Example 150 23.6 Compound of Example 165 2.4 Compound of Example 186 3.8 Compound of Example 187 6.0 Compound of Example 188 0.8 Compound of Example 191 2.1 Compound of Example 192 3.6 Compound of Example 193 4.4 Compound of Example 196 1.7 Compound of Example 233 3.2 Compound of Example 246 3.8 Compound of Example 247 6.6 Compound of Example 273 6.8 Compound of Example 276 4.5 Compound of Example 281 2.0 Compound of Example 285 1.4 Compound of Example 288 22.0 Compound of Example 300 9.9 Compound of Example 307 40.4 Compound of Example 322 40.1 Compound of Example 344 7.5 Compound of Example 346 8.8 Compound of Example 348 4.6 Compound of Example 405 4.4 Compound of Example 409 9.1 Compound of Example 468 7.5 Compound of Example 577 5.9 Compound of Example 579 5.1 Compound of Example 580 5.4 Compound of Example 582 6.0 Compound of Example 586 4.0 Compound of Example 587 1.9 Compound of Example 593 3.3 Compound of Example 610 5.9 Compound of Example 621 0.7 Compound of Example 641 76.0 Compound of Example 654 1.0 Compound of Example 717 4.8 Compound of Example 778 4.2 Compound of Example 780 0.6 Compound of Example 781 3.0 Compound of Example 791 0.7 Compound of Example 805 30.4 Compound of Example 841 0.9 Compound of Example 850 1.0 Compound of Example 867 11.7 Compound of Example 884 4.8 Compound of Example 895 3.0 Compound of Example 918 0.8 Compound of Example 962 31.9 Compound of Example 983 47.6 Compound of Example 993 8.7 Compound of Example 1026 4.2 Compound of Example 1047 0.7 Compound of Example 1083 2.5 Compound of Example 1113 1.7 Compound of Example 1121 0.7 Compound of Example 1124 0.8 Compound of Example 1318 6.6 Compound of Example 1326 1.8 Compound of Example 1333 39.6 Compound of Example 1341 42.7 Compound of Example 1534 4.0

(462) Pharmacological Study 3

(463) Measurement of Dopamine (DA) Uptake Inhibitory Activity of Test Compound Using Rat Brain Synaptosome

(464) Male Wistar rats were decapitated, and their brains were removed and dissected to remove the corpus striatum. The separated corpus striatum was placed in a 20-fold weight of a 0.32 molarity (M) sucrose solution and homogenized with a potter homogenizer. The homogenate was centrifuged at 1000 g at 4 C. for 10 minutes, and the supernatant was further centrifuged at 20000 g at 4 C. for 20 minutes. The pellet was suspended in an incubation buffer (20 mM HEPES buffer (pH 7.4) containing 10 mM glucose, 145 mM sodium chloride, 4.5 mM potassium chloride, 1.2 mM magnesium chloride, and 1.5 mM calcium chloride). The suspension was used as a crude synaptosome fraction.

(465) Uptake reaction was performed using each well of a 96-well round-bottom plate and a 200 l volume in total of a solution containing pargyline (final concentration: 10 M) and ascorbic acid (final concentration: 0.2 mg/ml).

(466) Specifically, a solvent, unlabeled DA, and serially diluted test compounds were separately added to the wells, and the synaptosome fraction was added in an amount 1/10 of the final volume to each well and preincubated at 37 C. for 10 minutes. Then, a tritium-labeled DA solution (final concentration: 2 nM) was added thereto to initiate uptake reaction at 37 C. Ten minutes later, the uptake reaction was terminated by suction filtration through a 96-well glass fiber filter plate. Furthermore, the filter was washed with a cold saline and then sufficiently dried. MicroScint-O (PerkinElmer Co., Ltd.) was added thereto, and the residual radioactivity on the filter was measured.

(467) An uptake value obtained by the addition of only the solvent was defined as 100%, and an uptake value (nonspecific uptake value) obtained by the addition of the unlabeled DA (final concentration: 10 M) was defined as 0%. A 50% inhibitory concentration was calculated from the test compound concentrations and inhibitory activities thereat. The results are shown in Table 62.

(468) TABLE-US-00166 TABLE 62 Test compound 50% Inhibitory concentration (nM) Compound of Example 2 85.9 Compound of Example 7 78.9 Compound of Example 8 377.8 Compound of Example 10 64.8 Compound of Example 13 85.4 Compound of Example 15 68.4 Compound of Example 27 31.9 Compound of Example 33 15.1 Compound of Example 72 47.9 Compound of Example 77 41.2 Compound of Example 85 95.7 Compound of Example 106 336.8 Compound of Example 112 263.7 Compound of Example 118 8.3 Compound of Example 120 187.2 Compound of Example 124 9.1 Compound of Example 125 5.2 Compound of Example 130 3.9 Compound of Example 131 8.3 Compound of Example 132 3.9 Compound of Example 136 7.7 Compound of Example 150 200.5 Compound of Example 165 6.8 Compound of Example 186 29.8 Compound of Example 187 12.1 Compound of Example 188 7.9 Compound of Example 191 13.5 Compound of Example 192 8.6 Compound of Example 193 5.7 Compound of Example 196 18.3 Compound of Example 233 38.8 Compound of Example 246 8.8 Compound of Example 247 8.7 Compound of Example 273 8.7 Compound of Example 276 10.9 Compound of Example 281 6.6 Compound of Example 285 43.9 Compound of Example 288 74.7 Compound of Example 300 81.3 Compound of Example 307 68.2 Compound of Example 322 67.7 Compound of Example 344 9.8 Compound of Example 346 7.8 Compound of Example 348 27.3 Compound of Example 405 74.8 Compound of Example 409 165.3 Compound of Example 468 54.0 Compound of Example 577 47.9 Compound of Example 579 46.5 Compound of Example 580 202.0 Compound of Example 582 68.8 Compound of Example 586 93.0 Compound of Example 587 76.1 Compound of Example 593 9.7 Compound of Example 610 13.2 Compound of Example 621 128.5 Compound of Example 641 9.7 Compound of Example 654 9.0 Compound of Example 717 60.1 Compound of Example 778 4.9 Compound of Example 780 4.3 Compound of Example 781 5.2 Compound of Example 791 160.9 Compound of Example 805 83.8 Compound of Example 841 5.1 Compound of Example 850 7.0 Compound of Example 867 85.7 Compound of Example 884 52.8 Compound of Example 895 19.9 Compound of Example 918 42.0 Compound of Example 962 69.5 Compound of Example 983 172.6 Compound of Example 993 38.6 Compound of Example 1026 12.3 Compound of Example 1047 1.1 Compound of Example 1083 53.7 Compound of Example 1113 26.0 Compound of Example 1121 29.9 Compound of Example 1124 49.3 Compound of Example 1318 83.5 Compound of Example 1326 91.8 Compound of Example 1333 73.0 Compound of Example 1341 113.3 Compound of Example 1534 214.8

(469) Pharmacological Study 4

(470) Forced Swimming Test

(471) This test was conducted according to the method of Porsolt et al. (Porsolt, R. D., et al., Behavioural despair in mice: A primary screening test for antidepressants. Arch. int. Pharmacodyn. Ther., 229, pp 327-336 (1977)).

(472) A test compound was suspended in a 5% gum arabic/saline (w/v), and this suspension was orally administered to male ICR mice (CLEA Japan, Inc. (JCL), 5 to 6 week old). One hour later, the mice were placed in a water tank having a water depth of 9.5 cm and a water temperature of 21 to 25 C. and immediately thereafter allowed to try to swim for 6 minutes. Then, a time during which the mouse was immobile (immobility time) was measured for the last 4 minutes. A SCANET MV-20 AQ system manufactured by Melquest Ltd. was used in the measurement and analysis of the immobility time.

(473) In this experiment, the animals treated with the test compounds exhibited a reduction in immobility time. This demonstrates that the test compounds are useful as antidepressants.