Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors

Abstract

The N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 1 or 2; L represents a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from C.sub.1-4alkyl, C.sub.1-3alkyloxy-C.sub.1-4alkyl-, hydroxy-C.sub.1-4alkyl, hydroxy, C.sub.1-3alkyloxy- or phenyl-C.sub.1-4alkyl; M represents a direct bond or a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from hydroxy, C.sub.1-4alkyl or C.sub.1-4alkyloxy; R.sup.1 and R.sup.2 each independently represent hydrogen, halo, cyano, hydroxy, C.sub.1-4alkyl optionally substituted with halo, C.sub.1-4alkyloxy- optionally substituted with one or where possible two or three substituents selected from hydroxy, Ar.sup.1 and halo; or R.sup.1 and R.sup.2 taken together with the phenyl ring to which they are attached form naphtyl or 1,3-benzodioxolyl, wherein said naphtyl or 1,3-benzodioxolyl are optionally substituted with halo; R.sup.3 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.4 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.5 represents hydrogen, C.sub.1-4alkyl or Ar.sup.2—C.sub.1-4alkyl-; R.sup.6 represents hydrogen, halo, C.sub.1-4alkyl or C.sub.1-4alkyoxy-; Ar.sup.1 and Ar.sup.2 each independently represent phenyl or naphtyl wherein said phenyl and naphtyl are optionally substituted with C.sub.1-4alkyl, C.sub.1-4alkyloxy-, or phenyl-C.sub.1-4alkyl;
for use as a medicine. ##STR00001##

Claims

1. A method for treating obesity, diabetes, obesity related cardiovascular diseases, dementia, cognition, osteoporosis and glaucoma, comprising administering an effective amount of a compound having formula ##STR00180## the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein n is 2; L represents a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from C.sub.1-4alkyl, C.sub.1-3alkloxy-C.sub.1-4alkyl-, hydroxy-C.sub.1-4alkyl, hydroxy, C.sub.1-3alkyloxy- or phenyl-C.sub.1-4alkyl; M represents a direct bond or a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from hydroxy, C.sub.1-4alkyl or C.sub.1-4alkyloxy; R.sup.1 and R.sup.2 each independently represent hydrogen, halo, cyano, hydroxy, C.sub.1-4alkyl optionally substituted with halo, C.sub.1-4alkyloxy- optionally substituted with one or where possible two or three substituents selected from hydroxy, Ar.sup.1 and halo; or R.sup.1 and R.sup.2 taken together with the phenyl ring to which they are attached form naphtyl or 1,3-benzodioxolyl, wherein said naphtyl or 1,3-benzodioxolyl are optionally substituted with halo; R.sup.3 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.4 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, cyano or hydroxy; R.sup.5 represents hydrogen, C.sub.1-4alkyl or Ar.sup.2—C.sub.1-4alky-; R.sup.6 represents hydrogen, halo, C.sub.1-4alkyl or C.sub.1-4alkyoxy-; Ar.sup.1 and Ar.sup.2 each independently represent phenyl or naphtyl wherein said phenyl and naphtyl are optionally substituted with C.sub.1-4alkyl, C.sub.1-4alkyloxy-, or phenyl-C.sub.1-4alkyl, wherein the effective amount of the compound having formula (I) treats obesity, diabetes, obesity related cardiovascular diseases, dementia, cognition, osteoporosis and glaucoma.

2. The method of claim 1 wherein; n is 2; L represents a C.sub.1-3alkyl linker optionally substituted with one or two substituents selected from C.sub.1-4alkyl, C.sub.1-3alkyloxy-C.sub.1-4alkyl-, hydroxy-C.sub.1-4alkyl, hydroxy, C.sub.1-3alkyloxy- or phenyl-C.sub.1-4alkyl; in particular L represents a C.sub.1-linker optionally substituted with C.sub.1-4alkyl; preferably L represents a C.sub.1-linker substituted with C.sub.1-4alkyl, more preferably a C.sub.1-linker substituted with methyl; M represents a direct bond or a C.sub.1-2alkyl optionally substituted with one or two substituents selected from hydroxy, C.sub.1-4alkyl or C.sub.1-4alkyloxy-; preferably M represents a C.sub.1-linker optionally substituted with C.sub.1-4 alkyl; R.sup.1 represents hydrogen, hydroxy, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy-, or C.sub.1-4alkyloxy substituted with halo; R.sup.2 represents hydrogen, halo, C.sub.1-4 alkyl, C.sub.1-4alkyloxy- or Ar.sup.1—C.sub.1-4 alkyloxy-; R.sup.3 represents hydrogen, halo, C.sub.1-4alkyl, C.sub.1-4alkyloxy- or cyano; R.sup.4 represents hydrogen, halo, C.sub.1-4alkyl or C.sub.1-4alkyloxy-; R.sup.5 represents hydrogen, C.sub.1-4alkyl or Ar.sup.2—C.sub.1-4alkyl; in particular hydrogen; R.sup.6 represents hydrogen, halo, or C.sub.1-4alkyloxy; in particular hydrogen, chloro, fluoro, bromo or methoxy; Ar.sup.1 represents phenyl; Ar.sup.2 represents phenyl or naphtyl.

3. The method of claim 1, wherein R.sup.6 is at the para position, L represents a C.sub.2-alkyl linker and M represents a C.sub.1-linker.

4. The method of claim 1, wherein L represents a C.sub.1-linker substituted with a C.sub.1-4alkyl, C.sub.1-4alkyloxyC.sub.1-4alkyl-, hydroxyC.sub.1-4alkyl- or phenylC.sub.1-4alkyl- wherein said C.sub.1-4alkyl, C.sub.1-4alkyloxyC.sub.1-4alkyl-, hydroxyC.sub.1-4alkyl- or phenylC.sub.1-4alkyl-is in the S-configuration.

5. The method of claim 1, wherein the administering comprises a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective 11β-HSD1 inhibitory amount of the compound having formula (I).

6. The method of claim 5, wherein the pharmaceutical composition is prepared by mixing a pharmaceutically acceptable carrier with an effective 11β-HSD1 inhibitory amount of the compound having formula (I).

Description

EXPERIMENTAL PART

(1) Hereinafter, the term ‘RT’ means room temperature, ‘THF’ means tetrahydrofuran, ‘Et.sub.2O’ means diethylether, ‘DCM means dichloromethane, ‘LDA’ means (diisopropylamino)lithium.

A. Preparation of the Intermediates

Example A1

(2) Preparation of Intermediate 1

(3) ##STR00006##

(4) To a stirred solution of alfa-(S)-methyl benzylamine (0.05 mol) and triethylamine (Et.sub.3N) (0.055 mol) in DCM (200 ml) was added dropwise a solution of 4-chlorobutanoyl chloride (0.055 mol) in DCM (100 ml) at −10° C. After the addition, the reaction mixture was stirred at room temperature until total conversion (TLC monitoring). The reaction mixture was washed twice with 1N HCl. To the organic phase were added 100 ml of 50% sodium hydroxide solution together with benzyl-triethyl ammonium chloride (0.05 mol). The mixture was stirred vigorously at room temperature overnight. The thus obtained reaction mixture was washed with 1N HCl, 5% NaHCO.sub.3 solution, water and brine. The organic phase was separated, dried over magnesium sulphate and concentrated to give 9.5 g of intermediate 1 as colourless oil.

(5) Alternatively intermediate 1 is prepared according to the following reaction scheme;

(6) ##STR00007##

(7) To a stirred solution of 7 ml Et.sub.3N in 300 ml CH.sub.2Cl.sub.2 was introduced dropwise within 0.5 hour a solution of 6.00 g (0.0495 mol) 1 in 100 ml CH.sub.2Cl.sub.2. The mixture was stirred at RT until no starting amine 1 was monitored by TLC (eluted with Et.sub.2O; the formation of the intermediate 2 could be monitored R.sub.f=0.5). The mixture was washed with 2N HCl (to remove the Et.sub.3N still present). To the reaction mixture were introduced TEBA (benzyltriethylammonium chloride) 1.13 g (0.00495 mol) and NaOH (aq.) (50 g in 60 ml H.sub.2O). The mixture was stirred overnight, organic layer was separated and acidified with 2N HCl. It was washed with NaHCO.sub.3 (5%), H.sub.2O and dried (NaSO.sub.4). After evaporation of the solvent 10.10 g crude product were isolated. It was chromatographed (column h=260 mm, Ø=46 mm, 195 g silicagel 230-400 mesh, eluent Et.sub.2O) to give 1.43 g of intermediate 3 and 7.28 g of 4 (78%).

(8) NMR data for 4: CDCl3, 1.52 (d, 3H, CH.sub.3); 1.93 (m, 2H, CH.sub.2); 2.42 (m, 2H, CH.sub.2); 2.99 and 3.31 (2×m, H.sup.A and H.sup.B, NCH.sub.2); 5.50 (quart, 1H, NCH); 7.32-7.48 (m, 5H-aromatic).

Example A2

(9) a) Preparation of Intermediate 5

(10) ##STR00008##

(11) A mixture of α-methyl-α-(2-oxoethyl)-benzeneacetonitrile (0.0086 mol) and (S)-α-methyl-benzenemethanamine (0.009 mol) in methanol (50 ml) was hydrogenated overnight with palladium on activated carbon (0.5 g) as a catalyst in the presence of a thiophene solution (1 ml). After uptake of hydrogen (1 equiv.), the catalyst was filtered off and the filtrate was evaporated, yielding 2.2 g of intermediate 5.

(12) b) Preparation of Intermediate 6

(13) ##STR00009##

(14) A mixture of intermediate 5 (0.007 mol) in sulfuric acid (25 ml) was stirred at room temperature over the weekend. The reaction mixture was poured out into ice, then neutralised with a NaOH solution. (50%) and extracted with dichloromethane. The organic layer was separated, washed, dried, filtered and the solvent was evaporated, yielding 1.8 g (85.7%) of intermediate 6.

(15) c) Preparation of Intermediate 7

(16) ##STR00010##

(17) A mixture of intermediate 6 (0.0057 mol) in hydrobromic acid (48%) (50 ml) was stirred and refluxed for 1 hour, then for 3 hours. The reaction mixture was cooled and filtered, yielding 1.4 g of intermediate (7).

B. Preparation of the Compounds

Example B1

(18) Preparation of Compound 1

(19) ##STR00011##

(20) And of Compound 2

(21) ##STR00012##

(22) To a stirred solution of 0.60 g (3.17 mmol) of intermediate 1 in 15 ml THF, cooled to −80° C., were added 1.2 equivalents of LDA (2M solution in THF/heptane/ethylbenzene) and the mixture was stirred for 30-45 minutes at −80° C. The corresponding benzylhalogenide, i.e. 1-methyl-2-chloromethylbenzene (1.05 equivalents) was added at −80° C. and the reaction mixture was stirred 1 hour at this temperature and for one additional hour at −60° C. The reaction was monitored by TLC and kept at −60° C. until completion. The thus obtained reaction mixture was hydrolized with 2N HCl, extracted with Et.sub.2O, washed with 5% aq. NaHCO.sub.3 and dried over Na.sub.2SO.sub.4. The purification of the diastereoisomers occurred by column chromatography on silica gel (230-400 mesh) with petroleum ether/Et.sub.2O (from 2:1 to 4:1 depending on the corresponding compound), yielding compounds 1 and 2.

Example B2

(23) Preparation of Compound 13

(24) ##STR00013##

(25) And of Compound 14

(26) ##STR00014##

(27) In a flame dried Schlenk-flask 0.80 g (4.23 mmol) of intermediate 1 were dissolved in 5 ml THF and cooled to −80° C. LDA (1.3 equivalent, 2.7 ml, ca. 2M commercial solution in THF/heptane/ethylbenzene) was introduced via syringe and the mixture was stirred for 30 minutes at −80° C. 2,6-Dichlorobenzyl bromide (1.42 g, 5.92 mmol) was introduced in solid form and the reaction mixture was stirred for 30 minutes at −80° C. until completion of the reaction (proved by TLC). The mixture was quenched with 2N HCl, then extracted with Et.sub.2O and the organic layer washed with NaHCO.sub.3 (5% aq.), H.sub.2O, and dried with Na.sub.2SO.sub.4. After evaporation of the solvent 1.81 g of the crude product were isolated. It was chromatographed (column h=580 mm, Ø=32 mm, 180 g silicagel 230-400 mesh, eluent petroleum ether/Et.sub.2O=5:1) to give 0.61 g Compound 14 ( ) (colourless crystals m.p. 75-76° C.) and 0.75 g Compound 13 ( ) (colourless crystals m.p. 98-99° C.), corresponds to 93% total yield.

(28) Table 1 lists the compounds that were prepared according to the above Examples.

(29) TABLE-US-00001 TABLE 1 Co. No. 3 Co. No. 4 Co. No. 5 Co. No. 6 Co. No. 7 0 Co. No. 8 Co. No. 9 Co. No. 10 Co. No. 11 Co. No. 12 Co. No. 13 Co. No. 14 Co. No. 15 Co. No. 16 Co. No. 17 0 Co. No. 18 Co. No. 19 Co. No. 20 Co. No. 21 Co. No. 22 Co. No. 23 Co. No. 24 Co. No. 25 Co. No. 26 Co. No. 27 0 Co. No. 28 Co. No. 29 Co. No. 30 Co. No. 31 Co. No. 32 Co. No. 33 Co. No. 34 Co. No. 35 Co. No. 36 Co. No. 37 0 Co. No. 38 Co. No. 39 Co. No. 40 Co. No. 41 Co. No. 42 Co. No. 43 Co. No. 44 Co. No. 45 Co. No. 46 Co. No. 47 0 Co. No. 48 Co. No. 49 Co. No. 50 Co. No. 51 Co. No. 52 Co. No. 53 Co. No. 54 Co. No. 55 Co. No. 56 Co. No. 57 0 Co. No. 58 Co. No. 59 Co. No. 60 Co. No. 61 Co. No. 62 Co. No. 63 Co. No. 64 Co. No. 65 Co. No. 66 Co. No. 67 0 Co. No. 68 Co. No. 69 Co. No. 70 Co. No. 71 Co. No. 72 Co. No. 73 Co. No. 74 Co. No. 75 Co. No. 76 Co. No. 77 0 Co. No. 78 Co. No. 79 Co. No. 80 Co. No. 81 Co. No. 82 Co. No. 83 Co. No. 84 Co. No. 85 Co. No. 86 Co. No. 87 00 Co. No. 88 01 Co. No. 89 02 Co. No. 90 03 Co. No. 91 04 Co. No. 92 05 Co. No. 93 06 Co. No. 94 07 Co. No. 95 08 Co. No. 96 09 Co. No. 97 0 Co. No. 98 Co. No. 99 Co. No. 100 Co. No. 101 Co. No. 102 Co. No. 103 Co. No. 104 Co. No. 105 Co. No. 106 Co. No. 107 0 Co. No. 108 Co. No. 109 Co. No. 110 Co. No. 111 Co. No. 112 Co. No. 113 Co. No. 114 Co. No. 115 Co. No. 116 Co. No. 117 0 Co. No. 118 Co. No. 119 Co. No. 120 Co. No. 121 Co. No. 122 Co. No. 123 Co. No. 124 Co. No. 125 Co. No. 126 Co. No. 127 0 Co. No. 128 Co. No. 129 Co. No. 130 Co. No. 131 Co. No. 132 Co. No. 133 Co. No. 134 Co. No. 135 Co. No. 136 Co. No. 137 0 Co. No. 138 Co. No. 139 Co. No. 140 Co. No. 141 Co. No. 142 Co. No. 143 Co. No. 144 Co. No. 145 Co. No. 146 Co. No. 147 0 Co. No. 148 Co. No. 149 Co. No. 150 Co. No. 151 Co. No. 152 Co. No. 153 Co. No. 154 Co. No. 155 Co. No. 156 Co. No. 157 0 Co. No. 158 Co. No. 159 Co. No. 160 Co. No. 161 Co. No. 162 Co. No. 163 Co. No. 164 Co. No. 165

Example B3

(30) Preparation of Compound 166

(31) ##STR00178##

(32) A mixture of intermediate 7 (0.00033 mol) in thionyl chloride (2 ml) was stirred and refluxed for 2 hours, then stirred and refluxed over the weekend at room temperature. The solvent was evaporated and the residue was dissolved in dichloromethane, washed with water and filtered through Extrelut, then evaporated. The residue was purified by flash column chromatography on Triconex flash tubes (eluent: CH.sub.2Cl.sub.2/EtOAc 95/5). The product fractions were collected and the solvent was evaporated, yielding 0.0588 g (62.5%) of compound 166.

(33) In a Similar Way was Prepared Compound 167

(34) ##STR00179##

(35) TABLE-US-00002 Co. melting No. NMR data point (° C.) 1 CDCl.sub.3; 1.52 (d, CH.sub.3); 1.45-1.67 (m, H.sup.A-CH.sub.2); 1.91-2.09 (m, H.sup.B- CH.sub.2); 2.33 (s, CH.sub.3); 2.47-2.60 (m, H.sup.A-CH.sub.2); 2.68-2.83 (m, CH); 2.83-2.97 (dt, H.sup.A-CH.sub.2); 3.10-3.25 (m, H.sup.B-CH.sub.2); 3.32-3.43 (dd, H.sup.B-CH.sub.2); 5.52 (q, CH); 7.03-7.18 (m, 4H-aromatic); 7.20-7.39 (m, 5H-aromatic) 2 CDCl.sub.3; 1.41 (d, CH.sub.3); 1.46-1.62 (m, H.sup.A-CH.sub.2); 1.72-1.89 (m, H.sup.B- CH.sub.2); 2.23 (s, CH.sub.3); 2.40-2.62 (m, CH, H.sup.A-CH.sub.2); 2.62-2.75 (m, H.sup.A-CH.sub.2); 3.00-3.12 (dt, H.sup.B-CH.sub.2); 3.19-3.30 (dd, H.sup.B-CH.sub.2); 5.43 (q, CH); 6.93-7.07 (m, 4H-aromatic); 7.08-7.25 (m, 5H-aromatic) 3 CDCl.sub.3; 1.38 (d, CH.sub.3); 1.51-1.69 (m, H.sup.A-CH.sub.2); 1.79-1.95 (m, H.sup.B- CH.sub.2); 2.25 (s, CH.sub.3); 2.53-2.78 (m, CH, 2x H.sup.A-CH.sub.2); 2.90-3.03 (dt, H.sup.B-CH.sub.2); 3.04-3.19 (m, H.sup.B-CH.sub.2); 5.44 (q, CH); 7.03 (s, 4H- aromatic); 7.12-7.30 (m, 5H-aromatic) 4 CDCl.sub.3; 1.53 (d, CH.sub.3); 1.51-1.70 (m, H.sup.A-CH.sub.2); 1.92-2.08 (m, H.sup.B- CH.sub.2); 2.33 (s, CH.sub.3); 2.61-2.88 (m, CH, 2x H.sup.A-CH.sub.2); 3.11-3.27 (m, 2x H.sup.B-CH.sub.2); 5.52 (q, CH); 7.09 (s, 4H-aromatic); 7.18-7.38 (m, 5H-aromatic) 5 CDCl.sub.3; 1.45 (d, CH.sub.3); 1.59-1.80 (m, H.sup.A-CH.sub.2); 1.82-2.02 (m, H.sup.B- CH.sub.2); 2.62-2.88 (m, CH, 2x H.sup.A-CH.sub.2); 2.91-3.10 (m, H.sup.B-CH.sub.2); 3.13-3.31 (m, H.sup.B-CH.sub.2); 5.52 (q, CH); 7.09-7.42 (m, 10H-aromatic) 6 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.48-1.67 (m, H.sup.A-CH.sub.2); 1.88-2.04 (m, H.sup.B- CH.sub.2); 2.60-2.87 (m, CH, 2x H.sup.A-CH.sub.2); 3.08-3.28 (m, 2x H.sup.B-CH.sub.2); 5.49 (q, CH); 7.10-7.36 (m, 10H-aromatic) 7 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.50-1.65 (m, H.sup.A-CH.sub.2); 1.82-1.98 (m, H.sup.B- CH.sub.2); 2.50-2.63 (m, H.sup.A-CH.sub.2); 2.75-2.92 (m, CH, H.sup.A-CH.sub.2); 3.07-3.20 (m, H.sup.B-CH.sub.2); 3.30-3.42 (dd, H.sup.B-CH.sub.2); 3.79 (s, CH.sub.3); 5.51 (q, CH); 6.78-6.90 (m, 2H-aromatic); 7.10-7.19 (m, 2H-aromatic); 7.19-7.37 (m, 5H-aromatic) 8 CDCl.sub.3; 1.42 (d, CH.sub.3); 1.51-1.70 (m, H.sup.A-CH.sub.2); 1.70-1.86 (m, H.sup.B- CH.sub.2); 2.47-2.61 (m, H.sup.A-CH.sub.2); 2.63-2.80 (m, CH, H.sup.A-CH.sub.2); 2.98-3.12 (dt, H.sup.B-CH.sub.2); 3.20-3.32 (dd, H.sup.B-CH.sub.2); 3.73 (s, CH.sub.3); 5.45 (q, CH); 6.71-6.85 (m, 2H-aromatic); 7.03-7.30 (m, 7H-aromatic) 9 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.58-1.81 (m, H.sup.A-CH.sub.2); 1.83-2.00 (m, H.sup.B- CH.sub.2); 2.71-2.90 (m, CH, 2x H.sup.A-CH.sub.2); 3.10-3.22 (dt, H.sup.B-CH.sub.2); 3.33-3.49 (m, H.sup.B-CH.sub.2); 5.53 (q, CH); 7.09-7.38 (m, 9H-aromatic) 10 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.52-1.68 (m, H.sup.A-CH.sub.2); 1.90-2.07 (m, H.sup.B- CH.sub.2); 2.70-2.97 (m, CH, 2x H.sup.A-CH.sub.2); 3.12-3.25 (m, H.sup.B-CH.sub.2); 3.37-3.49 (dd, H.sup.B-CH.sub.2); 5.50 (q, CH); 7.09-7.39 (m, 9H-aromatic) 11 CDCl.sub.3; 1.46 (d, CH.sub.3); 1.50-1.73 (m, H.sup.A-CH.sub.2); 1.78-1.97 (m, H.sup.B- CH.sub.2); 2.67-2.86 (m, CH, 2x H.sup.A-CH.sub.2); 3.03-3.18 (dt, H.sup.B-CH.sub.2); 3.30-3.48 (m, H.sup.B-CH.sub.2); 5.46 (q, CH); 7.00-7.32 (m, 8H-aromatic) 12 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.50-1.67 (m, H.sup.A-CH.sub.2); 1.90-2.07 (m, H.sup.B- CH.sub.2); 2.75-2.96 (m, CH, 2x H.sup.A-CH.sub.2); 3.10-3.25 (m, H.sup.B-CH.sub.2); 3.40-3.51 (dd, H.sup.B-CH.sub.2); 5.50 (q, CH); 7.02-7.37 (m, 8H-aromatic) 13 CDCl.sub.3; 1.56 (d, CH.sub.3); 1.78-1.92 (m, CH.sub.2); 2.76-2.88 (m, H.sup.A-CH.sub.2); 2.88-3.00 (m, CH); 3.01-3.16 (m, H.sup.A-CH.sub.2); 3.28-3.38 (m, H.sup.B- CH.sub.2); 3.43-3.57 (dd, H.sup.B-CH.sub.2); 5.53 (q, CH); 7.01-7.12 (m, 1H- aromatic); 7.18-7.38 (m, 7H-aromatic) 14 CDCl.sub.3; 1.52 (d, CH.sub.3); 1.68-1.88 (m, H.sup.A-CH.sub.2); 1.83-1.99 (m, H.sup.B- CH.sub.2); 2.88-3.08 (m, CH, 2x H.sup.A-CH.sub.2); 3.08-3.24 (m, H.sup.B-CH.sub.2); 3.48-3.60 (dd, H.sup.B-CH.sub.2); 5.51 (q, CH); 7.02-7.13 (m, 1H-aromatic); 7.22-7.42 (m, 7H-aromatic) 15 CDCl.sub.3; 1.46 (d, CH.sub.3); 1.60-1.77 (m, H.sup.A-CH.sub.2); 1.87-2.02 (m, H.sup.B- CH.sub.2); 2.32 (s, CH.sub.3); 2.61-2.83 (m, CH, 2x H.sup.A-CH.sub.2); 2.97-3.09 (dt, H.sup.B-CH.sub.2); 3.11-3.27 (m, H.sup.B-CH.sub.2); 5.52 (q, CH); 6.95-7.07 (m, 3H- aromatic); 7.11-7.37 (m, 6H-aromatic) 16 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.51-1.63 (m, H.sup.A-CH.sub.2); 1.90-2.07 (m, H.sup.B- CH.sub.2); 2.31 (s, CH.sub.3); 2.58-2.70 (m, H.sup.A-CH.sub.2); 2.70-2.89 (m, CH, H.sup.A-CH.sub.2); 3.09-3.28 (m, 2x H.sup.B-CH.sub.2); 5.50 (q, CH); 6.93-7.06 (m, 3H-aromatic); 7.09-7.37 (m, 6H-aromatic) 17 CDCl.sub.3; 1.46 (d, CH.sub.3); 1.57-1.73 (m, H.sup.A-CH.sub.2); 1.88-2.02 (m, H.sup.B- CH.sub.2); 2.63-2.83 (m, CH, 2x H.sup.A-CH.sub.2); 2.97-3.09 (dt, H.sup.B-CH.sub.2); 3.10-3.25 (m, H.sup.B-CH.sub.2); 5.51 (q, CH); 7.04-7.37 (m, 9H-aromatic) 18 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.46-1.62 (m, H.sup.A-CH.sub.2); 1.90-2.07 (m, H.sup.B- CH.sub.2); 2.62-2.87 (m, CH, 2x H.sup.A-CH.sub.2); 3.09-3.23 (m, 2x H.sup.B-CH.sub.2); 5.49 (q, CH); 7.00-7.36 (m, 9H-aromatic) 19 CDCl.sub.3; 1.47 (d, CH.sub.3); 1.60-1.78 (m, H.sup.A-CH.sub.2); 1.87-2.03 (m, H.sup.B- CH.sub.2); 2.61-2.87 (m, CH, 2x H.sup.A-CH.sub.2); 3.00-3.13 (dt, H.sup.B-CH.sub.2); 3.16-3.27 (m, H.sup.B-CH.sub.2); 3.79 (s, CH.sub.3); 5.51 (q, CH); 7.71-7.85 (m, 3H-aromatic); 7.16-7.85 (m, 6H-aromatic) 20 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.51-1.69 (m, H.sup.A-CH.sub.2); 1.92-2.07 (m, H.sup.B- CH.sub.2); 2.58-2.90 (m, CH, 2x H.sup.A-CH.sub.2); 3.10-3.28 (m, 2x H.sup.B-CH.sub.2); 3.77 (s, CH.sub.3); 5.50 (q, CH); 6.70-6.80 (m, 3H-aromatic); 7.11-7.37 (m, 6H-aromatic) 21 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.60-1.77 (m, H.sup.A-CH.sub.2); 1.87-2.01 (m, H.sup.B- CH.sub.2); 2.61-2.82 (m, CH, 2x H.sup.A-CH.sub.2); 2.96-3.08 (dt, H.sup.B-CH.sub.2); 3.08-3.19 (m, H.sup.B-CH.sub.2); 3.77 (s, CH.sub.3); 5.50 (q, CH); 6.78-6.86 (m, 2H-aromatic); 7.08-7.18 (m, 2H-aromatic); 7.20-7.37 (m, 5H- aromatic) 22 CDCl.sub.3; 1.49 (d, CH.sub.3); 1.50-1.68 (m, H.sup.A-CH.sub.2); 1.89-2.05 (m, H.sup.B- CH.sub.2); 2.60-2.82 (m, CH, 2x H.sup.A-CH.sub.2); 3.05-3.21 (m, 2x H.sup.B-CH.sub.2); 3.76 (s, CH.sub.3); 5.48 (q, CH); 6.71-6.80 (m, 2H-aromatic); 7.01-7.13 (m, 2H-aromatic); 7.14-7.33 (m, 5H-aromatic) 23 CDCl.sub.3; 1.60-1.78 (m, H.sup.A-CH.sub.2); 1.93-2.09 (m, H.sup.B-CH.sub.2); 2.68-2.88 (m, CH, CH.sub.2); 2.90-3.21 (m, 2x H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.27-3.38 (dd, H.sup.B-CH.sub.2); 3.42-3.65 (m, CH.sub.2); 7.12-7.67 (m, 9H-aromatic) 24 CDCl.sub.3; 1.47-1.72 (m, H.sup.A-CH.sub.2); 1.89-2.04 (m, H.sup.B-CH.sub.2); 2.50-2.75 (m, CH, H.sup.A-CH.sub.2); 2.76-2.88 (t, CH.sub.2); 2.93-3.12 (m, CH.sub.2); 3.12-3.21 (dd, H.sup.B-CH.sub.2); 3.40-3.63 (m, CH.sub.2); 3.79 (s, CH.sub.3); 6.71-6.80 (m, 3H-aromatic); 7.12-7.33 (m, 6H-aromatic) 25 CDCl.sub.3; 1.61-1.79 (m, H.sup.A-CH.sub.2); 1.93-2.08 (m, H.sup.B-CH.sub.2); 2.32 (s, CH.sub.3); 2.62-2.84 (m, CH, H.sup.A-CH.sub.2); 2.96-3.25 (m, H.sup.A-CH.sub.2, 2x H.sup.B- CH.sub.2); 4.44 (dd, CH.sub.2); 7.05-7.34 (m, 9H-aromatic) 26 CDCl.sub.3; 1.45 (d, CH.sub.3); 1.58-1.73 (m, H.sup.A-CH.sub.2); 1.81-1.99 (m, H.sup.B- CH.sub.2); 2.31 (s, CH.sub.3); 2.61-2.82 (m, CH, 2x H.sup.A-CH.sub.2); 2.75-3.08 (dt, H.sup.B-CH.sub.2); 3.09-3.23 (m, H.sup.B-CH.sub.2); 5.52 (q, CH); 7.02-7.14 (m, 4H- aromatic); 7.18-7.37 (m, 5H-aromatic) 27 CDCl.sub.3; 1.42 (d, CH.sub.3); 1.40-1.60 (m, H.sup.A-CH.sub.2); 1.81-1.99 (m, H.sup.B- CH.sub.2); 2.23 (s, CH.sub.3); 2.50-2.78 (m, CH, 2x H.sup.A-CH.sub.2); 3.00-3.18 (m, 2x H.sup.B-CH.sub.2); 5.41 (q, CH); 6.92-7.07 (m, 4H-aromatic); 7.10-7.32 (m, 5H-aromatic) 28 CDCl.sub.3; 1.53-1.71 (m, H.sup.A-CH.sub.2); 1.89-2.05 (m, H.sup.B-CH.sub.2); 2.23 (s, CH.sub.3); 2.41-2.55 (m, H.sup.A-CH.sub.2); 2.59-2.75 (m, CH); 2.80-2.90 (t, CH.sub.2); 3.03-3.20 (m, CH.sub.2); 3.23-3.35 (dd, H.sup.B-CH.sub.2); 3.44-3.68 (m, CH2); 7.07-7.34 (m, 9H-aromatic) 29 CDCl.sub.3; 1.57-1.73 (m, H.sup.A-CH.sub.2); 1.89-2.04 (m, H.sup.B-CH.sub.2); 2.32 (s, CH.sub.3); 2.50-2.75 (m, CH, H.sup.A-CH.sub.2); 2.76-2.88 (t, CH.sub.2); 2.91-3.21 (m, CH.sub.2, H.sup.B-CH.sub.2); 3.41-3.65 (m, CH.sub.2); 6.94-7.08 (m, 3H- aromatic); 7.12-7.33 (m, 6H-aromatic) 30 CDCl.sub.3; 1.60-1.76 (m, H.sup.A-CH.sub.2); 1.88-2.01 (m, H.sup.B-CH.sub.2); 2.68-2.90 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.00-3.19 (m, CH.sub.2); 3.27-3.42 (m, H.sup.B- CH.sub.2); 3.43-3.67 (m, CH2); 7.10-7.37 (m, 9H-aromatic) 31 CDCl.sub.3; 1.53-1.72 (m, H.sup.A-CH.sub.2); 1.88-2.03 (m, H.sup.B-CH.sub.2); 2.69-2.90 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.01-3.20 (m, CH.sub.2); 3.31-3.46 (m, H.sup.B- CH.sub.2); 3.46-3.67 (m, CH2); 7.07-7.38 (m, 8H-aromatic) 32 CDCl.sub.3; 1.72-1.97 (m, CH.sub.2); 2.80-2.91 (t, CH.sub.2); 2.91-3.27 (m, CH, 2x H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.38-3.48 (dd, H.sup.B-CH.sub.2); 3.48-3.68 (m, CH.sub.2); 7.03-7.35 (m, 8H-aromatic) 33 CDCl.sub.3; 1.56-1.72 (m, H.sup.A-CH.sub.2); 1.80-1.97 (m, H.sup.B-CH.sub.2); 2.47-2.60 (m, H.sup.A-CH.sub.2); 2.68-2.80 (m, CH); 2.78-2.88 (t, CH.sub.2); 2.99-3.17 (m, CH.sub.2); 3.23-3.35 (dd, H.sup.B-CH.sub.2); 3.42-3.64 (m, CH.sub.2); 3.81 (s, CH.sub.3); 6.80-6.92 (m, 2H-aromatic); 7.10-7.35 (m, 7H-aromatic) 34 CDCl.sub.3; 1.55-1.71 (m, H.sup.A-CH.sub.2); 1.77-2.02 (m, H.sup.B-CH.sub.2); 2.53-2.76 (m, CH, H.sup.A-CH.sub.2); 2.77-2.85 (t, CH.sub.2); 2.90-3.02 (dt, H.sup.A-CH.sub.2); 3.02-3.14 (m, H.sup.B-CH.sub.2); 3.14-3.23 (dd, H.sup.B-CH.sub.2); 3.40-3.62 (m, CH.sub.2); 7.12-7.33 (m, 10H-aromatic) 35 CDCl.sub.3; 1.56-1.72 (m, H.sup.A-CH.sub.2); 1.88-2.02 (m, H.sup.B-CH.sub.2); 2.32 (s, CH.sub.3); 2.51-2.73 (m, CH, H.sup.A-CH.sub.2); 2.76-2.87 (t, CH.sub.2); 2.90-3.18 (m, CH.sub.2, H.sup.B-CH.sub.2); 3.40-3.63 (m, CH.sub.2); 7.03-7.33 (m, 9H- aromatic) 36 CDCl.sub.3; 1.38 (d, CH.sub.3); 1.52-1.70 (m, H.sup.A-CH.sub.2); 1.79-1.96 (m, H.sup.B- CH.sub.2); 2.58-2.77 (m, CH, 2x H.sup.A-CH.sub.2); 2.90-3.01 (dt, H.sup.B-CH.sub.2); 3.07-3.22 (m, H.sup.B-CH.sub.2); 5.44 (q, CH); 7.08-7.29 (m, 10H-aromatic) 37 CDCl.sub.3; 1.38 (d, CH.sub.3); 1.40-1.58 (m, H.sup.A-CH.sub.2); 1.77-1.92 (m, H.sup.B- CH.sub.2); 2.50-2.75 (m, CH, 2x H.sup.A-CH.sub.2); 2.94-3.18 (m, 2x H.sup.B-CH.sub.2); 5.39 (q, CH); 7.01-7.28 (m, 10H-aromatic) 38 CDCl.sub.3; 1.42 (d, CH.sub.3); 1.52-1.70 (m, H.sup.A-CH.sub.2); 1.70-1.87 (m, H.sup.B- CH.sub.2); 2.47-2.61 (m, H.sup.A-CH.sub.2); 2.64-2.80 (m, CH, H.sup.A-CH.sub.2); 3.00-3.12 (dt, H.sup.B-CH.sub.2); 3.20-3.32 (dd, H.sup.B-CH.sub.2); 3.74 (s, CH.sub.3); 5.45 (q, CH); 6.72-6.84 (m, 2H-aromatic); 7.03-7.28 (m, 7H-aromatic) 39 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.42-1.59 (m, H.sup.A-CH.sub.2); 1.77-1.91 (m, H.sup.B- CH.sub.2); 2.42-2.54 (m, H.sup.A-CH.sub.2); 2.70-2.87 (m, CH, H.sup.A-CH.sub.2); 3.00-3.13 (m, H.sup.B-CH.sub.2); 3.22-3.35 (dd, H.sup.B-CH.sub.2); 3.72 (s, CH.sub.3); 5.44 (q, CH); 6.71-6.82 (m, 2H-aromatic); 7.02-7.30 (m, 7H-aromatic) 40 CDCl.sub.3; 1.38 (d, CH.sub.3); 1.49-1.67 (m, H.sup.A-CH.sub.2); 1.69-1.87 (m, H.sup.B- CH.sub.2); 2.60-2.77 (m, CH, 2x H.sup.A-CH.sub.2); 2.97-3.10 (dt, H.sup.B-CH.sub.2); 3.23-3.38 (m, H.sup.B-CH.sub.2); 5.41 (q, CH); 6.95-7.26 (m, 9H-aromatic) 41 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.38-1.59 (m, H.sup.A-CH.sub.2); 1.80-1.99 (m, H.sup.B- CH.sub.2); 2.62-2.87 (m, CH, 2x H.sup.A-CH.sub.2); 3.01-3.15 (m, H.sup.B-CH.sub.2); 3.30-3.41 (dd, H.sup.B-CH.sub.2); 5.41 (q, CH); 6.95-7.11 (m, 2H-aromatic); 7.12-7.29 (m, 7H-aromatic) 42 CDCl.sub.3; 1.48 (d, CH.sub.3); 1.54-1.73 (m, H.sup.A-CH.sub.2); 1.79-1.97 (m, H.sup.B- CH.sub.2); 2.68-2.87 (m, CH, 2x H.sup.A-CH.sub.2); 3.08-3.22 (m, H.sup.B-CH.sub.2); 3.35-3.52 (m, H.sup.B-CH.sub.2); 5.49 (q, CH); 7.02-7.23 (m, 8H-aromatic) 43 CDCl.sub.3; 1.39 (d, CH.sub.3); 1.32-1.53 (m, H.sup.A-CH.sub.2); 1.79-1.96 (m, H.sup.B- CH.sub.2); 2.60-2.83 (m, CH, 2x H.sup.A-CH.sub.2); 3.00-3.13 (m, H.sup.B-CH.sub.2); 3.28-3.42 (m, H.sup.B-CH.sub.2); 5.38 (q, CH); 6.91-7.27 (m, 8H-aromatic) 44 CDCl.sub.3; 1.45 (d, CH.sub.3); 1.67-1.80 (m, CH.sub.2); 2.64-2.78 (m, H.sup.A-CH.sub.2); 2.76-2.89 (m, CH); 2.90-3.03 (m, H.sup.A-CH.sub.2); 3.13-3.26 (m, H.sup.B- CH.sub.2); 3.37-3.47 (dd, H.sup.B-CH.sub.2); 5.43 (q, CH); 6.90-7.00 (m, 1H- aromatic); 7.08-7.26 (m, 7H-aromatic) 45 CDCl.sub.3; 1.41 (d, CH.sub.3); 1.57-1.73 (m, H.sup.A-CH.sub.2); 1.72-1.88 (m, H.sup.B- CH.sub.2); 2.78-3.12 (m, CH, 2x H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.38-3.48 (dd, H.sup.B- CH.sub.2); 5.40 (q, CH); 6.90-7.01 (m, 1H-aromatic); 7.10-7.30 (m, 7H-aromatic) 46 CDCl.sub.3; 1.39 (d, CH.sub.3); 1.50-1.68 (m, H.sup.A-CH.sub.2); 1.80-1.97 (m, H.sup.B- CH.sub.2); 2.56-2.78 (m, CH, 2x H.sup.A-CH.sub.2); 2.89-3.03 (dt, H.sup.B-CH.sub.2); 3.03-3.18 (m, H.sup.B-CH.sub.2); 5.43 (q, CH); 6.97-7.30 (m, 9H-aromatic) 47 CDCl.sub.3; 1.39 (d, CH.sub.3); 1.33-1.52 (m, H.sup.A-CH.sub.2); 1.79-1.95 (m, H.sup.B- CH.sub.2); 2.52-2.77 (m, CH, 2x H.sup.A-CH.sub.2); 2.97-3.14 (m, 2x H.sup.B-CH.sub.2); 5.38 (q, CH); 6.89-7.27 (m, 9H-aromatic) 48 CDCl.sub.3; 1.61-1.79 (m, H.sup.A-CH.sub.2); 1.93-2.08 (m, H.sup.B-CH.sub.2); 2.61-2.87 (m, CH, H.sup.A-CH.sub.2); 2.98-3.18 (m, CH.sub.2); 3.19-3.29 (dd, H.sup.B-CH.sub.2); 3.78 (s, CH.sub.3); 4.45 (q, CH.sub.2); 6.72-6.83 (m, 3H-aromatic); 7.13-7.37 (m, 6H-aromatic) 49 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.58-1.77 (m, H.sup.A-CH.sub.2); 1.85-2.00 (m, H.sup.B- CH.sub.2); 2.65-2.82 (m, CH, H.sup.A-CH.sub.2); 2.90-3.03 (m, H.sup.A-CH.sub.2); 3.05-3.18 (dt, H.sup.B-CH.sub.2); 3.28-3.40 (dd, H.sup.B-CH.sub.2); 5.43 (q, CH); 7.12-7.30 (m, 6H-aromatic); 7.33-7.58 (m, 3H-aromatic) 50 CDCl.sub.3; 1.37 (d, CH.sub.3); 1.52-1.68 (m, H.sup.A-CH.sub.2); 1.78-1.93 (m, H.sup.B- CH.sub.2); 2.55-2.77 (m, CH, 2x H.sup.A-CH.sub.2); 2.89-3.12 (m, 2x H.sup.B-CH.sub.2); 3.71 (s, CH.sub.3); 5.43 (q, CH); 6.75 (m, 2H-aromatic); 7.05 (m, 2H- aromatic); 7.12-7.29 (m, 5H-aromatic) 51 CDCl.sub.3; 1.41-1.60 (m, H.sup.A-CH.sub.2); 1.77-1.94 (m, H.sup.B-CH.sub.2); 2.51-2.71 (m, CH, H.sup.A-CH.sub.2); 2.81-3.14 (m, CH.sub.2, H.sup.B-CH.sub.2); 4.31 (q, CH.sub.2); 6.90-7.23 (m, 9H-aromatic) 52 CDCl.sub.3; 1.46 (d, CH.sub.3); 1.60-1.78 (m, H.sup.A-CH.sub.2); 1.88-2.03 (m, H.sup.B- CH.sub.2); 2.61-2.85 (m, CH, 2x H.sup.A-CH.sub.2); 3.00-3.13 (dt, H.sup.B-CH.sub.2); 3.14-3.28 (m, H.sup.B-CH.sub.2); 3.79 (s, CH.sub.3); 5.51 (q, CH); 6.71-6.83 (m, 3H-aromatic); 7.13-7.38 (m, 6H-aromatic) 53 CDCl.sub.3; 1.60-1.79 (m, H.sup.A-CH.sub.2); 1.87-2.05 (m, H.sup.B-CH.sub.2); 2.60-2.89 (m, CH, H.sup.A-CH.sub.2); 2.89-3.17 (m, CH.sub.2, H.sup.B-CH.sub.2); 4.42 (q, CH.sub.2); 6.60-6.90 (m, 3H-aromatic); 7.01-7.36 (m, 6H-aromatic); 8.32 (s, OH) 54 CDCl.sub.3; 1.63-1.85 (m, H.sup.A-CH.sub.2); 1.95-2.16 (m, H.sup.B-CH.sub.2); 2.75-2.96 (m, CH); 2.98-3.23 (m, CH.sub.2, H.sup.A-CH.sub.2); 3.32-3.53 (dd, H.sup.B-CH.sub.2); 4.46 (s, CH.sub.2); 7.07-7.68 (m, 9H-aromatic) 55 CDCl.sub.3; 1.60-1.77 (m, H.sup.A-CH.sub.2); 1.95-2.10 (m, H.sup.B-CH.sub.2); 2.35 (s, CH.sub.3); 2.52-2.68 (m, H.sup.A-CH.sub.2); 2.68-2.77 (m, CH); 3.09-3.19 (m, CH.sub.2); 3.36-3.44 (dd, H.sup.B-CH.sub.2); 4.49 (s, CH.sub.2); 7.08-7.20 (m, 4H- aromatic); 7.20-7.38 (m, 5H-aromatic) 56 CDCl.sub.3; 1.60-1.78 (m, H.sup.A-CH.sub.2); 1.92-2.07 (m, H.sup.B-CH.sub.2); 2.32 (m, CH.sub.3); 2.61-2.86 (m, CH, H.sup.A-CH.sub.2); 2.97-3.27 (m, CH.sub.2, H.sup.B-CH.sub.2); 4.44 (q, CH.sub.2); 6.95-7.08 (m, 3H-aromatic); 7.11-7.36 (m, 6H- aromatic) 57 CDCl.sub.3; 1.52-1.70 (m, H.sup.A-CH.sub.2); 1.79-1.97 (m, H.sup.B-CH.sub.2); 2.64-2.86 (m, CH, H.sup.A-CH.sub.2); 2.95-3.07 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.28-3.42 (m, H.sup.B-CH.sub.2); 4.37 (s, CH.sub.2); 6.99-7.30 (m, 9H-aromatic) 58 CDCl.sub.3; 1.60-1.79 (m, H.sup.A-CH.sub.2); 1.93-2.09 (m, H.sup.B-CH.sub.2); 2.79-2.97 (m, CH, H.sup.A-CH.sub.2); 3.07-3.19 (m, CH.sub.2); 3.41-3.56 (m, H.sup.B-CH.sub.2); 4.47 (s, CH.sub.2); 7.07-7.37 (m, 8H-aromatic) 59 CDCl.sub.3; 1.77-1.88 (m, CH.sub.2); 2.81-3.20 (m, 2x CH.sub.2, H.sup.A-CH.sub.2); 3.32-3.50 (m, H.sup.B-CH.sub.2); 4.40 (q, CH.sub.2); 6.95-7.04 (m, 1H-aromatic); 7.12-7.30 (7H-aromatic) 60 CDCl.sub.3; 1.62-1.79 (m, H.sup.A-CH.sub.2); 1.86-2.02 (m, H.sup.B-CH.sub.2); 2.57-2.68 (m, H.sup.A-CH.sub.2); 2.79-2.94 (m, CH); 3.03-3.13 (m, CH.sub.2); 3.32-3.42 (dd, H.sup.B-CH.sub.2); 3.81 (s, CH.sub.3); 4.46 (s, CH.sub.2); 6.80-6.92 (m, 2H- aromatic); 7.11-7.37 (m, 7H-aromatic) 61 CDCl.sub.3; 1.50-1.68 (m, H.sup.A-CH.sub.2); 1.82-1.97 (m, H.sup.B-CH.sub.2); 2.56-2.77 (m, CH, H.sup.A-CH.sub.2); 2.83-3.07 (m, CH.sub.2); 3.08-3.22 (m, H.sup.B-CH.sub.2); 4.34 (q, CH.sub.2); 7.03-7.26 (m, 10H-aromatic) 62 CDCl.sub.3; 1.46 (d, CH.sub.3); 1.52-1.69 (m, H.sup.A-CH.sub.2); 1.80-1.97 (m, H.sup.B- CH.sub.2); 2.28 (s, CH.sub.3); 2.44-2.58 (m, H.sup.A-CH.sub.2); 2.58-2.69 (m, CH); 2.69-2.82 (m, H.sup.A-CH.sub.2); 3.08-3.19 (dt, H.sup.B-CH.sub.2); 3.24-3.35 (dd, H.sup.B-CH.sub.2); 5.47 (q, CH); 7.00-7.12 (m, 4H-aromatic); 7.14-7.32 (m, 5H-aromatic) 63 CDCl.sub.3; 1.39 (d, CH.sub.3); 1.52-1.70 (m, H.sup.A-CH.sub.2); 1.79-1.95 (m, H.sup.B- CH.sub.2); 2.25 (s, CH.sub.3); 2.53-2.77 (m, CH, 2x H.sup.A-CH.sub.2); 2.90-3.01 (dt, H.sup.B-CH.sub.2); 3.05-3.20 (m, H.sup.B-CH.sub.2); 5.45 (q, CH); 6.89-6.98 (m, 3H- aromatic); 7.05-7.30 (m, 6H-aromatic) 64 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.45-1.63 (m, H.sup.A-CH.sub.2); 1.91-2.08 (m, H.sup.B- CH.sub.2); 2.71-2.87 (m, CH, H.sup.A-CH.sub.2); 2.90-3.03 (m, H.sup.A-CH.sub.2); 3.04-3.19 (m, H.sup.B-CH.sub.2); 3.27-3.39 (dd, H.sup.B-CH.sub.2); 5.41 (q, CH); 7.10-7.29 (m, 6H-aromatic); 7.31-7.46 (m, 2H-aromatic); 7.49-7.57 (m, 1H-aromatic) 65 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.47-1.62 (m, H.sup.A-CH.sub.2); 1.83-1.98 (m, H.sup.B- CH.sub.2); 2.53-2.77 (m, CH, 2x H.sup.A-CH.sub.2); 3.01-3.15 (m, 2x H.sup.B-CH.sub.2); 3.71 (s, CH.sub.3); 5.41 (q, CH); 6.67-6.75 (m, 2H-aromatic); 6.98-7.07 (m, 2H-aromatic); 7.09-7.28 (m, 5H-aromatic) 66 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.50-1.67 (m, H.sup.A-CH.sub.2); 1.91-2.07 (m, H.sup.B- CH.sub.2); 2.58-2.90 (m, CH, 2x H.sup.A-CH.sub.2); 3.10-3.27 (m, 2x H.sup.B-CH.sub.2); 3.77 (s, CH.sub.3); 5.49 (q, CH); 6.69-6.80 (m, 3H-aromatic); 7.10-7.34 (m, 6H-aromatic) 67 CDCl.sub.3; 1.53 (d, CH.sub.3); 1.49-1.68 (m, H.sup.A-CH.sub.2); 1.93-2.10 (m, H.sup.B- CH.sub.2); 2.35 (s, CH.sub.3); 2.50-2.62 (m, H.sup.A-CH.sub.2); 2.70-2.85 (m, CH); 2.87-2.98 (dt, H.sup.A-CH.sub.2); 3.13-3.27 (m, H.sup.B-CH.sub.2); 3.34-3.45 (dd, H.sup.B-CH.sub.2); 5.53 (q, CH); 7.05-7.20 (m, 4H-aromatic); 7.22-7.40 (m, 5H-aromatic) 68 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.53-1.65 (m, H.sup.A-CH.sub.2); 1.83-1.99 (m, H.sup.B- CH.sub.2); 2.23 (s, CH.sub.3); 2.49-2.81 (m, CH, 2x H.sup.A-CH.sub.2); 3.03-3.20 (m, 2x H.sup.B-CH.sub.2); 5.43 (q, CH); 6.88-6.98 (m, 3H-aromatic); 7.02-7.29 (m, 6H-aromatic) 69 CDCl.sub.3; 1.37-1.58 (m, H.sup.A-CH.sub.2); 1.56 (d, CH.sub.3); 1.61-1.77 (m, H.sup.B- CH.sub.2); 2.27 (s, CH.sub.3); 2.38 (s, CH.sub.3); 2.73-2.93 (m, CH, H.sup.A-CH.sub.2); 3.12-3.27 (dt, H.sup.B-CH.sub.2); 4.97 (d, CH); 5.51 (q, CH); 6.90-7.04 (m, 2H-aromatic); 7.20-7.38 (m, 6H-aromatic) 70 CDCl.sub.3; 1.45 (d, CH.sub.3); 1.53-1.72 (m, H.sup.A-CH.sub.2); 1.77-1.91 (m, H.sup.B- 58-60 CH.sub.2); 2.58-2.79 (m, CH, 2x H.sup.A-CH.sub.2); 3.08-3.30 (m, 2x H.sup.B-CH.sub.2); 5.45 (q, CH); 6.69-6.82 (m, 2H-aromatic); 7.00-7.29 (m, 6H- aromatic) 71 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.57-1.63 (m, H.sup.A-CH.sub.2); 1.80-1.97 (m, H.sup.B- CH.sub.2); 2.52-2.90 (m, CH, 2x H.sup.A-CH.sub.2); 3.01-3.17 (m, H.sup.B-CH.sub.2); 3.19-3.28 (m, H.sup.B-CH.sub.2); 5.42 (q, CH); 6.68-6.82 (m, 2H-aromatic); 6.98-7.13 (m, 1H-aromatic); 7.16-7.32 (m, 5H-aromatic) 72 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.52-1.68 (m, CH.sub.2); 1.94-2.09 (m, H.sup.A-CH.sub.2); 2.09-2.25 (m, CH); 2.25-2.38 (m, H.sup.B-CH.sub.2); 2.52-2.76 (m, CH.sub.2); 2.74-2.81 (m, H.sup.A-CH.sub.2); 3.10-3.22 (dt, H.sup.B-CH.sub.2); 5.43 (q, CH); 7.01-7.28 (m, 10H-aromatic) 73 CDCl.sub.3; 1.42 (d, CH.sub.3); 1.40-1.66 (m, CH.sub.2); 1.98-2.26 (m, CH, H.sup.A- CH.sub.2); 2.27-2.44 (m, H.sup.B-CH.sub.2); 2.49-2.74 (m, CH.sub.2); 2.78-2.90 (dt, H.sup.A-CH.sub.2); 3.04-3.19 (m, H.sup.B-CH.sub.2); 5.41 (q, CH); 7.02-7.30 (m, 10H-aromatic) 74 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.51-1.70 (m, H.sup.A-CH.sub.2); 1.70-1.88 (m, H.sup.B- CH.sub.2); 1.97-2.13 (m, H.sup.A-CH.sub.2); 2.17-2.32 (m, CH); 2.34-2.50 (m, H.sup.B-CH.sub.2); 2.70-2.85 (q, H.sup.A-CH.sub.2); 3.04-3.25 (m, CH.sub.2, H.sup.B-CH.sub.2); 5.45 (q, CH); 7.08-7.31 (m, 7H-aromatic); 7.31-7.48 (m, 2H- aromatic); 7.62 (m, 1H-aromatic); 7.75 (m, 1H-aromatic); 8.02 (m, 1H-aromatic) 75 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.48-1.66 (m, H.sup.A-CH.sub.2); 1.67-1.83 (m, H.sup.B- CH.sub.2); 2.02-2.20 (m, H.sup.A-CH.sub.2); 2.20-2.32 (m, CH); 2.40-2.57 (m, H.sup.B-CH.sub.2); 2.80-2.93 (dt, H.sup.A-CH.sub.2); 3.02-3.22 (m, CH.sub.2, H.sup.B-CH.sub.2); 5.43 (q, CH); 7.08-7.31 (m, 7H-aromatic); 7.32-7.49 (m, 2H- aromatic); 7.63 (m, 1H-aromatic); 7.77 (m, 1H-aromatic); 8.01 (m, 1H-aromatic) 76 CDCl.sub.3; 1.39-1.83 (m, 2x CH.sub.2); 1.53 (d, CH.sub.3); 2.38 (s, 2x CH.sub.3); 2.50-2.67 (m, CH); 2.69-2.88 (m, 2x H.sup.A-CH.sub.2); 3.05-3.19 (m, H.sup.B- CH.sub.2); 2.55-2.67 (dd, H.sup.B-CH.sub.2); 6.18 (q, CH); 7.00 (s, 3H- aromatic); 7.17-7.34 (m, 5H-aromatic) 77 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.38-1.84 (m, 2x CH.sub.2); 2.38 (s, 2xCH.sub.3); 100-104 2.50-2.67 (m, CH); 2.70-2.87 (m, 2x H.sup.A-CH.sub.2); 3.03-3.16 (m, H.sup.B- CH.sub.2); 3.51-3.62 (dd, H.sup.B-CH.sub.2); 6.17 (q, CH); 7.01 (s, 3H- aromatic); 7.22-7.40 (m, 5H-aromatic) 78 CDCl.sub.3; 1.53 (d, CH.sub.3); 1.37-1.88 (m, 2x CH.sub.2); 2.77-2.99 (m, CH, H.sup.A-CH.sub.2); 3.06-3.20 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.72-3.85 (dd, H.sup.B- CH.sub.2); 6.17 (q, CH); 7.01-7.13 (m, 1H-aromatic); 7.18-7.40 (m, 7H-aromatic) 79 CDCl.sub.3; 1.45 (d, CH.sub.3); 1.39-1.79 (m, 2x CH.sub.2); 2.63-2.92 (m, CH, 121-125 H.sup.A-CH.sub.2); 2.96-3.14 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.62-3.78 (dd, H.sup.B- CH.sub.2); 6.08 (q, CH); 6.98-7.07 (m, 1H-aromatic); 7.14-7.33 (m, 7H-aromatic) 80 CDCl.sub.3; 1.73-1.97 (m, CH.sub.2); 2.78-3.06 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.07-3.28 (m, CH.sub.2); 3.37-3.67 (m, CH.sub.2, H.sup.B-CH.sub.2); 6.90-7.32 (m, 7H-aromatic) 81 CDCl.sub.3; 1.73-1.98 (m, CH.sub.2); 2.77-3.27 (m, CH, 2x CH.sub.2, H.sup.A-CH.sub.2); 3.37-3.67 (m, CH.sub.2, H.sup.B-CH.sub.2); 7.02-7.38 (m, 7H-aromatic) 82 CDCl.sub.3; 1.70-1.99 (m, CH.sub.2); 2.73-3.25 (m, CH, 2x CH.sub.2, H.sup.A-CH.sub.2); 3.34-3.63 (m, CH.sub.2, H.sup.B-CH.sub.2); 7.08 (m, 2H-aromatic); 7.27 (m, 2H- aromatic); 7.40 (m, 2H-aromatic) 83 CDCl.sub.3; 1.48-1.63 (m, H.sup.A-CH.sub.2); 1.76-1.92 (m, H.sup.B-CH.sub.2); 2.24 (s, 2x CH.sub.3); 2.43-2.60 (m, CH, H.sup.A-CH.sub.2); 2.78 (t, CH.sub.2); 2.95-3.25 (m, CH.sub.2, H.sup.B-CH.sub.2); 3.37-3.61 (m, CH.sub.2); 6.92 (s, 3H-aromatic); 7.08-7.27 (m, 5H-aromatic) 84 CDCl.sub.3; 1.57-1.75 (m, H.sup.A-CH.sub.2); 1.83-2.00 (m, H.sup.B-CH.sub.2); 2.55-2.90 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.08-3.29 (m, CH.sub.2, H.sup.B-CH.sub.2); 3.38-3.67 (m, CH.sub.2); 6.77-6.91 (m, 2H-aromatic); 7.08-7.34 (m, 6H- aromatic) 85 CDCl.sub.3; 1.52-1.70 (m, H.sup.A-CH.sub.2); 1.95-2.01 (m, H.sup.B-CH.sub.2); 70-71 2.63-2.78 (m, CH, H.sup.A-CH.sub.2); 2.83 (t, CH.sub.2); 2.99-3.19 (m, CH.sub.2); 3.20-3.34 (m, H.sup.B-CH.sub.2); 3.41-3.65 (m, CH.sub.2); 6.83-6.93 (dt, 1H-aromatic); 7.08 (dd, 1H-aromatic); 7.13-7.32 (m, 6H-aromatic) 86 CDCl.sub.3; 1.48-1.63 (m, H.sup.A-CH.sub.2); 1.79-1.96 (m, H.sup.B-CH.sub.2); 2.53-2.67 (m, CH, H.sup.A-CH.sub.2); 2.70-2.81 (t, CH.sub.2); 2.92-3.20 (m, CH.sub.2, H.sup.B- CH.sub.2); 3.34-3.58 (m, CH.sub.2); 5.85 (s, CH.sub.2); 6.66 (s, 1H-aromatic); 6.73 (s, 1H-aromatic); 7.07-7.25 (m, 5H-aromatic) 87 CDCl.sub.3; 1.25-1.77 (m, 2x CH.sub.2); 2.29 (s, CH.sub.3); 2.33-2.50 (m, CH, H.sup.A-CH.sub.2); 2.81 (dt, CH.sub.2); 2.95-3.12 (m, CH.sub.2); 3.40-3.57 (m, CH.sub.2, H.sup.B-CH.sub.2); 6.98-7.27 (m, 9H-aromatic) 88 CDCl.sub.3; 1.22-1.78 (m, 2x CH.sub.2); 2.43-2.59 (m, CH); 2.60-2.74 (m, 104-105 H.sup.A-CH.sub.2); 2.74-2.88 (t, CH.sub.2); 2.93-3.09 (m, CH.sub.2); 3.37-3.55 (m, CH.sub.2, H.sup.B-CH.sub.2); 6.82 (dt, 1H-aromatic); 7.00 (dd, 1H-aromatic); 7.08-7.27 (m, 6H-aromatic) 89 CDCl.sub.3; 1.53-1.70 (m, H.sup.A-CH.sub.2); 1.88-2.02 (m, H.sup.B-CH.sub.2); 87.5-89.5 2.49-2.68 (m, CH, H.sup.A-CH.sub.2); 2.80 (t, CH.sub.2); 2.91-3.13 (m, CH.sub.2, H.sup.B-CH.sub.2); 3.39-3.62 (m, CH.sub.2); 5.90 (s, CH.sub.2); 6.58-6.73 (m, 3H-aromatic); 7.12-7.32 (m, 5H-aromatic) 90 mixture of 2 diastereoisomers 91 CDCl.sub.3; 1.52 (d, CH.sub.3); 2.45-2.66 (m, H.sup.A-CH.sub.2); 2.00-2.21 (m, H.sup.B- CH.sub.2); 2.28 (s, 2x CH.sub.3); 2.67-2.87 (m, CH, H.sup.A-CH.sub.2); 3.19-3.31 (dt, H.sup.B-CH.sub.2); 3.46-3.62 (m, CH); 5.51 (q, CH); 5.57 (s, OH); 6.92 (s, 1H-aromatic); 6.99 (d, 1H-aromatic); 7.19-7.38 (m, 5H-aromatic) 7.43 (d, 1H-aromatic) 92 CDCl.sub.3; 1.72-1.97 (m, CH.sub.2); 2.75-3.26 (m, CH, 2x CH.sub.2, H.sup.A-CH.sub.2); 3.39-3.62 (m, CH.sub.2, H.sup.B-CH.sub.2); 3.78 (s, CH.sub.3); 6.84 (m. 2H- aromatic); 7.08-7.19 (m, 3H-aromatic); 7.28 (d, 2H-aromatic) 93 CDCl.sub.3; 1.72-1.90 (m, CH.sub.2); 2.30 (s, CH.sub.3); 2.75-2.88 (t, CH.sub.2); 2.88-3.27 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.38-3.48 (dd, H.sup.B-CH.sub.2); 3.48-3.60 (m, CH.sub.2); 7.00-7.16 (m, 5H-aromatic); 7.25 (d, 2H-aromatic) 94 CDCl.sub.3; 0.89 (t, CH.sub.3); 1.66-1.99 (m, CH.sub.2, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 2.69-2.89 (m, CH, H.sup.A-CH.sub.2); 2.99 (m, H.sup.A-CH.sub.2); 3.19 (m, H.sup.B-CH.sub.2); 3.43 (dd, H.sup.B-CH.sub.2); 5.15 (t, CH); 6.98 (t, 1H-aromatic); 7.22 (7H- aromatic) 95 CDCl.sub.3; 0.94 (t, CH.sub.3); 1.64-2.11 (m, 2x CH.sub.2); 2.90-3.08 (m, CH, 2x H.sup.A-CH.sub.2); 3.08-3.21 (m, H.sup.B-CH.sub.2); 3.42-3.58 (m, H.sup.B-CH.sub.2); 5.23 (q, CH); 7.07 (t, 1H-aromatic); 7.20-7.38 (m, 7H-aromatic) 96 CDCl.sub.3; 0.91 (t, CH.sub.3); 1.70-1.82 (m, CH.sub.2); 1.82-2.01 (m, CH.sub.2); 2.71-2.92 (m, CH, H.sup.A-CH.sub.2); 2.94-3.08 (m, H.sup.A-CH.sub.2); 3.16-3.28 (m, H.sup.B-CH.sub.2); 3.40-3.50 (dd, H.sup.B-CH.sub.2); 5.17 (q, CH); 7.00 (t, 1H- aromatic); 7.12-7.27 (m, 7H-aromatic) 97 CDCl.sub.3; 0.85 (t, CH.sub.3); 1.57-2.00 (m, 2x CH.sub.2); 2.82-2.99 (m, CH, 2x H.sup.A-CH.sub.2); 2.99-3.11 (m, H.sup.B-CH.sub.2); 3.32-3.49 (m, H.sup.B-CH.sub.2); 5.14 (q, CH); 6.98 (t, 1H-aromatic); 7.11-7.29 (m, 7H-aromatic) 98 CDCl.sub.3; 1.81-1.96 (m, CH.sub.2); 2.85-3.17 (m, CH, 2x H.sup.A-CH.sub.2); 3.37-3.55 (m, 2x H.sup.B-CH.sub.2); 3.44 (s, CH.sub.3); 3.77-3.87 (m, H.sup.A-CH.sub.2); 3.89-4.00 (m, H.sup.B-CH.sub.2); 5.50 (q, CH); 7.09 (t, 1H-aromatic); 7.20-7.38 (m, 7H-aromatic) 99 CDCl.sub.3, 1.73-2.00 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 2.92-3.34 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.40 (s, CH.sub.3); 3.42-3.60 (m, H.sup.B-CH.sub.2); 3.76-3.97 (m, CH.sub.2); 5.49 (dd, CH); 7.02-7.11 (m, 1H-aromatic); 7.21-7.40 (m, 7H-aromatic) 100 CDCl.sub.3; 1.81-1.97 (m, CH.sub.2); 2.85-3.18 (m, CH, 2x H.sup.A-CH.sub.2); 3.38-3.57 (m, 2x H.sup.B-CH.sub.2); 3.43 (s, CH.sub.3); 3.77-3.88 (m, H.sup.A-CH.sub.2); 3.90-4.01 (m, H.sup.B-CH.sub.2); 5.50 (q, CH); 7.07 (t, 1H-aromatic); 7.20-7.39 (m, 7H-aromatic) 101 CDCl.sub.3; 1.73-2.02 (m, CH.sub.2); 2.95-3.60 (m, CH, 2x H.sup.A-CH.sub.2, 2x H.sup.B- CH.sub.2); 3.40 (s, CH.sub.3); 3.74-3.85 (m, H.sup.A-CH.sub.2); 3.88-3.98 (m, H.sup.B- CH.sub.2); 5.50 (q, CH); 7.07 (t, 1H-aromatic); 7.21-7.40 (m, 7H- aromatic) 102 contains 10% from isomer LIB-90-B CDCl.sub.3; 1.60-1.86 (m, CH.sub.2); 2.62-3.50 (m, CH, 3x H.sup.A-CH.sub.2, 3x H.sup.B- CH.sub.2); 5.67 (q, CH); 7.02 (t, 1H-aromatic); 7.11-7.43 (m, 12H- aromatic) 103 mixture of diastereoisomers A and B CDCl.sub.3; 1.50-1.83 (m, CH.sub.2); 2.48-3.45 (m, CH, 3x H.sup.A-CH.sub.2, 3x H.sup.B- CH.sub.2); 5.61-5.80 (m, CH); 7.00 (t, 1H-aromatic); 7.11-7.43 (m, 12H-aromatic) 104 CDCl.sub.3; 1.83-1.98 (m, CH.sub.2); 2.92-3.20 (m, CH, 2x H.sup.A-CH.sub.2); 3.29-3.42 (m, H.sup.B-CH.sub.2); 3.42-3.58 (m, H.sup.B-CH.sub.2); 3.72 (s, OH); 3.98-4.12 (m, H.sup.A-CH.sub.2); 4.12-4.26 (m, H.sup.B-CH.sub.2); 5.02 (q, CH); 7.08 (t, 1H- aromatic); 7.22-7.40 (m, 7H-aromatic) 105 CDCl.sub.3; 1.80 (m, CH.sub.2); 2.97-3.33 (m, H.sup.A-CH.sub.2, CH, CH.sub.2), 3.41-3.58 (m, H.sup.B-CH.sub.2); 3.91 (t, OH); 3.98-4.21 (m, CH.sub.2), 5.04 (q, CH), 7.08 (t, 1H-aromatic); 7.19-7.42 (m, 7H-aromatic) 106 CDCl.sub.3; 1.82-2.01 (m, CH.sub.2); 2.93-3.20 (m, CH, 2x H.sup.A-CH.sub.2); 3.27-3.40 (m, H.sup.B-CH.sub.2); 3.46-3.61 (m, OH, H.sup.B-CH.sub.2); 3.98-4.11 (m, H.sup.A- CH.sub.2); 4.12-4.27 (m, H.sup.B-CH.sub.2); 4.97 (q, CH); 7.10 (t, 1H-aromatic); 7.21-7.42 (m, 7H-aromatic) 107 CDCl.sub.3; 1.78-2.04 (m, CH.sub.2); 2.96-3.34 (m, CH, 2x H.sup.A-CH.sub.2, H.sup.B- CH.sub.2); 3.41-3.59 (m, H.sup.B-CH.sub.2); 3.84-3.97 (m, OH); 3.08-4.21 (m, CH.sub.2); 5.05 (q, CH); 7.09 (t, 1H-aromatic); 7.18-7.42 (m, 7H- aromatic) 108 CDCl.sub.3; 1.50-1.70 (m, H.sup.A-CH.sub.2); 1.88-2.05 (m, H.sup.B-CH.sub.2); 2.56-2.73 (m, CH, H.sup.A-CH.sub.2); 2.73-2.88 (t, CH.sub.2); 2.94-3.23 (m, H.sup.A-CH.sub.2, 2x H.sup.B-CH.sub.2); 3.39-3.63 (m, CH.sub.2); 6.68-6.85 (m, 2H-aromatic); 7.07-7.32 (m, 6H-aromatic) 109 CDCl.sub.3; 1.52-1.70 (m, H.sup.A-CH.sub.2); 1.85-2.01 (m, H.sup.B-CH.sub.2); 2.50-2.69 (m, CH, H.sup.A-CH.sub.2); 2.72-2.85 (t, CH.sub.2); 2.86-2.99 (dt, H.sup.A-CH.sub.2); 2.99-3.13 (m, 2x H.sup.B-CH.sub.2); 3.41-3.58 (m, CH.sub.2); 3.85 (s, CH.sub.3); 5.11 (s, CH.sub.2); 6.62 (dd, 1H-aromatic); 6.77 (d, 2H-aromatic); 7.10-7.46 (m, 10H-aromatic) 110 CDCl.sub.3; 1.58-1.77 (m, H.sup.A-CH.sub.2); 1.80-1.96 (m, CH.sub.2); 1.96-2.11 (m, H.sup.B-CH.sub.2); 2.36 (s, CH.sub.3); 2.47-2.79 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.18-3.29 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.30-3.43 (m, CH.sub.2, H.sup.B-CH.sub.2); 7.08-7.34 (m, 9H-aromatic) 111 CDCl.sub.3; 1.60-2.07 (m, CH.sub.2, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 2.56-2.68 (t, CH.sub.2); 2.71-2.88 (m, CH, H.sup.A-CH.sub.2); 3.13-3.27 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.29-3.48 (m, CH.sub.2, H.sup.B-CH.sub.2); 7.08-7.40 (m, 9H-aromatic) 112 CDCl.sub.3; 1.57-1.74 (m, H.sup.A-CH.sub.2); 1.76-1.92 (m, CH.sub.2); 1.92-2.08 (m, H.sup.B-CH.sub.2); 2.61 (t, CH.sub.2); 2.68-2.87 (m, CH, H.sup.A-CH.sub.2); 3.13-3.27 (m, H.sup.A-CH.sub.2, H.sup.B-CH.sub.2); 3.28-3.42 (m, CH.sub.2, H.sup.B-CH.sub.2); 6.82-6.96 (dt, 1H-aromatic); 7.03-7.33 (m, 7H-aromatic) 113 CDCl.sub.3; 1.61-1.79 (m, H.sup.A-CH.sub.2); 1.81-2.08 (m, CH.sub.2, H.sup.B-CH.sub.2); 2.38 (s, 2x CH.sub.3); 2.58-2.73 (m, CH, CH.sub.2, H.sup.A-CH.sub.2); 3.15-3.46 (m, CH.sub.2, H.sup.A-CH.sub.2, 2x H.sup.B-CH.sub.2); 7.04 (s, 3H-aromatic); 7.13-7.35 (m, 5H- aromatic) 114 CDCl.sub.3; 1.76-2.00 (m, 2x CH.sub.2); 2.63 (t, CH.sub.2); 2.82-3.55 (m, CH, 3x CH.sub.2); 7.01-7.36 (m, 8H-aromatic) 115 CDCL.sub.3; 1.77 (s, CH.sub.3); 1.79 (s, CH.sub.3); 1.88 (m, CH.sub.2); 2.82-2.97 (m, CH); 3.05 (t, H.sup.A-CH.sub.2); 3.18-3.40 (m, CH.sub.2); 3.45 (dd, H.sup.B-CH.sub.2); 7.07 (t, 1H-aromatic); 7.17-7.39 (m, 7H-aromatic) 116 CDCl.sub.3; 1.52 (d, CH.sub.3); 1.78-2.17 (m, 3x CH.sub.2); 2.82-3.19 (m, 2x CH.sub.2, H.sup.A-CH.sub.2); 3.20-3.37 (m, H.sup.B-CH.sub.2); 5.62 (q, CH); 7.10-7.50 (m, 13H-aromatic); 7.55-7.67 (m, 2H-aromatic); 7.69-7.80 (m, 2H- aromatic); 7.93 (d, 1H-aromatic); 8.01 (d, 1H-aromatic) 117 mixture of 2 diastereoisomers CDCl.sub.3; 1.10 (d, 0.4x CH.sub.3); 1.45 (d, 0.6x CH.sub.3); 1.55 (s, 0.6x CH.sub.3); 1.62 (s, 0.4x CH.sub.3); 1.50-1.97 (m, CH.sub.2); 2.48-3.66 (m, CH, 3x CH.sub.2); 4.70-5.19 (OH); 5.26 (q, 0.4 CH); 5.43 (q, 0.6x CH); 6.97-7.44 (m, 9H-aromatic) 118 2 diastereoisomers 119 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.60-1.79 (m, HA -CH.sub.2); 1.85-2.00 (m, H.sup.B- CH.sub.2); 2.68-2.89 (m, CH, 2x H.sup.A-CH.sub.2); 3.17 (dt, H.sup.B-CH.sub.2); 3.36 (d, H.sup.B-CH.sub.2); 3.85 (s, 2x CH.sub.3); 5.52 (q, CH); 6.78 (d, 1H-aromatic); 7.00 (d, 1H-aromatic); 7.29 (m, 5H-aromatic) 120 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.60 (m, H.sup.A-CH.sub.2); 1.98 (m, H.sup.B-CH.sub.2); 2.68-2.93 (m, CH, 2x H.sup.A-CH.sub.2); 3.16 (m, H.sup.B-CH.sub.2); 3.40 (dd, H.sup.B-CH.sub.2); 3.84 (s, 2x CH.sub.3); 5.49 (q, CH); 6.72 (d, 1H-aromatic); 6.97 (d, 1H- aromatic); 7.28 (m, 5H-aromatic) 121 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.55-1.70 (m, H.sup.A-CH.sub.2); 1.91-2.08 (m, H.sup.B- CH.sub.2); 2.60-2.89 (m, CH, 2x H.sup.A-CH.sub.2); 3.06-3.23 (m, H.sup.B-CH.sub.2); 3.84 (s, CH.sub.3); 5.12 (s, CH.sub.2); 5.49 (q, CH); 6.58-6.68 (dd, 1H- aromatic); 6.71-6.82 (m, 2H-aromatic); 7.16-7.48 (m, 10H- aromatic) 122 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.59-1.77 (m, H.sup.A-CH.sub.2); 1.83-2.01 (m, H.sup.B- CH.sub.2); 2.61-2.83 (m, CH, 2x H.sup.A-CH.sub.2); 2.93-3.20 (m, 2x H.sup.B-CH.sub.2); 3.87 (s, CH.sub.3); 5.12 (s, CH.sub.2); 5.51 (q, CH); 6.61-6.72 (dd, 1H- aromatic); 6.73-6.83 (m, 2H-aromatic); 7.17-7.45 (m, 10H- aromatic) 123 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.56-1.86 (m, CH.sub.2); 2.02-2.47 (m, CH, CH.sub.2); 2.59-2.90 (m, H.sup.A-CH.sub.2, CH.sub.2); 3.18-3.31 (dt, H.sup.B-CH.sub.2); 3.79 (s, CH.sub.3); 5.51 (q, CH); 6.87-6.91 (m, 2H-aromatic); 7.08-7.36 (m, 7H-aromatic) 124 CDCl.sub.3; 1.49 (d, CH.sub.3); 1.52-1.69 (m, CH.sub.2); 2.08-2.33 (m, CH, H.sup.A- CH.sub.2); 2.37-2.52 (m, H.sup.B-CH.sub.2); 2.58-2.79 (m, CH.sub.2); 2.83-2.98 (dt, H.sup.A-CH.sub.2); 3.12-3.27 (m, H.sup.B-CH.sub.2); 3.78 (s, CH.sub.3); 5.49 (q, CH); 6.74-6.90 (m, 2H-aromatic); 7.08-7.38 (m, 7H-aromatic) 125 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.48-1.68 (m, CH.sub.2); 1.93-2.22 (m, CH, H.sup.A- CH.sub.2); 2.23-2.39 (m, H.sup.B-CH.sub.2); 2.48-2.70 (m, CH.sub.2); 2.70-2.82 (m, H.sup.A-CH.sub.2); 3.10-3.22 (dt, H.sup.B-CH.sub.2); 3.75 (s, CH.sub.3); 3.78 (s, CH.sub.3); 5.42 (q, CH); 6.60-6.72 (m, 3H-aromatic); 7.10-7.27 (m, 5H- aromatic) 126 CDCl.sub.3; 1.48 (d, CH.sub.3); 1.45-1.70 (m, CH.sub.2); 2.04-2.38 (m, CH, H.sup.A- CH.sub.2); 2.35-2.51 (m, H.sup.B-CH.sub.2); 2.52-2.74 (m, CH.sub.2); 2.85-2.97 (dt, H.sup.A-CH.sub.2); 3.12-3.26 (m, H.sup.B-CH.sub.2); 3.81 (s, CH.sub.3); 3.84 (s, CH.sub.3); 5.46 (q, CH); 6.67-6.79 (m, 3H-aromatic); 7.17-7.35 (m, 5H- aromatic) 127 CDCl.sub.3; 1.56 (d, CH.sub.3); 1.60-1.79 (m, CH.sub.2); 2.08-2.29 (m, CH, H.sup.A- CH.sub.2); 2.37 (s, CH.sub.3); 2.39-2.54 (m, H.sup.B-CH.sub.2); 2.69-2.80 (t, CH.sub.2); 2.82-2.97 (m, H.sup.A-CH.sub.2); 3.23-3.36 (dt, H.sup.B-CH.sub.2); 5.56 (q, CH); 7.07-7.22 (m, 4H-aromatic); 7.22-7.40 (m, 5H-aromatic) 128 CDCl.sub.3; 1.55 (d, CH.sub.3); 1.55-1.75 (m, CH.sub.2); 2.10-2.30 (m, CH, H.sup.A- CH.sub.2); 2.35 (s, CH.sub.3); 2.46-2.61 (m, H.sup.B-CH.sub.2); 2.66-2.78 (t, CH.sub.2); 2.90-3.03 (dt, H.sup.A-CH.sub.2); 3.18-3.32 (m, H.sup.B-CH.sub.2); 5.55 (q, CH); 7.04-7.22 (m, 4H-aromatic); 7.23-7.40 (m, 5H-aromatic) 129 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.33-1.62 (m, CH.sub.2); 2.06-2.24 (m, CH, H.sup.A- CH.sub.2); 2.33-2.44 (dq, H.sup.B-CH.sub.2); 2.71-2.92 (m, CH.sub.2, H.sup.A-CH.sub.2); 3.09-3.22 (m, H.sup.B-CH.sub.2); 5.41 (q, CH); 6.80-6.92 (m, 1H-aromatic); 6.93-7.11 (m, 2H-aromatic); 7.13-7.30 (m, 5H-aromatic) 130 CDCl.sub.3; 1.53 (d, CH.sub.3); 1.56-1.76 (m, CH.sub.2); 2.02-2.19 (m, H.sup.A-CH.sub.2); 2.19-2.32 (m, CH); 2.32-2.49 (m, H.sup.B-CH.sub.2); 2.53-2.78 (m, CH.sub.2); 2.78-2.93 (m, H.sup.A-CH.sub.2); 2.92 (s, 2x CH.sub.3); 3.20-3.32 (dt, H.sup.B-CH.sub.2); 5.54 (q, CH); 6.71 (d, 2H-aromatic); 7.11 (d, 2H-aromatic); 7.22-7.39 (m, 5H-aromatic) 131 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.50-1.71 (m, CH.sub.2); 2.08-2.33 (m, CH, H.sup.A- CH.sub.2); 2.38-2.53 (m, H.sup.B-CH.sub.2); 2.53-2.76 (m, CH.sub.2); 2.85-2.99 (m, H.sup.A-CH.sub.2); 2.92 (s, 2x CH.sub.3); 3.13-3.28 (m, H.sup.B-CH.sub.2); 5.51 (q, CH); 6.70 (d, 2H-aromatic); 7.10 (d, 2H-aromatic); 7.21-7.39 (m, 5H- aromatic) 132 CDCl.sub.3; 1.52 (d, CH.sub.3); 1.56-1.73 (m, CH.sub.2); 2.01-2.17 (m, H.sup.A-CH.sub.2); 2.17-2.29 (m, CH); 2.30-2.46 (m, H.sup.B-CH.sub.2); 2.54-2.77 (m, CH.sub.2); 2.78-2.90 (m, H.sup.A-CH.sub.2); 3.19-3.31 (dt, H.sup.B-CH.sub.2); 3.77 (s, CH.sub.3); 5.52 (q, CH); 6.82 (d, 2H-aromatic); 7.13 (d, 2H-aromatic); 7.20-7.38 (m, 5H-aromatic) 133 CDCl.sub.3; 1.49 (d, CH.sub.3); 1.48-1.69 (m, CH.sub.2); 2.04-2.32 (m, CH, H.sup.A- CH.sub.2); 2.33-2.50 (m, H.sup.B-CH.sub.2); 2.51-2.76 (m, CH.sub.2); 2.84-2.97 (dt, H.sup.A-CH.sub.2); 3.11-3.26 (m, H.sup.B-CH.sub.2); 3.75 (s, CH.sub.3); 5.48 (q, CH); 6.81 (d, 2H-aromatic); 7.11 (d, 2H-aromatic); 7.18-7.37 (m, 5H- aromatic) 134 CDCL.sub.3; 1.31 (d, CH.sub.3); 1.52 (d, CH.sub.3); 1.61 (m, CH.sub.2); 1.98-2.16 (m, CH, H.sup.A-CH.sub.2); 2.36 (dt, H.sup.B-CH.sub.2); 2.68-2.90 (m, CH, H.sup.A-CH.sub.2); 3.22 (dt, H.sup.B-CH.sub.2); 5.50 (q, CH); 7.12-7.38 (m, 10H-aromatic) 135 CDCl.sub.3; 1.19 (d, CH.sub.3); 1.24 (m, H.sup.A-CH.sub.2); 1.39 (d, CH.sub.3); 1.45 (m, H.sup.B-CH.sub.2); 1.77 (m, H.sup.A-CH.sub.2); 2.10-2.21 (m, H.sup.B-CH.sub.2); 2.25-2.39 (m, CH); 2.74 (dt, H.sup.A-CH.sub.2); 2.87 (m, CH); 3.02 (m, H.sup.B-CH.sub.2); 5.39 (q, CH); 7.03-7.27 (m, 10H aromatic) 136 CDCl.sub.3; 1.28 (d, CH.sub.3); 1.37-1.65 (m, CH.sub.2); 1.49 (d, CH.sub.3); 1.73-1.92 (m, H.sup.A-CH.sub.2); 2.17-2.43 (m, CH, H.sup.B-CH.sub.2); 2.68-2.81 (m, H.sup.A- CH.sub.2); 2.85-3.02 (m, CH); 3.09-3.21 (dt, H.sup.B-CH.sub.2); 5.50 (q, CH); 7.12-7.37 (m, 10H-aromatic) 137 CDCl.sub.3; 1.30 (d, CH.sub.3), 1.44 (d, CH.sub.3); 1.5 (m, CH.sub.2); 2.01-2.21 (m, CH, H.sup.A-CH.sub.2); 2.27-2.42 (dt, H.sup.B-CH.sub.2); 2.68-2.82 (m, CH); 2.83-2.95 (dt, H.sup.A-CH.sub.2), 3.05-3.19 (m, H.sup.B-CH.sub.2); 5.46 (q, CH); 7.15-7.38 (m, 10H-aromatic) 138 CDCl.sub.3; 0.77 (t, CH.sub.3); 1.20-1.85 (m, 2x CH.sub.2, H.sup.A-CH.sub.2); 1.48 (d, CH.sub.3); 2.19-2.39 (m, CH, H.sup.B-CH.sub.2); 2.61-2.79 (m, CH, H.sup.A-CH.sub.2); 3.03-3.18 (m, H.sup.B-CH.sub.2); 5.48 (q, CH); 7.11-7.37 (m, 10H-aromatic) 139 CDCl.sub.3; 0.80 (t, CH.sub.3); 1.51 (d, CH.sub.3); 1.51-1.78 (m, 2x CH.sub.2); 2.01 (m, CH, H.sup.A-CH.sub.2); 2.35 (dt, H.sup.B-CH.sub.2); 2.47 (m, CH); 2.72 (m, H.sup.A- CH.sub.2); 3.20 (dt, H.sup.B-CH.sub.2); 5.49 (q, CH); 7.13-7.32 (10H-aromatic) 140 mixture of 3 diastereoisomers CDCL.sub.3, 0.70-0.84 (m, CH.sub.3); 1.18-1.84 (m, 2x CH.sub.2, CH.sub.3); 1.93-2.18 (m, H.sup.A-CH.sub.2, 0.6x CH); 2.23-2.55 (m, H.sup.B-CH.sub.2, 0.4x CH, 0.7x CH); 2.67-3.94 (m, H.sup.A-CH.sub.2, 0.3x CH); 3.00-3.26 (m, H.sup.B-CH.sub.2); 5.39-5.55 (m, CH); 7.10-7.40 (m, 10H-aromatic) 141 CDCl.sub.3; 0.79 (t, CH.sub.3); 1.17-1.82 (m, 2x CH.sub.2); 1.43 (d, CH.sub.3); 1.98-2.08 (m, CH, H.sup.A-CH.sub.2); 2.25-2.52 (m, CH, H.sup.B-CH.sub.2); 2.82-2.95 (m, H.sup.A-CH.sub.2); 3.00-3.18 (m, H.sup.B-CH.sub.2); 5.45 (q, CH); 7.12-7.39 (m, 10H-aromatic) 142 CDCl.sub.3; 1.12 (s, CH.sub.3); 1.27 (d, CH.sub.3); 1.43-1.60 (m, H.sup.A-CH.sub.2); 1.79-1.92 (m, H.sup.B-CH.sub.2); 2.27 (s, CH.sub.3); 2.51-2.62 (m, CH.sub.2); 2.73 (d, H.sup.A- CH.sub.2); 2.96 (d, H.sup.B-CH.sub.2); 5.40 (q, CH); 6.97-7.24 (m, 9H-aromatic) 143 CDCl.sub.3; 1.16 (s, CH.sub.3); 1.39 (d, CH.sub.3); 1.49-1.61 (m, H.sup.A-CH.sub.2); 1.65-1.80 (m, H.sup.B-CH.sub.2); 2.19 (s, CH.sub.3); 2.41-2.52 (dt, H.sup.A-CH.sub.2); 2.70 (d, H.sup.A-CH.sub.2); 2.96 (d, H.sup.B-CH.sub.2); 2.97-3.09 (m, H.sup.A-CH.sub.2); 5.36 (q, CH); 6.88-7.22 (m, 9H-aromatic) 144 CDCl.sub.3; 0.81 (t, CH.sub.3); 1.20 (d, CH.sub.3); 1.40-1.78 (m, 2x CH.sub.2); 2.25 (s, CH.sub.3); 2.27-2.39 (m, H.sup.A-CH.sub.2); 2.43-2.57 (m, H.sup.B-CH.sub.2); 2.72 (d, H.sup.A-CH.sub.2); 2.97 (d, H.sup.B-CH.sub.2); 5.41 (q, CH); 6.94-7.27 (m, 9H- aromatic) 145 CDCl.sub.3; 0.97 (t, CH.sub.3); 1.46 (d, CH.sub.3); 1.52-1.89 (m, 2x CH.sub.2); 2.25 (s, CH.sub.3); 2.30-2.47 (m, H.sup.A-CH.sub.2); 2.74 (d, H.sup.A-CH.sub.2); 2.98-3.13 (m, H.sup.B-CH.sub.2); 3.10 (d, H.sup.B-CH.sub.2); 5.48 (q, CH); 6.90-7.27 (m, 9H- aromatic) 146 mixture of 2 diastereoisomers CDCl.sub.3; 0.79-0.93 (m, CH.sub.3); 1.19 (d, 0.7x CH.sub.3); 1.38 (d, 0.3x CH.sub.3); 1.08-1.79 (m, 3x CH.sub.2); 2.17 (s, 0.3x CH.sub.3); 2.25 (s, 0.7x CH.sub.3); 2.27-2.38 (m, H.sup.A-CH.sub.2); 2.43-2.57 (m, H.sup.B-CH.sub.2); 2.60-2.77 (m, H.sup.A-CH.sub.2); 2.89-3.07 (m, H.sup.B-CH.sub.2); 5.40 (q, CH); 6.92-7.28 (m, 9H-aromatic) 147 mixture of 2 diastereoisomers 148 CDCl.sub.3; 1.48 (d, CH.sub.3); 1.53-1.69 (m, H.sup.A-CH.sub.2); 1.74-1.90 (m, H.sup.B- CH.sub.2); 2.29 (s, 2x CH.sub.3); 2.49-2.78 (m, CH, 2x H.sup.A-CH.sub.2); 3.12-3.31 (m, 2x H.sup.B-CH.sub.2); 5.47 (q, CH); 6.93 (s, 3H-aromatic); 7.11-7.30 (m, 5H-aromatic) 149 CDCl.sub.3; 1.44 (d, CH.sub.3); 1.40-1.60 (m, H.sup.A-CH.sub.2); 1.80-1.96 (m, H.sup.B- CH.sub.2); 2.25 (s, 2x CH.sub.3); 2.49-2.67 (m, CH, H.sup.A-CH.sub.2); 2.81-2.92 (dt, H.sup.A-CH.sub.2); 3.00-3.13 (m, H.sup.B-CH.sub.2); 3.21-3.36 (m, H.sup.B-CH.sub.2); 5.43 (q, CH); 6.91 (s, 3H-aromatic); 7.13-7.32 (m, 5H-aromatic) 150 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.59-1.78 (m, H.sup.A-CH.sub.2); 1.87-2.02 (m, H.sup.B- CH.sub.2); 2.70-2.89 (m, CH, 2x H.sup.A-CH.sub.2); 3.10-3.23 (dt, H.sup.B-CH.sub.2); 3.28-3.43 (m, H.sup.B-CH.sub.2); 5.51 (q, CH); 6.87-6.98 (dt, 1H-aromatic); 7.10 (dd, 1H-aromatic); 7.21-7.38 (m, 6H-aromatic) 151 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.50-1.67 (m, H.sup.A-CH.sub.2); 1.92-2.08 (m, H.sup.B- CH.sub.2); 2.73-2.93 (m, CH, 2x H.sup.A-CH.sub.2); 3.12-3.25 (m, H.sup.B-CH.sub.2); 3.28-3.44 (m, H.sup.B-CH.sub.2); 5.49 (q, CH); 6.80-6.91 (dt, 1H-aromatic); 7.08 (dd, 1H-aromatic); 7.19-7.38 (m, 6H-aromatic) 152 CDCl.sub.3; 1.46 (d, CH.sub.3); 1.59-1.76 (m, H.sup.A-CH.sub.2); 1.87-2.02 (m, H.sup.B- CH.sub.2); 2.59-2.86 (m, CH, 2x H.sup.A-CH.sub.2); 2.99-3.18 (m, 2x H.sup.B-CH.sub.2); 5.51 (q, CH); 5.91 (s, CH.sub.2); 6.60-6.75 (m, 3H-aromatic); 7.19-7.38 (m, 5H-aromatic) 153 contains 8% from isomer LIB-59-A CDCl.sub.3; 1.50 (d, CH.sub.3); 1.48-1.67 (m, H.sup.A-CH.sub.2); 1.89-2.08 (m, H.sup.B- CH.sub.2); 2.58-2.87 (m, CH, 2x H.sup.A-CH.sub.2); 3.04-3.22 (m, 2x H.sup.B-CH.sub.2); 5.49 (q, CH); 5.90 (s, CH.sub.2); 6.59-7.75 (m, 3H-aromatic); 7.18-7.37 (m, 5H-aromatic) 154 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.55-1.72 (m, H.sup.A-CH.sub.2); 1.78-1.93 (m, H.sup.B- CH.sub.2); 2.60-2.81 (m, CH, 2x H.sup.A-CH.sub.2); 3.04-3.28 (m, 2x H.sup.B-CH.sub.2); 5.44 (q, CH); 5.86 (s, CH.sub.2); 6.69 (s, 1H-aromatic); 6.73 (s, 1H- aromatic); 7.12-7.30 (m, 5H-aromatic) 155 CDCl.sub.3; 1.43 (d, CH.sub.3); 1.45-1.58 (m, H.sup.A-CH.sub.2); 1.83-1.99 (m, H.sup.B- CH.sub.2); 2.58-2.86 (m, CH, 2x H.sup.A-CH.sub.2); 3.03-3.18 (m, H.sup.B-CH.sub.2); 3.18-3.27 (dd, H.sup.B-CH.sub.2); 5.41 (q, CH); 5.85 (s, CH.sub.2); 6.69 (s, 1H- aromatic); 6.71 (s, 1H-aromatic); 7.11-7.29 (m, 5H-aromatic) 156 CDCl.sub.3; 1.51 (d, CH.sub.3); 1.55-1.72 (m, CH.sub.2); 1.91-2.08 (m, H.sup.A-CH.sub.2); 2.37-2.57 (m, CH, H.sup.B-CH.sub.2); 2.72-2.87 (m, H.sup.A-CH.sub.2); 3.14-3.28 (m, H.sup.B-CH.sub.2); 3.19 (s, CH.sub.3); 4.34 (m, CH); 5.50 (q, CH); 7.20-7.39 (m, 10H-aromatic) 157 CDCl.sub.3; 1.50 (d, CH.sub.3); 1.51-1.68 (m, H.sup.A-CH.sub.2); 1.72-1.88 (m, H.sup.B- CH.sub.2); 2.10-2.23 (m, CH, H.sup.A-CH.sub.2); 2.43-2.58 (m, H.sup.B-CH.sub.2); 2.85-2.95 (dt, H.sup.A-CH.sub.2); 3.12-3.23 (m, H.sup.B-CH.sub.2); 3.21 (s, CH.sub.3); 4.43 (dd, CH); 5.46 (q, CH); 7.19-7.38 (m, 10H-aromatic) 158 CDCl.sub.3; 1.23 (d, CH.sub.3); 1.35 (d, CH.sub.3); 1.73 (m, CH.sub.2); 2.65 (m, CH, H.sup.A-CH.sub.2); 2.91 (m, H.sup.B-CH.sub.2); 3.37 (m, CH); 5.44 (q, CH); 7.18 (m, 10H-aromatic) 159 CDCl.sub.3; 1.14 (d, CH.sub.3); 1.35 (d, CH.sub.3); 1.50-1.65 (m, H.sup.A-CH.sub.2); 1.65-1.80 (m, H.sup.B-CH.sub.2), 2.39-2.62 (m, CH, CH.sub.2); 3.23-3.38 (m, CH); 5.33 (q, CH); 7.05-7.23 (m, 10H-aromatic) 160 CDCl.sub.3; 1.15 (d, CH.sub.3); 1.41 (d, CH.sub.3); 1.63-1.78 (m, CH.sub.2); 2.68-2.80 (m, CH, H.sup.A-CH.sub.2); 3.00-3.13 (m, H.sup.B-CH.sub.2); 3.38-3.50 (m, CH); 5.44 (q, CH); 7.03-7.30 (m, 10H-aromatic) 161 CDCl.sub.3; 1.36 (d, CH.sub.3); 1.37 (d, CH.sub.3); 1.41-1.59 (m, H.sup.A-CH.sub.2); 1.72-1.90 (m, H.sup.B-CH.sub.2); 2.32-2.47 (dt, CH); 2.57-2.70 (m, H.sup.A-CH.sub.2); 2.89-3.02 (m, H.sup.B-CH.sub.2); 3.25-3.39 (m, CH); 5.32 (q, CH); 6.82-6.94 (m, 2H-aromatic); 7.01-7.20 (m, 8H-aromatic) 162 CDCl.sub.3; 1.27 (d, 0.65x CH.sub.3); 1.44 (d, 0.35x CH.sub.3); 1.52 (d, 0.35x CH.sub.3); 1.55 (d, 0.65x CH.sub.3); 1.65-2.02 (m, CH.sub.2); 2.38 (s, 0.35x CH.sub.3); 2.43 (s, 0.65x CH.sub.3); 2.62-2.87 (m, CH, H.sup.A-CH.sub.2); 2.97-3.08 (m, 0.35x H.sup.B-CH.sub.2); 3.13-3.26 (m, 0.65x H.sup.B-CH.sub.2); 3.27-3.39 (m, 0.35x CH); 3.74-3.88 (m, 0.65x CH); 5.47-5.62 (m, CH); 7.05-7.39 (m, 9H-aromatic) 163 CDCl.sub.3; 1.09 (d, 0.8x CH.sub.3); 1.40 (d, 0.2x CH.sub.3); 1.42 (d, CH.sub.3); 1.57-1.87 (m, CH.sub.2); 2.19 (s, 0.2x CH.sub.3); 2.32 (s, 0.8x CH.sub.3); 2.57-2.70 (m, CH, 0.2x H.sup.A-CH.sub.2); 2.74-2.87 (dt, 0.8x H.sup.A-CH.sub.2); 2.92-3.20 (m, 0.2x CH, H.sup.B-CH.sub.2); 3.66-3.78 (m, 0.8x CH); 5.32-5.51 (m, CH); 6.90-7.29 (m, 9H-aromatic) 164 CDCl.sub.3; 1.84 (m, CH.sub.2); 2.15 (m, CH.sub.2); 2.43-2.59 (m, 2x CH.sub.2); 3.05-3.27 (m, 2x CH.sub.2); 3.86 (s, 2x CH.sub.3); 5.12 (s, 2x CH.sub.2); 6.66 (dd, 2H-aromatic); 6.73-6.84 (m, 4H-aromatic); 6.89-6.99 (m, 2H- aromatic) 7.11-7.46 (m, 13H-aromatic) 165 mixture of diastereoisomers 166 CDCl.sub.3; 1.54 (d, 3H, CH.sub.3); 1.60 (s, 3H, CH.sub.3); 1.96-2.14 (m, 1H, H.sup.A-CH.sub.2); 2.28-2.41 (m, 1H, H.sup.B-CH.sub.2); 2.84-2.93 (m, 1H, H.sup.A- NCH.sub.2); 3.12-3.31 (m, H.sup.B-NCH.sub.2); 5.58 (m, CH); 7.28-7.54 (m, 10H-aromatic) 167 CDCl.sub.3; 1.54 (d, 3H, CH.sub.3); 1.60 (s, 3H, CH.sub.3); 1.96-2.14 (m, 1H, H.sup.A-CH.sub.2); 2.28-2.41 (m, 1H, H.sup.B-CH.sub.2); 2.84-2.93 (m, 1H, H.sup.A- NCH.sub.2); 3.12-3.31 (m, H.sup.B-NCH.sub.2); 5.58 (m, CH); 7.28-7.54 (m, 10H-aromatic)

C. Pharmacological Examples

Example C.1: Enzymatic Assays to Test the Effect of Compounds on 11b-Hydroxysteroid Dehydrogenase Type 1 and Type 2

(36) The effects of compounds on 11b-HSD1 dependent conversion of cortisone into cortisol (reductase activity) was studied in a reaction mixture containing 30 mM Tris-HCl buffer pH 7.2, 180 μM NADPH, 1 mM EDTA, 2 μM cortisone, 1 μl drug and/or solvent and 11 μg recombinant protein in a final volume of 100 μl.

(37) The effect on the 11b-HSD1-dehydrogenase activity (conversion of cortisol into cortisone) was measured in a reaction mixture containing 0.1M sodium phosphate buffer pH 9.0, 300 μM NADP, 25 μM cortisol, 1 μl drug and/or solvent and 3.5 μg recombinant protein in a final volume of 100 μl.

(38) The effects on the 11b-HSD2 dependent dehydrogenase activity was studied in a reaction mixture containing 0.1M sodium phosphate buffer pH 7.5, 300 μM NAD, 100 nM cortisol (of which 2 nM is 3H-radio labelled), 1 μl drug and/or solvent and 2.5 μg recombinant protein in a final volume of 100 μl.

(39) All incubations were performed for 45 min at 37 C in a water bath. The reaction was stopped by adding 100 μl acetonitrile containing 20 μg corticosterone as internal standard. After centrifugation, the product formation was analysed in the supernatant by HPLC on a Hypersyl BDS-C18 column using 0.05 mM ammonium acetate/methanol (50/50) as solvent. In all of the aforementioned assays, the drugs to be tested were taken from a stock solution and tested at a final concentration ranging from −10.sup.−5M to 3.10.sup.−9M. From the thus obtained dose response curves, the pIC50 value was calculated and scored as follows; Score 1=pIC50 value<5, Score 2=pIC50 value in the range of 5 to 6, Score 3=pIC50 value>6. Some of the thus obtained results are summarized in the table below. (in this table NT stands for Not Tested).

Example C2: Cellular Assays to Test the Effect of Compounds on 11b-Hydroxysteroid Dehydrogenase Type 1 and Type 2

(40) The effects on 11b-HSD1 activity was measured in differentiated 3T3-L1 cells and rat hepatocytes.

(41) Mouse fibroblast 3T3-L1 cells (ATCC-CL-173) were seeded at a density of 16500 cells/ml in 12 well plates and grown for 7 days in DMEM medium (supplemented with 10% heat inactivated foetal calf serum, 2 mM glutamine and 25 mg gentamycin) at 37 C in a humidified 5% CO2 atmosphere. Medium was refreshed twice a week. Fibroblasts were differentiated into adipocytes at 37 C in a 5% CO2 humidified atmosphere in growth medium containing 2 μg/ml insulin, 55 μg/ml IBMX and 39.2 μg/ml dexamethasone.

(42) Primary hepatocytes from male rats were seeded on BD-Biocoat Matrigel matrix multiwell plates at a density of 250000 cells/well and incubated for 10 days at 37 C in a 5% CO2 humidified atmosphere in DMEM-HAM's F12 medium containing 5% Nu-serum, 100 U/ml penicillin, 100 μg/ml streptomycin, 0.25 μg/ml amphotericin B, 50 μg/ml gentamycin sulfate, 5 μg/ml insulin and 392 ng/ml dexamethasone. Medium was refreshed 3 times a week.

(43) Following a 4 hour pre-incubation with test compound, 0.5 μCi .sup.3H-cortisone or dehydrocorticosterone, was added to the cultures. One hour later, the medium was extracted on Extrelut.sup.3-columns with 15 ml diethyl ether and the extract was analysed by HPLC as described above.

(44) The effects on 11b-HSD2 activity was studied in HepG2 and LCC-PK1-cells HepG2-cells (ATCC HB-8065) were seeded in 12 well plates at a density of 100,000 cells/ml and grown at 37 C in a humidified 5% CO2 atmosphere in MEM-Rega-3 medium supplemented with 10% heat inactivated foetal calf serum, 2 mM L-glutamine and sodium bicarbonate). Medium was refreshed twice a week.

(45) Pig kidney cells (LCC-PK1, ATCC CRL-1392) were seeded at a density of 150,000 cells/ml in 12 well plates and grown at 37 C in a humidified 5% CO2 atmosphere in Medium 199 supplemented with Earls modified salt solution, 100 U/ml penicillin, 100 μg/ml streptomycin and 10% foetal calf serum. Medium was refreshed twice a week. Twenty four hours prior to the onset of the experiment, medium was changed by medium containing 10% charcoal stripped foetal calf serum.

(46) Following a 4 hour pre-incubation with test compound, 0.5 μCi .sup.3H-cortisol or corticosterone, was added to the cultures. One hour later, the medium was extracted on Extrelut.sup.3-columns with 15 ml diethyl ether and the extract was analysed by HPLC as described above.

(47) As for the enzymatic assays, the compounds to be tested were taken from a stock solution and tested at a final concentration ranging from −10.sup.−5M to 3.10.sup.−9M. From the thus obtained dose response curves, the pIC50 value was calculated and scored as follows; Score 1=pIC50 value<5, Score 2=pIC50 value in the range of 5 to 6, Score 3=pIC50 value>6. Some of the thus obtained results are summarized in the table below (in this table NT stands for Not Tested).

(48) TABLE-US-00003 [C1] [C2] HSD2 HSD1-prot [C1] HSD2 [C2] HSD1 cellular Compound Reduct prot Dehydro cellular 3T3-L1 HepG2 Number Score Score Score Score 1 3 1 3 1 2 2 NT 2 1 3 3 NT 2 1 4 1 NT 2 1 5 2 NT 2 1 6 2 NT 2 1 7 2 1 3 1 8 2 NT 2 NT 9 2 1 3 1 10 3 1 3 1 11 3 NT 2 NT 12 2 NT 2 NT 13 3 1 3 1 14 3 1 3 1 15 2 NT 2 NT 16 1 NT 2 NT 17 2 NT 2 NT 18 2 NT 2 NT 19 2 NT 3 NT 20 1 NT 1 NT 21 2 NT 3 NT 22 1 NT 2 NT 23 2 NT 3 NT 24 2 NT 1 NT 25 1 NT 3 NT 26 1 NT 2 NT 27 1 1 3 1 28 1 1 3 1 29 2 NT 2 NT 30 3 1 3 1 31 2 1 3 1 32 3 1 3 1 33 1 NT 3 NT 34 1 NT 2 NT 35 1 1 3 1 36 1 NT 2 NT 37 1 NT 2 NT 38 1 NT 2 NT 39 1 NT 2 NT 40 2 NT 3 NT 41 2 1 3 1 42 1 NT 2 NT 43 2 NT 2 NT 44 1 NT 2 NT 45 3 1 3 1 46 1 NT 1 NT 47 1 NT 2 NT 48 1 NT 2 NT 49 2 NT 3 NT 50 1 NT 2 NT 51 1 NT 2 NT 52 1 NT 2 NT 53 1 NT 2 NT 54 1 NT 2 NT 55 1 NT 2 NT 56 1 NT 2 NT 57 2 1 3 1 58 2 NT 2 NT 59 2 1 3 1 60 1 NT 2 NT 61 1 NT 2 NT 62 1 NT 2 NT 63 1 NT 2 NT 64 1 NT 2 NT 65 1 1 3 1 66 1 NT 2 NT 67 2 NT 3 NT 68 1 NT 2 NT 69 2 NT 3 1 70 1 NT 3 1 71 3 NT 3 1 72 1 NT 2 NT 73 3 NT 2 NT 74 2 NT 2 NT 75 3 NT 2 NT 76 3 NT 2 NT 77 3 NT 3 1 78 3 NT 3 NT 79 3 NT 3 NT 80 3 NT 3 1 81 1 NT 3 NT 82 3 NT 2 NT 83 3 NT 1 NT 84 2 NT 3 NT 85 2 NT 1 NT 86 2 NT 3 NT 87 1 NT 2 NT 88 2 NT 2 NT 89 1 NT 2 NT 90 1 NT 2 NT 91 2 NT 3 NT 92 3 NT 2 NT 93 1 NT 1 NT 94 1 NT 3 NT 95 3 NT 2 NT 96 2 NT 1 NT 97 3 2 1 1 98 1 NT 2 NT 99 3 NT 3 NT 100 2 NT 1 NT 101 1 NT 1 NT 102 1 NT 1 NT 103 1 NT 1 NT 104 1 NT 2 NT 105 3 NT 3 NT 106 2 NT 1 NT 107 2 NT 1 NT 108 2 NT 2 NT 109 1 NT 2 NT 110 2 NT 2 NT 111 2 NT 2 NT 112 2 NT 2 NT 113 2 NT 2 NT 114 1 NT 3 NT 115 1 NT 3 NT 116 1 NT 1 NT 117 3 NT 3 NT 118 1 NT 2 NT 119 3 2 3 1 120 2 NT 3 NT 121 1 NT 1 NT 122 2 NT 2 NT 123 2 NT 2 NT 124 2 NT 2 NT 125 1 NT 1 NT 126 1 NT 1 NT 127 2 NT 2 NT 128 2 NT 2 NT 129 2 NT 2 NT 130 1 NT 2 NT 131 1 NT 2 NT 132 2 NT 2 NT 133 1 NT 2 NT 134 3 NT 3 NT 135 1 NT 3 NT 136 2 NT 2 NT 137 3 NT 3 NT 138 2 NT 2 NT 139 3 NT 3 NT 140 1 NT 3 NT 141 3 NT 1 NT 142 1 NT 2 NT 143 1 NT 2 NT 144 1 NT 1 NT 145 1 NT 1 NT 146 1 NT 1 NT 147 1 NT 1 NT 148 1 NT 3 1 149 1 NT 3 1 150 3 NT 3 NT 151 3 NT 3 NT 152 2 NT 3 NT 153 2 NT 2 NT 154 1 NT 3 2 155 3 NT 3 NT 156 2 NT 2 NT 157 2 NT 3 NT 158 3 NT 3 NT 159 3 NT 3 NT 160 3 NT 1 NT 161 2 NT 1 NT 162 3 2 3 1 163 3 2 3 1 164 1 NT 1 NT 165 1 NT 1 NT 166 NT NT 2 NT 167 NT NT 1 NT

D. Composition Examples

(49) The following formulations exemplify typical pharmaceutical compositions suitable for systemic or topical administration to animal and human subjects in accordance with the present invention.

(50) “Active ingredient” (A.I.) as used throughout these examples relates to a compound of formula (I) or a pharmaceutically acceptable addition salt thereof.

Example D.1: Film-Coated Tablets

(51) Preparation of Tablet Core

(52) A mixture of A.I. (100 g), lactose (570 g) and starch (200 g) was mixed well and thereafter humidified with a solution of sodium dodecyl sulfate (5 g) and polyvinyl-pyrrolidone (10 g) in about 200 ml of water. The wet powder mixture was sieved, dried and sieved again. Then there was added microcrystalline cellulose (100 g) and hydrogenated vegetable oil (15 g). The whole was mixed well and compressed into tablets, giving 10.000 tablets, each comprising 10 mg of the active ingredient.

(53) Coating

(54) To a solution of methyl cellulose (10 g) in denaturated ethanol (75 ml) there was added a solution of ethyl cellulose (5 g) in CH.sub.2Cl.sub.2 (150 ml). Then there were added CH.sub.2Cl.sub.2 (75 ml) and 1,2,3-propanetriol (2.5 ml). Polyethylene glycol (10 g) was molten and dissolved in dichloromethane (75 ml). The latter solution was added to the former and then there were added magnesium octadecanoate (2.5 g), polyvinyl-pyrrolidone (5 g) and concentrated color suspension (30 ml) and the whole was homogenated. The tablet cores were coated with the thus obtained mixture in a coating apparatus.