PYRIMIDINE COMPOUND AND MEDICAL USE THEREOF

Abstract

The present invention relates to a pyrimidine compound or a pharmaceutically acceptable salt thereof represented by the following formula [I]

##STR00001##

wherein each symbol is as defined in the specification and a method of therapeutically or prophylactically treating an undesirable cell proliferation, comprising administering such a compound. The compound of the present invention has superior activity in suppressing undesirable cell proliferation, particularly, an antitumor activity, and is useful as an antitumor agent for the prophylaxis or treatment of cancer, rheumatism, and the like. In addition, the compound of the present invention can be a more effective antitumor agent when used in combination with other antitumor agents such as an alkylating agent or metabolism antagonist.

Claims

1. A method of therapeutically treating goiter in a mammal comprising administering to the mammal a therapeutic amount of a compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof: ##STR00678## wherein X.sup.1 and X.sup.2 are the same or different and each is a carbon atom or a nitrogen atom, a ##STR00679## moiety is ##STR00680## R.sup.1, R.sup.2, and R.sup.6 are the same or different and each is a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, wherein the C.sub.1-6 alkyl group and the C.sub.2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, or ##STR00681## wherein m is 0 or an integer of 1 to 4, ring Cy is a C.sub.3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, the C.sub.3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, R.sup.3, R.sup.4, and R.sup.5 are the same or different and each is a hydrogen atom, a hydroxyl group, a C.sub.1-6 alkyl group, a C.sub.2-6 alkenyl group, wherein the C.sub.1-6 alkyl group and the C.sub.2-6 alkenyl group are optionally substituted by 1 to 3 substituents selected from the following group A, a C.sub.3-12 carbon ring group or a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and the C.sub.3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from the following group B, or R.sup.2 and R.sup.3 are optionally linked to form a C.sub.1-4 alkylene group, or R.sup.4 and R.sup.5 are optionally linked to form a C.sub.1-4 alkylene group, wherein group A is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C.sub.1-4 alkyl group, 5) OR.sup.A1 wherein R.sup.A1 is a hydrogen atom or a C.sub.1-4 alkyl group, 6) SR.sup.A2 wherein R.sup.A1 is a hydrogen atom or a C.sub.1-4 alkyl group, 7) NR.sup.A3R.sup.A4 wherein R.sup.A3 and R.sup.A4 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 8) COOR.sup.A5 wherein R.sup.A5 is a hydrogen atom or a C.sub.1-4 alkyl group, 9) NR.sup.A6COR.sup.A7 wherein R.sup.A6 is a hydrogen atom or a C.sub.1-4 alkyl group, R.sup.A7 is a C.sub.1-4 alkyl group, a C.sub.3-12 carbon ring group or a heterocyclic group, 10) NR.sup.A8COOR.sup.A9 wherein R.sup.A8 and R.sup.A9 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 11) a C.sub.3-12 carbon ring group and 12) a heterocyclic group, wherein the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, each of the C.sub.1-4 alkyl groups of the above-mentioned 4), R.sup.A1, R.sup.A2, R.sup.A3, R.sup.A4, R.sup.A5, R.sup.A6, R.sup.A7, R.sup.A8 and R.sup.A9 is optionally substituted by the same or different 1 to 3 substituents selected from the following group C, and each of the C.sub.3-12 carbon ring groups of the above-mentioned 11) and R.sup.A7, and the heterocyclic groups of 12) and R.sup.A7 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C group B is a group consisting of 1) a halogen atom, 2) a nitro group, 3) a cyano group, 4) a C.sub.1-8 alkyl group, 5) a C.sub.2-4 alkenyl group, 6) a C.sub.2-4 alkynyl group, 7) OR.sup.B1 wherein R.sup.B1 is a hydrogen atom or a C.sub.1-4 alkyl group, 8) SR.sup.B2 wherein R.sup.B2 is a hydrogen atom or a C.sub.1-4 alkyl group, 9) NR.sup.B3R wherein R.sup.B3 is a hydrogen atom, a C.sub.1-4 alkyl group, a C.sub.3-12 carbon ring group or a heterocyclic group, and R.sup.B4 is a hydrogen atom or a C.sub.1-4 alkyl group, 10) NR.sup.B5COR.sup.B6 wherein R.sup.B5 is a hydrogen atom or a C.sub.1-4 alkyl group, and R.sup.B6 is a hydrogen atom, a C.sub.1-4 alkyl group, a C.sub.3-12 carbon ring group or a heterocyclic group, 11) NR.sup.B7COOR.sup.B8 wherein R.sup.B7 and R.sup.B8 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 12) NR.sup.B9CONR.sup.B10R.sup.B11 wherein R.sup.B9, R.sup.B10 and R.sup.B11 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 13) NR.sup.B12CONR.sup.B13OR.sup.B14 wherein R.sup.B12, R.sup.B13 and R.sup.B14 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 14) NR.sup.B15SO.sub.2R.sup.B16 wherein R.sup.B15 is a hydrogen atom or a C.sub.1-4 alkyl group, and R.sup.B16 is a C.sub.1-4 alkyl group, a C.sub.3-12 carbon ring group or a heterocyclic group, 15) SO.sub.2R.sup.B17 wherein R.sup.B17 is a C.sub.1-4 alkyl group or a heterocyclic group, 16) SO.sub.2NR.sup.B18R.sup.B19 wherein R.sup.B18 and R.sup.B19 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 17) P(O)(R.sup.B20)(R.sup.B21) wherein R.sup.B20 and R.sup.B21 are the same or different and each is a C.sub.1-4 alkyl group, 18) COOR.sup.B22 wherein R.sup.B22 is a hydrogen atom or a C.sub.1-4 alkyl group, 19) CONR.sup.B23R.sup.B24 wherein R.sup.B23 and R.sup.B24 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 20) NR.sup.B25SO.sub.2NR.sup.B26R.sup.B27 wherein R.sup.B25, R.sup.B26 and R.sup.B27 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 21) NR.sup.B28SO.sub.2NR.sup.B29CONR.sup.B30R.sup.B31 wherein R.sup.B28, R.sup.B29, R.sup.B30 and R.sup.B31 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 22) a C.sub.3-12 carbon ring group and 23) a heterocyclic group wherein each of the C.sub.1-8 alkyl group of the above-mentioned 4), and the C.sub.1-4 alkyl groups for R.sup.B1 to R.sup.B31 is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, each of the C.sub.2-4 alkenyl group of 5) and the C.sub.2-4 alkynyl group of 6) is optionally substituted by the same or different 1 to 3 substituents selected from the above-mentioned group A, the heterocyclic group is a saturated or unsaturated ring group having, besides carbon atom, 1 to 4 hetero atoms selected from an oxygen atom, a nitrogen atom and a sulfur atom, and each of the C.sub.3-12 carbon ring group of the above-mentioned 22), R.sup.B3, R.sup.B6 and R.sup.B16, and the heterocyclic group of the above-mentioned 23), R.sup.B3, R.sup.B6, R.sup.B16 and R.sup.B17 is optionally substituted by the same or different 1 to 5 substituents selected from the following group C, and group C is a group consisting of 1) a halogen atom, 2) a cyano group, 3) a C.sub.1-4 alkyl group, 4) OR.sup.C1 wherein R.sup.C1 is a hydrogen atom or a C.sub.1-4 alkyl group, 5) NR.sup.C2R.sup.C3 wherein R.sup.C2 and R.sup.C3 are the same or different and each is a hydrogen atom or a C.sub.1-4 alkyl group, 6) COOR.sup.C4 wherein R.sup.C4 is a hydrogen atom or a C.sub.1-4 alkyl group and 7) an oxo group, whereupon the undesirable cell proliferation is treated.

2. The method of claim 1, wherein the compound is represented by the following formula [I-1]: ##STR00682## wherein each symbol in the formula is as defined in claim 1.

3. The method of claim 1, wherein the compound is represented by the following formula [I-2]: ##STR00683## wherein each symbol in the formula is as defined in claim 1.

4. The method of claim 1, wherein the compound is represented by the following formula [I-3]: ##STR00684## wherein each symbol in the formula is as defined in claim 1.

5. The method of claim 1, wherein R.sup.1 is a C.sub.1-6 alkyl group.

6. The method of claim 1, wherein R.sup.1 is ##STR00685## wherein m is 0, and ring Cy is a C.sub.3-12 carbon ring group, wherein the C.sub.3-12 carbon ring group is optionally substituted by 1 to 5 substituents selected from group B of claim 1.

7. The method of claim 1, wherein R.sup.1 is a C.sub.3-8 cycloalkyl group.

8. The method of claim 7, wherein R.sup.1 is a cyclopropyl group.

9. The method of claim 1, wherein R.sup.2 is ##STR00686## wherein m is 0, and ring Cy is a C.sub.3-12 carbon ring group or a heterocyclic group, wherein the C.sub.3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from group B of claim 1.

10. The method of claim 1, wherein R.sup.3 is a C.sub.1-6 alkyl group.

11. The method of claim 1, wherein R.sup.4 is a hydrogen atom.

12. The method of claim 1, wherein R.sup.5 is a hydrogen atom.

13. The method of claim 1, wherein R.sup.6 is ##STR00687## wherein m is 0, and ring Cy is a C.sub.3-12 carbon ring group or a heterocyclic group, wherein the C.sub.3-12 carbon ring group and the heterocyclic group are optionally substituted by 1 to 5 substituents selected from group B of claim 1.

14.-24. (canceled)

25. The method of claim 1, wherein the compound of formula [I] is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

26. The method of claim 25, wherein the compound is the sodium salt thereof.

27. The method of claim 25, wherein the compound is the hydrate thereof.

28. The method of claim 25, wherein the compound is the acetic acid solvate thereof.

29. The method of claim 25, wherein the compound is the dimethylsulfoxide solvate thereof.

30. The method of claim 25, wherein the compound is the ethanol solvate thereof.

31. The method of claim 25, wherein the compound is the nitromethane solvate thereof.

32. The method of claim 25, wherein the compound is the chlorobenzene solvate thereof.

33. The method of claim 25, wherein the compound is the 1-pentanol solvate thereof.

34. The method of claim 25, wherein the compound is the isopropyl alcohol solvate thereof.

35. The method of claim 25, wherein the compound is the ethylene glycol solvate thereof.

36. The method of claim 25, wherein the compound is the 3-methylbutanol solvate thereof.

37. The method of any one of claims 1-13, further comprising administering to the mammal a therapeutic amount of at least one antitumor compound that is not a compound of the formula [I].

38. The method of claim 1, further comprising administering to the mammal a therapeutic amount of at least one antitumor compound that is not a compound of the formula [I], wherein the compound of formula [I] is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

39. The method of claim 38, wherein the compound is the sodium salt thereof.

40. The method of claim 38, wherein the compound is the hydrate thereof.

41. The method of claim 38, wherein the compound is the acetic acid solvate thereof.

42. The method of claim 38, wherein the compound is the dimethylsulfoxide solvate thereof.

43. The method of claim 38, wherein the compound is the ethanol solvate thereof.

44. The method of claim 38, wherein the compound is the nitromethane solvate thereof.

45. The method of claim 38, wherein the compound is the chlorobenzene solvate thereof.

46. The method of claim 38, wherein the compound is the 1-pentanol solvate thereof.

47. The method of claim 38, wherein the compound is the isopropyl alcohol solvate thereof.

48. The method of claim 38, wherein the compound is the ethylene glycol solvate thereof.

49. The method of claim 38, wherein the compound is the 3-methylbutanol solvate thereof.

Description

EXAMPLES

Example 1-1

Synthesis of N-{3-[5-(4-bromo-2-fluoro-phenylamino)-3-cyclopropyl-8-methyl-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-d]pyrimidin-1-yl]phenyl}-methanesulfonamide

Step 1 Synthesis of 1-cyclopropyl-3-(nitrophenyl)urea

[0273] ##STR00045##

[0274] To a solution of cyclopropylamine 1 (9 g) in tetrahydrofuran (250 ml) was added 3-nitrophenylisocyanate 2 (25 g) by small portions, and the mixture was stirred at room temperature for 1 hr. The solid precipitated from the reaction mixture was filtered by suction, washed with ethyl acetate, and dried to give 1-cyclopropyl-3-(nitrophenyl)urea 3 (33 g, 99%) as a yellow solid.

Step 2 Synthesis of 1-cyclopropyl-3-(3-nitrophenyl)pyrimidine-2,4,6-trione

[0275] ##STR00046##

[0276] To 1-cyclopropyl-3-(nitrophenyl)urea 3 (33 g) obtained in Step 1 were added acetic anhydride (99 ml) and malonic acid 4 (17 g), and the mixture was stirred under heating at 110 C. for 4 hrs. The reaction mixture was concentrated under reduced pressure. Chloroform was added to the residue, and the mixture was stirred at room temperature for 10 min. Chloroform insoluble material was filtered by suction and dried to give 1-cyclopropyl-3-(3-nitrophenyl)pyrimidine-2,4,6-trione 5 (28 g, 65%) as a brown solid.

Step 3 Synthesis of 6-chloro-3-cyclopropyl-1-(3-nitrophenyl)-1H-pyrimidine-2,4-dione

[0277] ##STR00047##

[0278] To 1-cyclopropyl-3-(3-nitrophenyl)pyrimidine-2,4,6-trione 5 (28 g) obtained in Step 2 was added water (3 ml), phosphorus oxychloride (72 ml) was added dropwise by small portions with stirring, and the mixture was stirred with heating at 110 C. for 1 hr. The reaction mixture was poured into ice water by small portions, and the precipitated solid was filtered by suction. The filtrate was dissolved in chloroform (300 ml), washed with water (30 ml) and brine (30 ml), and the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:acetone=9:1) to give a 2:1 mixture (10 g, 34%) of 6-chloro-3-cyclopropyl-1-(3-nitrophenyl)-1H-pyrimidine-2,4-dione 6 and 4-chloro-3-cyclopropyl-1-(3-'s nitrophenyl)-1H-pyrimidine-2,6-dione 7 as a white solid.

Step 4 Synthesis of 3-cyclopropyl-6-methylamino-1-(3-nitrophenyl)-1H-pyrimidine-2,4-dione

[0279] ##STR00048##

[0280] To the mixture (30 g) of 6-chloro-3-cyclopropyl-1-(3-nitrophenyl)-1H-pyrimidine-2,4-dione 6 and 4-chloro-3-cyclopropyl-1-(3-nitrophenyl)-1H-pyrimidine-2,6-dione 7 obtained in Step 3 were added ethanol (300 ml) and a 40% solution (150 ml) of methylamine in methanol, and the mixture was stirred with heating at 80 C. for 4.5 hrs, ice-cooled and the precipitated solid was filtered by suction. The residue was washed with water (1 liter) and dried to give 3-cyclopropyl-6-methylamino-1-(3-nitrophenyl)-1H-pyrimidine-2,4-dione 8 (16 g, 55%) as a white solid.

Step 5 Synthesis of 3-cyclopropyl-5-hydroxy-8-methyl-1-(3-nitrophenyl)-1H, 8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0281] ##STR00049##

[0282] To 3-cyclopropyl-6-methylamino-1-(3-nitrophenyl)-1H-pyrimidine-2,4-dione 8 (16 g) obtained in Step 4 were added diphenyl ether (160 ml) and diethyl malonate 9 (40 ml), and the mixture was stirred under heating at 230 C. for 11 hrs while evaporating the resulting ethanol. The reaction mixture was purified by column chromatography (chloroform.fwdarw.chloroform:acetone-9:1) to give 3-cyclopropyl-5-hydroxy-8-methyl-1-(3-nitrophenyl)-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 10 (10 g, 51%) as a brown foamy oil.

Step 6 Synthesis of toluene-4-sulfonic acid 3-cyclopropyl-8-methyl-1-(3-nitrophenyl)-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl ester

[0283] ##STR00050##

[0284] To 3-cyclopropyl-5-hydroxy-8-methyl-1-(3-nitrophenyl)-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 10 (18 g) obtained in Step 5 were added acetonitrile (180 ml), tosyl chloride 11 (11 g) and triethylamine (8 ml), and the mixture was stirred with heating under reflux at 110 C. for 1 hr. The reaction mixture was concentrated under reduced pressure. Water (100 ml) was added to the residue and the mixture was extracted with chloroform (800 ml). The organic layer was washed with brine (50 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from chloroform:diethyl ether=1:5 to give toluene-4-sulfonic acid 3-cyclopropyl-8-methyl-1-(3-nitrophenyl)-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 12 (21 g, 82%) as a white solid.

Step 7 Synthesis of toluene-4-sulfonic acid 1-(3-aminophenyl)-3-cyclopropyl-8-methyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl Ester

[0285] ##STR00051##

[0286] To a suspension of toluene-4-sulfonic acid 3-cyclopropyl-8-methyl-1-(3-nitrophenyl)-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 12 (21 g) obtained in Step 6 in tetrahydrofuran was added stannous chloride dihydrate (45 g), and the mixture was stirred at room temperature for 4 hrs. The reaction mixture was alkalified with saturated aqueous sodium hydrogen carbonate, an insoluble inorganic product was filtered off by suction using celite as a filtration aides, and the filtrate was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:acetone=9:1) to give toluene-4-sulfonic acid 1-(3-aminophenyl)-3-cyclopropyl-8-methyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 13 (15 g, 74%) as a white solid.

Step 8 Synthesis of toluene-4-sulfonic acid 3-cyclopropyl-1-(3-methanesulfonylaminophenyl)-8-methyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl Ester

[0287] ##STR00052##

[0288] To toluene-4-sulfonic acid 1-(3-aminophenyl)-3-cyclopropyl-8-methyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 13 (5 g) obtained in Step 7 was added pyridine (40 ml), a solution of methanesulfonyl chloride 14 (0.9 ml) in chloroform (10 ml) was added dropwise with stirring under ice-cooling, and the mixture was stirred for 3 hrs in an ice bath. The reaction mixture was concentrated under reduced pressure, 2N hydrochloric acid was added and the mixture was extracted with chloroform. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resultant solid was suspended in diethyl ether:hexane-1:1, and filtered by suction to give toluene-4-sulfonic acid 3-cyclopropyl-1-(3-methanesulfonylaminophenyl)-8-methyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 15 (5.5 g, 95%) as a white solid.

Step 9 Synthesis of N-{3-[5-(4-bromo-2-fluoro-phenylamino)-3-cyclopropyl-8-methyl-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-d]pyrimidin-1-yl]phenyl}-methanesulfonamide

[0289] ##STR00053##

[0290] To toluene-4-sulfonic acid 3-cyclopropyl-1-(3-methanesulfonylaminophenyl)-8-methyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl ester 15 (3.5 g) obtained in Step 8 was added 2-fluoro-4-bromoaniline 16 (23 g), and the mixture was stirred under heating at 135 C. for 3 hrs. The reaction mixture was purified by column chromatography (chloroform:acetone=9:1) to give N-{3-[5-(4-bromo-2-fluoro-phenylamino)-3-cyclopropyl-8-methyl-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-d]pyrimidin-1-yl]phenyl}-methanesulfonamide 17 (3.0 g, 83%) as a white solid.

[0291] MS ESI m/e: 590, 592 (M+H), 588, 590 (MH).

[0292] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.08 (m, 2H), 2.66 (s, 1H), 3.02 (s, 1H), 5.36 (s, 1H), 7.13 (d, J=9.0 Hz, 1H), 7.24-7.30 (m, 2H), 7.43-7.54 (m, 3H), 7.74 (d, J=9.0 Hz, 1H), 10.00 (brs, 1H), 10.53 (brs, 1H).

Examples 1-2 to 1-343

[0293] In the same manner as in Example 1-1, the compounds of Examples 1-2 to 1-343 were obtained. The structural formulas thereof are shown in Tables 1-1 to 1-58 with Example 1-1.

TABLE-US-00001 TABLE 1-1 Ex. No. structural formula 1-1 [00054] 1-2 [00055] 1-3 [00056] 1-4 [00057] 1-5 [00058] 1-6 [00059]

TABLE-US-00002 TABLE 1-2 Ex. No. structural formula 1-7 [00060] 1-8 [00061] 1-9 [00062] 1-10 [00063] 1-11 [00064] 1-12 [00065]

TABLE-US-00003 TABLE 1-3 Ex. No. structural formula 1-13 [00066] 1-14 [00067] 1-15 [00068] 1-16 [00069] 1-17 [00070] 1-18 [00071]

TABLE-US-00004 TABLE 1-4 Ex. No. structural formula 1-19 [00072] 1-20 [00073] 1-21 [00074] 1-22 [00075] 1-23 [00076] 1-24 [00077]

TABLE-US-00005 TABLE 1-5 Ex. No. structural formula 1-25 [00078] 1-26 [00079] 1-27 [00080] 1-28 [00081] 1-29 [00082] 1-30 [00083]

TABLE-US-00006 TABLE 1-6 Ex. No. structural formula 1-31 [00084] 1-32 [00085] 1-33 [00086] 1-34 [00087] 1-35 [00088] 1-36 [00089]

TABLE-US-00007 TABLE 1-7 Ex. No. structural formula 1-37 [00090] 1-38 [00091] 1-39 [00092] 1-40 [00093] 1-41 [00094] 1-42 [00095]

TABLE-US-00008 TABLE 1-8 Ex. No. structural formula 1-43 [00096] 1-44 [00097] 1-45 [00098] 1-46 [00099] 1-47 [00100] 1-48 [00101]

TABLE-US-00009 TABLE 1-9 Ex. No. structural formula 1-49 [00102] 1-50 [00103] 1-51 [00104] 1-52 [00105] 1-53 [00106] 1-54 [00107]

TABLE-US-00010 TABLE 1-10 Ex. No. structural formula 1-55 [00108] 1-56 [00109] 1-57 [00110] 1-58 [00111] 1-59 [00112] 1-60 [00113]

TABLE-US-00011 TABLE 1-11 Ex. No. structural formula 1-61 [00114] 1-62 [00115] 1-63 [00116] 1-64 [00117] 1-65 [00118] 1-66 [00119]

TABLE-US-00012 TABLE 1-12 Ex. No. structural formula 1-67 [00120] 1-68 [00121] 1-69 [00122] 1-70 [00123] 1-71 [00124] 1-72 [00125]

TABLE-US-00013 TABLE 1-13 Ex. No. structural formula 1-73 [00126] 1-74 [00127] 1-75 [00128] 1-76 [00129] 1-77 [00130] 1-78 [00131]

TABLE-US-00014 TABLE 1-14 Ex. No. structural formula 1-79 [00132] 1-80 [00133] 1-81 [00134] 1-82 [00135] 1-83 [00136] 1-84 [00137]

TABLE-US-00015 TABLE 1-15 Ex. No. structural formula 1-85 [00138] 1-86 [00139] 1-87 [00140] 1-88 [00141] 1-89 [00142] 1-90 [00143]

TABLE-US-00016 TABLE 1-16 Ex. No. structural formula 1-91 [00144] 1-92 [00145] 1-93 [00146] 1-94 [00147] 1-95 [00148] 1-96 [00149]

TABLE-US-00017 TABLE 1-17 Ex. No. structural formula 1-97 [00150] 1-98 [00151] 1-99 [00152] 1-100 [00153] 1-101 [00154] 1-102 [00155]

TABLE-US-00018 TABLE 1-18 Ex. No. structural formula 1-103 [00156] 1-104 [00157] 1-105 [00158] 1-106 [00159] 1-107 [00160] 1-108 [00161]

TABLE-US-00019 TABLE 1-19 Ex. No. structural formula 1-109 [00162] 1-110 [00163] 1-111 [00164] 1-112 [00165] 1-113 [00166] 1-114 [00167]

TABLE-US-00020 TABLE 1-20 Ex. No. structural formula 1-115 [00168] 1-116 [00169] 1-117 [00170] 1-118 [00171] 1-119 [00172] 1-120 [00173]

TABLE-US-00021 TABLE 1-21 Ex. No. structural formula 1-121 [00174] 1-122 [00175] 1-123 [00176] 1-124 [00177] 1-125 [00178] 1-126 [00179]

TABLE-US-00022 TABLE 1-22 Ex. No. structural formula 1-127 [00180] 1-128 [00181] 1-129 [00182] 1-130 [00183] 1-131 [00184] 1-132 [00185]

TABLE-US-00023 TABLE 1-23 Ex. No. structural formula 1-133 [00186] 1-134 [00187] 1-135 [00188] 1-136 [00189] 1-137 [00190] 1-138 [00191]

TABLE-US-00024 TABLE 1-24 Ex. No. structural formula 1-139 [00192] 1-140 [00193] 1-141 [00194] 1-142 [00195] 1-143 [00196] 1-144 [00197]

TABLE-US-00025 TABLE 1-25 Ex. No. structural formula 1-145 [00198] 1-146 [00199] 1-147 [00200] 1-148 [00201] 1-149 [00202] 1-150 [00203]

TABLE-US-00026 TABLE 1-26 Ex. No. structural formula 1-151 [00204] 1-152 [00205] 1-153 [00206] 1-154 [00207] 1-155 [00208] 1-156 [00209]

TABLE-US-00027 TABLE 1-27 Ex. No. structural formula 1-157 [00210] 1-158 [00211] 1-159 [00212] 1-160 [00213] 1-161 [00214] 1-162 [00215]

TABLE-US-00028 TABLE 1-28 Ex. No. structural formula 1-163 [00216] 1-164 [00217] 1-165 [00218] 1-166 [00219] 1-167 [00220] 1-168 [00221]

TABLE-US-00029 TABLE 1-29 Ex. No. structural formula 1-169 [00222] 1-170 [00223] 1-171 [00224] 1-172 [00225] 1-173 [00226] 1-174 [00227]

TABLE-US-00030 TABLE 1-30 Ex. No. structural formula 1-175 [00228] 1-176 [00229] 1-177 [00230] 1-178 [00231] 1-179 [00232] 1-180 [00233]

TABLE-US-00031 TABLE 1-31 Ex. No. structural formula 1-181 [00234] 1-182 [00235] 1-183 [00236] 1-184 [00237] 1-185 [00238] 1-186 [00239]

TABLE-US-00032 TABLE 1-32 Ex. No. structural formula 1-187 [00240] 1-188 [00241] 1-189 [00242] 1-190 [00243] 1-191 [00244] 1-192 [00245]

TABLE-US-00033 TABLE 1-33 Ex. No. structural formula 1-193 [00246] 1-194 [00247] 1-195 [00248] 1-196 [00249] 1-197 [00250] 1-198 [00251]

TABLE-US-00034 TABLE 1-34 Ex. No. structural formula 1-199 [00252] 1-200 [00253] 1-201 [00254] 1-202 [00255] 1-203 [00256] 1-204 [00257]

TABLE-US-00035 TABLE 1-35 Ex. No. structural formula 1-205 [00258] 1-206 [00259] 1-207 [00260] 1-208 [00261] 1-209 [00262] 1-210 [00263]

TABLE-US-00036 TABLE 1-36 Ex. No. structural formula 1-211 [00264] 1-212 [00265] 1-213 [00266] 1-214 [00267] 1-215 [00268] 1-216 [00269]

TABLE-US-00037 TABLE 1-37 Ex. No. structural formula 1-217 [00270] 1-218 [00271] 1-219 [00272] 1-220 [00273] 1-221 [00274] 1-222 [00275]

TABLE-US-00038 TABLE 1-38 Ex. No. structural formula 1-223 [00276] 1-224 [00277] 1-225 [00278] 1-226 [00279] 1-227 [00280] 1-228 [00281]

TABLE-US-00039 TABLE 1-39 Ex. No. structural formula 1-229 [00282] 1-230 [00283] 1-231 [00284] 1-232 [00285] 1-233 [00286] 1-234 [00287]

TABLE-US-00040 TABLE 1-40 Ex. No. structural formula 1-235 [00288] 1-236 [00289] 1-237 [00290] 1-238 [00291] 1-239 [00292] 1-240 [00293]

TABLE-US-00041 TABLE 1-41 Ex. No. structural formula 1-241 [00294] 1-242 [00295] 1-243 [00296] 1-244 [00297] 1-245 [00298] 1-246 [00299]

TABLE-US-00042 TABLE 1-42 Ex. No. structural formula 1-247 [00300] 1-248 [00301] 1-249 [00302] 1-250 [00303] 1-251 [00304] 1-252 [00305]

TABLE-US-00043 TABLE 1-43 Ex. No. structural formula 1-253 [00306] 1-254 [00307] 1-255 [00308] 1-256 [00309] 1-257 [00310] 1-258 [00311]

TABLE-US-00044 TABLE 1-44 Ex. No. structural formula 1-259 [00312] 1-260 [00313] 1-261 [00314] 1-262 [00315] 1-263 [00316] 1-264 [00317]

TABLE-US-00045 TABLE 1-45 Ex. No. structural formula 1-265 [00318] 1-266 [00319] 1-267 [00320] 1-268 [00321] 1-269 [00322] 1-270 [00323]

TABLE-US-00046 TABLE 1-46 Ex. No. structural formula 1-271 [00324] 1-272 [00325] 1-273 [00326] 1-274 [00327] 1-275 [00328] 1-276 [00329]

TABLE-US-00047 TABLE 1-47 Ex. No. structural formula 1-277 [00330] 1-278 [00331] 1-279 [00332] 1-280 [00333] 1-281 [00334] 1-282 [00335]

TABLE-US-00048 TABLE 1-48 Ex. No. structural formula 1-283 [00336] 1-284 [00337] 1-285 [00338] 1-286 [00339] 1-287 [00340] 1-288 [00341]

TABLE-US-00049 TABLE 1-49 Ex. No. structural formula 1-289 [00342] 1-290 [00343] 1-291 [00344] 1-292 [00345] 1-293 [00346] 1-294 [00347]

TABLE-US-00050 TABLE 1-50 Ex. No. structural formula 1-295 [00348] 1-296 [00349] 1-297 [00350] 1-298 [00351] 1-299 [00352] 1-300 [00353]

TABLE-US-00051 TABLE 1-51 Ex. No. structural formula 1-301 [00354] 1-302 [00355] 1-303 [00356] 1-304 [00357] 1-305 [00358] 1-306 [00359]

TABLE-US-00052 TABLE 1-52 Ex. No. structural formula 1-307 [00360] 1-308 [00361] 1-309 [00362] 1-310 [00363] 1-311 [00364] 1-312 [00365]

TABLE-US-00053 TABLE 1-53 Ex. No. structural formula 1-313 [00366] 1-314 [00367] 1-315 [00368] 1-316 [00369] 1-317 [00370] 1-318 [00371]

TABLE-US-00054 TABLE 1-54 Ex. No. structural formula 1-319 [00372] 1-320 [00373] 1-321 [00374] 1-322 [00375]

TABLE-US-00055 TABLE 1-55 Ex. No. structural formula 1-323 [00376] 1-324 [00377] 1-325 [00378] 1-326 [00379] 1-327 [00380] 1-328 [00381]

TABLE-US-00056 TABLE 1-56 Ex. No. structural formula 1-329 [00382] 1-330 [00383] 1-331 [00384] 1-332 [00385]

TABLE-US-00057 TABLE 1-57 Ex. No. structural formula 1-333 [00386] 1-334 [00387] 1-335 [00388] 1-336 [00389] 1-337 [00390] 1-338 [00391]

TABLE-US-00058 TABLE 1-58 Ex. No. structural formula 1-339 [00392] 1-340 [00393] 1-341 [00394] 1-342 [00395] 1-343 [00396]

Example 2-1

Synthesis of 5-(4-chloro-phenylamino)-8-methyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione

Step 1 Synthesis of 1,3-diphenyl-pyrimidine-2,4,6-trione

[0294] ##STR00397##

[0295] Acetic anhydride (290 ml) was added to 1,3-diphenylurea 18 (148 g), malonic acid 4 (81.6 g) was added under a nitrogen atmosphere, and the mixture was stirred at 90 C. for 3 hrs. The mixture was stirred at 100 C. for 1.5 hrs and allowed to cool to room temperature. The reaction mixture was concentrated under reduced pressure. Ethanol (500 ml) was added to the residue, and the mixture was stirred at 90 C. When the mixture was cooled to 40 C., the crystals were collected by filtration, washed with ethanol and dried to give 1,3-diphenyl-pyrimidine-2,4,6-trione 19 (78.0 g, yield 40%).

Step 2 Synthesis of 6-chloro-1,3-diphenyl-1H-pyrimidine-2,4-dione

[0296] ##STR00398##

[0297] To 1,3-diphenyl-pyrimidine-2,4,6-trione 19 (78.0 g) obtained in Step 1 was added water (16 ml). Phosphorus oxychloride (422 ml) was added dropwise under stirring at room temperature over 50 min. After the completion of the dropwise addition, the mixture was stirred under heating at 110 C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was added to ice water by small portions and the mixture was stirred at room temperature and extracted with ethyl acetate. The organic layer was washed with brine and saturated aqueous sodium hydrogen carbonate, and dried over anhydrous sodium sulfate. Anhydrous sodium sulfate was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=2:1-3:2) to give 6-chloro-1,3-diphenyl-1H-pyrimidine-2,4-dione 20 (61.5 g, yield 74%) as pale-yellow crystals.

Step 3 Synthesis of 6-methylamino-1,3-diphenyl-1H-pyrimidine-2,4-dione

[0298] ##STR00399##

[0299] In the same manner as in Step 4 of Example 1-1 and using 6-chloro-1,3-diphenyl-1H-pyrimidine-2,4-dione 20 (5.0 g) obtained in Step 2, ethanol (25 ml), a 40% solution (21.7 ml) of methylamine in methanol, 6-methylamino-1,3-diphenyl-1H-pyrimidine-2,4-dione 21 (4.42 g, yield 90%) was obtained as colorless crystals.

Step 4 Synthesis of ethyl (6-methylamino-2,4-dioxo-1,3-diphenyl-1,2,3,4-tetrahydro-pyrimidine-5-thiocarbonyl)-carbamate

[0300] ##STR00400##

[0301] To 6-methylamino-1,3-diphenyl-1H-pyrimidine-2,4-dione 21 (1.18 g) obtained in Step 3 was added N,N-dimethylformamide (5.9 ml), ethyl isothiocyanate formate 22 (0.52 ml) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 1 hr. Water (30 ml) was added to the reaction mixture, and the crystals were collected by filtration and washed with water to give crude ethyl (6-methylamino-2,4-dioxo-1,3-diphenyl-1,2,3,4-tetrahydro-pyrimidine-5-thiocarbonyl)-carbamate 23 (1.68 g) as pale-yellow crystals, which were used for the next step without purification.

Step 5 Synthesis of 5-mercapto-8-methyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione

[0302] ##STR00401##

[0303] To crude ethyl (6-methylamino-2,4-dioxo-1,3-diphenyl-1,2,3,4-tetrahydro-pyrimidine-5-thiocarbonyl)-carbamate 23 (1.58 g) obtained in Step 4 was added N,N-dimethylformamide (8.4 ml), triethylamine (0.63 ml) was added under a nitrogen atmosphere, and the mixture was stirred at room temperature for 30 min. Water (25 ml) was added, the mixture was stirred, 1N hydrochloric acid (5.0 ml) was added, and the mixture was stirred at room temperature for 1 hr. The crystals were collected by filtration, washed with water and dried to give crude 5-mercapto-8-methyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione 24 (1.53 g, over weight) as yellow crystals, which were used for the next step without purification.

Step 6 Synthesis of 8-methyl-5-methylsulfanyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione

[0304] ##STR00402##

[0305] To crude 5-mercapto-8-methyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione 24 (100 mg) obtained in Step 5 was added N,N-dimethylformamide (0.5 ml). Under a nitrogen atmosphere, potassium carbonate (44 mg) and methyl iodide 25 (20 l) were successively added, and the mixture was stirred at room temperature for 3 hrs. Water was added, and the mixture was extracted with chloroform. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. Anhydrous sodium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=4:1-3:1) to give 8-methyl-5-methylsulfanyl-1,3-diphenyl-1H, 8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione 26 (91 15 mg, yield 89%) as brown crystals.

Step 7 Synthesis of 5-(4-chloro-phenylamino)-8-methyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione

[0306] ##STR00403##

[0307] To 8-methyl-5-methylsulfanyl-1,3-diphenyl-1H,8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione 26 (149 mg) obtained in Step 6 was added toluene (2 ml), 4-chloroaniline 27 (97 mg) was added, and the mixture was stirred under reflux for 3.5 hrs. After allowing to cool to room temperature, diethyl ether was added. The crystals were collected by filtration, washed with diethyl ether and dried to give 5-(4-chloro-phenylamino)-8-methyl-1,3-diphenyl-H, 8H-pyrimido[4,5-d]pyrimidine-2,4,7-trione 28 (94 mg, yield 53%) as colorless crystals.

[0308] MS ESI m/e: 472 (M+H), 470 (MH).

[0309] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.68 (s, 3H), 7.34-7.39 (m, 2H), 7.41-7.61 (m, 10H), 7.80-7.87 (m, 2H), 11.34 (s, 1H).

Example 2-2

[0310] In the same manner as in Example 2-1, the compounds of Example 2-2 were obtained. The structural formulas thereof are shown in Table 2-1 with Example 2-1. Table 2-1

TABLE-US-00059 TABLE 2-1 Ex. No. structural formula 2-1 [00404] 2-2 [00405]

Example 3-1

Synthesis of 5-(4-bromo-phenylamino)-3-cyclopropyl-6,8-dimethyl-1-phenylamino-1H,6H-pyrido[4,3-d]pyrimidine-2,4,7-trione

Step 1 Synthesis of 1-(4-bromo-phenyl)-3-cyclopropyl-urea

[0311] ##STR00406##

[0312] Under a nitrogen atmosphere, tetrahydrofuran (80 ml) was added to 4-bromophenyl isocyanate 30 (10.0 g), and a solution of cyclopropylamine 1 (3.17 g) in tetrahydrofuran (20 ml) was added dropwise with stirring under ice-cooling. After the completion of the dropwise addition, the mixture was stirred at room temperature for 3 hrs, and the reaction mixture was concentrated under reduced pressure. Diethyl ether-hexane [1:1 (volume ratio), 100 ml] was added to the residue and, after stirring, the crystals were collected by filtration and dried to give 1-(4-bromo-phenyl)-3-cyclopropyl-urea 31 (12.9 g, over weight) as colorless crystals, which were used for the next step without purification.

Step 2 Synthesis of 1-(4-bromo-phenyl)-3-cyclopropyl-pyrimidine-2,4,6-trione

[0313] ##STR00407##

[0314] To 1-(4-bromo-phenyl)-3-cyclopropyl-urea 31 (12.9 g) obtained in Step 1 was added acetic anhydride (25.8 ml), malonic acid 4 (5.79 g) was added under a nitrogen atmosphere, and the mixture was stirred at 100 C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was concentrated under reduced pressure. Diethyl ether-ethanol [4:1 (volume ratio), 100 ml] was added to the residue and, after stirring, the crystals were collected by filtration and dried to give 1-(4-bromo-phenyl)-3-cyclopropyl-pyrimidine-2,4,6-trione 32 (11.9 g, yield 73%) as pale-yellow crystals.

Step 3 Synthesis of 1-(4-bromo-phenyl)-6-chloro-3-cyclopropyl-1H-pyrimidine-2,4-dione

[0315] ##STR00408##

[0316] To 1-(4-bromo-phenyl)-3-cyclopropyl-pyrimidine-2,4,6-trione 32 (11.8 g) obtained in Step 2 was added water (1.31 ml) and phosphorus oxychloride (17.0 ml) was added dropwise with stirring at room temperature. After the completion of the dropwise addition, the mixture was stirred at 110 C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was added to ice water by small portions and the mixture was stirred. The mixture was stirred at room temperature and extracted with chloroform. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate-2:1.fwdarw.chloroform:acetone=30:1) to give a 1:1.4 mixture (11.6 g, yield 93%) of 1-(4-bromo-phenyl)-6-chloro-3-cyclopropyl-1H-pyrimidine-2,4-dione 33 and 3-(4-bromo-phenyl)-6-chloro-1-cyclopropyl-1H-pyrimidine-2,4,-dione 34 as a pale-yellow foamy oil.

Step 4 Synthesis of 1-(4-bromo-phenyl)-3-cyclopropyl-6-methylamino-1H-pyrimidine-2,4-dione

[0317] ##STR00409##

[0318] A 1:1.3 mixture (5.34 g, yield 78%) of 1-(4-bromo-phenyl)-3-cyclopropyl-6-methylamino-1H-pyrimidine-2,4-dione 35 and 3-(4-bromo-phenyl)-1-cyclopropyl-6-methylamino-1H-pyrimidine-2,4-dione 36 was obtained as colorless crystals in the same manner as the synthesis of compound 8 and using a 1:1.4 mixture (7.00 g) of 1-(4-bromo-phenyl)-6-chloro-3-cyclopropyl-1H-pyrimidine-2,4-dione 33 and 3-(4-bromo-phenyl)-6-chloro-1-cyclopropyl-1H-pyrimidine-2,4,-dione 34 obtained in Step 3, ethanol (20.9 ml) and a 40% solution (10.5 ml) of methylamine in methanol.

Step 5 Synthesis of 1-(4-bromo-phenyl)-3-cyclopropyl-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0319] ##STR00410##

[0320] 1-(4-Bromo-phenyl)-3-cyclopropyl-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 38 (0.40 g, yield 32%) was obtained as pale-yellow crystals in the same manner as in Step 5 of Example 1-1 and using a 1:1.3 mixture (1.00 g) of 1-(4-bromo-phenyl)-3-cyclopropyl-6-methylamino-1H-pyrimidine-2,4-dione 35 and 3-(4-bromo-phenyl)-1-cyclopropyl-6-methylamino-1H-pyrimidine-2,4-dione 36 obtained in Step 4, 2-methyl-diethyl malonate 37 (2.56 ml) and diphenyl ether (1.49 g).

Step 6 Synthesis of toluene-4-sulfonic acid 1-(4-bromo-phenyl)-3-cyclopropyl-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl Ester

[0321] ##STR00411##

[0322] To 1-(4-bromo-phenyl)-3-cyclopropyl-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 38 (400 mg) obtained in Step 5 was added acetonitrile (8.0 ml), tosyl chloride 11 (458 mg) and triethylamine (0.34 ml) were added under a nitrogen atmosphere, and the mixture was stirred under reflux for 30 hrs. After allowing to cool to room temperature, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:acetone-25:1-20:1) to give toluene-4-sulfonic acid 1-(4-bromo-phenyl)-3-cyclopropyl-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 39 (407 mg, yield 74%) as ocher crystals.

Step 7 Synthesis of 1-(4-bromo-phenyl)-3-cyclopropyl-6,8-dimethyl-5-phenylamino-1H, 8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0323] ##STR00412##

[0324] To toluene-4-sulfonic acid 1-(4-bromo-phenyl)-3-cyclopropyl-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 39 (100 mg) obtained in Step 6 was added aniline 40 (0.64 ml), and the mixture was stirred at 150 C. for 2.5 hrs. After allowing to cool to room temperature, diethyl ether-hexane [1:1 (volume ratio), 30 ml] was added to the reaction mixture, and the crystals were collected by filtration. The obtained crystals were purified by column chromatography (chloroform:acetone-15:1) to give 1-(4-bromo-phenyl)-3-cyclopropyl-6,8-dimethyl-5-phenylamino-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 41 (81 mg, yield 93%) as pale-yellow crystals.

Step 8 Synthesis of 5-(4-bromo-phenylamino)-3-cyclopropyl-6,8-dimethyl-1-phenylamino-1H,6H-pyrido[4,3-d]pyrimidine-2,4,7-trione

[0325] ##STR00413##

[0326] To 1-(4-bromo-phenyl)-3-cyclopropyl-6,8-dimethyl-5-phenylamino-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 41 (78 mg) obtained in Step 7 was added chloroform-methanol [1:1 (volume ratio), 2.0 ml], potassium carbonate (22 mg) was added, and the mixture was stirred at room temperature for 10 hrs. The mixture was further stirred under reflux for 3 hrs, and allowed to cool to room temperature. The mixture was concentrated under reduced pressure and purified by column chromatography (chloroform:acetone-50:l) to give 5-(4-bromo-phenylamino)-3-cyclopropyl-6,8-dimethyl-1-phenylamino-1H,6H-pyrido[4,3-d]pyrimidine-2,4,7-trione 42 (23 mg, yield 26%) as colorless crystals.

[0327] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0328] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.77-0.82 (m, 2H), 1.09-1.15 (m, 2H), 1.36 (s, 3H), 2.72-2.74 (m, 1H), 3.20 (s, 3H), 6.86 (d, 2H), 7.28-7.32 (m, 2H), 7.34-7.51 (m, 5H), 11.36 (s, 1H).

Example 3-7

Synthesis of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide

Step 1 Synthesis of N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide

[0329] ##STR00414##

[0330] To trifluoromethanesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 43 (30.0 g) obtained in the same manner in Example 4-2, Step 6 to be mentioned later and N-(3-aminophenyl)methanesulfonamide 44 (10.9 g) were added N,N-dimethylacetamide (60.0 ml) and 2,6-lutidine (6.82 ml), and the mixture was stirred at 130 C. for 3.5 hrs. After allowing to cool to room temperature, methanol (60 ml) was added with stirring and the mixture was stirred for 2 hrs. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide 45 (30.5 g, yield 96%) as colorless crystals.

Step 2 Synthesis of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide

[0331] ##STR00415##

[0332] Under a nitrogen atmosphere, to a solution (18.5 g) of 28% sodium methoxide in methanol was added tetrahydrofuran (284 ml), N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide 45 (28.4 g) obtained in Step 1 was added, and the mixture was stirred at room temperature for 1 hr. Acetic acid (12.5 ml) was added, and the mixture was stirred at room temperature for 1 hr and concentrated under reduced pressure. A 9:1 mixed solvent (426 mL) of 1-butanol and water was added to the obtained solid, and the mixture was stirred with heating under reflux for 3 hrs. The mixture was allowed to return to room temperature and stirred overnight, and the crystals were collected by filtration and dried. A 9:1 mixed solvent (426 mL) of 1-butanol and water was added again to the obtained crystals, and the mixture was stirred with heating under reflux for 3 hrs. The mixture was allowed to return to room temperature and stirred overnight. The crystals were collected by filtration and washed with a 9:1 mixed solvent of methanol and water and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide 46 (26.35 g, yield 93%) as white crystals.

[0333] MS ESI m/e: 652 (M+H), 650 (MH).

[0334] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.25 (s, 3H), 2.57-2.67 (m, 1H), 3.01 (s, 3H), 3.08 (s, 3H), 6.92(t, J=9.0 Hz, 1H), 7.09-7.14 (m, 1H), 7.20-7.26 (m, 2H), 7.37-7.45 (m, 1H), 7.52-7.58 (m, 1H), 7.79(dd, J=1.8, 9.0 Hz, 1H), 9.89(s, 1H), 11.08 (s, 1H).

Example 3-2 to 3-6, 3-8 and 3-9

[0335] In the same manner as in Examples 3-1 and 3-7, the compounds of Examples 3-2 to 3-6, 3-8 and 3-9 were obtained. The structural formulas thereof are shown in Table 3-1 to 3-2 with Examples 3-1 and 3-7.

TABLE-US-00060 TABLE 3-1 Ex. No. structural formula 3-1 [00416] 3-2 [00417] 3-3 [00418] 3-4 [00419] 3-5 [00420] 3-6 [00421]

TABLE-US-00061 TABLE 3-2 Ex. No. structural formula 3-7 [00422] 3-8 [00423] 3-9 [00424]

Example 3-10

[0336] By treating N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide 46 according to conventional methods, sodium salt and potassium salt thereof were obtained.

N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide Sodium Salt

[0337] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.47 (brs, 2H), 0.70-0.90 (m, 2H), 1.23 (s, 3H), 2.35 (brs, 1H), 2.82 (s, 3H), 3.22 (s, 3H), 6.69 (t, J=8.8 Hz, 1H), 6.81 (d, J=8.1 Hz, 1H), 6.98 (s, 1H), 7.02 (d, J=8.8 Hz, 1H), 7.10-7.30 (m, 2H), 7.38 (d, J=9.2 Hz, 1H), 10.22 (brs, 1H).

[0338] MS (ESI) m/z 652 [MH].sup.+.

N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide Potassium Salt

Example 4-1

N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

Step 1 Synthesis of 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)urea

[0339] ##STR00425##

[0340] Under a nitrogen atmosphere, to N,N-carbonyldiimidazole (39.9 g) were added N,N-dimethylformamide (200 ml) and triethylamine (34.3 ml) and a solution of 2-fluoro-4-iodoaniline 47 (48.5 g) in N,N-dimethylformamide (50 ml) was added dropwise with stirring under ice-cooling. After the completion of the dropwise addition, the mixture was stirred at room temperature for 18 hrs. The reaction mixture was ice-cooled, and cyclopropylamine (21.3 ml) was added dropwise. The reaction mixture was stirred at room temperature for 1 hr and added dropwise to water-toluene [2:1 (volume ratio), 750 ml] with stirring. The precipitated crystals were collected by filtration and dried to give 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)urea 48 (61.3 g, yield 93.4%) as colorless crystals.

Step 2 Synthesis of 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)pyrimidine-2,4,6-trione

[0341] ##STR00426##

[0342] To 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)urea 48 (61.0 g) obtained in Step 1 and malonic acid 4 (19.9 g) were added acetic anhydride (300 ml) and acetyl chloride (27.2 ml), and the mixture was stirred under a nitrogen atmosphere at 60 C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was added dropwise to water-toluene [2:1 (volume ratio), 900 ml] with stirring. The precipitated crystals were collected by filtration and dried to give 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)pyrimidine-2,4,6-trione 49 (60.9 g, yield 82%) as pale-yellow crystals.

Step 3 Synthesis of 6-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione

[0343] ##STR00427##

[0344] To 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-pyrimidine-2,4,6-trione 49 (59.0 g) obtained in Step 2 were added phosphorus oxychloride (85.0 ml) and dimethylaniline (29.0 ml), and water (8.3 ml) was added dropwise to the mixture at room temperature with stirring. After the completion of the dropwise addition, the mixture was stirred with heating at 110 C. for 1 hr. After allowing to cool to room temperature, the reaction mixture was added dropwise to ice water-toluene [2:1 (volume ratio), 900 ml] with stirring. The mixture was stirred at room temperature for 1 hr. The organic layer was separated, and washed successively with water (300 ml) and brine (300 ml). Anhydrous magnesium sulfate and activated carbon were added and the mixture was stirred. Anhydrous magnesium sulfate and activated carbon were filtered off, and the filtrate was concentrated under reduced pressure to give a 1:2 mixture (62.9 g) of 6-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 50 and 6-chloro-1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 51 as a yellow foamy oil, which was used for the next step without purification.

Step 4 Synthesis of 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4-dione

[0345] ##STR00428##

[0346] To a 1:2 mixture (62.9 g) of 6-chloro-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 50 and 6-chloro-1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 51 obtained in Step 3 were added methanol (189 ml) and a solution (126 ml) of 40% methylamine in methanol, and the mixture was stirred at room temperature for 2 hrs. The precipitated crystals were filtered off and the filtrate was concentrated under reduced pressure. The residue was extracted with chloroform (200 ml) and water (200 ml), and the organic layer was washed with brine (200 ml) and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off and the filtrate was concentrated under reduced pressure to give a 2:1 mixture (34.55 g) of 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4-dione 52 and 1-cyclopropyl-3-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4,-dione 53 as yellow crystals, which were used for the next step without purification.

Step 5 Synthesis of 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0347] ##STR00429##

[0348] To a 2:1 mixture (34.6 g) of 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6-methylamino-1H-pyrimidine-2,4-dione 52 and 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl) 6-methylamino-1H-pyrimidine-2,4,-dione 53 obtained in Step 4, and 2-methylmalonic acid 54 (10.2 g) was added acetic anhydride (173 ml), and the mixture was stirred at 100 C. for 2 hrs. After allowing to cool to room temperature, the reaction mixture was concentrated under reduced pressure. Acetone (104 ml) was added to the residue, and the mixture was stirred with heating under reflux for 30 min. After allowing to cool to room temperature, the precipitated crystals were collected by filtration and dried to give 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55 (15.1 g, yield from 48, 21%) as colorless crystals.

Step 6 Synthesis of trifluoromethanesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester

[0349] ##STR00430##

[0350] Under a nitrogen atmosphere, to 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55 (33.0 g) obtained in Step 5 were added chloroform (165 ml) and 2,6-lutidine (10.4 ml), and trifluoromethanesulfonic anhydride 56 (14.4 ml) was added dropwise under ice-cooling with stirring. After the completion of the dropwise addition, the mixture was stirred at same temperature for 30 min and at room temperature for 2 hrs. The reaction mixture was washed successively with aqueous sodium hydrogen carbonate (165 ml), 1N hydrochloric acid (165 ml) and brine (165 ml) and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off and the filtrate was concentrated under reduced pressure. 2-Propanol (198 ml) was added to the residue, and the mixture was stirred with heating under reflux, and allowed to return to room temperature. The crystals were collected by filtration and dried to give trifluoromethanesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 43 (31.9 g, yield 93%) as colorless crystals.

Step 7 Synthesis of N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}acetamide

[0351] ##STR00431##

[0352] To trifluoromethanesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 43 (25.0 g) obtained in Step 6 and 3-aminoacetanilide 57 (7.33 g) were added N,N-dimethylacetamide (50.0 ml) and 2,6-lutidine (5.68 ml), and the mixture was stirred at 130 C. for 5 hrs. After allowing to cool to room temperature, methanol-water [1:2 (volume ratio), 150 ml] was added with stirring. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}acetamide 58 (24.8 g, yield 99%) as colorless crystals.

Step 8 Synthesis of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide

[0353] ##STR00432##

[0354] Under a nitrogen atmosphere, to a solution (1.57 g) of 28% sodium methoxide in methanol was added tetrahydrofuran (40 ml), N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}acetamide 58 (5.00 g) obtained in Step 7 was added, and the mixture was stirred at room temperature for 4 hrs. Acetic acid (0.56 ml) was added, and the mixture was stirred at room temperature for 30 min. Water (40 ml) was added and the mixture was further stirred for 1 hr. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 59 (4.75 g, yield 95%) as colorless crystals.

[0355] MS ESI m/e: 616 (M+H), 614 (MH).

[0356] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.36(t, J=8.2 Hz, 1H), 7.52-7.63 (m, 3H), 7.79 (dd, J=2.0, 10.4 Hz, 1H), 10.10 (s, 1H), 11.08 (s, 1H).

Example 4-1 (Alternative Method)

N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

Step 1 Synthesis of 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea

[0357] ##STR00433##

[0358] Under a nitrogen atmosphere, to N,N-carbonyldiimidazole (82.1 g) were added N,N-dimethylformamide (400 ml) and triethylamine (70.5 ml), and a solution of 2-fluoro-4-iodoaniline 47 (100 g) in N,N-dimethylformamide (100 ml) was added dropwise under ice-cooling. After the completion of the dropwise addition, the mixture was stirred at room temperature for 5 hrs. The reaction mixture was ice-cooled, and cyclopropylamine (44.0 ml) was added dropwise. The mixture was stirred at room temperature for 1 hr, and the reaction mixture was added dropwise to water-toluene [2:1 (volume ratio), 1500 ml] with stirring. The precipitated crystals were collected by filtration and dried to give 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea 48 (129 g, yield 95.5%) as colorless crystals.

Step 2 Synthesis of 1-(2-cyano-acetyl)-1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea

[0359] ##STR00434##

[0360] Under a nitrogen atmosphere, to 1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea 48 (167 g) and cyanoacetic acid 73 (80.0 g), was added N,N-dimethylformamide (836 ml), and methanesulfonyl chloride (72.8 ml) was added dropwise with stirring at room temperature. The mixture was stirred at room temperature for 4 hrs. The reaction mixture was cooled with water, and water-isopropanol [2:1 (volume ratio), 1670 ml] was added dropwise. The mixture was stirred under water-cooling for 1 hr, and the precipitated crystals were collected by filtration and dried to give 1-(2-cyano-acetyl)-1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea 74 (192 g).

Step 3 Synthesis of 6-amino-3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-1H-pyrimidine-2,4-dione

[0361] ##STR00435##

[0362] To 1-(2-cyano-acetyl)-1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-urea 74 (192 g) were added water (962 ml) and 2N aqueous sodium hydroxide solution (24.9 ml), and the mixture was stirred with heating at 80 C. for 1 hr. After allowing to cool to room temperature, the crystals were collected by filtration and dried to give 6-amino-3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-1H-pyrimidine-2,4-dione 75 (178 g, yield from 48, 88%) as pale-yellow crystals.

Step 4 Synthesis of N-[1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl]-N,N-dimethyl-formamidine

[0363] ##STR00436##

[0364] Under a nitrogen atmosphere, to 6-amino-3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-1H-pyrimidine-2,4-dione 75 (178 g) were added N,N-dimethylformamide (356 ml) and N,N-dimethylformamide dimethylacetal (178 ml), and the mixture was stirred at room temperature for 2 hrs. Isopropanol (178 ml) was added with stirring at room temperature, and water (1068 ml) was added dropwise. The mixture was stirred at room temperature for 2 hrs, and the precipitated crystals were collected by filtration and dried to give N-[1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl]-N,N-dimethyl-formamidine 76 (188 g, yield 92%) as yellow crystals.

Step 5 Synthesis of 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6-methylamino-1H-pyrimidine-2,4-dione

[0365] ##STR00437##

[0366] Under a nitrogen atmosphere, to t-butanol-ethanol [2:1 (volume ratio), 250 ml] was added sodium borohydride (6.41 g), and the mixture was stirred at room temperature for 1 hr. Under water-cooling, N-[1-cyclopropyl-3-(2-fluoro-4-iodo-phenyl)-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidin-4-yl]-N,N-dimethyl-formamidine 76 (50.0 g) was added, and the mixture was stirred for 2.5 hrs. Under water-cooling, water (225 ml) and 10% aqueous citric acid solution (175 ml) were successively added dropwise, and the mixture was stirred for 3 hrs. The precipitated crystals were collected by filtration and dried to give crude crystals (34.5 g, LC purity 91%) of 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6-methylamino-1H-pyrimidine-2,4-dione 52, which were used for the next reaction without purification.

Step 6 Synthesis of 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0367] ##STR00438##

[0368] Under a nitrogen atmosphere, to 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6-methylamino-1H-pyrimidine-2,4-dione 52 (34.4 g) and 2-methyl-malonic acid 54 (15.2 g) was added acetic anhydride (34.4 ml), and the mixture was stirred with heating at 100 C. for 3 hrs. After allowing to cool to 50C, acetone (68.8 ml) was added dropwise, and the mixture was stirred as it was for 30 min. Water (172 ml) was further added dropwise, and the mixture was stirred for 1 hr. After allowing to cool to room temperature with stirring, the precipitated crystals were collected by filtration and dried to give crude crystals (37.7 g, LC purity 91%) of 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55. Isopropanol (92.0 ml) was added to the obtained crude crystals (30.7 g), and the mixture was stirred at room temperature for 4 hrs. The crystals were collected by filtration and dried to give 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55 (25.9 g, yield from 76, 58%) as pale-yellow crystals.

Step 7 Synthesis of p-toluenesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl Ester

[0369] ##STR00439##

[0370] Under a nitrogen atmosphere, to 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-5-hydroxy-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 55 (23.9 g) was added acetonitrile (167 ml), and the mixture was stirred under ice-cooling. Triethylamine (11.0 ml) and trimethylamine hydrochloride (2.37 g) were added, and a solution of p-toluenesulfonyl chloride 11 (12.3 g) in acetonitrile (72.0 ml) was added dropwise. The mixture was stirred under ice-cooling for 1 hr, and stirred at room temperature for 3 hrs. Methanol (239 ml) was added, and the mixture was stirred at room temperature for 1 hr. The crystals were collected by filtration and dried to give p-toluenesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 77 (28.7 g, yield 91%) as colorless crystals.

Step 8 Synthesis of N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide

[0371] ##STR00440##

[0372] To p-toluenesulfonic acid 3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 77 (28.0 g) and 3-aminoacetanilide 57 (13.2 g) were added N,N-dimethylacetamide (84.0 ml) and 2,6-lutidine (15.3 ml), and the mixture was stirred at 130 C. for 4 hrs. After allowing to cool with stirring, methanol (196 ml) was added dropwise, and the mixture was stirred at room temperature. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide 58 (25.2 g, yield 93%) as colorless crystals.

Step 9 Synthesis of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

[0373] ##STR00441##

[0374] Under a nitrogen atmosphere, to N-{3-[3-cyclopropyl-1-(2-fluoro-4-iodo-phenyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-zs hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide 58 (45.7 g) was added tetrahydrofuran (366 ml), and a solution (15.7 g) of 28% sodium methoxide in methanol was added dropwise with stirring at room temperature and the mixture was stirred at room temperature for 4 hrs. Acetic acid (5.61 ml) was added, and the mixture was stirred at room temperature for 30 min. With stirring at 70 C. in an oil bath, water (366 ml) was added dropwise, and the mixture was stirred for 1 hr. After allowing to cool with stirring, the crystals were collected by filtration and dried to give crystal 1 (46.0 g) of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 59.

[0375] N,N-Dimethylacetamide (184 ml) was added to crystal 1 (46.0 g), and the mixture was stirred with heating at 130 C. After complete dissolution, the solution was filtered by suction using with paper (5B), and washed with N,N-dimethylacetamide (92.0 ml). The filtrate was stirred under heating at 130 C., 1-butanol (138 ml) and water (96.0 ml) were successively added dropwise, and the mixture was stirred for 30 min. Water (46.0 ml) was further added dropwise, and the mixture was stirred for 30 min allowed to cool with stirring. The crystals were collected by filtration and dried to give crystal 2 (41.7 g) of N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 59 as colorless crystals.

[0376] To crystal 2 (41.5 g) was added 1-butanol-water [19:1 (volume ratio), 415 ml], and the mixture was stirred at 130 C. for 18 hrs. After allowing to cool with stirring, the crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 59 (40.7 g, yield 89%) as colorless crystals.

Example 4-3

N-{3-[3-cyclopropyl-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide

Step 1 Synthesis of N-{3-[3-cyclopropyl-5-(2-fluoro-4-trimethylsilanylethynylphenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide

[0377] ##STR00442##

[0378] Under a nitrogen atmosphere, to N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 59 (14.5 g) obtained in Example 4-1 were added chloroform (145 ml), trimethylsilylacetylene 60 (4.99 ml) and triethylamine (13.1 ml). Copper(I) iodide (22 mg) and bis(triphenylphosphine)palladium(II)chloride (83 mg) were added, and the mixture was stirred at room temperature for 20 hrs. The mixture was concentrated under reduced pressure, activated carbon (435 mg) and methanol (435 ml) were added to the residue, and the mixture was stirred with heating at reflux for 2 hrs. Activated carbon was filtered off while it was hot, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:acetone=10:1-4:1) and toluene-acetone [5:1 (volume ratio), 87 ml] was added to the obtained crystals. The mixture was stirred at 80 C. for 1 hr. After allowing to cool to room temperature, the crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(2-fluoro-4-trimethylsilanylethynylphenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 61 (12.9 g, yield 93%) as pale-yellow crystals.

Step 2 Synthesis of N-{3-[3-cyclopropyl-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide

[0379] ##STR00443##

[0380] To N-{3-[3-cyclopropyl-5-(2-fluoro-4-trimethylsilanylethynylphenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 61 (1.00 g) obtained in Step 2 and potassium carbonate (236 mg) was added methanol/N,N-dimethylformamide [1:1 (volume ratio), 10.0 ml], and the mixture was stirred at room temperature for 20 hrs. The mixture was neutralized with 2N hydrochloric acid, water (10.0 ml) was added, and the mixture was stirred at room temperature for 1 hr. The crystals were collected by filtration and dried to give N-{3-[3-cyclopropyl-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 62 (815 mg, yield 93%) as pale-yellow crystals.

[0381] MS ESI m/e: 514 (M+H), 512 (MH).

[0382] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.70 (m, 2H), 0.91-0.99 (m, 2H), 1.26 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.10 (s, 3H), 4.30 (s, 3H), 7.01-7.06 (m, 1H), 7.09(t, J=8.4 Hz, 1H), 7.31(dd, J=1.6, 8.4 Hz, 1H), 7.36 (t, J=7.8 Hz, 1H), 7.52 (dd, J=1.6, 11.6 Hz, 1H), 7.57-7.63 (m, 2H), 10.10 (s, 1H), 11.10 (s, 1H).

Example 4-16

N-{3-[5-(2-fluoro-4-iodophenylamino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide

Step 1 Synthesis of 1-(2-fluoro-4-iodophenyl)-3-methylurea

[0383] ##STR00444##

[0384] Under a nitrogen atmosphere, to N,N-carbonyldiimidazole (61.4 g) were added N,N-dimethylformamide (300 ml) and triethylamine (52.8 ml) and a solution of 2-fluoro-4-iodoaniline 47 (74.8 g) in N,N-dimethylformamide (75 ml) was added dropwise with stirring under ice-cooling. After the completion of the dropwise addition, the mixture was stirred at room temperature for 5 hrs. The reaction mixture was ice-cooled, and a solution (60 ml) of 40% methylamine in methanol was added dropwise. The mixture was stirred at room temperature for 1 hr, and the reaction mixture was added dropwise to water-toluene [2:1 (volume ratio), 1125 ml] under stirring. The precipitated crystals were collected by filtration and dried to give 1-(2-fluoro-4-iodophenyl)-3-methylurea 63 (87.9 g, yield 94.8%) as colorless crystals.

Step 2 Synthesis of 1-(2-fluoro-4-iodophenyl)-3-methylpyrimidine-2,4,6-trione

[0385] ##STR00445##

[0386] Under a nitrogen atmosphere, to 1-(2-fluoro-4-iodophenyl)-3-methylurea 63 (87.9 g) obtained in Step 1 and malonic acid 4 (31.1 g) were added acetic anhydride (264 ml) and acetyl chloride (42.5 ml), and the mixture was stirred at 65 C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was added dropwise to water-toluene [2:1 (volume ratio), 800 ml] with stirring, and hexane (132 ml) was successively added. The precipitated crystals were collected by filtration and dried to give 1-(2-fluoro-4-iodophenyl)-3-methylpyrimidine-2,4,6-trione 64 (75.3 g, yield 69.5%) as pale-yellow crystals.

Step 3 Synthesis of 6-chloro-1-(2-fluoro-4-iodophenyl)-3-methyl-1H-pyrimidine-2,4-dione

[0387] ##STR00446##

[0388] Under a nitrogen atmosphere, to 1-(2-fluoro-4-iodophenyl)-3-methylpyrimidine-2,4,6-trione 64 (75.3 g) were added phosphorus oxychloride (116.3 ml) and dimethylaniline (39.5 ml) and water (11.6 ml) was added dropwise with stirring under room temperature. After the completion of the dropwise addition, the mixture was stirred at 125 C. for 1 hr. After allowing to cool to room temperature, the reaction mixture was added dropwise with stirring to ice water (500 ml)/chloroform (150 ml). The mixture was stirred at room temperature for 1 hr, and chloroform (150 ml) was added. The organic layer was separated, washed successively with water (300 ml) and brine (300 ml), and dried over anhydrous sodium sulfate.

[0389] Anhydrous sodium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. To a solution of the residue in chloroform (250 ml), silica gel (200 ml) was added and the mixture was stirred. Silica gel was filtered off and washed with chloroform/ethyl acetate [10:1 (volume ratio), 11]. The filtrate was concentrated under reduced pressure to give a 6:5 mixture (75.7 g, yield 95.6%) of 6-chloro-1-(2-fluoro-4-iodophenyl)-3-methyl-1H-pyrimidine-2,4-dione 65 and 6-chloro-3-(2-fluoro-4-iodophenyl)-1-methyl-1H-pyrimidine-2,4-dione 66 as pale-yellow crystals.

Step 4 Synthesis of 1-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dione

[0390] ##STR00447##

[0391] To a 6:5 mixture (75.7 g) of 6-chloro-1-(2-fluoro-4-iodophenyl)-3-methyl-1H-pyrimidine-2,4-dione 65 and 6-chloro-3-(2-fluoro-4-iodophenyl)-1-methyl-1H-pyrimidine-2,4-dione 66 obtained in Step 3 were added methanol (227 ml) and 40% solution (152 ml) of methylamine in methanol, and the mixture was stirred at room temperature for 2.5 hrs. The reaction mixture was concentrated under reduced pressure, and toluene (150 ml) and water (150 ml) were added to the residue, and the mixture was stirred under heating at reflux for 30 min. After allowing to return to room temperature, the crystals were collected by filtration and dried to give a 6:5 mixture (59.6 g, yield 79.9%) of 1-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-1H-pyrimidine-2,4-dione 67 and 3-(2-fluoro-4-iodophenyl)-1-methyl-6-methylamino-H-pyrimidine-2,4-dione 68 as pale-yellow crystals.

Step 5 Synthesis of 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0392] ##STR00448##

[0393] To a 6:5 mixture (59.6 g) of 1-(2-fluoro-4-iodophenyl)-3-methyl-6-methylamino-H-pyrimidine-2,4-dione 67 and 3-(2-fluoro-4-iodophenyl)-1-methyl-6-methylamino-1H-pyrimidine-2,4-dione 68 obtained in Step 4 and 2-methyl-malonic acid 54 (20.7 g) was added acetic anhydride (180 ml), and the mixture was stirred with heating at 95 C. for 1 hr. After allowing to cool to room temperature, the mixture was concentrated under reduced pressure. Tetrahydrofuran (350 ml) was added to the residue, and the mixture was stirred with heating under reflux for 1 hr. After allowing to cool to room temperature, the crystals were filtered off. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (chloroform:tetrahydrofuran=18:1). Toluene (150 ml) was added to the obtained solid, and the mixture was stirred with heating under reflux for 30 min. After allowing to return to room temperature, the crystals were collected by filtration and dried to give 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 69 (27.0 g, yield 37%) as colorless crystals.

Step 6 Synthesis of trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)-3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl Ester

[0394] ##STR00449##

[0395] Under a nitrogen atmosphere, to 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3,6,8-trimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 69 (27.0 g) obtained in Step 5 were added chloroform (200 ml) and 2,6-lutidine (11.1 ml) and trifluoromethanesulfonic anhydride 56 (14.9 ml) was added dropwise under ice-cooling with stirring. After the completion of the dropwise addition, the mixture was stirred at the same temperature for 30 min, and at room temperature for 3 hrs. With stirring under ice-cooling, water (200 ml) was added to the reaction mixture. The organic layer was separated, washed successively with water (300 ml) and brine (300 ml), and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. 2-Propanol (150 ml) was added to the residue, and seed crystals were added at room temperature to allow precipitation of the crystals. The mixture was stirred with heating under reflux for 30 min, and allowed to cool to room temperature. The crystals were collected by filtration and dried to give trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)-3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 70 (22.9 g, yield 66%) as colorless crystals.

Step 7 Synthesis of N-{3-[1-(2-fluoro-4-iodophenyl)-3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide

[0396] ##STR00450##

[0397] To trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)-3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-yl ester 70 (3.00 g) obtained in Step 6 and N-(3-aminophenyl)methanesulfonamide 44 (1.14 g) were added N,N-dimethylacetamide (6.00 ml) and 2,6-lutidine (0.712 ml), and the mixture was stirred at 130 C. for 4 hrs. After allowing to cool to room temperature, methanol/water [1:2 (volume ratio), 18.0 ml] was added under stirring. The crystals were collected by filtration and dried to give N-{3-[1-(2-fluoro-4-iodophenyl)-3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide 71 (3.13 g, yield 98%) as a pale-gray solid.

Step 8 Synthesis of N-{3-[5-(2-fluoro-4-iodophenylamino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide

[0398] ##STR00451##

[0399] Under ice-cooling, to a suspension of N-{3-[1-(2-fluoro-4-iodophenyl)-3,6,8-trimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydro-pyrido[2,3-d]pyrimidin-5-ylamino]phenyl}methanesulfonamide 71 (3.10 g) obtained in Step 7 in tetrahydrofuran (31.0 ml) was added dropwise a mixture of potassium t-butoxide (1.33 g), methanol (0.482 ml) and tetrahydrofuran (15.5 ml), and the mixture was stirred under ice-cooling for 2 hrs. Acetic acid (1.36 ml) was added, the mixture was allowed to warm to room temperature and stirred for 1 hr. The reaction mixture was concentrated, methanol/water [1:2 (volume ratio), 45.0 ml] was added, and the mixture was further stirred at room temperature for 1 hr. The crystals were collected by filtration and dried to give N-{3-[5-(2-fluoro-4-iodophenylamino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide 72 (3.01 g, yield 97%) as a pale-gray solid.

[0400] MS ESI m/e: 626(M+H), 624 (MH).

[0401] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.26 (s, 3H), 3.01 (s, 3H), 3.09 (s, 3H), 3.21 (s, 3H), 6.93(t, J=8.3 Hz, 1H), 7.11-7.15 (m, 1H), 7.20-7.28 (m, 2H), 7.42(t, J=8.3 Hz, 1H), 7.52-7.57 (m, 1H), 7.76-7.81 (m, 1H), 9.94 (brs, 1H), 11.21 (brs, 1H).

Example 4-144

N-{3-[5-(2-Fluoro-4-iodophenylamino)-3-(4-hydroxybutyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

Step 1 Synthesis of (2-fluoro-4-iodophenyl)-urea

[0402] ##STR00452##

[0403] Under argon atmosphere, to a solution of 2-fluoro-4-iodoaniline 47 (20.0 g) and triethylamine (23.6 ml) in chloroform (200 ml) was added N,N-carbonyldiimidazole (27.4 g) with stirring under ice-cooling. After the completion of the addition, the mixture was stirred under ice-cooling for 15 min and at room temperature for 4 hrs. The reaction mixture was ice-cooled, and 28% aqueous ammonia (100 ml) was added dropwise. The mixture was stirred at room temperature for 1.5 hrs. The precipitated crystals were collected by filtration, washed with water and dried to give (2-fluoro-4-iodophenyl)-urea 78 (23.5 g, yield 98.8%) as pale-pink crystals.

Step 2 Synthesis of 1-(2-cyanoacetyl)-3-(2-fluoro-4-iodophenyl)-urea

[0404] ##STR00453##

[0405] To a mixture of (2-fluoro-4-iodophenyl)-urea 78 (21.7 g) and cyanoacetic acid 73 (7.88 g) in N,N-dimethylformamide (108 ml) was added, and methanesulfonyl chloride (7.17 ml) was added dropwise with stirring at room temperature. The mixture was stirred at room temperature for 2 hrs, and water-isopropyl alcohol [1:2 (volume ratio), 210 ml] was added dropwise. The mixture was stirred at room temperature for 1 hr. The precipitated crystals were collected by filtration and washed with water to give 1-(2-cyanoacetyl)-3-(2-fluoro-4-iodophenyl)-urea 79 (wet crystals), which was used for the next reaction in the form of wet crystals.

Step 3 Synthesis of 6-amino-1-(2-fluoro-4-iodophenyl)-1H-yrimidine-2,4-dione

[0406] ##STR00454##

[0407] To a suspension of 1-(2-cyanoacetyl)-3-(2-fluoro-4-iodophenyl)-urea 79 (wet crystals) in water (110 ml) was added 2N aqueous sodium hydroxide solution (3.96 ml), and the mixture was stirred with heating at 85 C. for 1 hr. After allowing to cool to room temperature, 2N hydrochloric acid (3.96 ml) and isopropyl alcohol (44.0 ml) were successively added dropwise. The mixture was stirred at room temperature for 1.5 hrs, the precipitated crystals were collected by filtration, washed with isopropyl alcohol, and dried to give a mixture of 6-amino-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 80 and 78 (21.8 g) as colorless crystals, which were used for the next reaction without purification.

Step 4 Synthesis of N-[3-(2-fluoro-4-iodophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]-N,N-dimethylformamidine

[0408] ##STR00455##

[0409] To a mixture (21.8 g) of 6-amino-1-(2-fluoro-4-iodophenyl)-1H-pyrimidine-2,4-dione 80 and 78 was added N,N-dimethylformamide (42.0 ml) and N,N-dimethylformamidedimethylacetal (21.0 ml) and the mixture was stirred at room temperature for 4.5 hrs. With stirring at room temperature, isopropyl alcohol (20.0 ml) was added, and water (100 ml) was added dropwise. The mixture was stirred at room temperature for 45 min, and the precipitated crystals were collected by filtration, washed with water and dried to give N-[3-(2-fluoro-4-iodophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]-N,N-dimethylformamidine 81 (21.7 g, yield 67.7% from 78) as colorless crystals.

Step 5 Synthesis of N-[3-(2-fluoro-4-iodophenyl)-1-(4-methoxybenzyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]-N,N-dimethylformamidine

[0410] ##STR00456##

[0411] To a solution of N-[3-(2-fluoro-4-iodophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]-N,N-dimethylformamidine 81 (20.0 g) in N,N-dimethylformamide (150 ml) was added 1,8-diazabicyclo[5.4.0]undec-7-en (14.9 ml) and 4-methoxybenzyl chloride 82 (10.1 ml) at room temperature. The mixture was stirred with heating at 75 C. for 2.5 hrs, 1,8-diazabicyclo[5.4.0]undec-7-en (7.50 ml) and 4-methoxybenzyl chloride (4.00 ml) were added, and the mixture was stirred with heating at the same temperature for 2.5 hrs. After allowing to cool to room temperature, isopropyl alcohol (150 ml) and water (300 ml) were successively added dropwise. The mixture was stirred overnight at room temperature, and the precipitated crystals were collected by filtration and dried to give N-[3-(2-fluoro-4-iodophenyl)-1-(4-methoxybenzyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]-N,N-dimethylformamidine 83 (20.2 g, yield 77.8%) as yellow crystals.

Step 6 Synthesis of 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6-methylamino-1H-pyrimidine-2,4-dione

[0412] ##STR00457##

[0413] To a suspension of sodium borohydride (326 mg) in t-butanol/ethanol [2:1 (volume ratio), 18.0 ml] was added N-[3-(2-fluoro-4-iodophenyl)-1-(4-methoxybenzyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl]-N,N-dimethylformamidine 83 (3.00 g) with stirring at room temperature. The mixture was stirred at room temperature for 1 hr, and at 65 C. for 2 hrs. With stirring at the same temperature, water (30.0 ml) and ammonium chloride (461 mg) were successively added, and the mixture was stirred to allow to cool to room temperature. The reaction solution was extracted twice with ethyl acetate. The organic layers were combined, washed successively with saturated aqueous hydrogen carbonate solution and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained crude product was purified by column chromatography to give 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6-methylamino-1H-pyrimidine-2,4-dione 84 (2.57 g, yield 93.1%) as a pale-yellow solid.

Step 7 Synthesis of 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3-(4-methoxybenzyl)-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione

[0414] ##STR00458##

[0415] To a suspension of 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6-methylamino-1H-pyrimidine-2,4-dione 84 (13.3 g) in acetic anhydride (13.0 ml) was added 2-methyl-malonic acid 54 (4.90 g), and the mixture was stirred with heating at 90 C. for 3 hrs and at 100 C. for 1 hr. After allowing to cool to about 50C, acetone (13.3 ml) was added dropwise, and water (75.0 ml) was further added. After seeding with compound 85, acetone (30.0 ml) was added, and the mixture was stirred for 1.5 hrs. Water (30.0 ml) as added and the mixture was stirred for 45 min, and allowed to cool to room temperature. The precipitated crystals were collected by filtration, washed with water and dried to give 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3-(4-methoxybenzyl)-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 85 (14.1 g, yield 90.7%) as pale-ocher crystals.

Step 8 Synthesis of trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl Ester

[0416] ##STR00459##

[0417] Under argon atmosphere, to a solution of 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3-(4-methoxybenzyl)-6,8-dimethyl-1H,8H-pyrido[2,3-d]pyrimidine-2,4,7-trione 85 (14.1 g) in chloroform (70.0 ml) was added 2,6-lutidine (3.79 ml) and trifluoromethanesulfonic anhydride 56 (5.47 ml) under ice-cooling, and the mixture was stirred under ice-cooling for 1 hr, and at room temperature for 1.5 hrs. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution and chloroform to allow partitioning. The organic layer was washed once with saturated aqueous sodium hydrogen carbonate solution, twice with 1N hydrochloric acid, once with saturated aqueous sodium chloride solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. To the obtained crude product was added isopropyl alcohol (35.0 ml), and the mixture was stirred with heating at an outer temperature of 95 C. for 30 min. After allowing to cool with stirring to room temperature, isopropyl alcohol (35.0 ml) was added, and the mixture was stirred for 1 hr. The precipitated crystals were collected by filtration, washed with isopropyl alcohol and dried to give trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl ester 86 (14.4 g, yield 82.8%) as brown crystals.

Step 9 Synthesis of N-{3-[1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide

[0418] ##STR00460##

[0419] To trifluoromethanesulfonic acid 1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-yl ester 86 (1.10 g) and 3-aminoacetanilide 57 (285 mg) were added, N,N-dimethylacetamide (2.20 ml) and 2,6-lutidine (221 l), and the mixture was stirred at 130 C. for 2 hrs. After allowing to return to room temperature, methanol (12.0 ml) was added dropwise with stirring. The precipitated crystals were collected by filtration, washed with methanol and dried to give N-{3-[1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide 87 (1.04 g, yield 94.6%) as colorless crystals.

Step 10 Synthesis of N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

[0420] ##STR00461##

[0421] To a solution (305 mg) of 28% sodium methoxide in methanol were added tetrahydrofuran (4.00 ml) and N-{3-[1-(2-fluoro-4-iodophenyl)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-1,2,3,4,7,8-hexahydropyrido[2,3-d]pyrimidin-5-ylamino]-phenyl}-acetamide 87 (1.00 g). The wall was washed with tetrahydrofuran (4.00 ml). The mixture was stirred at room temperature for 1.5 hrs., 2N hydrochloric acid (900 l) was added, and the mixture was concentrated under reduced pressure. To the residue was added isopropyl alcohol, methanol and water, and after refluxing, the mixture was allowed to cool to room temperature with stirring. The precipitated crystals were collected by filtration, washed with methanol, and dried to give N-{3-[15-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 88 (974 mg, yield 97.2%) as colorless crystals.

Step 11 Synthesis of N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

[0422] ##STR00462##

[0423] To a suspension of N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-methoxybenzyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 88 (960 mg) in anisole (10.0 ml) was added aluminum chloride (1.94 g) with stirring in a water bath. The mixture was stirred at room temperature for 37 hrs, methanol (12.0 ml) was added dropwise, and the mixture was concentrated under reduced pressure. The obtained residue was dissolved in methanol (12.0 ml), and 2N hydrochloric acid (20.0 ml) was added dropwise with stirring in a water bath. The mixture was stirred at room temperature for 1 hr, hexane (10.0 ml) was added, and the mixture was stirred for 1 hr. The precipitated crystals were collected by filtration, washed with hexane, water and methanol, and dried to give N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 89 (620 mg, yield 78.1%) as colorless crystals.

Step 12 Synthesis of N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

[0424] ##STR00463##

[0425] Under argon atmosphere, to a suspension of N-{3-[5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 89 (75.0 mg), 4-benzyloxybutyl alcohol 90 (25.0 l) and triphenylphosphine (37.0 mg) in tetrahydrofuran (1.00 ml) was added diisopropyl azodicarboxylate (28.0 l) with stirring under ice cooling. The mixture was stirred at the same temperature for 2 hrs, and 4-benzyloxybutyl alcohol (13.0 l), triphenylphosphine (19.0 mg) and diisopropyl azodicarboxylate (14.0 l) were added. The mixture was stirred at the same temperature for 1 hr, and water and ethyl acetate were added to allow partitioning. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (chloroform:ethyl acetate-2:1.fwdarw.1:1) and thin layer chromatography (hexane:acetone=1:1) for further purification to give N-{3-[3-(4-benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 91 (74 mg, yield 77%) as a pale-yellow amorphous form.

Step 13 Synthesis of N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-hydroxybutyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide

[0426] ##STR00464##

[0427] N-{3-[3-(4-Benzyloxybutyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 91 (74 mg) was stirred under reflux for 5.5 hrs in trifluoroacetic acid (1.00 ml). The reaction mixture was concentrated under reduced pressure, and ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added to the residue to allow partitioning. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To the residue was added diisopropyl ether (1.00 ml), and the mixture was stirred at 60 C. to allow cooling to room temperature with stirring. The crystals were collected by filtration, washed with diisopropyl ether, and dried to give compound 93 (26 mg) as colorless crystals. Compound 93 was stirred in a mixed solution of saturated aqueous sodium hydrogen carbonate solution (300 l), methanol (300 l) and ethyl acetate (300 l) at room temperature for 1 hr, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To the residue were added ethyl acetate, hexane and diethyl ether, and the mixture was stirred at room temperature for 1 hr. The precipitated crystals were collected by filtration, washed with hexane and dried to give N-{3-[5-(2-fluoro-4-iodophenylamino)-3-(4-hydroxybutyl)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 92 (5 mg, yield 8%) as colorless crystals.

Examples 4-2, 4-4-15, 4-17-143 and 4-145-148

[0428] In the same manner as in Examples 4-1, 4-3 and 4-16, the compounds of Examples 4-2, 4-4-15, 4-17-133 and 4-138-4-140 were obtained. In addition, in the same manner as in Example 4-144, the compounds of Examples 4-83-86, Examples 4-134-137, 4-141-143 and 4-145-148 were obtained. The structural formulas thereof are shown in Table 4-1 to 4-25 with Examples 4-1, 4-3, 4-16 and 4-144.

TABLE-US-00062 TABLE 4-1 Ex. No. structural formula 4-1 [00465] 4-2 [00466] 4-3 [00467] 4-4 [00468] 4-5 [00469] 4-6 [00470]

TABLE-US-00063 TABLE 4-2 Ex. No. structural formula 4-7 [00471] 4-8 [00472] 4-9 [00473] 4-10 [00474] 4-11 [00475] 4-12 [00476]

TABLE-US-00064 TABLE 4-3 Ex. No. structural formula 4-13 [00477] 4-14 [00478] 4-15 [00479] 4-16 [00480] 4-17 [00481] 4-18 [00482]

TABLE-US-00065 TABLE 4-4 Ex. No. structural formula 4-19 [00483] 4-20 [00484] 4-21 [00485] 4-22 [00486] 4-23 [00487] 4-24 [00488]

TABLE-US-00066 TABLE 4-5 Ex. No. stuctural formula 4-25 [00489] 4-26 [00490] 4-27 [00491] 4-28 [00492] 4-29 [00493] 4-30 [00494]

TABLE-US-00067 TABLE 4-6 Ex. No. structural formula 4-31 [00495] 4-32 [00496] 4-33 [00497] 4-34 [00498] 4-35 [00499] 4-36 [00500]

TABLE-US-00068 TABLE 4-7 Ex. No. structural formula 4-37 [00501] 4-38 [00502] 4-39 [00503] 4-40 [00504] 4-41 [00505] 4-42 [00506]

TABLE-US-00069 TABLE 4-8 Ex. No. structural formula 4-43 [00507] 4-44 [00508] 4-45 [00509] 4-46 [00510] 4-47 [00511] 4-48 [00512]

TABLE-US-00070 TABLE 4-9 Ex. No. structural formula 4-49 [00513] 4-50 [00514] 4-51 [00515] 4-52 [00516] 4-53 [00517] 4-54 [00518]

TABLE-US-00071 TABLE 4-10 Ex. No. structural formula 4-55 [00519] 4-56 [00520] 4-57 [00521] 4-58 [00522] 4-59 [00523] 4-60 [00524]

TABLE-US-00072 TABLE 4-11 Ex. No. structural formula 4-61 [00525] 4-62 [00526] 4-63 [00527] 4-64 [00528] 4-65 [00529] 4-66 [00530]

TABLE-US-00073 TABLE 4-12 Ex. No. structural formula 4-67 [00531] 4-68 [00532] 4-69 [00533] 4-70 [00534] 4-71 [00535] 4-72 [00536]

TABLE-US-00074 TABLE 4-13 Ex. No. structural formula 4-73 [00537] 4-74 [00538] 4-75 [00539] 4-76 [00540] 4-77 [00541] 4-78 [00542]

TABLE-US-00075 TABLE 4-14 Ex. No. structural formula 4-79 [00543] 4-80 [00544] 4-81 [00545] 4-82 [00546] 4-83 [00547] 4-84 [00548]

TABLE-US-00076 TABLE 4-15 Ex. No. structural formula 4-85 [00549] 4-86 [00550] 4-87 [00551] 4-88 [00552] 4-89 [00553] 4-90 [00554]

TABLE-US-00077 TABLE 4-16 Ex. No. structural formula 4-91 [00555] 4-92 [00556] 4-93 [00557] 4-94 [00558] 4-95 [00559] 4-96 [00560]

TABLE-US-00078 TABLE 4-17 Ex. No. structural formula 4-97 [00561] 4-98 [00562] 4-99 [00563] 4-100 [00564] 4-101 [00565] 4-102 [00566]

TABLE-US-00079 TABLE 4-18 Ex. No. structural formula 4-103 [00567] 4-104 [00568] 4-105 [00569] 4-106 [00570] 4-107 [00571] 4-108 [00572]

TABLE-US-00080 TABLE 4-19 Ex. No. structural formula 4-109 [00573] 4-110 [00574] 4-111 [00575] 4-112 [00576] 4-113 [00577] 4-114 [00578]

TABLE-US-00081 TABLE 4-20 Ex. No. structural formula 4-115 [00579] 4-116 [00580] 4-117 [00581] 4-118 [00582] 4-119 [00583] 4-120 [00584]

TABLE-US-00082 TABLE 4-21 Ex. No. structural formula 4-121 [00585] 4-122 [00586] 4-123 [00587] 4-124 [00588] 4-125 [00589] 4-126 [00590]

TABLE-US-00083 TABLE 4-22 Ex. No. structural formula 4-127 [00591] 4-128 [00592] 4-129 [00593] 4-130 [00594] 4-131 [00595]

TABLE-US-00084 TABLE 4-23 Ex. No. structural formula 4-132 [00596] 4-133 [00597] 4-134 [00598] 4-135 [00599] 4-136 [00600] 4-137 [00601]

TABLE-US-00085 TABLE 4-24 Ex. No. structural formula 4-138 [00602] 4-139 [00603] 4-140 [00604] 4-141 [00605] 4-142 [00606] 4-143 [00607]

TABLE-US-00086 TABLE 4-25 Ex. No. structural formula 4-144 [00608] 4-145 [00609] 4-146 [00610] 4-147 [00611] 4-148 [00612]

Example 4-149

[0429] By treating N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 59 by a conventional method, sodium salt, hydrate, acetic acid solvate, dimethylsulfoxide solvate, ethanol solvate, nitromethane solvate, chlorobenzene solvate, 1-pentanol solvate, isopropyl alcohol solvate, ethylene glycol solvate and 3-methylbutanol solvate thereof were obtained. N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide sodium salt: .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.35-0.41 (m, 2H), 0.71-0.77 (m, 2H), 1.16 (s, 3H), 2.02 (s, 3H), 2.18-2.24 (m, 1H), 3.32 (s, 3H), 6.59 (t, J=8.8 Hz, 1H), 6.94 (d, J=8.6 Hz, 1H), 7.04 (d, J=10.2 Hz, 1H), 7.19 (d, J=11.1 Hz, 1H), 7.27 (t, J=8.0 Hz, 1H), 7.34 (s, 1H), 7.64 (d, J=8.3 Hz, 1H), 10.00 (s, 1H).

[0430] MS (ESI) m/z 616 [MH].sup.+.

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Hydrate

[0431] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.08 (s, 3H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=8.2 Hz, 1H), 7.52-7.63 (m, 3H), 7.79 (dd, J=2.0, 10.4 Hz, 1H), 10.09 (s, 1H), 11.08 (s, 1H).

[0432] MS (ESI) m/z 616 [MH].sup.+.

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Acetic Acid Solvate

[0433] .sup.1H-NMR (DMSO-ds, 400 MHz) 0.63-0.70 (m, 2H), 0.92-0.98 (m, 2H), 1.25 (s, 3H), 1.91 (s, 3H), 2.04 (s, 3H), 2.59-2.65 (m, 1H), 3.08 (s, 3H), 6.92 (t, J=8.6 Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=7.6 Hz, 1H), 7.53-7.62 (m, 3H), 7.79(dd, J=10.4 Hz, 1H), 10.08 (s, 1H), 11.07 (s, 1H), 11.94 (s, 1H).

[0434] MS (ESI) m/z 616 [MH]+.

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Dimethyl Sulfoxide Solvate

[0435] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.76-0.82 (m, 2H), 1.09-1.15 (m, 2H), 1.41 (s, 3H), 2.14 (s, 3H), 2.62 (s, 6H), 2.71-2.77 (m, 1H), 3.20 (s, 3H), 6.70 (t, J=8.4 Hz, 1H), 7.00 (brs, 1H), 7.32 (brs, 2H), 7.43-7.47 (m, 1H), 7.52 (dd, J=2.0, 9.6 Hz, 1H), 7.71 (brs, 2H), 11.30 (s, 1H).

[0436] MS (ESI) m/z 616 [MH].sup.+.

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Ethanol Solvate

[0437] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.06 (t, J=7.1 Hz, 3H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 3.40-3.49 (m, 2H), 4.33 (t, J=5.1 Hz, 1H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=8.2 Hz, 1H), 7.52-7.63 (m, 3H), 7.79 (dd, J=2.0, 10.4 Hz, 1H), 10.08 (s, 1H), 11.07 (s, 1H).

[0438] MS (ESI) m/z 616 [MH].sup.+.

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Nitromethane Solvate

[0439] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 4.42 (s, 2H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=8.2 Hz, 1H), 7.52-7.63 (m, 3H), 7.79 (dd, J=2.0, 10.4 Hz, 1H), 10.08 (s, 1H), 11.07 (s, 1H).

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Chlorobenzene Solvate

[0440] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.29-7.45 (m, 5H), 7.50-7.63 (m, 3H), 7.79 (dd, J=2.0, 10.4 Hz, 1H), 10.08 (s, 1H), 11.07 (s, 1H).

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 1-pentanol Solvate

[0441] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.70 (m, 2H), 0.86 (t, J=7.0 Hz, 1.5H), 0.90-0.99 (m, 2H), 1.22-1.30 (m, 5H), 1.35-1.44 (m, 1H), 2.04 (s, 3H), 2.56-2.67 (m, 1H), 3.08 (s, 3H), 3.33-3.41 (m, 1H), 4.30 (t, J=5.1 Hz, 0.5H), 6.91 (t, J=8.5 Hz, 1H), 7.00-7.06 (m, 1H), 7.36 (t, J=8.3 Hz, 1H), 7.52-7.62 (m, 3H), 7.74-7.81 (m, 1H), 10.08 (s, 1H), 11.07 (s, 1H).

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Isopropyl Alcohol Solvate

[0442] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.69 (m, 2H), 0.91-0.98 (m, 2H), 1.04 (d, J=6.0 Hz, 6H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 3.73-3.81 (m, 1H), 4.34 (d, J=4.2 Hz, 1H), 6.92 (t, J=8.7 Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=8.3 Hz, 1H), 7.52-7.62 (m, 3H), 7.79 (dd, J=1.8, 10.2 Hz, 1H), 10.10 (s, 1H), 11.08 (s, 1H).

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide Ethylene Glycol Solvate

[0443] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.24 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 3.36-3.41 (m, 4H), 4.37-4.44 (m, 2H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.36 (t, J=8.2 Hz, 1H), 7.52-7.63 (m, 3H), 7.79 (dd, J=2.0, 10.4 Hz, 1H), 10.10 (s, 1H), 11.08 (s, 1H).

N-{3-[3-Cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-acetamide 3-methyl-1-butanol Solvate

[0444] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.64-0.69 (m, 2H), 0.85 (d, J=6.7 Hz, 6H), 0.92-0.98 (m, 2H), 1.25 (s, 3H), 1.31 (q, J=6.7 Hz, 2H), 1.60-1.70 (m, 1H), 2.04 (s, 3H), 2.59-2.66 (m, 1H), 3.08 (s, 3H), 3.38-3.44 (m, 2H), 4.26 (t, J=5.1 Hz, 1H), 6.92 (t, J=8.7 Hz, 1H), 7.01-7.05 (m, 1H), 7.35 (t, J=8.0 Hz, 1H), 7.52-7.62 (m, 3H), 7.78 (dd, J=1.9, 10.2 Hz, 1H), 10.08 (s, 1H), 11.07 (s, 1H).

Example 4-150

[0445] By treating N-{3-[3-cyclopropyl-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide 62 according to a conventional method, acetic acid solvate was obtained.

N-{3-[3-cyclopropyl-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide Acetic Acid Solvate

[0446] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.60-0.70 (m, 2H), 0.90-1.00 (m, 2H), 1.26 (s, 3H), 1.91 (s, 3H), 2.04 (s, 3H), 2.59-2.66 (m, 1H), 3.10 (s, 3H), 4.29 (s, 1H), 7.01-7.05 (m, 1H), 7.08 (t, J=8.6 Hz, 1H), 7.31 (dd, J=1.6, 8.3 Hz, 1H), 7.36(t, J=8.1 Hz, 1H), 7.52 (dd, J=1.6, 11.3 Hz, 1H), 7.57-7.62 (m, 2H), 10.09 (s, 1H), 11.09 (s, 1H), 11.94 (s, 1H).

[0447] MS (ESI) m/z 514 [MH].sup.+.

Example 4-151

[0448] By treating N-{3-[5-(2-fluoro-4-iodophenylamino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide 72 according to a conventional method, a sodium salt was obtained.

N-{3-[5-(2-fluoro-4-iodophenylamino)-3,6,8-trimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}methanesulfonamide Sodium Salt

[0449] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.25 (s, 3H), 2.78 (s, 3H), 2.97 (s, 3H), 3.24 (s, 3H), 6.68 (t, J=8.7 Hz, 1H), 6.77(d, J=7.5 Hz, 1H), 6.90-7.00 (m, 2H), 7.10-7.30 (m, 2H), 7.37(d, J=10.0 Hz, 1H), 10.30 (brs, 1H).

[0450] MS (ESI) m/z 626 [MH].sup.+.

Example 1001-6010

[0451] The compounds shown in Tables 11-1 to 11-6 can be obtained in the same manner as in Examples 1-1 to 1-148 or by other conventional method employed as necessary.

TABLE-US-00087 TABLE 11-1 [00613] [00614] Example No. R.sup.1 Example No. R.sup.1 1001 2-FPh 1002 2-FPh 1003 3-FPh 1004 3-FPh 1005 4-FPh 1006 4-FPh 1007 2-MePh 1008 2-MePh 1009 3-MePh 1010 3-MePh 1011 4-MePh 1012 4-MePh 1013 2-MeOPh 1014 2-MeOPh 1015 3-MeOPh 1016 3-MeOPh 1017 4-MeOPh 1018 4-MeOPh 1019 2-Py 1020 2-Py 1021 3-Py 1022 3-Py 1023 4-Py 1024 4-Py 1025 2-MeS(CH2)2 1026 2-MeS(CH2)2 1027 2-HS(CH2)2 1028 2-HS(CH2)2 1029 4-(Me)2NBzl 1030 4-(Me)2NBzl 1031 3-(Me)2NBzl 1032 3-(Me)2NBzl 1033 2-(Me)2NBzl 1034 2-(Me)2NBzl 1035 4-(Me)2NPhenethyl 1036 4-(Me)2NPhenethyl 1037 4-HOPhenethyl 1038 4-HOPhenethyl 1039 4-HOBzl 1040 4-HOBzl 1041 3-HOBzl 1042 3-HOBzl 1043 2-HOBzl 1044 2-HOBzl 1045 4-MeOBzl 1046 4-MeOBzl 1047 4-Py(CH2)2 1048 4-Py(CH2)2 1049 3-Py(CH2)2 1050 3-Py(CH2)2 1051 2-Py(CH2)2 1052 2-Py(CH2)2 1053 [00615] 1054 [00616] 1055 [00617] 1056 [00618] 1057 Allyl 1058 Allyl 1059 CF3CH2 1060 CF3CH2 1061 n-Propyl 1062 n-Propyl 1063 Cyclopropylmethyl 1064 Cyclopropylmethyl 1065 HO 1066 HO 1067 HO(CH2)2O 1068 HO(CH2)2O 1069 HO(CH2)3O 1070 HO(CH2)3O 1071 [00619] 1072 [00620] 1073 [00621] 1074 [00622] 1075 [00623] 1076 [00624] 1077 [00625] 1078 [00626] 1079 [00627] 1080 [00628] 1081 [00629] 1082 [00630] 1083 [00631] 1084 [00632] Py: Pyridyl, Ph: Phenyl Bzl: Benzyl

TABLE-US-00088 TABLE 11-2 [00633] Example No. R1 2001 [00634] 2002 [00635] 2003 [00636] 2004 [00637] 2005 [00638] 2006 [00639] 2007 [00640] 2008 [00641] 2009 [00642] 2010 [00643] 2011 [00644] 2012 [00645] 2013 [00646] 2014 [00647] 2015 [00648] 2016 [00649] 2017 [00650] 2018 [00651] 2019 [00652] 2020 [00653]

TABLE-US-00089 TABLE 11-3 [00654] Example No. R.sup.3 R.sup.4 R.sup.5 3001 Allyl Me H 3002 n-Propyl Me H 3003 CF3CH2 Me H 3004 MeO(CH2)2 Me H 3005 (Me)2N(CH2)2 Me H 3006 Ph Me H 3007 3-Py Me H 3008 Me Allyl H 3009 Me MeO H 3010 Me Cyclopropyl H 3011 Me Me HO 3012 Me Me MeO

TABLE-US-00090 TABLE 11-4 [00655] Example No. R.sup.3 R.sup.4 R.sup.5 4001 Allyl Me H 4002 n-Propyl Me H 4003 CF3CH2 Me H 4004 MeO(CH2)2 Me H 4005 (Me)2N(CH2)2 Me H 4006 Ph Me H 4007 3-Py Me H 4008 Me Allyl H 4009 Me MeO H 4010 Me Cyclopropyl H 4011 Me Me HO 4012 Me Me MeO

TABLE-US-00091 TABLE 11-5 [00656] Example No. R.sup.6 5001 [00657] 5002 [00658] 5003 [00659] 5004 [00660] 5005 [00661] 5006 [00662] 5007 [00663] 5008 [00664] 5009 [00665] 5010 [00666]

TABLE-US-00092 TABLE 11-6 [00667] Example No. R.sup.6 6001 [00668] 6002 [00669] 6003 [00670] 6004 [00671] 6005 [00672] 6006 [00673] 6007 [00674] 6008 [00675] 6009 [00676] 6010 [00677]

Example 5 (Evaluation of Growth Inhibitory Effect Against Cancer Cell Lines)

[0452] Renal cancer cell line ACHN cell or colorectal cancer cell line HT-29 cells were cultured in a 96 well plate at 1.010.sup.4 cells/90 L/well for 24 hrs, then a test substance dissolved in DMSO (dimethyl sulfoxide) was added. After 18 hrs, .sup.3H-thymidine (0.25 Ci/well) was added and the cells were cultured for 6 hrs. Using a cell harvester, the cells were recovered on a UniFilter-96 GF/B glass filter and the .sup.3H radioactivity uptaken by the cells was measured by TopCount (Packard). As a control, DMSO was used and the activity of the test substance was expressed in the concentration (IC.sub.50) necessary for inhibiting .sup.3H radioactivity uptaken by the cell to 50% of that of the control group. The measurements were made in triplicate.

[0453] The results are shown in Tables 5-1 to 5-8 according to the following.

A: not less than 0.1 M and less than 1 M
B: not less than 0.01 M and less than 0.1 M
C: less than 0.01 M

TABLE-US-00093 TABLE 5-1 IC.sub.50 Example ACHN HT-29 No. cell cell 1-1 B C 1-2 A 1-7 A 1-11 A 1-55 A 1-88 A A 1-89 A B 1-95 A 1-96 A 1-97 A 1-99 A 1-100 A 1-106 A A 1-111 A 1-112 A B 1-113 A A 1-114 A A 1-116 A 1-117 A 1-126 A 1-127 A 1-129 A 1-132 A 1-133 A 1-136 A 1-138 A 1-140 A 1-142 A 1-143 A 1-151 A 1-152 A B 1-153 A 1-156 A 1-159 A 1-163 A 1-164 B

TABLE-US-00094 TABLE 5-2 IC.sub.50 Example ACHN HT-29 No. cell cell 1-165 A 1-166 B 1-168 B 1-171 B 1-175 A 1-176 A B 1-183 A 1-185 A B 1-186 B 1-188 A B 1-189 A 1-190 A 1-191 A B 1-192 A B 1-193 A C 1-199 A B 1-200 A B 1-201 A 1-205 A C 1-206 A 1-207 B C 1-208 B C 1-211 A 1-212 A C 1-213 A B 1-214 B 1-215 A 1-216 A 1-217 A 1-218 B 1-219 A B 1-221 B C 1-222 A B 1-223 A B 1-224 A C 1-225 A

TABLE-US-00095 TABLE 5-3 IC.sub.50 Example ACHN HT-29 No. cell cell 1-226 A B 1-227 B 1-228 A B 1-229 A 1-230 A 1-232 A B 1-233 A 1-234 A 1-235 A 1-236 A 1-240 B B 1-242 A B 1-243 A B 1-244 A 1-245 B C 1-246 A B 1-249 A B 1-252 B 1-253 A B 1-255 A 1-257 C C 1-258 A 1-259 A C 1-260 C C 1-262 B C 1-263 A C 1-264 A B 1-265 A B 1-266 A C 1-267 A B 1-268 B B 1-270 A B 1-271 B C 1-272 B B 1-273 A 3-1 A A

TABLE-US-00096 TABLE 5-4 IC.sub.50 Example ACHN HT-29 No. cell cell 1-274 C C 1-275 B C 1-276 A B 1-277 B 1-278 A B 1-279 A B 1-282 A B 1-283 A B 1-284 A B 1-285 B B 1-286 B C 1-287 A B 1-288 B 1-289 C C 1-290 B C 1-292 B 1-293 A A 1-294 B 1-295 A B 1-296 A C 1-297 B C 1-298 B C 1-299 A B 1-301 A B 1-302 B C 1-303 A B 1-304 A B 1-305 B 1-307 A B 1-308 A B 1-309 B C 1-310 B C 1-311 C C 1-313 B 1-313 B 1-315 A B

TABLE-US-00097 TABLE 5-5 IC.sub.50 Example ACHN HT-29 No. cell cell 1-316 A B 1-317 A B 1-318 A C 1-319 C C 1-320 B C 1-321 B C 1-322 B C 1-324 B 1-325 A B 1-326 A 1-327 A B 1-328 A B 1-333 B C 1-334 A 1-335 A B 1-336 B C 1-337 B C 1-338 B C 1-339 A 1-340 B C 1-341 B C 1-342 A C 1-343 A B 3-4 B C 3-5 B C 3-6 A C 3-7 C C 3-8 B C 4-1 C C 4-2 C C 4-3 B C 4-4 A 4-5 A B 4-6 B C 4-7 A 4-9 B C

TABLE-US-00098 TABLE 5-6 IC.sub.50 Example ACHN HT-29 No. cell cell 4-10 A B 4-11 B C 4-12 B C 4-13 A 4-15 B C 4-16 C C 4-19 B C 4-20 B C 4-21 B C 4-25 B C 4-26 B C 4-27 A 4-33 C C 4-34 C C 4-37 A B 4-39 A 4-40 B C 4-41 B B 4-42 B C 4-43 A B 4-44 A B 4-45 A B 4-46 A B 4-47 A 4-48 B C 4-49 B C 4-50 A B 4-51 B C 4-52 A A 4-53 A B 4-54 C C 4-55 B C 4-56 A B 4-57 A 4-58 B C 4-59 B C

TABLE-US-00099 TABLE 5-7 IC.sub.50 Example ACHN HT-29 No. cell cell 4-60 B C 4-61 B B 4-63 B 4-64 A B 4-66 A B 4-67 B C 4-70 B C 4-71 A B 4-72 B C 4-73 B C 4-74 B C 4-75 B 4-76 B C 4-77 B C 4-78 A B 4-80 B C 4-81 B C 4-82 B C 4-85 A 4-87 A B 4-88 C C 4-89 A B 4-90 A B 4-91 B C 4-92 B C 4-93 B C 4-94 A B 4-95 A B 4-96 A B 4-97 B C 4-98 B C 4-99 A C 4-101 B C 4-102 A B 4-103 A C 4-104 C C

TABLE-US-00100 TABLE 5-8 IC.sub.50 Example ACHN HT-29 No. cell cell 4-105 B C 4-106 B C 4-107 B C 4-108 B C 4-109 B C 4-110 B C 4-111 A B 4-112 A C 4-113 C C 4-114 B C 4-115 B C 4-116 A C 4-117 A C 4-118 B C 4-119 B C 4-120 B C 4-121 B C 4-122 B C 4-123 A C 4-124 B C 4-125 C C 4-126 C C 4-127 B C 4-128 B C 4-133 A 4-135 A 4-138 A 4-140 A 4-145 A 4-146 A 4-147 A 4-148 A

Example 6 (Evaluation of p15 Induction Activity)

[0454] ACHN cells or HT-29 cells were cultured in a 6 well plate at 2.510.sup.5 cells/1.8 mL/well for 24 hrs, then a test substance (0.1 M) dissolved in DMSO was added. After 24 hrs, cells were detached using trypsin-EDTA (ethylene diamine tetraacetic acid) and solubilized with NuPAGE LDS sample buffer (Invitrogen). Using an RC DC protein assay kit (BIO-RAD), the protein concentration of the sample was quantitated, and a sample in an amount corresponding to 10 g of BSA (bovine serum albumin) was analyzed by Western blotting using an anti-p15 antibody. The density of the band stained with the anti-p15 antibody was measured by a densitometer to quantify the amount of p15 protein. As a control, DMSO was used and the test was performed with n=2 and the average protein amount was determined.

[0455] The results are shown in Tables 6-1 to 6-6 according to the following.

+: As compared to DMSO, not less than 1.5-fold induction of p15 protein

TABLE-US-00101 TABLE 6-1 Example Induction of No. p15 protein 1-1 + 1-4 + 1-6 + 1-7 + 1-8 + 1-9 + 1-11 + 1-12 + 1-16 + 1-17 + 1-26 + 1-33 + 1-34 + 1-35 + 1-36 + 1-37 + 1-38 + 1-40 + 1-43 + 1-46 + 1-49 + 1-51 + 1-53 + 1-55 + 1-65 + 1-77 + 1-78 + 1-79 + 1-80 + 1-81 + 1-84 + 1-85 + 1-86 + 1-88 + 1-89 + 1-92 +

TABLE-US-00102 TABLE 6-2 Example Induction of No. p15 protein 1-93 + 1-94 + 1-95 + 1-96 + 1-97 + 1-99 + 1-100 + 1-102 + 1-103 + 1-104 + 1-106 + 1-107 + 1-108 + 1-109 + 1-110 + 1-111 + 1-112 + 1-113 + 1-114 + 1-116 + 1-117 + 1-126 + 1-127 + 1-131 + 1-132 + 1-133 + 1-136 + 1-137 + 1-138 + 1-142 + 1-143 + 1-146 + 1-151 + 1-152 + 1-153 + 1-154 +

TABLE-US-00103 TABLE 6-3 Example Induction of No. p15 protein 1-156 + 1-157 + 1-162 + 1-163 + 1-165 + 1-166 + 1-167 + 1-168 + 1-172 + 1-173 + 1-175 + 1-176 + 1-183 + 1-185 + 1-186 + 1-188 + 1-191 + 1-192 + 1-193 + 1-199 + 1-200 + 1-205 + 1-207 + 1-208 + 1-212 + 1-213 + 1-218 + 1-219 + 1-221 + 1-222 + 1-223 + 1-224 + 1-226 + 1-240 + 1-242 + 1-243 + 1-245 + 1-246 +

TABLE-US-00104 TABLE 6-4 Example Induction of No. p15 protein 1-264 + 1-265 + 1-266 + 1-268 + 1-271 + 1-272 + 1-282 + 1-283 + 1-284 + 1-285 + 1-286 + 1-287 + 1-289 + 1-290 + 1-293 + 1-295 + 1-296 + 1-297 + 1-298 + 1-301 + 1-317 + 1-318 + 1-319 + 1-320 + 1-321 + 1-322 + 1-325 + 1-327 + 1-328 + 1-333 + 1-336 + 1-337 + 1-338 + 1-340 + 1-341 + 1-342 + 3-4 + 3-6 +

TABLE-US-00105 TABLE 6-5 Example Induction of No. p15 protein 3-7 + 3-8 + 4-1 + 4-2 + 4-3 + 4-6 + 4-9 + 4-10 + 4-11 + 4-12 + 4-15 + 4-16 + 4-21 + 4-43 + 4-45 + 4-48 + 4-49 + 4-50 + 4-51 + 4-53 + 4-54 + 4-55 + 4-56 + 4-58 + 4-59 + 4-60 + 4-61 + 4-64 + 4-66 + 4-67 + 4-70 + 4-71 + 4-72 + 4-73 + 4-74 + 4-76 + 4-77 + 4-78 +

TABLE-US-00106 TABLE 6-6 Example Induction of No. p15 protein 4-80 + 4-81 + 4-82 + 4-88 + 4-89 + 4-90 + 4-91 + 4-92 + 4-93 + 4-97 + 4-98 + 4-101 + 4-102 + 4-103 + 4-104 + 4-105 + 4-106 + 4-107 + 4-108 + 4-109 + 4-110 + 4-111 + 4-112 + 4-113 + 4-114 + 4-115 + 4-116 + 4-117 + 4-118 + 4-119 + 4-120 + 4-121 + 4-122 + 4-123 + 4-124 + 4-125 + 4-126 + 4-127 + 4-128 +

Example 7 (Cell Cycle Analysis)

[0456] ACHN cells or HT-29 cells were cultured in a 6 well plate at 2.510.sup.5 cells/1.8 mL/well for 24 hrs, then a test substance (less than 10 M) dissolved in DMSO was added. After 24 hrs, cells were detached using trypsin-EDTA and the DNA content of single cell was analyzed by flow cytometry method using a CycleTEST PLUS (BECKTON DICKINSON) kit, and the proportion of the cells in the G0/G1 phase.Math.S phase.Math.G2/M phase was calculated. As a control, DMSO was used and the test was performed with n=2.

[0457] The results are shown in Tables 7-1 and 7-2 according to the following.

G1: the ratio of the cells in the G0/G1 phase was not less than 1.2-fold as compared to that of DMSO.

TABLE-US-00107 TABLE 7-1 Example CELL RATIO OF No. G0/G1 PHASE 1-2 G1 1-4 G1 1-6 G1 1-7 G1 1-9 G1 1-11 G1 1-21 G1 1-25 G1 1-26 G1 1-33 G1 1-34 G1 1-38 G1 1-43 G1 1-49 G1 1-50 G1 1-51 G1 1-55 G1 1-69 GI 1-77 G1 1-78 G1 1-84 G1 1-85 G1 1-86 G1 1-88 G1 1-89 G1 1-90 G1 1-91 G1 1-92 G1 1-93 G1 1-94 G1 1-95 G1 1-97 G1 1-99 G1 1-100 G1 1-101 G1 1-102 G1 1-103 G1 1-104 G1

TABLE-US-00108 TABLE 7-2 Example CELL RATIO OF No. G0/G1 PHASE 1583-7 G1 4-1 G1 4-3 G1 4-16 G1 4-70 G1 4-82 G1 4-104 G1 4-126 G1

Example 8 (Evaluation on the Nude-Mouse Xenograft Model)

[0458] HT-29 cells (5.010.sup.6 cells/100 L/head, suspended in HBSS (Hanks' solution)) in the logarithmic growth phase were implanted in a mouse (Balb/c-nu/nu) at the right lateral abdomen under ether anesthesia. After 5 days of implantation, the long diameter and short diameter of the tumor were measured, and the mice were divided into groups such that each group has an equivalent average tumor volume. For grouping, a grouping soft (general grouping system (Visions) was used. From the next day of the grouping, a test substance suspended in 0.5% MC (methyl cellulose) was repeatedly orally administered twice a day for 10 days (30 mg/kg). The tumor volume was measured twice a week and used as an index of antitumor activity. As a control, 0.5% MC was used and the test was performed with n=6-8.

[0459] The index (T/C (%)) of the antitumor activity was calculated according to the following formula.

T/C(%)=(The average tumor volume of the group treated with a test substance)/(The average tumor volume of the Vehicle group)100

[0460] The tumor volume was calculated according to the following formula.

Tumor volume(mm.sup.3)=LWW/2

(L: long diameter (mm) of tumor, W: short diameter (mm) of tumor)

TABLE-US-00109 TABLE 8 Example No. T/C(%) 1-257 26 3-8 27 4-1 3 4-15 31 4-16 10 4-49 35 4-54 11 4-70 31

Example 9 (p27 Protein Induction Test)

[0461] ACHN cells or HT-29 cells were cultured in a 6 well plate at 2.510.sup.5 cells/1.8 mL/well for 24 hrs, a test substance (0.1 1M) dissolved in DMSO was added. After 24 hrs, cells were detached using trypsin-EDTA (ethylene diamine tetraacetic acid) and solubilized with NuPAGE LDS sample buffer (Invitrogen). Using an RC DC protein assay kit (BIO-RAD), the protein concentration of the sample was quantitated, and a sample in an amount corresponding to 10 g of BSA (bovine serum albumin) was analyzed by Western blotting using an anti-p27 antibody. The density of the band stained with the anti-p27 antibody was measured by a densitometer to quantify the amount of p27 protein. As a control, DMSO was used and the test was performed with n=2 and the average protein amount was determined.

[0462] The results are shown in Tables 9-1 to 9-4 according to the following.

+: As compared to DMSO, not less than 1.5-fold induction of p27 protein

TABLE-US-00110 TABLE 9-1 Example Induction of No. p27 protein 1-1 + 1-89 + 1-112 + 1-114 + 1-142 + 1-152 + 1-175 + 1-182 + 1-185 + 1-186 + 1-218 + 1-219 + 1-221 + 1-222 + 1-224 + 1-226 + 1-228 + 1-240 + 1-242 + 1-243 + 1-245 + 1-249 + 1-253 + 1-257 + 1-259 + 1-260 + 1-262 + 1-263 + 1-264 + 1-265 + 1-266 + 1-268 + 1-271 + 1-272 + 1-274 + 1-275 + 1-279 + 1-282 +

TABLE-US-00111 TABLE 9-2 Example Induction of No. p27 protein 1-283 + 1-284 + 1-285 + 1-286 + 1-287 + 1-289 + 1-290 + 1-293 + 1-295 + 1-296 + 1-297 + 1-298 + 1-299 + 1-301 + 1-302 + 1-303 + 1-307 + 1-309 + 1-310 + 1-311 + 1-315 + 1-316 + 1-317 + 1-318 + 1-319 + 1-320 + 1-322 + 1-325 + 1-327 + 1-328 + 1-336 + 1-337 + 1-338 + 1-340 + 1-341 + 1-342 + 3-4 + 3-5 +

TABLE-US-00112 TABLE 9-3 Example Induction of No. p27 protein 3-6 + 3-7 + 3-6 + 4-1 + 4-2 + 4-3 + 4-6 + 4-9 + 4-10 + 4-11 + 4-12 + 4-15 + 4-16 + 4-21 + 4-43 + 4-45 + 4-48 + 4-49 + 4-50 + 4-51 + 4-53 + 4-54 + 4-55 + 4-56 + 4-58 + 4-59 + 4-60 + 4-61 + 4-64 + 4-66 + 4-67 + 4-70 + 4-71 + 4-72 + 4-73 + 4-74 + 4-76 + 4-77 +

TABLE-US-00113 TABLE 9-4 Example Induction of No. p27 protein 4-78 + 4-80 + 4-81 + 4-82 + 4-88 + 4-89 + 4-90 + 4-91 + 4-92 + 4-93 + 4-97 + 4-98 + 4-99 + 4-101 + 4-102 + 4-103 + 4-104 + 4-105 + 4-106 + 4-107 + 4-108 + 4-109 + 4-110 + 4-113 + 4-114 + 4-115 + 4-116 + 4-117 + 4-118 + 4-119 + 4-120 + 4-121 + 4-122 + 4-123 + 4-124 + 4-125 + 4-126 + 4-127 + 4-128 +

Example 10 (Evaluation of MEK Enzyme Inhibitory Activity)

[0463] To an evaluation system where Raf (B-Raf or c-Raf) and MEK (MEK1 or MEK2) were mixed, or MEK (MEK1 or MEK2) and ERK2 were mixed was added a test substance dissolved in DMSO, and an ATP solution containing [-32P]-ATP was added to start the enzyme reaction. After reacting at 30 C. for 20 min, the reaction mixture was subjected to SDS-PAGE (sodium dodecylsulfate-polyacrylamide gel electrophoresis) and radioactivity of phosphorylated MEK or ERK2 was measured by Bio Imaging Analyzer (BAS2000, Fuji photo film).

[0464] With the radioactivity of the solvent added control as 100%, inhibitory rate (%) by the test substance was determined, and IC.sub.50 value was calculated.

[0465] The test was performed with n=1 and the average values of two or three times of testing are shown. The results are summarized in Table 10.

TABLE-US-00114 TABLE 10 IC.sub.50 of various enzyme reaction system (M) enzyme Example 1-257 Example 4-1 B-Raf 0.0060 0.0067 MEK1 B-Raf 0.0188 0.0128 MEK2 c-Raf MEK1 c-Raf 0.0078 0.0130 MEK2 MEK1 1.3 0.290 ERK2 MEK2 1.6 0.190 ERK2

Example 11 (Evaluation on the Mouse Collagen Arthritis Model)

[0466] Bovine type II collagen (100 g) was resuspended with Freund's complete adjuvant and intracutaneously administered (initial immunization) to the tail head of mouse (DBA/1). Three weeks later, the same collagen was given to the tail head as boost, whereby multiple arthritis was induced. The test substance was oral administered forcibly once a day for 38 days from immediately before the initial immunization, and arthritis score after boost was calculated twice a week to examine the arthritis onset suppressing effect. For arthritis scores, the level of swelling of each of the four limbs of the mice was scored in 4 levels, and the average of the scores of four limbs was taken as the arthritis score of each individual. The test was performed with n=16.

[0467] The arthritis score at 17 days after boost (after consecutive administration for 38 days) was 2.2 for the medium administration group, and 0.57 (p<0.001, wilcoxson test) for the 1 mg/kg acetic acid solvate of compound of Example 4-1 administration group, thus showing a significant suppressive effect on the arthritis onset.

Example 12 (Evaluation on Inflammatory Cytokine Production)

[0468] The compounds of Example 4-1 and Example 4-16 suppressed production of TNF- or IL-6 upon stimulation of human peripheral blood-derived nomonuclear cell (PBMC) with LPS.

[0469] The MS and NMR data of the Example compounds shown in the above-mentioned Table 1-1 to Table 4-25 are shown below.

Example 1-1

[0470] MS ESI m/e: 590, 592 (M+H), 588, 590 (MH).

[0471] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.08 (m, 2H), 2.64-2.70 (m, 4H), 3.02 (s, 3H), 5.36 (s, 1H), 7.13 (d, J=9.0 Hz, 1H), 7.24-7.30 (m, 2H), 7.43-7.54 (m, 3H), 7.74 (d, J=9.0 Hz, 1H), 10.00 (brs, 1H), 10.53 (brs, 1H).

Example 1-2

Example 1-3

Example 1-4

[0472] MS ESI m/e: 470, 471(M+H), 473, 474, 469 (MH), 470, 471.

[0473] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.68 (s, 3H), 5.47 (s, 1H), 7.24-7.63 (m, 14H), 10.63 (brs, 1H).

Example 1-5

[0474] MS ESI m/e: 470, 471(M+H), 473, 474, 469 (MH), 470, 471.

[0475] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.68 (s, 3H), 5.60 (s, 1H), 7.25-7.57 (m, 14H), 10.52 (brs, 1H).

Example 1-6

[0476] MS ESI m/e: 451 (M+H), 449 (MH).

[0477] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.34 (s, 3H), 2.88 (s, 3H), 5.79 (s, 1H), 7.08-7.18 (m, 4H), 7.27-7.32 (m, 2H), 7.37-7.54 (m, 8H), 10.24 (s, 1H).

Example 1-7

[0478] MS ESI m/e: 480 (M+H).

[0479] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.87 (s, 3H), 2.95 (s, 6H), 5.66 (s, 1H), 6.67-6.73 (m, 2H), 7.05-7.11 (m, 2H), 7.27-7.32 (m, 2H), 7.37-7.55 (m, 8H), 10.24 (s, 1H).

Example 1-8

[0480] MS ESI m/e: 455 (M+H), 453 (MH).

[0481] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.88 (s, 3H), 5.69 (s, 1H), 7.03-7.10 (m, 2H), 7.17-7.23 (m, 2H), 7.27-7.32 (m, 2H), 7.37-7.55 (m, 8H), 10.24 (s, 1H).

Example 1-9

[0482] MS ESI m/e: 467 (M+H), 465 (MH).

[0483] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.88 (s, 3H), 3.81 (s, 3H), 5.67 (s, 1H), 6.86-6.95 (m, 2H), 7.12-7.20 (m, 2H), 7.28-7.34 (m, 2H), 7.37-7.58 (m, 8H), 10.14 (s, 1H).

Example 1-10

[0484] MS ESI m/e: 485 (M+H), 483 (MH).

[0485] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.86 (s, 3H), 4.32 (d, J=4.0 Hz, 2H), 5.39 (s, 1H), 7.23-7.31 (m, 6H), 7.34-7.38 (m, 2H), 7.39-7.52 (m, 6H), 9.03 (t, J=6.0 Hz, 1H).

Example 1-11

[0486] MS ESI m/e: 515, 517 (M+H), 513, 515 (MH).

[0487] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.67 (s, 3H), 5.56 (s, 1H), 7.25-7.29 (m, 2H), 7.34-7.38 (m, 2H), 7.41-7.55 (m, 8H), 7.57-7.61 (m, 2H), 10.48 (s, 1H).

Example 1-12

Example 1-13

Example 1-14

[0488] MS ESI m/e: 485 (M+H).

[0489] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.74 (s, 3H), 3.22 (s, 3H), 6.03 (s, 1H), 6.99-7.05 (m, 4H), 7.21-7.25 (m, 2H), 7.32-7.40 (m, 3H), 7.44-7.54 (m, 5H).

Example 1-15

[0490] MS ESI m/e: 443 (M+H).

[0491] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.17-1.95 (m, 11H), 2.63 (s, 3H), 5.28 (s, 1H), 7.31-7.55 (m, 10H), 8.76 (d, J=6.0 Hz, 1H).

Example 1-16

[0492] MS ESI m/e: 481 (M+H), 479 (MH).

[0493] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.88 (s, 3H), 5.69 (s, 1H), 5.99 (s, 2H), 6.85-6.82 (m, 3H), 7.28-7.34 (m, 2H), 7.37-7.58 (m, 8H), 10.12 (s, 1H).

Example 1-17

[0494] MS ESI m/e: 505, 507 (M+H), 503, 505 (MH).

[0495] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.90 (s, 3H), 5.87 (s, 1H), 7.07-7.11 (m, 1H), 7.26-7.31 (m, 2H), 7.35-7.56 (m, 10H), 10.45 (s, 1H).

Example 1-18

[0496] MS ESI m/e: 499 (M+H), 497 (MH).

[0497] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.56 (t, J=7.5 Hz, 3H), 1.05-1.12 (m, 2H), 3.30-3.40 (m, 2H), 5.54 (s, 1H), 7.31-7.56 (m, 14H), 10.52 (s, 1H).

Example 1-19

[0498] MS ESI m/e: 513 (M+H), 511 (MH).

[0499] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62 (s, 3H), 0.64 (s, 3H), 1.04 (d, J=6.0 Hz, 1H), 1.94-2.06 (m, 1H), 3.13 (brs, 1H), 5.56 (s, 1H), 7.32-7.60 (m, 14H), 10.58 (s, 1H).

Example 1-20

[0500] MS ESI m/e: 515 (M+H), 513 (MH).

[0501] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 3.04 (t, J=6.0 Hz, 2H), 3.09 (s, 3H), 3.61 (t, J=4.5 Hz, 2H), 5.53 (s, 1H), 7.32-7.60 (m, 14H), 10.52 (s, 1H).

Example 1-21

[0502] MS ESI m/e: 465 (M+H), 463 (MH).

[0503] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 1.19 (t, J=8.0 Hz, 3H), 2.61 (q, J=8.0 Hz, 2H), 2.66 (s, 3H), 5.46 (s, 1H), 7.17-7.21 (m, 2H), 7.25-7.29 (m, 2H), 7.34-7.38 (m, 2H), 7.41-7.55 (m, 8H), 10.37 (s, 1H).

Example 1-22

[0504] MS ESI m/e: 451 (M+H), 449 (MH).

[0505] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.21 (s, 3H), 2.66 (s, 3H), 5.12 (s, 1H), 7.18-7.55 (m, 14H), 10.22 (s, 1H).

Example 1-23

[0506] MS ESI m/e: 513 (M+H), 511 (MH).

[0507] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.68 (s, 3H), 5.65 (s, 1H), 7.33-7.56 (m, 15H), 7.66-7.74 (m, 4H), 10.56 (s, 1H).

Example 1-24

[0508] MS ESI m/e: 467 (M+H), 465 (MH).

[0509] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.89 (s, 3H), 3.82 (s, 3H), 5.83 (s, 1H), 6.91-6.98 (m, 2H), 7.13-7.19 (m, 1H), 7.27-7.33 (m, 2H), 7.37-7.54 (m, 9H), 10.21 (s, 1H).

Example 1-25

[0510] MS ESI m/e: 479 (M+H), 477 (MH).

[0511] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.25 (d, J=6.7 Hz, 6H), 2.85-2.95 (m, 1H), 2.88 (s, 3H), 5.80 (s, 1H), 7.12-7.17 (m, 2H), 7.19-7.24 (m, 2H), 7.27-7.32 (m, 2H), 7.37-7.55 (m, 8H), 10.24 (s, 1H).

Example 1-26

[0512] MS ESI m/e: 505, 507 (M+H), 503, 505 (MH).

[0513] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.89 (s, 3H), 5.70 (s, 1H), 7.22-7.32 (m, 3H), 7.37-7.55 (m, 10H), 10.39 (s, 1H).

Example 1-27

[0514] MS ESI m/e: 520 (M+H).

[0515] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.54-1.62 (m, 4H), 1.67-1.75 (m, 4H), 2.87 (s, 3H), 3.14 (t, J=5.6 Hz, 2H), 5.70 (s, 1H), 6.87-6.93 (m, 2H), 7.06-7.11 (m, 2H), 7.27-7.32 (m, 2H), 7.37-7.54 (m, 8H), 10.09 (s, 1H).

Example 1-28

[0516] MS ESI m/e: 508 (M+H), 506 (MH).

[0517] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.16 (t, J=7.1 Hz, 6H), 2.87 (s, 3H), 3.34 (q, J=7.1 Hz, 4H), 5.65 (s, 1H), 6.60-6.65 (m, 2H), 7.00-7.06 (m, 2H), 7.27-7.31 (m, 2H), 7.36-7.54 (m, 8H), 9.98 (s, 1H).

Example 1-29

[0518] MS ESI m/e: 527 (M+H), 525 (MH).

[0519] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.88 (s, 3H), 3.97 (s, 2H), 5.83 (s, 1H), 7.12-7.58 (m, 19H), 10.29 (s, 1H).

Example 1-30

[0520] MS ESI m/e: 522 (M+H), 520 (MH).

[0521] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.66 (s, 3H), 3.10-3.13 (m, 4H), 3.73-3.76 (m, 4H), 5.32 (s, 1H), 7.01 (d, J=9.0 Hz, 2H), 7.15 (d, J=9.0 Hz, 2H), 7.35-7.57 (m, 10H), 10.20 (brs, 1H).

Example 1-31

[0522] MS ESI m/e: 493 (M+H), 491 (MH).

[0523] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.90 (t, J=8.0 Hz, 3H), 1.26-1.36 (m, 2H), 1.52-1.60 (m, 2H), 2.58 (t, J=8.0 Hz, 2H), 2.66 (s, 3H), 5.46 (s, 1H), 7.18 (d, J=8.0 Hz, 2H), 7.25 (d, J=8.0 Hz, 2H), 7.35-7.37 (m, 2H), 7.41-7.54 (m, 8H), 10.36 (brs, 1H).

Example 1-32

[0524] MS ESI m/e: 409 (M+H), 407 (MH).

[0525] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 3.46 (s, 3H), 3.48 (s, 3H), 5.49 (s, 1H), 7.28-7.34 (m, 4H), 7.41-7.53 (m, 5H), 10.44 (brs, 1H).

Example 1-33

[0526] MS ESI m/e: 505 (M+H), 503 (MH).

[0527] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.67 (s, 3H), 5.78 (s, 1H), 7.34 (d, J=8.0 Hz, 2H), 7.40-7.53 (m, 10H), 7.73 (d, J=8.0 Hz, 2H), 10.75 (brs, 1H).

Example 1-34

[0528] MS ESI m/e: 485 (M+H), 483 (MH).

[0529] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.32 (s, 3H), 2.67 (s, 3H), 5.35 (s, 1H), 7.23-7.56 (m, 13H), 10.48 (brs, 1H).

Example 1-35

[0530] MS ESI m/e: 409 (M+H), 407 (MH).

[0531] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.61 (s, 3H), 3.26 (s, 3H), 5.50 (s, 1H), 7.35 (d, J=6.0 Hz, 2H), 7.44-7.54 (m, 5H), 7.49 (d, J=6.0 Hz, 2H), 10.62 (brs, 1H).

Example 1-36

[0532] MS ESI m/e: 431 (M+H).

[0533] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.00 (s, 9H), 2.86 (s, 3H), 2.92 (d, J=8.0 Hz, 2H), 5.43 (s, 1H), 7.24-7.29 (m, 2H), 7.34-7.53 (m, 8H), 8.78 (t, J=6.0 Hz, 1H).

Example 1-37

[0534] MS ESI m/e: 481 (M+H), 479 (MH).

[0535] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.70 (s, 3H), 5.85 (s, 1H), 7.36-7.54 (m, 10H), 7.43 (d, J=9.0 Hz, 2H), 7.97 (d, J=9.0 Hz, 2H), 10.81 (brs, 1H).

Example 1-38

[0536] MS ESI m/e: 465 (M+H), 463 (MH).

[0537] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.18 (t, J=7.5 Hz, 3H), 2.63 (q, J=7.5 Hz, 2H), 2.88 (s, 3H), 5.43 (s, 1H), 7.20-7.36 (m, 6H), 7.39-7.57 (m, 8H), 10.07 (s, 1H).Example 1-39 MS ESI m/e: 507 (M+H), 505 (MH).

[0538] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.78 (t, J=7.3 Hz, 6H), 1.44-1.77 (m, 4H), 2.25-2.38 (m, 1H), 2.89 (s, 3H), 5.85 (s, 1H), 7.10-7.19 (m, 4H), 7.28-7.34 (m, 2H), 7.38-7.57 (m, 8H), 10.28 (s, 1H).

Example 1-40

[0539] MS ESI m/e: 535 (M+H), 533 (MH).

[0540] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.85 (t, J=7.4 Hz, 6H), 1.08-1.24 (m, 4H), 1.45-1.64 (m, 4H), 2.45-2.58 (m, 1H), 2.89 (s, 3H), 5.84 (s, 1H), 7.10-7.18 (m, 4H), 7.28-7.34 (m, 2H), 7.38-7.57 (m, 8H), 10.27 (s, 1H).

Example 1-41

[0541] MS ESI m/e: 497 (M+H), 495 (MH).

[0542] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.79-1.00 (m, 4H), 1.70-1.78 (m, 1H), 5.73 (s, 1H), 7.12-7.18 (m, 2H), 7.26-7.34 (m, 4H), 7.35-7.55 (m, 8H), 10.35 (s, 1H).

Example 1-42

[0543] MS ESI m/e: 539, 541 (M+H), 537, 539 (MH).

[0544] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.92 (s, 3H), 5.80 (s, 1H), 7.14-7.19 (m, 2H), 7.19-7.24 (m, 2H), 7.30-7.36 (m, 4H), 7.45-7.51 (m, 4H), 10.24 (s, 1H).

Example 1-43

[0545] MS ESI m/e: 485(M+H), 483 (MH).

[0546] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.57 (s, 3H), 2.76 (s, 3H), 6.93 (d, J=9.0 Hz, 2H), 7.31-7.54 (m, 12H), 10.07 (brs, 1H).

Example 1-44

[0547] MS ESI m/e: 477(M+H), 475 (MH).

[0548] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.07-1.85 (m, 11H), 2.60 (s, 3H), 4.65-4.65 (m, 1H), 5.49 (s, 1H), 7.35-7.54 (m, 5H), 10.63 (brs, 1H).

Example 1-45

[0549] MS ESI m/e: 485 (M+H), 483 (MH).

[0550] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.63 (s, 3H), 5.10 (brs, 2H), 5.51 (s, 1H), 7.24-7.56 (m, 14H), 10.57 (s, 1H).

Example 1-46

[0551] MS ESI m/e: 452 (M+H).

[0552] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.67 (s, 3H), 5.47 (s, 1H), 7.19 (d, J=9.0 Hz, 2H), 7.29 (d, J=6.0 Hz, 2H), 7.35-7.40 (m, 2H), 7.41-7.57 (m, 8H), 10.40 (s, 1H).

Example 1-47

[0553] MS ESI m/e: 421 (M+H), 419 (MH).

[0554] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.19-2.30 (m, 2H), 4.09-4.20 (m, 4H), 5.73 (s, 1H), 7.11-7.19 (m, 2H), 7.23-7.36 (m, 4H), 7.45-7.60 (m, 3H), 10.49 (s, 1H).

Example 1-48

[0555] MS ESI m/e: 453(M+H), 451 (MH).

[0556] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.65 (s, 3H), 5.08 (s, 1H), 6.07 (brs, 2H), 6.52 (d, J=9.0 Hz, 1H), 7.29-7.57 (m, 11H), 7.80 (d, J=3.0 Hz, 1H), 9.94 (brs, 1H).

Example 1-49

[0557] MS ESI m/e: 466(M+H).

[0558] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.67 (s, 3H), 2.86 (s, 3H), 5.50 (s, 1H), 7.33-7.57 (m, 14H), 10.44 (brs, 1H).

Example 1-50

[0559] MS ESI m/e: 479 (M+H), 477 (MH).

[0560] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.90 (t, J=7.3 Hz, 3H), 1.51-1.66 (m, 2H), 2.57 (t, J=7.5 Hz, 2H), 2.88 (s, 3H), 5.43 (s, 1H), 7.17-7.30 (m, 4H), 7.30-7.37 (m, 2H), 7.39-7.58 (m, 8H), 10.07 (s, 1H).

Example 1-51

[0561] MS ESI m/e: 493 (M+H), 491 (MH).

[0562] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.88 (t, J=6.0 Hz, 3H), 1.26-1.38 (m, 2H), 1.49-1.61 (m, 2H), 2.55-2.61 (m, 2H), 2.88 (s, 3H), 5.43 (s, 1H), 7.14-7.34 (m, 6H), 7.39-7.56 (m, 8H), 10.07 (brs, 1H).

Example 1-52

[0563] MS ESI m/e: 528 (M+H), 526 (MH).

[0564] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.15 (s, 6H), 2.12-2.22 (m, 2H), 3.72 (t, J=6.5 Hz, 2H), 5.81 (s, 1H), 7.15-7.21 (m, 2H), 7.26-7.35 (m, 4H), 7.40-7.56 (m, 8H), 10.35 (s, 1H).

Example 1-53

[0565] MS ESI m/e: 485 (M+H), 483 (MH).

[0566] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.24 (s, 3H), 2.88 (s, 3H), 5.39 (s, 1H), 7.17-7.20 (m, 2H), 7.28-7.33 (m, 2H), 7.37-7.55 (m, 9H), 10.04 (s, 1H).

Example 1-54

[0567] MS ESI m/e: 472 (M+H), 470 (MH).

[0568] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.68 (s, 3H), 5.50 (s, 1H), 7.34-7.38 (m, 2H), 7.41-7.57 (m, 9H), 7.87 (dd, J=4.0, 8.0 Hz, 1H), 8.37 (d, J=4.0 Hz, 1H), 10.49 (s, 1H).

Example 1-55

[0569] MS ESI m/e: 494 (M+H), 492 (MH).

[0570] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.15 (s, 3H), 2.64 (s, 3H), 2.90 (s, so 6H), 4.92 (s, 1H), 6.63 (dd, J=3.0, 9.0 Hz, 1H), 6.69 (d, J=3.0 Hz, 1H), 7.03 (d, J=9.0 Hz, 1H), 7.36-7.57 (m, 10H), 9.89 (s, 1H).

Example 1-56

[0571] MS ESI m/e: 497 (M+H), 495 (MH).

[0572] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 4.24 (d, J=4.2 Hz, 2H), 4.87 (d, J=16.9 Hz, 1H), 5.02 (d, J=10.4 Hz, 1H), 5.40-5.51 (m, 1H), 5.83 (s, 1H), 7.16-7.21 (m, 2H), 7.26-7.30 (m, 2H), 7.31-7.36 (m, 2H), 7.36-7.41 (m, 2H), 7.43-7.55 (m, 6H), 10.40 (s, 1H).

Example 1-57

[0573] MS ESI m/e: 482 (M+H), 480 (MH).

[0574] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.93 (s, 3H), 6.20 (s, 1H), 7.28-7.33 (m, 2H), 7.35-7.44 (m, 4H), 7.46-7.59 (m, 6H), 8.20-8.27 (m, 2H), 10.95 (s, 1H).

Example 1-58

[0575] MS ESI m/e: 451(M+H), 449(MH).

[0576] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.83 (d, J=9.0 Hz, 6H), 1.90-2.04 (m, 1H), 3.45 (s, 3H), 3.98 (d, J=9.0 Hz, 2H), 5.50 (s, 1H), 7.28-7.34 (m, 4H), 7.43-7.55 (m, 5H), 10.30 (brs, 1H).

Example 1-59

[0577] MS ESI m/e: 444 (M+H), 442 (MH).

[0578] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 3.14 (s, 3H), 5.22 (s, 1H), 6.96-7.03 (m, 2H), 7.17-7.41 (m, 5H), 7.41-7.55 (m, 3H), 7.60 (d, J=3.7 Hz, 1H), 7.89 (d, J=3.7 Hz, 1H), 11.57 (s, 1H).

Example 1-60

[0579] MS ESI m/e: 457 (M+H), 455 (MH).

[0580] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 5.70 (s, 1H), 7.14-7.12 (m, 2H), 7.30-7.43 (m, 6H), 7.43-7.65 (m, 6H), 10.48 (s, 1H).

Example 1-61

[0581] MS ESI m/e: 466 (M+H), 464 (MH).

[0582] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.95 (s, 3H), 5.56 (s, 1H), 6.65-6.75 (m, 2H), 7.02-7.14 (m, 2H), 7.29-7.67 (m, 10H), 10.18 (s, 1H).

Example 1-62

[0583] MS ESI m/e: 506 (M+H), 504 (MH).

[0584] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.96 (6H, s), 4.23 (d, J=4.7 Hz, 2H), 4.88 (d, J=17.3 Hz, 1H), 5.02 (d, J=10.6 Hz, 1H), 5.40-5.55 (m, 1H), 5.69 (s, 1H), 6.68-6.75 (m, 2H), 7.07-7.14 (m, 2H), 7.27-7.33 (m, 2H), 7.37-7.56 (m, 8H), 10.10 (s, 1H).

Example 1-63

[0585] MS ESI m/e: 472 (M+H).

[0586] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.72 (s, 3H), 7.16 (d, J=9.0 Hz, 1H), 7.34-7.42 (m, 2H), 7.43-7.60 (m, 10H), 7.82 (dd, J=3.0, 6.0 Hz, 1H), 8.42 (d, J=3.0 Hz, 1H), 11.68 (s, 1H).

Example 1-64

[0587] MS ESI m/e: 487 (M+H).

[0588] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.94 (s, 3H), 3.12 (s, 6H), 7.26-7.32 (m, 2H), 7.34-7.54 (m, 8H), 7.68 (s, 1H), 9.00 (d, J=4.8 Hz, 1H), 10.26 (d, J=5.8 Hz, 1H).

Example 1-65

[0589] MS ESI m/e: 480 (M+H), 478 (MH).

[0590] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.24 (t, J=7.3 Hz, 3H), 2.68 (s, 3H), 3.27 (q, J=7.3 Hz, 2H), 5.53 (s, 1H), 7.29-7.60 (m, 16H), 10.46 (s, 1H).

Example 1-66

[0591] MS ESI m/e: 478 (M+H), 477(MH).

[0592] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.16 (d, J=6.8 Hz, 6H), 2.65 (s, 3H), 3.05-3.15 (m, 1H), 5.00 (s, 1H), 7.27-7.54 (m, 14H), 10.19 (brs, 1H).

Example 1-67

[0593] MS ESI m/e: 485 (M+H), 483(MH).

[0594] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.56 (t, J=7.0 Hz, 3H), 3.55 (q, 2H, J=7.0 Hz), 5.53 (s, 1H), 7.10-7.13 (m, 2H), 7.32-7.56 (m, 12H), 10.49 (brs, 1H).

Example 1-68

[0595] MS ESI m/e: 528 (M+H), 526 (MH).

[0596] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.15 (s, 6H), 2.88 (s, 3H), 3.31 (s, 2H), 5.65 (s, 1H), 7.21-7.54 (m, 13H), 10.50 (s, 1H).

Example 1-69

[0597] MS ESI m/e: 493 (M+H), 491(MH).

[0598] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.84 (d, J=6.6 Hz, 6H), 1.78-1.88 (m, 1H), 2.45 (d, J=7.2 Hz, 2H), 2.67 (s, 3H), 5.15 (s, 1H), 7.20-7.53 (m, 14H), 10.24 (brs, 1H).

Example 1-70

[0599] MS ESI m/e: 499, 501 (M+H), 497, 499 (MH).

[0600] .sup.1H-NMR (DMSO-ds, 300 MHz) 2.37 (s, 3H), 2.38 (s, 3H), 2.70 (s, 3H), 5.54 (s, 1H), 7.21-7.50 (m, 12H), 10.51 (brs, 1H).

Example 1-71

[0601] MS ESI m/e: 507, 508 (M+H), 505, 506(MH).

[0602] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.85 (d, J=6.5 Hz, 6H), 1.37-1.42 (m, 2H), 1.49-1.53 (m, 1H), 2.50-2.58 (m, 2H), 2.67 (s, 3H), 5.12 (s, 1H), 7.24-7.55 (m, 14H), 10.23 (brs, 1H).

Example 1-72

[0603] MS ESI m/e: 499 (M+H), 497 (MH).

[0604] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.12-2.44 (m, 6H), 2.84 (s, 3H), 5.83 (brs, 1H), 7.05-7.48 (m, 12H), 10.47-10.57 (m, 1H).

Example 1-73

[0605] MS ESI m/e: 522 (M+H), 520 (MH).

[0606] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.91 (t, J=7.3 Hz, 3H), 1.49-1.66 (m, 2H), 2.50 (t, J=7.7 Hz, 2H), 2.87 (s, 3H), 2.95 (s, 6H), 5.33 (s, 1H), 6.54-6.63 (m, 2H), 7.01-7.08 (m, 1H), 7.30-7.37 (m, 2H), 7.38-7.58 (m, 8H), 9.80 (s, 1H).

Example 1-74

[0607] MS ESI m/e: 506 (M+H), 504 (MH).

[0608] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.91-2.03 (m, 2H), 2.73 (t, J=6.4 Hz, 2H), 2.87 (s, 3H), 2.88 (s, 3H), 3.22 (t, J=5.7 Hz, 2H), 5.68 (s, 1H), 6.54 (d, J=8.4 Hz, 1H), 6.79-6.85 (m, 1H), 6.87-6.93 (m, 1H), 7.28-7.34 (m, 2H), 7.36-7.58 (m, 8H), 10.00 (s, 1H).

Example 1-75

[0609] MS ESI m/e: 531, 533 (M+H), 529, 531 (MH).

[0610] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.63 (s, 3H), 3.72 (s, 3H), 3.73 (s, 3H), 5.45 (s, 1H), 6.97 (t, J=9.1 Hz, 4H), 7.16-7.42 (m, 8H), 10.46 (brs, 1H).

Example 1-76

[0611] MS ESI m/e: 499, 501 (M+H), 497, 499 (MH).

[0612] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.26 (s. 3H), 2.27 (s, 3H), 2.63 (s, 3H), 5.46 (s, 1H), 7.09-7.42 (m, 12H), 10.42 (brs, 1H).

Example 1-77

[0613] MS ESI m/e: 483, 485 (M+H), 481, 483 (MH).

[0614] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.68 (s, 3H), 5.45 (s, 1H), 7.00-7.64 (m, 10H), 10.35 (brs, 1H).

Example 1-78

[0615] MS ESI m/e: 423 (M+H), 421 (MH).

[0616] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.30 (t, J=6.9 Hz, 3H), 2.82 (s, 3H), 4.08 (q, J=7.0 Hz, 2H), 5.77 (s, 1H), 7.19-7.25 (m, 2H), 7.31-7.39 (m, 4H), 7.41-7.54 (m, 3H), 10.53 (s, 1H).

Example 1-79

[0617] MS ESI m/e: 507, 508 (M+H), 505, 503 (MH).

[0618] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.64 (s, 3H), 5.46 (s, 1H), 7.23-7.51 (m, 12H), 10.37 (brs, 1H).

Example 1-80

[0619] MS ESI m/e: 463 (M+H), 461 (MH).

[0620] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.52-1.67 (m, 2H), 1.82-2.02 (m, 4H), 2.04-2.20 (m, 2H), 2.80 (s, 3H), 5.21-5.37 (m, 1H), 5.75 (s, 1H), 7.18-7.28 (m, 2H), 7.30-7.56 (m, 7H), 10.54 (s, 1H).

Example 1-81

[0621] MS ESI m/e: 437 (M+H), 435 (MH).

[0622] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.51 (d, J=7.0 Hz, 6H), 2.81 (s, 3H), 5.09-5.23 (m, 1H), 5.75 (s, 1H), 7.18-7.28 (m, 2H), 7.29-7.55 (m, 7H), 10.53 (s, 1H).

Example 1-82

[0623] MS ESI m/e: 437 (M+H), 435 (MH).

[0624] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.98 (t, J=7.4 Hz, 3H), 1.66-1.79 (m, 2H), 2.82 (s, 3H), 3.96 (t, J=7.6 Hz, 2H), 5.77 (s, 1H), 7.20-7.25 (m, 2H), 7.32-7.40 (m, 4H), 7.41-7.54 (m, 3H), 10.54 (s, 1H).

Example 1-83

[0625] MS ESI m/e: 451 (M+H), 449 (MH).

[0626] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.96 (t, J=7.4 Hz, 3H), 1.34-1.47 (m, 2H), 1.62-1.73 (m, 2H), 2.81 (s, 3H), 3.99 (t, J=7.6 Hz, 2H), 5.76 (s, 1H), 7.18-7.24 (m, 2H), 7.31-7.39 (m, 4H), 7.41-7.52 (m, 3H), 10.53 (s, 1H).

Example 1-84

[0627] MS ESI m/e: 435 (M+H), 433 (MH).

[0628] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.81-0.90 (m, 2H), 1.14-1.24 (m, 2H), 2.71-2.81 (m, 1H), 2.81 (s, 3H), 5.77 (s, 1H), 7.17-7.24 (m, 2H), 7.27-7.39 (m, 4H), 7.39-7.52 (m, 3H), 10.38 (s, 1H).

Example 1-85

[0629] MS ESI m/e: 423 (M+H), 421 (MH).

[0630] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.25-2.30 (m, 3H), 2.51-2.57 (m, 3H), 3.26-3.31 (m, 3H), 5.48-5.52 (m, 1H), 7.24-7.55 (m, 8H), 10.74 (s, 1H).

Example 1-86

[0631] MS ESI m/e: 423 (M+H), 421 (MH).

[0632] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.35 (s, 3H), 2.65 (s, 3H), 3.26 (s, 3H), 5.51 (s, 1H), 7.23-7.32 (m, 3H), 7.32-7.45 (m, 3H), 7.46-7.54 (m, 2H), 10.64 (s, 1H).

Example 1-87

[0633] MS ESI m/e: 423 (M+H), 421 (MH).

[0634] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) & 2.37 (s, 3H), 2.63 (s, 3H), 3.26 (s, 3H), 5.50 (s, 1H), 7.29-7.39 (m, 6H), 7.46-7.53 (m, 2H), 10.64 (s, 1H).

Example 1-88

[0635] MS ESI m/e: 444 (M+H), 442 (MH).

[0636] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.13-1.23 (m, 2H), 2.71-2.80 (m, 1H), 2.80 (s, 3H), 2.97 (s, 6H), 5.62 (s, 1H), 6.69-6.77 (m, 2H), 7.08-7.16 (m, 2H), 7.29-7.35 (m, 2H), 7.38-7.52 (m, 3H), 10.07 (s, 1H).

Example 1-89

[0637] MS ESI m/e: 479, 481 (M+H), 477, 479 (MH).

[0638] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.15-1.26 (m, 2H), 2.71-2.82 (m, 1H), 2.82 (s, 3H), 5.80 (s, 1H), 7.13-7.21 (m, 2H), 7.28-7.36 (m, 2H), 7.39-7.56 (m, 5H), 10.41 (s, 1H).

Example 1-90

[0639] MS ESI m/e: 477 (M+H), 475 (MH).

[0640] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.84 (s, 3H), 4.75 (q, J=8.4 Hz, 2H), 5.76 (s, 1H), 7.19-7.28 (m, 2H), 7.31-7.42 (m, 4H), 7.43-7.57 (m, 3H), 10.20 (s, 1H).

Example 1-91

[0641] MS ESI m/e: 513 (M+H), 511 (MH).

[0642] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64 (t, J=6.0 Hz, 3H), 1.21-1.41 (m, 2H), 2.15 (t, J=7.5 Hz, 2H), 2.76 (s, 3H), 6.93-7.07 (m, 2H), 7.27-7.37 (m, 4H), 7.39-7.64 (m, 8H), 9.92 (s, 1H).

Example 1-92

[0643] MS ESI m/e: 521, 523 (M+H), 519, 521 (MH).

[0644] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.85 (s, 3H), 4.75 (q, J=8.4 Hz, 2H), 5.78 (s, 1H), 7.14-7.22 (m, 2H), 7.32-7.40 (m, 2H), 7.44-7.58 (m, 5H), 10.20 (s, 1H).

Example 1-93

[0645] MS ESI m/e: 486 (M+H), 484 (MH).

[0646] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 2.83 (s, 3H), 2.97 (s, 6H), 4.75 (q, J=8.4 Hz, 2H), 5.61 (s, 1H), 6.67-6.81 (m, 2H), 7.08-7.18 (m, 2H), 7.32-7.40 (m, 2H), 7.41-7.56 (m, 3H), 9.92 (s, 1H).

Example 1-94

[0647] MS ESI m/e: 457 (M+H), 455 (MH).

[0648] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.18 (t, J=6.7 Hz, 3H), 2.66 (s, 3H), 3.93 (q, J=6.7 Hz, 2H), 5.50 (s, 1H), 7.36 (d, J=9.0 Hz, 2H), 7.46-7.56 (m, 4H), 7.57-7.66 (m, 2H), 10.62 (s, 1H).

Example 1-95

[0649] MS ESI m/e: 467, 469 (M+H), 465, 467 (MH).

[0650] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.28 (s, 3H), 2.53 (s, 3H), 3.28 (s, 3H), 5.51 (s, 1H), 7.23-7.35 (m, 4H), 7.38-7.44 (m, 2H), 7.58-7.65 (m, 2H), 10.72 (s, 1H).

Example 1-96

[0651] MS ESI m/e: 467, 469 (M+H), 465, 467 (MH).

[0652] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.29 (t, J=7.1 Hz, 3H), 2.81 (s, 3H), 4.07 (q, J=7.1 Hz, 2H), 5.78 (s, 1H), 7.14-7.19 (m, 2H), 7.31-7.36 (m, 2H), 7.40-7.53 (m, 5H), 10.53 (s, 1H).

Example 1-97

[0653] MS ESI m/e: 432 (M+H).

[0654] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.29 (t, J=7.1 Hz, 3H), 2.80 (s, 3H), 2.96 (s, 6H), 4.07 (q, J=7.0 Hz, 2H), 5.59 (s, 1H), 6.69-6.75 (m, 2H), 7.08-7.14 (m, 2H), 7.31-7.36 (m, 2H), 7.38-7.50 (m, 3H), 10.19 (s, 1H).

Example 1-98

[0655] MS ESI m/e: 435 (M+H), 433 (MH).

[0656] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.80-0.91 (m, 2H), 1.25-1.35 (m, 2H), 3.38-3.49 (m, 1H), 3.74 (s, 3H), 5.76 (s, 1H), 7.09-7.18 (m, 2H), 7.20-7.37 (m, 4H), 7.44-7.60 (m, 3H), 10.23 (s, 1H).

Example 1-99

[0657] MS ESI m/e: 432 (M+H).

[0658] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.27 (s, 3H), 2.51 (s, 3H), 2.92 (s, 6H), 3.27 (s, 3H), 5.21 (s, 1H), 6.76-6.84 (m, 2H), 7.06-7.14 (m, 2H), 7.23-7.38 (m, 2H), 7.38-7.44 (m, 2H), 10.35 (s, 1H).

Example 1-100

[0659] MS ESI m/e: 453 (M+H), 451 (MH).

[0660] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.92 (m, 2H), 1.14-1.24 (m, 2H), 2.74-2.83 (m, 1H), 2.86 (s, 3H), 5.76 (s, 1H), 7.18-7.33 (m, 5H), 7.33-7.40 (m, 2H), 7.45-7.55 (m, 1H), 10.41 (s, 1H).

Example 1-101

[0661] MS ESI m/e: 503 (M+H), 501 (MH).

[0662] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.78-0.91 (m, 2H), 1.14-1.26 (m, 2H), 2.73-2.86 (m, 1H), 2.82 (s, 3H), 5.76 (s, 1H), 7.19-7.29 (m, 2H), 7.32-7.41 (m, 2H), 7.42-7.50 (m, 1H), 7.61-7.79 (m, 2H), 7.80-7.89 (m, 1H), 10.50 (s, 1H).

Example 1-102

[0663] MS ESI m/e: 449 (M+H), 447 (MH).

[0664] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.74-0.96 (m, 2H), 1.11-1.31 (m, 2H), 2.30 (s, 3H), 2.74 (s, 3H), 2.76-2.85 (m, 1H), 5.76 (s, 1H), 7.04-7.12 (m, 1H), 7.18-7.43 (m, 7H), 10.53 (s, 1H).

Example 1-103

[0665] MS ESI m/e: 463 (M+H), 461 (MH).

[0666] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.76-0.90 (m, 2H), 1.11-1.27 (m, 2H), 1.26 (t, J=7.5 Hz, 3H), 2.40-2.67 (m, 2H), 2.71-2.84 (m, 1H), 2.75 (s, 3H), 5.76 (s, 1H), 7.08-7.14 (m, 1H), 7.18-7.47 (m, 7H), 10.54 (s, 1H).

Example 1-104

[0667] MS ESI m/e: 465 (M+H), 463 (MH).

[0668] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.79-0.94 (m, 2H), 1.11-1.28 (m, 2H), 2.71-2.83 (m, 1H), 2.84 (s, 3H), 3.84 (s, 3H), 5.76 (s, 1H), 7.00-7.13 (m, 2H), 7.19-7.30 (m, 3H), 7.32-7.40 (m, 2H), 7.41-7.52 (m, 1H), 10.52 (s, 1H).

Example 1-105

[0669] MS ESI m/e: 445 (M+H), 443 (MH).

[0670] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.92 (t, J=7.5 Hz, 3H), 1.36 (sext, J=7.5 Hz, 2H), 1.59 (quint, J=7.5 Hz, 2H), 2.33 (s, 3H), 2.62 (t, J=7.5 Hz, 2H), 2.75 (s, 3H), 3.45 (s, 3H), 5.43 (s, 1H), 7.08-7.45 (m, 8H), 10.37 (s, 1H).

Example 1-106

[0671] MS ESI m/e: 458 (M+H).

[0672] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.77-0.92 (m, 2H), 1.14-1.27 (m, 2H), 2.30 (s, 3H), 2.72 (s, 3H), 2.74-2.85 (m, 1H), 2.96 (s, 6H), 5.60 (s, 1H), 6.69-6.79 (m, 2H), 7.03-7.18 (m, 3H), 7.22-7.42 (m, 3H), 10.20 (s, 1H).

Example 1-107

[0673] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0674] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.68-1.79 (m, 2H), 2.19-2.32 (m, 2H), 2.59 (s, 3H), 2.60-2.75 (m, 2H), 4.88-4.98 (m, 1H), 5.49 (s, 1H), 7.29 (d, J=8.7 Hz, 2H), 7.41-7.53 (m, 5H), 7.60 (d, J=8.6 Hz, 2H), 10.52 (brs, 1H).

Example 1-108

[0675] MS ESI m/e: 535, 537 (M+H), 533, 535 (MH).

[0676] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.27 (s, 3H), 2.54 (s, 3H), 4.62-4.88 (m, 2H), 5.49 (s, 1H), 7.28-7.30 (m, 4H), 7.41-7.42 (m, 2H), 7.62 (d, J=9.0 Hz, 2H), 10.40 (brs, 1H).

Example 1-109

[0677] MS ESI m/e: 437 (M+H), 435 (MH).

[0678] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.30 (t, J=6.0 Hz, 3H), 2.30 (s, 3H), 2.75 (s, 3H), 4.09 (q, J=6.0 Hz, 2H), 5.75 (s, 1H), 7.12 (d, J=6.0 Hz, 1H), 7.19-7.43 (m, 7H), 10.65 (s, 1H).

Example 1-110

[0679] MS ESI m/e: 446 (M+H), 444 (MH).

[0680] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.30 (t, J=7.1 Hz, 3H), 2.30 (s, 3H), 2.73 (s, 3H), 2.96 (s, 6H), 4.09 (q, J=2.3 Hz, 2H), 4.84 (q, J=149.0 Hz, 2H), 6.68-6.77 (m, 2H), 7.08-7.17 (m, 3H), 7.25-7.32 (m, 1H), 7.33-7.38 (m, 2H), 10.31 (brs, 1H).

Example 1-111

[0681] MS ESI m/e: 481, 483 (M+H), 479, 481 (MH).

[0682] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.30 (t, J=6.0 Hz, 3H), 2.30 (s, 1H), 2.75 (s, 1H), 4.09 (q, J=7.0 Hz, 2H), 5.77 (s, 1H), 7.08-7.22 (m, 3H), 7.26-7.42 (m, 3H), 7.49-7.56 (m, 2H), 10.66 (brs, 1H).

Example 1-112

[0683] MS ESI m/e: 458 (M+H), 456 (MH).

[0684] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.93 (m, 2H), 1.14-1.24 (m, 2H), 2.23 (s, 3H), 2.71-2.82 (m, 1H), 2.79 (s, 3H), 2.95 (s, 6H), 5.29 (s, 1H), 6.55-6.64 (m, 2H), 7.02-7.10 (m, 1H), 7.29-7.36 (m, 2H), 7.38-7.53 (m, 3H), 9.86 (s, 1H).

Example 1-113

[0685] MS ESI m/e: 497, 499 (M+H), 495, 497 (MH).

[0686] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.92 (m, 2H), 1.14-1.24 (m, 2H), 2.73-2.83 (m, 1H), 2.86 (s, 3H), 5.78 (s, 1H), 7.12-7.21 (m, 2H), 7.21-7.34 (m, 3H), 7.45-7.55 (m, 3H), 10.41 (s, 1H).

Example 1-114

[0687] MS ESI m/e: 462 (M+H), 460 (MH).

[0688] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.93 (m, 2H), 1.13-1.25 (m, 2H), 2.72-2.84 (m, 1H), 2.84 (s, 3H), 2.96 (s, 6H), 5.60 (s, 1H), 6.69-6.77 (m, 2H), 7.08-7.15 (m, 2H), 7.17-7.31 (m, 3H), 7.43-7.53 (m, 1H), 10.09 (s, 1H).

Example 1-115

[0689] MS ESI m/e: 441 (M+H), 439 (MH).

[0690] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.31 (t, J=7.0 Hz, 3H), 2.86 (s, 3H), 4.08 (q, J=7.0 Hz, 2H), 5.75 (s, 1H), 7.18-7.40 (m, 7H), 7.46-7.56 (m, 1H), 10.54 (s, 1H).

Example 1-116

[0691] MS ESI m/e: 485, 487 (M+H), 483, 485 (MH).

[0692] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.31 (t, J=7.0 Hz, 3H), 2.86 (s, 3H), 4.08 (q, J=7.0 Hz, 2H), 5.77 (s, 1H), 7.13-7.21 (m, 2H), 7.24-7.34 (m, 3H), 7.46-7.56 (m, 3H), 10.55 (s, 1H).

Example 1-117

[0693] MS ESI m/e: 450 (M+H), 448 (MH).

[0694] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.31 (t, J=7.0 Hz, 3H), 2.85 (s, 3H), 2.96 (s, 6H), 4.08 (q, J=7.1 Hz, 2H), 5.59 (s, 1H), 6.69-6.77 (m, 2H), 7.08-7.17 (m, 2H), 7.22-7.34 (m, 3H), 7.43-7.54 (m, 1H), 10.21 (s, 1H).

Example 1-118

[0695] MS ESI m/e: 472 (M+H).

[0696] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.79-0.89 (m, 2H), 1.14-1.25 (m, 2H), 2.16 (s, 6H), 2.71 (s, 3H), 2.77-2.87 (m, 1H), 2.96 (s, 6H), 5.59 (s, 1H), 6.68-6.77 (m, 2H), 7.08-7.19 (m, 4H), 7.23-7.31 (m, 1H), 10.31 (s, 1H).

Example 1-119

[0697] MS ESI m/e: 480 (M+H).

[0698] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.10 (m, 2H), 2.68-2.79 (m, 1H), 2.71 (s, 1H), 5.21 (s, 1H), 6.79 (d, J=9.0 Hz, 2H), 7.12 (d, J=9.0 Hz, 2H), 7.39 (t, J=9.0 Hz, 2H), 7.65-7.75 (m, 1H), 10.11 (brs, 1H).

Example 1-120

[0699] MS ESI m/e: 515, 517 (M+H), 513, 515 (MH).

[0700] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.71-0.79 (m, 2H), 1.00-1.10 (m, 2H), 2.71-2.80 (m, 1H), 2.74 (s, 3H), 5.51 (s, 1H), 7.32 (d, J=9.0 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.62 (d, J=6.0 Hz, 2H), 7.64-7.76 (m, 1H), 10.47 (brs, 1H).

Example 1-121

[0701] MS ESI m/e: 471 (M+H), 469 (MH).

[0702] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.03-1.07 (m, 2H), 2.70-2.80 (m, 1H), 2.74 (s, 3H), 5.49 (s, 1H), 7.36-7.43 (m, 4H), 7.50 (d, J=9.0 Hz, 2H), 7.65-7.76 (m, 1H), 10.47 (brs, H).

Example 1-122

[0703] MS ESI m/e: 460 (M+H), 458 (MH).

[0704] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.16 (t, J=7.5 Hz, 3H), 1.18 (t, J=6.0 Hz, 3H), 2.52 (q, J=4.0 Hz, 2H), 2.50 (s, 3H), 2.92 (s, 6H), 3.94 (q, J=5.0 Hz, 2H), 5.20 (s, 1H), 6.79 (d, J=9.0 Hz, 2H), 7.12 (d, J=9.0 Hz, 2H), 7.33 (d, J=3.0 Hz, 2H), 7.47 (s, 2H), 10.35 (brs, H).

Example 1-123

[0705] MS ESI m/e: 495, 497 (M+H), 493, 495 (MH).

[0706] .sup.1H-NMR (DMSO-ds, 300 MHz) 1.16 (t, J=7.5 Hz, 3H), 1.18 (t, J=6.0 Hz, 3H), 2.50-2.56 (m, 2H), 2.53 (s, 3H), 3.96 (q, J=7.0 Hz, 2H), 5.51 (s, 1H), 7.29-7.34 (m, 4H), 7.46-7.48 (m, 2H), 7.62 (d, J=6.0 Hz, 2H), 10.74 (brs, H).

Example 1-124

[0707] MS ESI m/e: 451 (M+H), 499 (MH).

[0708] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.16 (t, J=6.0 Hz, 3H), 1.18 (t, J=6.0 Hz, 3H), 2.50-2.55 (m, 2H), 2.56 (s, 3H), 3.95 (q, J=8.0 Hz, 2H), 5.49 (s, 1H), 7.33-7.38 (m, 4H), 7.48-7.51 (m, 4H), 10.73 (brs, H).

Example 1-125

[0709] MS ESI m/e: 463 (M+H), 461 (MH).

[0710] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.78-0.88 (m, 2H), 1.16-1.29 (m, 2H), 2.15 (s, 6H), 2.72 (s, 3H), 2.77-2.88 (m, 1H), 5.74 (s, 1H), 7.11-7.40 (m, 7H), 10.64 (s, 1H).

Example 1-126

[0711] MS ESI m/e: 458 (M+H).

[0712] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.90 (m, 2H), 1.13-1.23 (m, 2H), 2.39 (s, 3H), 2.71-2.78 (m, 1H), 2.81 (s, 3H), 2.96 (s, 6H), 5.60 (s, 1H), 6.68-6.78 (m, 2H), 7.07-7.32 (m, 6H), 10.08 (brs, 1H).

Example 1-127

[0713] MS ESI m/e: 458 (M+H).

[0714] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.93 (m, 2H), 1.13-1.23 (m, 2H), 2.39 (s, 3H), 2.71-2.81 (m, 1H), 2.83 (s, 3H), 2.96 (s, 6H), 5.62 (s, 1H), 6.70-6.76 (m, 2H), 7.08-7.16 (m, 4H), 7.20-7.25 (m, 1H), 7.31-7.39 (m, 1H), 10.08 (brs, 1H).

Example 1-128

[0715] MS ESI m/e: 472 (M+H).

[0716] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.92 (m, 2H), 1.14-1.25 (m, 2H), 1.18 (t, J=7.0 Hz, 6H), 2.71-2.82 (m, 1H), 2.80 (s, 3H), 3.36 (q, J=7.0 Hz, 4H), 5.62 (s, 1H), 6.63-6.71 (m, 2H), 7.03-7.13 (m, 2H), 7.28-7.36 (m, 2H), 7.37-7.53 (m, 3H), 10.03 (s, 1H).

Example 1-129

[0717] MS ESI m/e: 431 (M+H), 429 (MH).

[0718] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.84-0.90 (m, 2H), 1.15-1.23 (m, 2H), 2.72-2.80 (m, 1H), 2.80 (s, 3H), 3.82 (s, 3H), 5.61 (s, 1H), 6.88-6.94 (m, 2H), 7.14-7.21 (m, 2H), 7.28-7.33 (m, 2H), 7.38-7.50 (m, 3H), 10.15 (s, 1H).

Example 1-130

[0719] MS ESI m/e: 408 (M+H).

[0720] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.68-0.73 (m, 4H), 0.96-1.02 (m, 2H), 1.05-1.12 (m, 2H), 2.54-2.63 (m, 1H), 2.91 (s, 6H), 3.30-3.40 (m, 1H), 3.48 (s, 3H), 5.14 (s, 1H), 6.77 (d, J=9.0 Hz, 2H), 7.06 (d, J=9.0 Hz, 2H), 10.04 (brs, H).

Example 1-131

[0721] MS ESI m/e: 468, 470 (M+H), 466, 468 (MH).

[0722] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.20 (t, J=7.5 Hz, 3H), 2.62 (s, 3H), 3.95 (q, J=7.0 Hz, 2H), 5.53 (s, 1H), 7.32 (d, J=9.0 Hz, 2H), 7.52-7.64 (m, 3H), 7.97 (d, J=9.0 Hz, 1H), 8.67 (d, J=15 Hz, 1H), 8.68 (d, J=15 Hz, 1H), 10.62 (brs, H).

Example 1-132

[0723] MS ESI m/e: 462 (M+H), 460 (MH).

[0724] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.82-0.89 (m, 2H), 1.15-1.22 (m, 2H), 2.72-2.79 (m, 1H), 2.82 (s, 3H), 2.96 (s, 6H), 5.60 (s, 1H), 6.69-6.75 (m, 2H), 7.07-7.21 (m, 4H), 7.27-7.33 (m, 2H), 10.03 (s, 1H).

Example 1-133

[0725] MS ESI m/e: 462 (M+H), 460 (MH).

[0726] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.89 (m, 2H), 1.15-1.23 (m, 2H), 2.72-2.80 (m, 1H), 2.85 (s, 3H), 2.96 (s, 6H), 5.61 (s, 1H), 6.69-6.75 (m, 2H), 7.03-7.19 (m, 5H), 7.39-7.46 (m, 1H), 10.01 (s, 1H).

Example 1-134

[0727] MS ESI m/e: 444 (M+H), 442 (MH).

[0728] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.93 (m, 2H), 1.13-1.24 (m, 2H), 2.72-2.82 (m, 1H), 2.82 (s, 3H), 2.96 (s, 6H), 5.90 (s, 1H), 6.55-6.62 (m, 2H), 6.63-6.69 (m, 1H), 7.19-7.24 (m, 1H), 7.30-7.35 (m, 2H), 7.38-7.53 (m, 3H), 10.31 (s, 1H).

Example 1-135

[0729] MS ESI m/e: 416 (M+H).

[0730] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.82 (m, 2H), 0.99-1.09 (m, 2H), 2.60 (s, 3H), 2.63-2.74 (m, 1H), 5.52 (s, 1H), 7.36-7.57 (m, 9H), 10.61 (s, 1H).

Example 1-136

[0731] MS ESI m/e: 430 (M+H).

[0732] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 0.98-1.08 (m, 2H), 2.60 (s, 3H), 2.63-2.72 (m, 1H), 2.89 (s, 3H), 5.51 (d, J=2.9 Hz, 1H), 7.38-7.56 (m, 9H), 10.59 (brs, 1H).

Example 1-137

[0733] MS ESI m/e: 444 (M+H), 442 (MH).

[0734] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 0.98-1.08 (m, 2H), 1.27 (t, J=7.5 Hz, 3H), 2.61 (s, 3H), 2.64-2.72 (m, 1H), 3.31 (q, J=7.0 Hz, 2H), 5.54 (s, 1H), 7.07-7.19 (m, 2H), 7.38-7.57 (m, 9H), 10.62 (brs, 1H).

Example 1-138

[0735] MS ESI m/e: 454 (M+H).

[0736] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.71-0.80 (m, 2H), 0.99-1.08 (m, 2H), 2.57 (s, 3H), 2.62-2.75 (m, 1H), 3.81 (s, 3H), 5.26 (s, 1H), 6.44 (d, J=3.0 Hz, 1H), 7.06 (dd, J=3.0, 3.0 Hz, 1H), 7.37-7.52 (m, 8H), 10.37 (brs, H).

Example 1-139

[0737] MS ESI m/e: 444 (M+H).

[0738] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.59 (s, 3H), 2.92 (s, 6H), 4.49 (d, J=3.0 Hz, 2H), 5.15 (d, J=9.0 Hz, 1H), 5.22 (dd, J=3.0, 9.0 Hz, 2H), 6.78 (d, J=6.0 Hz, 2H), 7.10 (d, J=6.0 Hz, 2H), 7.48-7.50 (m, 5H), 10.19 (brs, H).

Example 1-140

[0739] MS ESI m/e: 444 (M+H), 442 (MH).

[0740] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.60 (s, 3H), 3.03 (s, 6H), 4.50 (d, J=3.0 Hz, 2H), 5.17 (dd, J=21.0, 24.0 Hz, 2H), 5.38 (s, 1H), 5.79-5.92 (m, 1H), 7.19-7.38 (m, 4H), 7.41-7.55 (m, 5H), 10.42 (brs, H).

Example 1-141

[0741] MS ESI m/e: 456 (M+H), 454 (MH).

[0742] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.99-1.08 (m, 2H), 2.55 (s, 3H), 2.61-2.68 (m, 1H), 2.71 (s, 3H), 2.89 (t, J=9.0 Hz, 2H), 3.28 (t, J=7.5 Hz, 2H), 5.18 (s, 1H), 6.54 (d, J=9.0 Hz, 1H), 6.90 (d, J=6.0 Hz, 1H), 6.96 (s, 1H), 7.39-7.50 (m, 5H), 10.13 (brs, H).

Example 1-142

[0743] MS ESI m/e: 476 (M+H).

[0744] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.85-0.93 (m, 2H), 1.14-1.24 (m, 2H), 2.23 (s, 3H), 2.74-2.83 (m, 1H), 2.83 (s, 3H), 2.95 (s, 6H), 5.27 (s, 1H), 6.55-6.65 (m, 2H), 7.02-7.09 (m, 1H), 7.18-7.32 (m, 3H), 7.43-7.54 (m, 1H), 9.89 (s, 1H).

Example 1-143

[0745] MS ESI m/e: 462 (M+H), 460 (MH).

[0746] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.92 (m, 2H), 1.14-1.25 (m, 2H), 2.71-2.81 (m, 1H), 2.81 (s, 1H), 2.87 (s, 6H), 5.71 (s, 1H), 6.86-7.02 (m, 3H), 7.27-7.35 (m, 2H), 7.41-7.54 (m, 3H), 10.22 (brs, 1H).

Example 1-144

[0747] MS ESI m/e: 454 (M+H), 452 (MH).

[0748] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.80 (m, 2H), 1.00-1.09 (m, 2H), 2.58 (s, 3H), 2.64-2.71 (m, 1H), 3.78 (s, 3H), 5.40 (s, 1H), 6.45 (d, J=3.0 Hz, 1H), 6.97 (d, J=6.0 Hz, 1H), 7.34-7.51 (m, 7H), 7.60 (d, J=9.0 Hz, 1H), 8.30 (brs, H).

Example 1-145

[0749] MS ESI m/e: 479 (M+H), 477 (MH).

[0750] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.15-1.26 (m, 2H), 2.73-2.83 (m, 1H), 2.85 (s, 3H), 3.08 (s, 3H), 6.08 (s, 1H), 7.29-7.37 (m, 2H), 7.41-7.56 (m, 5H), 7.92-8.00 (m, 2H), 10.87 (s, 1H).

Example 1-146

[0751] MS ESI m/e: 461 (M+H), 459 (MH).

[0752] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.92 (m, 2H), 1.13-1.24 (m, 2H), 2.72-2.83 (m, 1H), 2.80 (s, 3H), 3.83 (s, 3H), 3.84 (s, 3H), 5.60 (s, 1H), 6.45-6.58 (m, 2H), 7.19-7.26 (m, 1H), 7.28-7.35 (m, 2H), 7.38-7.52 (m, 3H), 10.01 (s, 1H).

Example 1-147

[0753] MS ESI m/e: 458 (M+H), 456 (MH).

[0754] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.13-1.23 (m, 2H), 2.32 (s, 3H), 2.67-2.84 (m, 1H), 2.71 (s, 6H), 2.81 (s, 3H), 5.72 (s, 1H), 6.99-7.10 (m, 3H), 7.28-7.36 (m, 2H), 7.38-7.53 (m, 3H), 10.19 (s, 1H).

Example 1-148

[0755] MS ESI m/e: 512 (M+H), 510 (MH).

[0756] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.84-0.90 (m, 2H), 1.16-1.24 (m, 2H), 2.73-2.79 (m, 1H), 2.75 (s, 6H), 2.81 (s, 3H), 5.66 (s, 1H), 7.29-7.37 (m, 3H), 7.39-7.52 (m, 5H), 10.33 (brs, 1H).

Example 1-149

[0757] MS ESI m/e: 472 (M+H), 470 (MH).

[0758] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.84-0.91 (m, 2H), 1.17-1.25 (m, 2H), 1.91 (s, 3H), 2.74-2.81 (m, 1H), 2.83 (s, 3H), 3.28 (s, 3H), 5.84 (s, 1H), 7.18-7.24 (m, 2H), 7.29-7.35 (m, 4H), 7.40-7.52 (m, 3H), 10.47 (s, 1H).

Example 1-150

[0759] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0760] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.39-0.57 (m, 4H), 1.24-1.36 (m, 1H), 2.83 (s, 3H), 3.91 (d, J=7.0 Hz, 2H), 5.80 (s, 1H), 7.15-7.21 (m, 2H), 7.33-7.39 (m, 2H), 7.42-7.55 (m, 5H), 10.57 (s, 1H).

Example 1-151

[0761] MS ESI m/e: 497, 499 (M+H), 495, 497 (MH).

[0762] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.73-0.79 (m, 2H), 1.01-1.09 (m, 2H), 2.61 (s, 3H), 2.68-2.71 (m, 1H), 5.65 (s, 1H), 7.19 (d, J=9.0 Hz, 1H), 7.40-7.52 (m, 6H), 7.73 (t, J=9.0 Hz, 1H), 10.67 (brs, H).

Example 1-152

[0763] MS ESI m/e: 497, 499 (M+H), 495, 497 (MH).

[0764] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.79 (m, 2H), 1.01-1.09 (m, 2H), 2.60 (s, 3H), 2.62-2.72 (m, 1H), 5.37 (s, 1H), 7.42-7.52 (m, 7H), 7.73 (d, J=12.0 Hz, 1H), 10.55 (brs, H).

Example 1-153

[0765] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0766] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.81-1.17 (m, 6H), 2.29-2.35 (m, 1H), 2.58 (s, 3H), 5.50 (s, 1H), 7.29 (d, J=6.0 Hz, 2H), 7.39-7.52 (m, 5H), 7.61 (d, J=9.0 Hz, 2H), 10.56 (brs, H).

Example 1-154

[0767] MS ESI m/e: 445 (M+H), 443 (MH).

[0768] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.84-0.93 (m, 2H), 1.16-1.24 (m, 2H), 2.26 (s, 3H), 2.74-2.80 (m, 1H), 2.80 (s, 3H), 3.81 (s, 3H), 5.27 (s, 1H), 6.73-6.84 (m, 2H), 7.14 (d, J=9.0 Hz, 1H), 7.30-7.35 (m, 2H), 7.39-7.52 (m, 3H), 9.94 (brs, 1H).

Example 1-155

[0769] MS ESI m/e: 444 (M+H), 442 (MH).

[0770] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.00-1.10 (m, 2H), 2.60 (s, 3H), 2.64-2.76 (m, 1H), 2.76 (brs, 6H), 5.51 (brs, 1H), 7.09-7.58 (m, 8H), 10.46 (brs, 1H).

Example 1-156

[0771] MS ESI m/e: 493, 495 (M+H), 491, 495 (MH).

[0772] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.92 (m, 2H), 1.15-1.25 (m, 2H), 2.29 (s, 3H), 2.73-2.85 (m, 1H), 2.81 (s, 3H), 5.41 (s, 1H), 7.16 (d, J=8.4 Hz, 1H), 7.30-7.39 (m, 3H), 7.40-7.53 (m, 4H), 10.13 (s, 1H).

Example 1-157

[0773] MS ESI m/e: 493, 495 (M+H), 491, 495 (MH).

[0774] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.14-1.24 (m, 2H), 2.40 (s, 3H), 2.71-2.82 (m, 1H), 2.82 (s, 3H), 5.81 (s, 1H), 6.99 (dd, J=2.6, 8.4 Hz, 1H), 7.17 (d, J=2.6 Hz, 1H), 7.28-7.36 (m, 2H), 7.39-7.57 (m, 4H), 10.37 (s, 1H).

Example 1-158

[0775] MS ESI m/e: 454 (M+H), 452 (MH).

[0776] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.80 (m, 2H), 1.01-1.09 (m, 2H), 2.55 (s, 3H), 2.63-2.72 (m, 1H), 3.85 (s, 3H), 4.71 (s, 1H), 6.48 (d, J=3.0 Hz, 1H), 6.97 (d, J=15.0 Hz, 1H), 7.06 (t, J=9.0 Hz, 1H), 7.29 (d, J=3.0 Hz, 1H), 7.41-7.56 (m, 6H), 10.37 (brs, H).

Example 1-159

[0777] MS ESI m/e: 509, 511 (M+H), 507, 509 (MH).

[0778] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.79 (m, 2H), 0.96-1.08 (m, 2H), 2.61 (s, 3H), 2.61-2.74 (m, 1H), 3.77 (s, 3H), 5.49 (s, 1H), 7.07 (t, J=6.0 Hz, 1H), 7.20 (d, J=12.0 Hz, 1H), 7.29 (d, J=9.0 Hz, 2H), 7.38 (d, J=6.0 Hz, 1H), 7.48 (t, J=9.0 Hz, 1H), 7.60 (d, J=9.0 Hz, 2H), 10.60 (brs, H).

Example 1-160

[0779] MS ESI m/e: 455 (M+H), 453 (MH).

[0780] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.85-0.93 (m, 2H), 1.15-1.26 (m, 2H), 2.74-2.84 (m, 1H), 2.81 (s, 3H), 3.88 (s, 3H), 5.65 (s, 1H), 7.22-7.29 (m, 1H), 7.30-7.37 (m, 2H), 7.37-7.54 (m, 4H), 7.70 (d, J=1.8 Hz, 1H), 7.90 (s, 1H), 10.36 (s, 1H).

Example 1-161

[0781] MS ESI m/e: 455 (M+H), 453 (MH).

[0782] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.85-0.94 (m, 2H), 1.15-1.26 (m, 2H), 2.74-2.84 (m, 1H), 2.82 (s, 3H), 4.10 (s, 3H), 5.65 (s, 1H), 7.28-7.37 (m, 3H), 7.39-7.54 (m, 4H), 7.60-7.64 (m, 1H), 7.95-7.98 (m, 1H), 10.36 (s, 1H).

Example 1-162

[0783] MS ESI m/e: 437 (M+H), 435 (MH).

[0784] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.91 (m, 2H), 1.15-1.24 (m, 2H), 2.73-2.81 (m, 1H), 2.81 (s, 3H), 5.49 (s, 1H), 6.88-6.98 (m, 2H), 7.28-7.38 (m, 3H), 7.39-7.52 (m, 3H), 10.15 (s, 1H).

Example 1-163

[0785] MS ESI m/e: 469, 471 (M+H), 467, 469 (MH).

[0786] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.90 (m, 2H), 1.16-1.24 (m, 2H), 2.74-2.81 (m, 1H), 2.82 (s, 3H), 5.70 (s, 1H), 7.24-7.34 (m, 3H), 7.39-7.52 (m, 5H), 10.50 (s, 1H).

Example 1-164

[0787] MS ESI m/e: 485, 487 (M+H), 483, 485 (MH).

[0788] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 1.30 (t, J=7.1 Hz, 3H), 2.82 (s, 3H), 4.08 (q, J=7.0 Hz, 2H), 5.66 (s, 1H), 7.28-7.39 (m, 5H), 7.41-7.53 (m, 3H), 10.48 (s, 1H).

Example 1-165

[0789] MS ESI m/e: 440 (M+H), 438 (MH).

[0790] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.81 (m, 2H), 1.00-1.10 (m, 2H), 2.58 (s, 3H), 2.62-2.78 (m, 1H), 5.28 (s, 1H), 6.46 (s, 1H), 7.01 (d, J=9.0 Hz, 1H), 7.40-7.68 (m, 8H), 10.37 (brs, H), 11.22 (brs, H).

Example 1-166

[0791] MS ESI m/e: 527, 529 (M+H), 525, 527 (MH).

[0792] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.81 (m, 2H), 0.99-1.09 (m, 2H), 2.63 (s, 3H), 2.66-2.75 (m, 1H), 3.79 (s, 3H), 5.34 (s, 1H), 7.09 (t, J=7.5 Hz, 1H), 7.23 (d, J=9.0 Hz, 1H), 7.40 (d, J=6.0 Hz, 1H), 7.43-7.54 (m, 3H), 7.73 (d, J=9.0 Hz, 1H), 10.58 (brs, H).

Example 1-167

[0793] MS ESI m/e: 468 (M+H), 466 (MH).

[0794] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.94 (m, 2H), 1.14-1.26 (m, 2H), 1.49 (t, J=7.4 Hz, 3H), 2.72-2.84 (m, 1H), 2.81 (s, 3H), 4.19 (q, J=7.3 Hz, 2H), 5.68 (s, 1H), 6.47 (d, J=3.0 Hz, 1H), 7.10 (dd, J=1.9, 8.6 Hz, 1H), 7.16 (d, J=3.0 Hz, 1H), 7.29-7.38 (m, 3H), 7.38-7.55 (m, 4H), 10.27 (brs, 1H).

Example 1-168

[0795] MS ESI m/e: 433 (M+H), 431 (MH).

[0796] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.90 (m, 2H), 1.10-1.25 (m, 2H), 2.37 (s, 3H), 2.77 (m, 1H), 2.81 (s, 3H), 5.59 (s, 1H), 6.90-7.05 (m, 2H), 7.25 (t, J=8.3 Hz, 1H), 7.30-7.35 (m, 2H), 7.40-7.50 (m, 3H), 10.16 (s, 1H).

Example 1-169

[0797] MS ESI m/e: 438 (M+H), 436 (MH).

[0798] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.85 (m, 2H), 1.10-1.25 (m, 2H), 2.50-2.55 (m, 4H), 2.65-2.80 (m, 3H), 2.80 (s, 3H), 3.26 (q, J=5.8 Hz, 2H), 3.70-3.80 (m, 4H), 5.37 (s, 1H), 7.25-7.35 (m, 2H), 7.35-7.50 (m, 3H), 8.90 (brs, 1H).

Example 1-170

[0799] MS ESI m/e: 477 (M+H), 475 (MH).

[0800] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.92 (m, 2H), 1.15-1.26 (m, 2H), 1.76 (d, J=12.8 Hz, 6H), 2.72-2.82 (m, 1H), 2.84 (s, 3H), 5.99 (s, 1H), 7.29-7.36 (m, 2H), 7.39-7.56 (m, 5H), 7.70-7.82 (m, 2H), 10.67 (s, 1H).

Example 1-171

[0801] MS ESI m/e: 453 (M+H), 451 (MH).

[0802] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.68-0.79 (m, 2H), 0.98-1.09 (m, 2H), 2.58 (s, 3H), 2.61-2.71 (m, 1H), 5.32 (s, 1H), 7.34-7.63 (m, 8H), 10.52 (brs, H).

Example 1-172

[0803] MS ESI m/e: 417 (M+H), 415 (MH).

[0804] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.68-0.78 (m, 2H), 0.97-1.06 (m, 2H), 2.55 (s, 3H), 2.61-2.69 (m, 1H), 5.19 (s, 1H), 6.82 (d, J=9.0 Hz, 2H), 7.08 (d, J=6.0 Hz, 2H), 7.39-7.50 (m, 5H), 9.53 (brs, H), 10.18 (brs, H).

Example 1-173

[0805] MS ESI m/e: 419 (M+H), 417 (MH).

[0806] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.71-2.80 (m, 2H), 1.01-1.09 (m, 2H), 2.60 (s, 3H), 2.64-2.72 (m, 1H), 5.34 (s, 1H), 7.28-7.54 (m, 9H), 10.53 (brs, H).

Example 1-174

[0807] MS ESI m/e: 437 (M+H), 435 (MH).

[0808] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.78 (m, 2H), 0.96-1.08 (m, 2H), 2.57 (s, 3H), 2.61-2.72 (m, 1H), 4.84 (s, 1H), 7.24-7.52 (m, 8H), 10.15 (brs, H).

Example 1-175

[0809] MS ESI m/e: 449 (M+H), 447 (MH).

[0810] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.92 (m, 2H), 1.15-1.24 (m, 2H), 2.72-2.81 (m, 1H), 2.81 (s, 3H), 3.82 (s, 3H), 5.46 (d, J=1.6 Hz, 1H), 6.69-6.79 (m, 2H), 7.19-7.29 (m, 1H), 7.29-7.36 (m, 2H), 7.39-7.54 (m, 3H), 10.01 (brs, 1H).

Example 1-176

[0811] MS ESI m/e: 513, 515 (M+H), 511, 513 (MH).

[0812] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.91 (m, 2H), 1.16-1.24 (m, 2H), 2.75-2.82 (m, 1H), 2.82 (s, 3H), 5.73 (s, 1H), 7.30-7.36 (m, 2H), 7.38-7.53 (m, 4H), 7.41 (d, J=1.8 Hz, 1H), 7.66 (d, J=1.8 Hz, 1H), 10.53 (brs, 1H).

Example 1-177

[0813] MS ESI m/e: 507, 509 (M+H), 505, 507 (MH).

[0814] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.85-0.89 (m, 2H), 1.17-1.22 (m, 2H), 1.23 (t, J=7.5 Hz, 3H), 2.63 (q, J=7.5 Hz, 2H), 2.74-2.79 (m, 1H), 2.80 (s, 3H), 5.40 (s, 1H), 7.15 (d, J=8.4 Hz, 1H), 7.29-7.36 (m, 3H), 7.40-7.51 (m, 4H), 10.11 (brs, 1H).

Example 1-178

[0815] MS ESI m/e: 459 (M+H), 457 (MH).

[0816] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.73-0.79 (m, 2H), 1.00-1.09 (m, 2H), 2.63 (s, 3H), 2.65-2.72 (m, 1H), 3.86 (s, 3H), 5.84 (s, 1H), 7.42-7.56 (m, 6H), 7.99-8.03 (m, 2H), 10.96 (brs, 1H).

Example 1-179

[0817] MS ESI m/e: 383 (M+H).

[0818] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.79-0.87 (m, 2H), 1.12-1.21 (m, 2H), 2.69-2.76 (m, 1H), 2.80 (s, 3H), 3.36 (q, J=5.4 Hz, 2H), 3.44 (s, 3H), 3.66 (t, J=5.4 Hz, 2H), 5.39 (s, 1H), 7.23-7.31 (m, 2H), 7.37-7.51 (m, 3H), 8.80-8.88 (m, 1H).

Example 1-180

[0819] MS ESI m/e: 422 (M+H).

[0820] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.74 (m, 2H), 0.95-1.05 (m, 2H), 1.42-1.56 (m, 2H), 1.88-1.98 (m, 2H), 2.10-2.21 (m, 2H), 2.18 (s, 3H), 2.55 (s, 3H), 2.58-2.70 (m, 3H), 3.33-3.44 (m, 1H), 5.23 (s, 1H), 7.34-7.41 (m, 2H), 7.42-7.53 (m, 3H), 8.77-8.84 (m, 1H).

Example 1-181

[0821] MS ESI m/e: 365 (M+H).

[0822] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.59-0.67 (m, 2H), 0.77-0.89 (m, 4H), 1.11-1.21 (m, 2H), 2.42-2.50 (m, 1H), 2.66-2.76 (m, 1H), 2.81 (s, 3H), 5.81 (s, 1H), 7.24-7.28 (m, 1H), 7.29-7.31 (m, 1H), 7.37-7.51 (m, 3H), 8.68 (brs, 1H).

Example 1-182

[0823] MS ESI m/e: 450 (M+H).

[0824] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.77-0.86 (m, 2H), 1.01-1.12 (m, 6H), 1.12-1.21 (m, 2H), 1.54-1.74 (m, 2H), 2.03-2.15 (m, 2H), 2.25-2.41 (m, 2H), 2.66-2.76 (m, 1H), 2.79 (s, 3H), 2.82-2.94 (m, 2H), 3.25-3.41 (m, 1H), 5.40 (s, 1H), 7.25-7.28 (m, 1H), 7.29-7.32 (m, 1H), 7.37-7.51 (m, 3H), 8.71-8.79 (m, 1H).

Example 1-183

[0825] MS ESI m/e: 509, 511 (M+H), 507, 509 (MH).

[0826] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.90 (m, 2H), 1.13-1.24 (m, 2H), 2.71-2.81 (m, 2H), 2.85 (s, 3H), 3.84 (s, 3H), 5.78 (s, 1H), 6.93-7.00 (m, 2H), 7.13-7.19 (m, 2H), 7.19-7.23 (m, 2H), 7.47-7.53 (m, 2H), 10.42 (brs, 1H).

Example 1-184

[0827] MS ESI m/e: 410 (M+H).

[0828] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.88 (m, 2H), 1.09-1.22 (m, 2H), 1.85 (tt, J=7.0, 14.0 Hz, 2H), 2.26 (s, 6H), 2.40 (t, J=7.1 Hz, 2H), 2.67-2.77 (m, 1H), 2.79 (s, 3H), 3.22 (dt, J=5.5, 6.2 Hz, 3H), 5.40 (s, 1H), 7.25-7.33 (m, 2H), 7.37-7.52 (m, 3H), 8.74 (t, J=4.8 Hz, 1H).

Example 1-185

[0829] MS ESI m/e: 471, 473 (M+H), 469, 471 (MH).

[0830] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.62 (s, 3H), 3.27 (s, 3H), 5.37 (s, 1H), 7.40-7.60 (m, 7H), 7.70-7.80 (m, 1H), 10.61 (s, 1H).

Example 1-186

[0831] MS ESI m/e: 527, 529 (M+H), 525, 527 (MH).

[0832] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.90 (m, 2H), 1.13-1.24 (m, 2H), 2.71-2.82 (m, 1H), 2.85 (s, 3H), 3.84 (s, 3H), 5.64 (d, J=1.1 Hz, 1H), 6.94-7.01 (m, 2H), 7.17-7.24 (m, 2H), 7.29-7.33 (m, 2H), 7.34-7.40 (m, 1H), 10.35 (brs, 1H).

Example 1-187

[0833] MS ESI m/e: 459 (M+H), 457 (MH).

[0834] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.92 (m, 2H), 1.13-1.24 (m, 2H), 1.35 (d, J=6.0 Hz, 6H), 2.72-2.82 (m, 1H), 2.81 (s, 3H), 4.54 (sept, J=6.0 Hz, 1H), 5.63 (s, 1H), 6.85-6.94 (m, 2H), 7.12-7.20 (m, 2H), 7.29-7.35 (m, 2H), 7.38-7.53 (m, 3H), 10.15 (brs, 1H).

Example 1-188

[0835] MS ESI m/e: 513, 515 (M+H), 511, 513 (MH).

[0836] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.99-1.08 (m, 2H), 2.62-2.72 (m, 1H), 2.66 (s, 3H), 5.35 (d, J=1.1 Hz, 1H), 6.79-6.89 (m, 2H), 7.15-7.23 (m, 2H), 7.43-7.55 (m, 2H), 7.70-7.76 (m, 1H), 9.90 (brs, 1H), 10.57 (brs, 1H).

Example 1-189

[0837] MS ESI m/e: 509, 511 (M+H), 507, 509 (MH).

[0838] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.90 (m, 2H), 1.14-1.25 (m, 2H), 2.73-2.80 (m, 1H), 2.82 (s, 3H), 3.89 (s, 3H), 5.80 (s, 1H), 7.07-7.13 (m, 2H), 7.23-7.35 (m, 3H), 7.39-7.53 (m, 3H), 10.29 (brs, 1H).

Example 1-190

[0839] MS ESI m/e: 509, 511 (M+H), 507, 509 (MH).

[0840] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.08 (m, 2H), 2.67 (s, 3H), 2.66-2.68 (m, 1H), 3.78 (s, 3H), 5.53 (s, 1H), 6.97-7.06 (m, 3H), 7.31 (d, J=9.0 Hz, 2H), 7.41 (dd, J=9.0, 9.0 Hz, 1H), 7.62 (d, J=9.0 Hz, 2H), 10.58 (brs, H).

Example 1-191

[0841] MS ESI m/e: 527, 529 (M+H), 525, 527 (MH).

[0842] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.01-1.09 (m, 2H), 2.67 (s, 3H), 2.66-2.67 (m, 1H), 3.78 (s, 3H), 5.37 (s, 1H), 6.97-7.06 (m, 3H), 7.39-7.51 (m, 3H), 7.73 (d, J=12.0 Hz, 1H), 10.55 (brs, H).

Example 1-192

[0843] MS ESI m/e: 462 (M+H).

[0844] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.08 (m, 2H), 2.55 (s, 3H), 2.60-2.71 (m, 1H), 2.92 (s, 6H), 5.01 (s, 1H), 6.56-6.66 (m, 2H), 7.18 (dd, J=12.0, 9.0 Hz, 1H), 7.39-7.51 (m, 5H), 10.00 (brs, H).

Example 1-193

[0845] MS ESI m/e: 582, 584 (M+H), 580, 582 (MH).

[0846] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.75 (m, 2H), 1.03 (m, 2H), 2.60-2.75 (m, 1H), 2.69 (s, 3H), 3.11 (brs, 4H), 3.73 (brs, 4H), 5.38 (s, 1H), 6.85 (d, J=7.6 Hz, 1H), 7.02 (brs, 2H), 7.34 (t, J=8.5 Hz, 1H), 7.40-7.55 (m, 2H), 7.73 (d, J=11.1 Hz, 1H), 10.57 (s, 1H).

Example 1-194

[0847] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0848] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.80-0.89 (m, 2H), 1.12-1.23 (m, 2H), 2.68-2.80 (m, 1H), 2.79 (s, 3H), 4.37 (d, J=6.0 Hz, 2H), 5.33 (s, 1H), 7.18-7.33 (m, 4H), 7.39-7.52 (m, 5H), 9.14 (t, J=5.6 Hz, 1H).

Example 1-195

[0849] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0850] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.79-0.89 (m, 2H), 1.12-1.22 (m, 2H), 2.68-2.76 (m, 1H), 2.78 (s, 3H), 4.34 (d, J=5.6 Hz, 2H), 5.34 (s, 1H), 7.20-7.31 (m, 4H), 7.39-7.53 (m, 5H), 9.11 (t, J=5.3 Hz, 1H).

Example 1-196

[0851] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[0852] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.79-0.89 (m, 2H), 1.12-1.22 (m, 2H), 2.69-2.77 (m, 1H), 2.79 (s, 3H), 4.46 (d, J=5.6 Hz, 2H), 5.36 (s, 1H), 7.17 (dt, J=1.9, 7.5 Hz, 1H), 7.24-7.33 (m, 3H), 7.35 (dt, J=1.1, 7.7 Hz, 1H), 7.39-7.51 (m, 3H), 7.59 (dd, J=1.1, 7.9 Hz, 1H), 9.16 (t, J=5.7 Hz, 1H).

Example 1-197

[0853] MS ESI m/e: 445 (M+H), 443 (MH).

[0854] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.92 (m, 2H), 1.14-1.25 (m, 2H), 2.72-2.83 (m, 1H), 2.80 (s, 3H), 3.11 (s, 6H), 5.44 (s, 1H), 6.53 (d, J=9.0 Hz, 1H), 7.29-7.34 (m, 2H), 7.37 (dd, J=2.6, 9.0 Hz, 1H), 7.39-7.52 (m, 3H), 8.07 (d, J=2.6 Hz, 1H), 9.96 (brs, 1H).

Example 1-198

[0855] MS ESI m/e: 495, 497 (M+H), 493, 495 (MH).

[0856] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.78 (m, 2H), 0.98-1.08 (m, 2H), 2.59 (s, 3H), 2.61-2.72 (m, 1H), 5.50 (s, 1H), 7.04 (dd, J=2.3, 8.3 Hz, 1H), 7.13 (d, J=2.3 Hz, 1H), 7.30 (d, J=8.3 Hz, 1H), 7.38-7.55 (m, 5H), 10.45 (s, 1H), 10.48 (brs, 1H).

Example 1-199

[0857] MS ESI m/e: 540, 542 (M+H), 538, 540 (MH).

[0858] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.14-1.23 (m, 2H), 2.71-2.82 (m, 1H), 2.93 (s, 3H), 2.96 (s, 6H), 5.66 (s, 1H), 6.52 (t, J=2.1 Hz, 1H), 6.59 (dd, J=1.9, 8.3 Hz, 1H), 6.71 (dd, J=2.6, 8.6 Hz, 1H), 7.26-7.40 (m, 4H), 10.39 (brs, 1H).

Example 1-200

[0859] MS ESI m/e: 487, 489 (M+H), 485, 487(MH).

[0860] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.62 (s, 3H), 3.27 (s, 3H), 5.47 (s, 1H), 7.40-7.60 (m, 6H), 7.63 (dd, J=2.1, 8.6 Hz, 1H), 7.91 (d, J=2.1 Hz, 1H), 10.83 (s, 1H).

Example 1-201

[0861] MS ESI m/e: 569, 571 (M+H), 567, 569 (MH).

[0862] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.75 (m, 2H), 1.03 (m, 2H), 2.45-2.60 (m, 2H), 2.60 (s, 3H), 2.67 (m, 1H), 2.85 (t, J=7.4 Hz, 2H), 5.36 (s, 1H), 7.24 (d, J=7.9 Hz, 1H), 7.32 (brs, 2H), 7.41 (t, J=7.9 Hz, 1H), 7.45-7.55 (m, 2H), 7.73 (d, J=9.2 Hz, 1H), 10.54 (s, 1H), 12.15 (brs, 1H).

Example 1-202

[0863] MS ESI m/e: 499, 501 (M+H), 497, 499 (MH).

[0864] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.74-0.82 (m, 2H), 0.98-1.06 (m, 2H), 2.63-2.70 (m, 1H), 5.74 (s, 1H), 7.25-7.33 (m, 2H), 7.38-7.55 (m, 4H), 7.63 (dd, J=2.2, 8.8 Hz, 1H), 7.92 (d, J=2.2 Hz, 1H), 10.90 (brs, 1H), 11.14 (brs, 1H).

Example 1-203

[0865] MS ESI m/e: 482 (M+H).

[0866] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.77-0.79 (m, 2H), 1.02-1.17 (m, 2H), 2.18 (s, 3H), 2.34 (s, 3H), 2.57 (s, 3H), 2.65-2.68 (m, 1H), 3.66 (s, 3H), 5.24 (s, 1H), 6.98 (d, J=6.0 Hz, 1H), 7.29 (d, J=3.0 Hz, 1H), 7.40-7.56 (m, 6H), 10.35 (brs, H).

Example 1-204

[0867] MS ESI m/e: 468 (M+H).

[0868] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.80 (m, 2H), 1.00-1.09 (m, 2H), 2.41 (s, 3H), 2.57 (s, 3H), 2.62-2.71 (m, 1H), 3.68 (s, 3H), 5.26 (s, 1H), 6.23 (s, 1H), 6.97 (d, J=12.0 Hz, 1H), 7.33 (s, 1H), 7.42-7.52 (m, 6H), 10.35 (brs, H).

Example 1-205

[0869] MS ESI m/e: 547 (M+H), 545 (MH).

[0870] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.86 (m, 2H), 1.18 (m, 2H), 2.75 (m, 1H), 2.89 (s, 3H), 2.97 (s, 6H), 3.16 (t, J=4.8 Hz, 4H), 3.85 (t, J=4.8 Hz, 4H), 5.45 (s, 1H), 6.45 (s, 1H), 6.49 (d, J=3.8 Hz, 1H), 6.75-6.80 (m, 2H), 6.91 (d, J=8.3 Hz, 1H), 7.14 (t, J=9.0 Hz, 1H), 7.33 (t, J=8.4 Hz, 1H), 9.89 (s, 1H).

Example 1-206

[0871] MS ESI m/e: 595, 597 (M+H).

[0872] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.77 (m, 2H), 0.98-1.07 (m, 2H), 2.21 (s, 3H), 2.40-2.46 (m, 4H), 2.61-2.71 (m, 1H), 2.69 (s, 3H), 3.09-3.16 (m, 4H), 5.37 (s, 1H), 6.79-6.84 (m, 1H), 6.96-7.03 (m, 2H), 7.29-7.34 (m, 1H), 7.44-7.54 (m, 2H), 7.69-7.77 (m, 1H), 10.58 (brs, 1H).

Example 1-207

[0873] MS ESI m/e: 545 (M+H), 543 (MH).

[0874] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.92 (m, 2H), 1.14-1.25 (m, 2H), 2.72-2.82 (m, 1H), 2.82 (s, 3H), 5.69 (d, J=1.1 Hz, 1H), 7.28-7.36 (m, 2H), 7.40-7.59 (m, 6H), 10.36 (s, 1H).

Example 1-208

[0875] MS ESI m/e: 443 (M+H), 441 (MH).

[0876] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.81-0.91 (m, 2H), 1.16-1.23 (m, 2H), 2.73-2.80 (m, 1H), 2.82 (s, 3H), 3.12 (s, 1H), 5.80 (s, 1H), 7.26-7.33 (m, 3H), 7.35-7.52 (m, 5H), 10.50 (s, 1H).

Example 1-209

[0877] MS ESI m/e: 416 (M+H), 414 (MH).

[0878] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.79-0.88 (m, 2H), 1.12-1.22 (m, 2H), 2.68-2.77 (m, 1H), 2.79 (s, 3H), 4.42 (d, J=5.6 Hz, 2H), 5.37 (s, 1H), 7.26-7.35 (m, 3H), 7.38-7.52 (m, 3H), 7.65-7.72 (m, 1H), 8.57 (dd, J=1.5, 4.9 Hz, 1H), 8.63 (d, J=1.9 Hz, 1H), 9.15 (t, J=5.3 Hz, 1H).

Example 1-210

[0879] MS ESI m/e: 511, 513 (M+H), 509, 511 (MH).

[0880] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.80-0.90 (m, 2H), 1.13-1.23 (m, 2H), 2.70-2.78 (m, 1H), 2.79 (s, 3H), 4.43 (d, J=6.0 Hz, 2H), 5.33 (s, 1H), 6.98 (dd, J=9.0, 9.1 Hz, 1H), 7.28-7.33 (m, 2H), 7.35-7.53 (m, 5H), 9.12 (t, J=6.0 Hz, 1H).

Example 1-211

[0881] MS ESI m/e: 509, 511 (M+H), 507, 509 (MH).

[0882] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.92 (m, 2H), 1.14-1.25 (m, 2H), 2.73-2.84 (m, 1H), 2.81 (s, 3H), 3.83 (s, 3H), 5.46 (s, 1H), 6.89 (dd, J=3.0, 8.7 Hz, 1H), 7.21 (d, J=2.6 Hz, 1H), 7.29-7.36 (m, 3H), 7.38-7.54 (m, 3H), 10.17 (brs, 1H).

Example 1-212

[0883] MS ESI m/e: 580, 581 (M+H), 578, 580 (MH).

[0884] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.87 (m, 2H), 1.18 (m, 2H), 2.20 (m, 2H), 2.63 (t, J=8.1 Hz, 2H), 2.77 (m, 1H), 2.88 (s, 3H), 3.88 (t, J=7.1 Hz, 2H), 5.66 (s, 1H), 7.07 (d, J=7.9 Hz, 1H), 7.30-7.35 (m, 2H), 7.37 (d, J=9.2 Hz, 1H), 7.46 (t, J=8.1 Hz, 1H), 7.54 (d, J=8.6 Hz, 1H), 7.89 (d, J=2.0 Hz, 1H), 10.34 (s, 1H).

Example 1-213

[0885] MS ESI m/e: 513, 515 (M+H), 511, 513 (MH).

[0886] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.09 (m, 2H), 2.68 (s, 3H), 2.61-2.71 (m, 1H), 5.35 (s, 1H), 2.79-2.89 (m, 3H), 7.27 (dd, J=9.0, 9.0 Hz, 1H), 7.48-7.52 (m, 2H), 7.72 (d, J=6.0 Hz, 1H), 9.83 (brs, H), 10.53 (brs, H).

Example 1-214

[0887] MS ESI m/e: 594, 596 (M+H), 592, 594 (MH).

[0888] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.75 (m, 2H), 1.03 (m, 2H), 1.85 (brs, 4H), 2.39 (m, 2H), 2.67 (m, 4H), 3.62 (m, 2H), 5.36 (s, 1H), 7.33 (d, J=8.3 Hz, 1H), 7.35-7.40 (m, 2H), 7.45-7.55 (m, 3H), 7.74 (d, J=10.2 Hz, 1H), 10.54 (s, 1H).

Example 1-215

[0889] MS ESI m/e: 566, 568 (M+H), 564, 566 (MH).

[0890] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.80 (m, 2H), 0.99-1.11 (m, 2H), 1.90-2.01 (m, 4H), 2.64-2.74 (m, 1H), 2.74-2.75 (m, 1H), 3.13-3.27 (m, 4H), 5.39 (s, 1H), 6.54-6.65 (m, 3H), 7.20-7.30 (m, 1H), 7.45-7.55 (m, 2H), 7.71-7.78 (m, 1H), 10.60 (brs, 1H).

Example 1-216

[0891] MS ESI m/e: 580, 582 (M+H), 578, 580 (MH).

[0892] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.78 (m, 2H), 0.98-1.08 (m, 2H), 1.48-1.65 (m, 6H), 2.63-2.71 (m, 1H), 2.69 (s, 3H), 3.09-3.17 (m, 4H), 5.37 (s, 1H), 6.72-6.79 (m, 1H), 6.95-7.02 (m, 2H), 7.25-7.32 (m, 1H), 7.46-7.54 (m, 2H), 7.69-7.77 (m, 1H), 10.59 (brs, 1H).

Example 1-217

[0893] MS ESI m/e: 476 (M+H), 474 (MH).

[0894] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 1.01-1.13 (m, 5H), 2.58 (s, 3H), 2.61-2.72 (m, 1H), 2.90 (s, 3H), 3.42 (q, J=2.0 Hz, 2H), 5.04 (s, 1H), 6.62 (dd, J=9.0, 15.0 Hz, 2H), 7.18 (t, J=9.0 Hz, 1H), 7.40-7.59 (m, 5H), 10.01 (brs, 1H).

Example 1-218

[0895] MS ESI m/e: 584, 585 (M+H), 582, 584 (MH).

[0896] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.78 (m, 2H), 0.98-1.09 (m, 2H), 2.18 (s, 6H), 2.59 (t, J=3.0 Hz, 2H), 2.66 (s, 3H), 2.65-2.66 (m, 1H), 4.01 (t, J=4.5 Hz, 2H), 5.37 (s, 1H), 6.96-7.08 (m, 3H), 7.38-7.51 (m, 3H), 7.71 (d, J=12.0 Hz, 1H), 10.55 (brs, 1H).

Example 1-219

[0897] MS ESI m/e: 596, 598 (M+H), 594, 596 (MH).

[0898] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.75 (m, 2H), 1.03 (m, 2H), 2.67 (s, 4H), 3.75 (m, 2H), 3.98 (t, J=4.9 Hz, 2H), 4.21 (s, 2H), 5.36 (s, 1H), 7.37 (d, J=7.3 Hz, 1H), 7.40-7.60 (m, 5H), 7.73 (d, J=9.4 Hz, 1H), 10.53 (s, 1H).

Example 1-220

[0899] MS ESI m/e: 571, 573 (M+H), 569, 571 (MH).

[0900] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.74-0.76 (m, 2H), 0.99-1.10 (m, 2H), 2.65-2.67 (m, 1H), 2.66 (s, 3H), 4.71 (s, 2H), 5.37 (s, 1H), 6.99-7.08 (m, 3H), 7.41 (t, J=9.0 Hz, 1H), 7.45-7.52 (m, 2H), 7.74 (d, J=9.0 Hz, 1H), 10.55 (brs, 1H), 13.04 (brs, 1H).

Example 1-221

[0901] MS ESI m/e: 527 (M+H), 525 (MH).

[0902] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.14-1.25 (m, 2H), 2.71-2.82 (m, 1H), 2.82 (s, 3H), 5.82 (s, 1H), 7.01-7.09 (m, 2H), 7.28-7.35 (m, 2H), 7.39-7.54 (m, 3H), 7.66-7.74 (m, 2H), 10.42 (s, 1H).

Example 1-222

[0903] MS ESI m/e: 425 (M+H), 423 (MH).

[0904] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.15-1.24 (m, 2H), 2.71-2.83 (m, 1H), 2.83 (s, 3H), 3.09 (s, 1H), 5.92 (s, 1H), 7.22-7.29 (m, 2H), 7.29-7.35 (m, 2H), 7.40-7.57 (m, 5H), 10.54 (s, 1H).

Example 1-223

[0905] MS ESI m/e: 575, 577 (M+H), 573, 575 (MH).

[0906] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.84-0.91 (m, 2H), 1.17-1.26 (m, 2H), 2.73-2.80 (m, 1H), 2.81 (s, 3H), 3.11 (s, 3H) 5.65 (s, 1H), 7.27-7.35 (m, 2H), 7.35-7.40 (m, 1H), 7.51-7.56 (m, 1H), 7.68-7.75 (m, 1H), 8.00-8.05 (m, 2H), 10.22 (s, 1H).

Example 1-224

[0907] MS ESI m/e: 604, 606 (M+H), 602, 604 (MH).

[0908] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.15-1.27 (m, 2H), 2.72-2.81 (m, 1H), 2.76 (s, 6H), 2.81 (s, 3H), 5.65 (d, J=1.1 Hz, 1H), 7.29-7.34 (m, 2H), 7.35-7.43 (m, 1H), 7.45-7.51 (m, 1H), 7.63-7.72 (m, 1H), 7.83-7.89 (m, 2H), 10.25 (s, 1H).

Example 1-225

[0909] MS ESI m/e: 575, 577 (M+H), 573, 575 (MH).

[0910] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.16-1.27 (m, 2H), 2.72-2.83 (m, 1H), 2.83 (brs, 3H), 3.10 (s, 3H), 5.63 (brs, 1H), 7.28-7.35 (m, 2H), 7.36-7.42 (m, 1H), 7.58 (d, J=8.4 Hz, 2H), 8.10 (d, J=8.4 Hz, 2H), 10.22 (s, 1H).

Example 1-226

[0911] MS ESI m/e: 604, 606 (M+H), 602, 604 (MH).

[0912] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.91 (m, 2H), 1.17-1.25 (m, 2H), 2.71-2.81 (m, 1H), 2.75 (s, 6H), 2.84 (brs, 3H), 5.58 (brs, 1H), 7.26-7.35 (m, 2H), 7.35-7.40 (m, 1H), 7.52 (d, J=8.1 Hz, 2H), 7.89 (d, J=8.1 Hz, 2H), 10.21 (s, 1H).

Example 1-227

[0913] MS ESI m/e: 598, 600 (M+H), 596, 598 (MH).

[0914] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.78 (m, 2H), 0.99-1.09 (m, 2H), 1.84 (t, J=6.0 Hz, 2H), 2.13 (s, 6H), 2.34 (t, J=6.0 Hz, 2H), 2.66-2.68 (m, 1H), 2.67 (s, 3H), 4.00 (t, J=6.0 Hz, 2H), 5.37 (s, 1H), 6.96-7.09 (m, 3H), 7.40 (dd, J=6.0, 6.0 Hz, 1H), 7.48-7.51 (m, 2H), 7.74 (d, J=9.0 Hz, 1H), 10.56 (brs, 1H).

Example 1-228

[0915] MS ESI m/e: 604, 606 (M+H), 602, 604 (MH).

[0916] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 0.98-1.10 (m, 2H), 2.61-2.71 (m, 1H), 2.68 (s, 3H), 2.96 (s, 3H), 3.25 (s, 3H), 5.37 (s, 1H), 7.39 (d, J=6.0 Hz, 1H), 7.45-7.58 (m, 5H), 7.74 (d, J=9.0 Hz, 1H), 10.53 (brs, 1H).

Example 1-229

[0917] MS ESI m/e: 443 (M+H), 441 (MH).

[0918] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.90 (m, 2H), 1.14-1.24 (m, 2H), 1.27 (d, J=7.1 Hz, 6H), 2.72-2.81 (m, 1H), 2.81 (s, 3H), 2.92 (sept, J=6.8 Hz, 1H), 5.77 (s, 1H), 7.16-7.22 (m, 2H), 7.22-7.28 (m, 2H), 7.29-7.35 (m, 2H), 7.39-7.53 (m, 3H), 10.28 (brs, 1H).

Example 1-230

[0919] MS ESI m/e: 429 (M+H), 427 (MH).

[0920] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.15-1.24 (m, 2H), 1.25 (t, J=7.5 Hz, 3H), 2.66 (q, J=7.5 Hz, 2H), 2.72-2.81 (m, 1H), 2.81 (s, 3H), 5.76 (s, 1H), 7.15-7.24 (m, 4H), 7.29-7.36 (m, 2H), 7.39-7.53 (m, 3H), 10.29 (brs, 1H).

Example 1-231

[0921] MS ESI m/e: 426 (M+H), 424 (MH).

[0922] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.90 (m, 2H), 1.15-1.25 (m, 2H), 2.72-2.82 (m, 1H), 2.84 (s, 3H), 6.07 (s, 1H), 7.28-7.34 (m, 2H), 7.36-7.42 (m, 2H), 7.44-7.55 (m, 3H), 7.64-7.70 (m, 2H), 10.84 (brs, 1H).

Example 1-232

[0923] MS ESI m/e: 626, 628 (M+H), 624, 626 (MH).

[0924] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.01-1.09 (m, 2H), 2.41-2.48 (m, 4H), 2.67 (s, 3H), 2.64-2.70 (m, 3H), 3.45-3.60 (m, 4H), 4.06-4.10 (m, 2H), 5.36 (s, 1H), 7.00 (d, J=3.0 Hz, 1H), 7.03-7.05 (m, 2H), 7.38-0.53 (m, 3H), 7.72 (d, J=6.0 Hz, 1H), 10.54 (brs, 1H).

Example 1-233

[0925] MS ESI m/e: 610, 612 (M+H), 608, 610 (MH).

[0926] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.00-1.09 (m, 2H), 1.62-1.71 (m, 4H), 2.43-2.55 (m, 4H), 2.64 (s, 3H), 2.61-2.70 (m, 1H), 2.77 (t, J=3.0 Hz, 2H), 4.06 (t, J=3.0 Hz, 2H), 5.37 (s, 1H), 6.99 (d, J=3.0 Hz, 1H), 7.02-7.04 (m, 2H), 7.39 (dd, J=3.0, 3.0 Hz, 1H), 7.50-7.52 (m, 2H), 7.74 (d, J=3.0 Hz, 1H), 10.54 (brs, 1H).

Example 1-234

[0927] MS ESI m/e: 624, 626 (M+H), 622, 624 (MH).

[0928] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.01-1.09 (m, 2H), 1.32-1.41 (m, 2H), 1.41-1.52 (m, 4H), 2.37-2.46 (m, 4H), 2.60-2.71 (m, 3H), 2.67 (s, 3H), 4.07 (t, J=6.0 Hz, 2H), 5.38 (s, 1H), 7.01 (dd, J=6.0, 9.0 Hz, 1H), 7.05-7.06 (m, 2H), 7.40 (dd, J=9.0, 9.0 Hz, 1H), 7.49-7.51 (m, 2H), 7.74 (d, J=12.0 Hz, 1H), 10.55 (brs, 1H).

Example 1-235

[0929] MS ESI m/e: 612, 614 (M+H), 610, 612 (MH).

[0930] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.96 (t, J=7.5 Hz, 6H), 0.99-1.09 (m, 2H), 2.46-2.59 (m, 5H), 2.68 (s, 3H), 2.75 (t, J=3.0 Hz, 2H), 4.00 (t, J=3.0 Hz, 2H), 5.37 (s, 1H), 7.00 (dd, J=3.0, 3.0 Hz, 1H), 7.01-7.06 (m, 2H), 7.40 (dd, J=6.0, 3.0 Hz, 1H), 7.49-7.52 (m, 2H), 7.74 (d, J=18.0 Hz, 1H), 10.56 (brs, 1H).

Example 1-236

[0931] MS ESI m/e: 653, 655 (M+H), 651, 653 (MH).

[0932] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.71-0.79 (m, 2H), 0.96 (t, J=7.5 Hz, 6H), 0.99-1.09 (m, 2H), 1.80-1.91 (m, 2H), 2.13 (s, 3H), 2.46-2.59 (m, 10H), 2.60-2.73 (m, 4H), 4.00 (t, J=3.0 Hz, 2H), 5.37 (s, 1H), 7.00 (dd, J=3.0, 3.0 Hz, 1H), 7.01-7.06 (m, 2H), 7.40 (dd, J=6.0, 3.0 Hz, 1H), 7.49-7.52 (m, 2H), 7.74 (d, J=18.0 Hz, 1H), 10.56 (brs, 1H).

Example 1-237

[0933] MS ESI m/e: 444 (M+H), 442 (MH).

[0934] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.92 (m, 2H), 1.16-1.26 (m, 2H), 2.73-2.83 (m, 1H), 2.85 (s, 3H), 6.01 (s, 1H), 7.29-7.35 (m, 2H), 7.43-7.56 (m, 5H), 7.60-7.70 (m, 1H), 10.93 (s, 1H).

Example 1-238

[0935] MS ESI m/e: 473 (M+H), 471 (MH).

[0936] .sup.1H-NMR (DMSO-d, 400 MHz) 0.71-0.79 (m, 2H), 1.00-1.08 (m, 2H), 2.60 (s, 3H), 2.63-2.71 (m, 1H), 4.31 (d, J=5.8 Hz, 2H), 5.38 (t, J=5.9 Hz, 1H), 5.50 (s, 1H), 7.29-7.35 (m, 1H), 7.39-7.58 (m, 7H), 10.71 (s, 1H).

Example 1-239

[0937] MS ESI m/e: 501 (M+H), 499 (MH).

[0938] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.82-0.90 (m, 2H), 1.15-1.24 (m, 2H), 1.63 (s, 6H), 2.07 (s, 1H), 2.73-2.81 (m, 1H), 2.82 (s, 3H), 5.78 (s, 1H), 7.16-7.25 (m, 2H), 7.28-7.33 (m, 2H), 7.34-7.52 (m, 4H), 10.46 (s, 1H).

Example 1-240

[0939] MS ESI m/e: 445 (M+H), 443 (MH).

[0940] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.84-0.90 (m, 2H), 1.16-1.24 (m, 2H), 2.73-2.82 (m, 1H), 2.82 (s, 3H), 5.31 (d, J=10.9 Hz, 1H), 5.74 (d, J=17.6 Hz, 1H), 5.72 (s, 1H), 6.66 (dd, J=10.9, 17.8 Hz, 1H), 7.14-7.25 (m, 2H), 7.28-7.39 (m, 3H), 7.40-7.51 (m, 3H), 10.34 (s, 1H).

Example 1-241

[0941] MS ESI m/e: 487 (M+H), 485 (MH).

[0942] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.15-1.24 (m, 2H), 2.73-2.83 (m, 1H), 2.83 (s, 3H), 3.47 (s, 3H), 4.33 (s, 2H), 5.79 (s, 1H), 7.22-7.35 (m, 4H), 7.35-7.56 (m, 4H), 10.49 (s, 1H).

Example 1-242

[0943] MS ESI m/e: 447 (M+H), 445 (MH).

[0944] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.84-0.90 (m, 2H), 1.15-1.22 (m, 2H), 1.25 (t, J=7.6 Hz, 3H), 2.66 (q, J=7.6 Hz, 2H), 2.73-2.81 (m, 1H), 2.81 (s, 3H), 5.59 (d, J=1.2 Hz, 1H), 6.96-7.04 (m, 2H), 7.23-7.34 (m, 3H), 7.39-7.51 (m, 3H), 10.16 (s, 1H).

Example 1-243

[0945] MS ESI m/e: 555, 557 (M+H), 553, 555 (MH).

[0946] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.92 (m, 2H), 1.14-1.25 (m, 2H), 1.43 (t, J=4.9 Hz, 1H), 1.88 (quint, J=7.3 Hz, 2H), 2.72-2.81 (m, 1H), 2.76 (t, J=7.7 Hz, 2H), 2.82 (s, 3H), 3.65 (q, J=5.7 Hz, 2H), 5.66 (s, 1H), 7.10-7.19 (m, 2H), 7.26-7.33 (m, 3H), 7.35-7.45 (m, 2H), 10.34 (brs, 1H).

Example 1-244

[0947] MS ESI m/e: 486, 488 (M+H), 484, 486 (MH). 1H-NM R (DMSO-d.sub.6, 300 MHz) 1.19 (t, J=6.0 Hz, 3H), 2.50-2.53 (m, 1H), 2.62 (s, 3H), 3.95 (q, J=7.0 Hz, 2H), 5.37 (s, 1H), 7.48-7.52 (m, 2H), 7.60 (dd, J=3.0, 3.0 Hz, 1H), 7.74 (d, J=12.0 Hz, 1H), 7.97 (d, J=6.0 Hz, 1H), 8.73 (d, J=45.0 Hz, 1H), 10.58 (brs, 1H).

Example 1-245

[0948] MS ESI m/e: 554, 556 (M+H), 552, 554 (MH).

[0949] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.99-1.09 (m, 2H), 2.04 (s, 3H), 2.63-2.68 (m, 1H), 2.66 (s, 3H), 5.35 (s, 1H), 7.08 (d, J=9.0 Hz, 1H), 7.41 (dd, J=6.0, 6.0 Hz, 1H), 7.49-7.51 (m, 2H), 7.61-7.77 (m, 3H), 10.18 (brs, 1H), 10.54 (brs, 1H).

Example 1-246

[0950] MS ESI m/e: 500 (M+H), 498 (MH).

[0951] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.14-1.25 (m, 2H), 2.38 (s, 6H), 2.72-2.83 (m, 1H), 2.83 (s, 3H), 3.48 (s, 2H), 5.77 (d, J=0.7 Hz, 1H), 7.20-7.55 (m, 8H), 10.45 (s, 1H).

Example 1-247

[0952] MS ESI m/e: 489 (M+H), 487 (MH).

[0953] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.81 (m, 2H), 0.99-1.10 (m, 2H), 2.61 (s, 3H), 2.64-2.74 (m, 1H), 5.57 (s, 1H), 6.58 (d, J=16.1 Hz, 1H), 7.40-7.64 (m, 8H), 7.81 (d, J=12.1 Hz, 1H), 10.80 (s, 1H), 12.44 (brs, 1H).

Example 1-248

[0954] MS ESI m/e: 491 (M+H), 489 (MH).

[0955] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.72-0.78 (m, 2H), 0.99-1.07 (m, 2H), 2.59 (t, J=7.6 Hz, 2H), 2.58 (s, 3H), 2.63-2.70 (m, 1H), 2.86 (t, J=7.5 Hz, 2H), 5.25 (d, J=1.2 Hz, 1H), 7.12-7.17 (m, 1H), 7.24-7.30 (m, 1H), 7.35-7.54 (m, 6H), 10.40 (s, 1H), 12.18 (s, 1H).

Example 1-249

[0956] MS ESI m/e: 447 (M+H), 445 (MH).

[0957] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.79 (m, 2H), 0.99-1.07 (m, 2H), 2.59 (s, 3H), 2.63-2.70 (m, 1H), 5.45 (s, 1H), 7.25-7.30 (m, 2H), 7.31-7.37 (m, 2H), 7.41-7.55 (m, 5H), 10.49 (brs, 1H).

Example 1-250

[0958] MS ESI m/e: 501 (M+H), 499 (MH).

[0959] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 1.00-1.08 (m, 2H), 2.62 (s, 1H), 2.66-2.71 (m, 1H), 5.76 (s, 1H), 7.41-7.55 (m, 7H), 7.76 (d, J=8.3 Hz, 2H), 10.86 (brs, 1H).

Example 1-251

[0960] MS ESI m/e: 458 (M+H), 456 (MH).

[0961] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.72-0.82 (m, 2H), 0.99-1.09 (m, 2H), 2.58 (s, 3H), 2.63-2.74 (m, 1H), 5.13 (d, J=1.1 Hz, 1H), 6.45-6.50 (m, 1H), 7.33-7.61 (m, 8H), 10.28 (brs, 1H), 11.28 (brs, 1H).

Example 1-252

[0962] MS ESI m/e: 582, 584 (M+H), 580, 582 (MH).

[0963] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.91 (m, 2H), 1.14-1.25 (m, 2H), 1.76-1.90 (m, 2H), 2.26-2.38 (m, 2H), 2.26 (brs, 6H), 2.65-2.73 (m, 2H), 2.74-2.80 (m, 1H), 2.83 (s, 3H), 5.65 (d, J=0.7 Hz, 1H), 7.10-7.16 (m, 2H), 7.24-7.29 (m, 1H), 7.30-7.34 (m, 2H), 7.34-7.44 (m, 2H), 10.34 (brs, 1H).

Example 1-253

[0964] MS ESI m/e: 584, 586 (M+H), 582, 584 (MH).

[0965] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.90 (m, 2H), 1.15-1.23 (m, 2H), 2.73-2.80 (m, 1H), 2.93 (s, 3H), 2.97 (s, 3H), 3.34 (s, 3H), 3.44-3.56 (m, 4H), 5.66 (d, J=1.1 Hz, 2H), 6.55-6.60 (m, 2H), 6.70-6.76 (m, 1H), 7.22-7.40 (m, 4H), 10.39 (brs, 1H).

Example 1-254

[0966] MS ESI m/e: 457 (M+H), 455 (MH).

[0967] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.82-0.89 (m, 2H), 1.15-1.23 (m, 2H), 2.06 (s, 3H), 2.72-2.80 (m, 1H), 2.82 (s, 3H), 5.74 (s, 1H), 7.14-7.21 (m, 2H), 7.28-7.36 (m, 3H), 7.39-7.51 (m, 3H), 10.38 (s, 1H).

Example 1-255

[0968] MS ESI m/e: 624, 626 (M+H), 622, 624 (MH).

[0969] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.13-1.24 (m, 2H), 1.74-1.90 (m, 2H), 2.28-2.38 (m, 2H), 2.38-2.46 (m, 4H), 2.65-2.72 (m, 2H), 2.73-2.80 (m, 1H), 2.83 (s, 3H), 3.68-3.74 (m, 4H), 5.65 (d, J=1.1 Hz, 1H), 7.10-7.17 (m, 2H), 7.23-7.28 (m, 1H), 7.29-7.33 (m, 2H), 7.34-7.44 (m, 2H), 10.33 (brs, 1H).

Example 1-256

[0970] MS ESI m/e: 549 (M+H), 547 (MH).

[0971] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.66-0.77 (m, 2H), 0.89-1.05 (m, 2H), 2.54-2.61 (m, 1H), 2.56 (s, 3H), 7.36-7.45 (m, 4H), 7.53-7.63 (m, 3H), 7.65-7.71 (m, 2H), 12.88 (brs, 1H).

Example 1-257

[0972] MS ESI m/e: 638 (M+H), 636 (MH).

[0973] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.74 (m, 2H), 1.03 (m, 2H), 2.65 (s, 4H), 3.02 (s, 3H), 5.38 (s, 1H), 7.13 (d, J=8.6 Hz, 1H), 7.20-7.40 (m, 3H), 7.46 (t, J=8.1 Hz, 1H), 7.63 (d, J=9.3 Hz, 1H), 7.81 (d, J=10.1 Hz, 1H), 10.00 (s, 1H), 10.54 (s, 1H).

Example 1-258

[0974] MS ESI m/e: 461 (M+H), 459 (MH).

[0975] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.91 (m, 2H), 0.96 (t, J=7.3 Hz, 3H), 1.14-1.25 (m, 2H), 1.58-1.72 (m, 2H), 2.60 (t, J=7.7 Hz, 2H), 2.72-2.82 (m, 1H), 2.82 (s, 3H), 5.61 (d, J=1.1 Hz, 1H), 6.94-7.04 (m, 2H), 7.24-7.36 (m, 3H), 7.41-7.53 (m, 3H), 10.18 (s, 1H).

Example 1-259

[0976] MS ESI m/e: 521 (M+H), 519 (MH).

[0977] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.92 (m, 2H), 1.17-1.27 (m, 2H), 2.72-2.82 (m, 1H), 2.82 (s, 3H), 3.12 (s, 3H), 3.14 (s, 1H), 5.80 (d, J=0.7 Hz, 1H), 7.28-7.36 (m, 2H), 7.37-7.45 (m, 1H), 7.51-7.57 (m, 1H), 7.68-7.77 (m, 1H), 8.01-8.07 (m, 2H), 10.40 (s, 1H).

Example 1-260

[0978] MS ESI m/e: 536 (M+H), 534 (MH).

[0979] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.82-0.93 (m, 2H), 1.29-1.28 (m, 2H), 2.71-2.81 (m, 1H), 2.89 (s, 3H), 3.10 (s, 3H), 3.15 (s, 1H), 5.82 (s, 1H), 6.81-6.88 (m, 1H), 7.08 (d, J=9.0 Hz, 1H), 7.21-7.39 (m, 3H), 7.39-7.51 (m, 2H), 10.49 (brs, H).

Example 1-261

[0980] MS ESI m/e: 499, 501 (M+H).

[0981] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.30 (t, J=7.0 Hz, 3H), 3.63 (s, 3H), 4.13 (q, J=7.0 Hz, 2H), 5.57 (s, 2H), 5.78 (s, 1H), 7.20-7.50 (m, 8H), 10.33 (s, 1H).

Example 1-262

[0982] MS ESI m/e: 604, 606 (M+H), 602, 604 (MH).

[0983] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 0.99-1.07 (m, 2H), 1.18 (t, J=7.5 Hz, 3H), 2.61-2.70 (m, 4H), 3.13 (q, J=7.0 Hz, 2H), 5.35 (s, 1H), 7.08-7.14 (m, 1H), 7.25-7.34 (m, 2H), 7.41-7.54 (m, 3H), 7.71-7.77 (m, 1H), 10.04 (brs, 1H), 10.53 (s, 1H).

Example 1-263

[0984] MS ESI m/e: 570, 572 (M+H), 568, 570 (MH).

[0985] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.07 (m, 2H), 2.63-2.73 (m, 1H), 2.66 (s, 3H), 3.99 (d, J=6.0 Hz, 2H), 5.36 (s, 1H), 5.65 (t, J=6.0 Hz, 1H), 7.10-7.15 (m, 1H), 7.39-7.52 (m, 3H), 7.71-7.85 (m, 3H), 9.91 (brs, 1H), 10.54 (brs, 1H).

Example 1-264

[0986] MS ESI m/e: 512, 514 (M+H), 510, 512 (MH).

[0987] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.77 (m, 2H), 0.97-1.08 (m, 2H), 2.62-2.71 (m, 1H), 2.74 (s, 3H), 5.35 (d, J=1.5 Hz, 1H), 5.38 (brs, 2H), 6.47-6.53 (m, 1H), 6.54-6.57 (m, 1H), 6.58-6.63 (m, 1H), 7.11 (t, J=7.9 Hz, 1H), 7.44-7.53 (m, 2H), 7.70-7.77 (m, 1H), 10.55 (brs, 1H).

Example 1-265

[0988] MS ESI m/e: 459 (M+H), 457 (MH).

[0989] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.66-0.74 (m, 2H), 0.83-0.91 (m, 2H), 0.97-1.06 (m, 2H), 1.14-1.24 (m, 2H), 1.85-1.96 (m, 1H), 2.72-2.81 (m, 1H), 2.81 (s, 3H), 5.58 (d, J=1.1 Hz, 1H), 6.82-6.92 (m, 2H), 7.21-7.29 (m, 1H), 7.29-7.36 (m, 2H), 7.39-7.53 (m, 3H), 10.16 (s, 1H).

Example 1-266

[0990] MS ESI m/e: 584, 586 (M+H), 582, 584 (MH).

[0991] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 0.99-1.08 (m, 2H), 2.63-2.71 (m, 1H), 2.66 (s, 3H), 3.32 (s, 3H), 3.37 (s, 3H), 4.00 (brs, 2H), 5.36 (d, J=0.8 Hz, 1H), 7.10-7.16 (m, 1H), 7.40-7.52 (m, 3H), 7.71-7.80 (m, 3H), 10.00 (brs, 1H), 10.54 (brs, 1H).

Example 1-267

[0992] MS ESI m/e: 658, 660 (M+H), 656, 658 (MH).

[0993] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.70-0.79 (m, 2H), 0.99-1.10 (m, 2H), 2.62-2.76 (m, 1H), 2.66 (s, 3H), 4.48-4.64 (m, 2H), 5.36 (s, 1H), 7.17 (d, J=9.0 Hz, 1H), 7.28-7.33 (m, 2H), 7.43-7.52 (m, 3H), 7.74 (d, J=12.0 Hz, 1H), 10.52 (brs, 1H), 10.72 (brs, 1H).

Example 1-268

[0994] MS ESI m/e: 554 (M+H), 552 (MH).

[0995] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.92 (m, 2H), 1.14-1.24 (m, 2H), 1.26 (t, J=7.7 Hz, 3H), 1.37 (t, J=7.3 Hz, 3H), 2.67 (q, J=7.6 Hz, 2H), 2.71-2.81 (m, 1H), 2.85 (s, 3H), 3.17 (q, J=7.5 Hz, 2H), 5.60 (d, J=1.1 Hz, 1H), 6.94-7.08 (m, 4H), 7.22-7.33 (m, 3H), 7.38-7.47 (m, 1H), 10.15 (s, 1H).

Example 1-269

[0996] MS ESI m/e: 541, 543 (M+H), 539, 541 (MH).

[0997] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.98-1.10 (m, 2H), 2.60 (s, 3H), 2.62-2.71 (m, 1H), 5.37 (d, J=1.1 Hz, 1H), 7.43-7.57 (m, 2H), 7.61-7.78 (m, 3H), 7.95-8.05 (m, 2H), 10.54 (brs, 1H), 13.34 (brs, 1H).

Example 1-270

[0998] MS ESI m/e: 540, 542 (M+H), 538, 540 (MH).

[0999] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 0.98-1.09 (m, 2H), 2.61 (s, 3H), 2.63-2.74 (m, 1H), 5.38 (s, 1H), 7.45-7.58 (m, 3H), 7.58-7.65 (m, 2H), 7.70-7.78 (m, 1H), 7.90 (brs, 1H), 7.94-8.00 (m, 1H), 8.11 (brs, 1H), 10.54 (brs, 1H).

Example 1-271

[1000] MS ESI m/e: 618, 620 (M+H), 616, 618 (MH).

[1001] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.71-0.77 (m, 2H), 0.92 (t, J=7.5 Hz, 3H), 1.00-1.07 (m, 2H), 1.66 (q, J=7.0 Hz, 2H), 2.62-2.70 (m, 4H), 3.05-3.13 (m, 2H), 5.36 (s, 1H), 7.09-7.13 (m, 1H), 7.23-7.32 (m, 2H), 7.41-7.53 (m, 3H), 7.71-7.77 (m, 1H), 10.05 (brs, 1H), 10.53 (s, 1H).

Example 1-272

[1002] MS ESI m/e: 618, 620 (M+H), 616, 618 (MH).

[1003] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 0.99-1.08 (m, 2H), 1.23 (d, J=6.0 Hz, 6H), 2.62-2.70 (m, 4H), 3.19-3.29 (m, 1H), 5.36 (s, 1H), 7.07-7.13 (m, 1H), 7.26-7.34 (m, 2H), 7.39-7.54 (m, 3H), 7.71-7.76 (m, 1H), 10.00 (brs, 1H), 10.53 (s, 1H).

Example 1-273

[1004] MS ESI m/e: 469 (M+H), 467 (M1).

[1005] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.80-0.90 (m, 2H), 1.10-1.30 (m, 2H), 2.78 (m, 1H), 2.83 (s, 3H), 5.97 (s, 1H), 7.30-7.35 (m, 2H), 7.35-7.55 (m, 5H), 7.65 (d, J=8.5 Hz, 2H), 10.67 (s, 1H).

Example 1-274

[1006] MS ESI m/e: 652 (M+H), 650 (MH).

[1007] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.98-1.08 (m, 2H), 1.17 (t, J=7.3 Hz, 3H), 2.61-2.71 (m, 1H), 2.64 (s, 3H), 3.13 (q, J=7.3 Hz, 2H), 5.38 (brs, 1H), 7.09-7.15 (m, 2H), 7.24-7.38 (m, 3H), 7.40-7.49 (m, 1H), 7.60-7.67 (m, 1H), 7.81 (dd, J=1.8, 9.9 Hz, 1H), 10.04 (s, 1H).

Example 1-275

[1008] MS ESI m/e: 540 (M+H), 538 (MH).

[1009] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.91 (m, 2H), 1.15-1.23 (m, 2H), 1.26 (t, J=7.6 Hz, 3H), 2.67 (q, J=7.6 Hz, 2H), 2.72-2.80 (m, 1H), 2.85 (s, 3H), 3.05 (s, 3H), 5.60 (d, J=1.2 Hz, 1H), 6.98-7.05 (m, 2H), 7.05-7.10 (m, 1H), 7.23-7.31 (m, 4H), 7.40-7.47 (m, 1H), 10.16 (s, 1H).

Example 1-276

[1010] MS ESI m/e: 653, 655 (M+H).

[1011] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.87 (t, J=7.2 Hz, 3H), 1.00-1.08 (m, 2H), 1.22-1.36 (m, 2H), 1.43-1.54 (m, 2H), 2.15 (t, J=7.3 Hz, 20), 2.63-2.72 (m, 1H), 2.66 (s, 3H), 3.86 (d, J=5.3 Hz, 2H), 5.36 (s, 1H), 7.05-7.12 (m, 1H), 7.40-7.52 (m, 3H), 7.61-7.77 (m, 3H), 8.08-8.15 (m, 1H), 10.20 (brs, 1H), 10.54 (brs, 1H).

Example 1-277

[1012] MS ESI m/e: 597, 599 (M+H), 595, 597 (MH).

[1013] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.78 (m, 2H), 0.99-1.07 (m, 2H), 2.28 (s, 6H), 2.64-2.70 (m, 1H), 2.67 (s, 3H), 3.09 (brs, 2H), 5.36 (d, J=1.1 Hz, 1H), 7.10-7.14 (m, 1H), 7.40-7.52 (m, 3H), 7.71-7.79 (m, 3H), 9.97 (brs, 1H), 10.54 (brs, 1H).

Example 1-278

[1014] MS ESI m/e: 568, 570 (M+H), 566, 568 (MH).

[1015] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 0.99-1.11 (m, 5H), 2.33 (q, J=7.0 Hz, 2H), 2.63-2.71 (m, 4H), 5.36 (s, 1H), 7.04-7.10 (m, 1H), 7.42 (t, J=7.5 Hz, 1H), 7.46-7.54 (m, 2H), 7.61-7.67 (m, 1H), 7.70-7.77 (m, 2H), 10.08 (s, 1H), 10.54 (s, 1H).

Example 1-279

[1016] MS ESI m/e: 582, 584 (M+H), 580, 582 (MH).

[1017] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 0.91 (t, J=7.5 Hz, 3H), 0.99-1.07 (m, 2H), 1.60 (q, J=8.0 Hz, 2H), 2.29 (t, J=7.5 Hz, 2H), 2.63-2.71 (m, 4H), 5.36 (s, 1H), 7.42 (t, J=7.5 Hz, 1H), 7.46-7.54 (m, 2H), 7.62-7.76 (m, 3H), 10.09 (s, 1H), 10.54 (s, 1H).

Example 1-280

[1018] MS ESI m/e: 644, 646 (M+H), 642, 644 (MH).

[1019] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.68-0.80 (m, 2H), 0.97-1.08 (m, 2H), 2.61-2.72 (m, 1H), 2.64 (s, 3H), 5.36 (d, J=0.7 Hz, 1H), 6.88-7.01 (m, 1H), 7.05-7.17 (m, 2H), 7.23-7.34 (m, 1H), 7.47 (dd, J=2.3, 8.7 Hz, 1H), 7.52 (t, J=8.1 Hz, 1H), 7.73 (dd, J=1.5, 10.2 Hz, 1H), 10.56 (brs, 1H).

Example 1-281

[1020] MS ESI m/e: 485 (M+H), 483 (MH).

[1021] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.71-0.81 (m, 2H), 1.00-1.10 (m, 2H), 2.60 (s, 3H), 2.61-2.72 (m, 1H), 5.52 (s, 1H), 7.41-7.56 (m, 98), 10.62 (brs, 1H).

Example 1-282

[1022] MS ESI m/e: 624, 626 (M+H), 622, 624 (MH).

[1023] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.71-0.81 (m, 2H), 0.97-1.10 (m, 2H), 2.61-2.72 (m, 1H), 2.65 (s, 3H), 5.07 (s, 2H), 5.36 (s, 1H), 7.19 (d, J=9.0 Hz, 1H), 7.28-7.38 (m, 2H), 7.42-7.56 (m, 3H), 7.74 (d, J=9.0 Hz, 1H), 10.53 (brs, 1H), 10.64 (brs, 1H).

Example 1-283

[1024] MS ESI m/e: 526, 528 (M+H), 524, 526 (MH).

[1025] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.71-0.79 (m, 2H), 0.99-1.09 (m, 2H), 2.66 (d, J=6.0 Hz, 3H), 2.64-2.67 (m, 1H), 2.74 (s, 3H), 5.36 (s, 1H), 5.92-5.98 (m, 1H), 6.50-6.60 (m, 3H), 7.19 (t, J=7.5 Hz, 1H), 7.49-7.54 (m, 2H), 7.74 (d, J=12.0 Hz, 1H), 10.57 (brs, 1H).

Example 1-284

[1026] MS ESI m/e: 652, 654 (M+H), 650, 652 (MH).

[1027] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.68-0.80 (m, 2H), 0.99-1.09 (m, 2H), 2.33 (s, 3H), 2.61-2.70 (m, 1H), 5.35 (s, 1H), 7.04 (d, J=12.0 Hz, 1H), 7.13 (d, J=6.0 Hz, 1H), 7.30-7.38 (m, 2H), 7.49-7.62 (m, 5H), 7.73-7.80 (m, 3H), 10.48 (brs, 1H), 10.52 (brs, 1H).

Example 1-285

[1028] MS ESI m/e: 465 (M+H), 463 (MH).

[1029] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.71-0.78 (m, 2H), 1.01-1.07 (m, 2H), 2.53 (s, 3H), 2.59 (s, 3H), 2.64-2.72 (m, 1H), 5.25 (d, J=1.1 Hz, 1H), 7.17 (dd, J=1.9, 8.7 Hz, 1H), 7.32 (dd, J=1.9, 11.3 Hz, 1H), 7.39-7.55 (m, 6H), 10.41 (brs, 1H).

Example 1-286

[1030] MS ESI m/e: 558 (M+H), 556 (MH).

[1031] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.78 (m, 2H), 0.99-1.07 (m, 2H), 2.53 (s, 3H), 2.63-2.69 (m, 1H), 2.65 (s, 3H), 3.02 (s, 3H), 5.25 (d, J=1.1 Hz, 1H), 7.11-7.19 (m, 2H), 7.24-7.35 (m, 3H), 7.39-7.50 (m, 2H), 9.99 (brs, 1H), 10.39 (brs, 1H).

Example 1-287

[1032] MS ESI m/e: 582, 584 (M+H), 580, 582 (MH).

[1033] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.78 (m, 2H), 0.99-1.12 (m, 8H), 2.53-2.70 (m, 5H), 5.36 (s, 1H), 7.05-7.11 (m, 1H), 7.42 (t, J=7.5 Hz, 1H), 7.46-7.55 (m, 2H), 7.62-7.68 (m, 1H), 7.70-7.77 (m, 2H), 10.05 (s, 1H), 10.54 (s, 1H).

Example 1-288

[1034] MS ESI m/e: 576, 578 (M+H), 574, 576 (MH).

[1035] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.80 (m, 2H), 1.00-1.08 (m, 2H), 2.60-2.70 (m, 4H), 5.37 (s, 1H), 7.47-7.58 (m, 4H), 7.65-7.77 (m, 3H), 7.88-7.93 (m, 2H), 10.52 (s, 1H).

Example 1-289

[1036] MS ESI m/e: 550 (M+H), 548 (MH).

[1037] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.78 (m, 2H), 0.99-1.09 (m, 2H), 1.18 (t, J=7.3 Hz, 3H), 2.63-2.71 (m, 1H), 2.66 (s, 3H), 3.13 (q, J=7.5 Hz, 2H), 4.32 (s, 1H), 5.51 (s, 1H), 7.09-7.15 (m, 1H), 7.24-7.35 (m, 2H), 7.36-7.41 (m, 1H), 7.41-7.49 (m, 1H), 7.50-7.61 (m, 2H), 10.04 (s, 1H), 10.72 (s, 1H).

Example 1-290

[1038] MS ESI m/e: 518 (M+H), 516 (MH).

[1039] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.71-0.78 (m, 2H), 1.00-1.08 (m, 2H), 2.61-2.71 (m, 1H), 2.66 (s, 3H), 3.03 (s, 3H), 4.19 (s, 1H), 5.64 (s, 1H), 7.11-7.16 (m, 1H), 7.24-7.29 (m, 1H), 7.30-7.37 (m, 3H), 7.43-7.49 (m, 1H), 7.51-7.56 (m, 2H), 10.01 (s, 1H), 10.70 (s, 1H).

Example 1-291

[1040] MS ESI m/e: 483 (M+H), 481 (MH).

[1041] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.80 (m, 2H), 0.98-1.10 (m, 2H), 2.60 (s, 3H), 2.62-2.73 (m, 1H), 3.68 (q, J=11.6 Hz, 2H), 5.54 (s, 1H), 7.30-7.38 (m, 2H), 7.39-7.56 (m, 7H), 10.60 (brs, 1H).

Example 1-292

[1042] MS ESI m/e: 554, 556 (M+H), 552, 554 (MH).

[1043] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.81 (m, 2H), 0.98-1.09 (m, 2H), 2.60 (s, 3H), 2.63-2.71 (m, 1H), 2.79 (d, J=4.5 Hz, 3H), 5.38 (d, J=1.1 Hz, 1H), 7.45-7.55 (m, 2H), 7.57-7.65 (m, 2H), 7.71-7.77 (m, 1H), 7.84-7.89 (m, 1H), 7.89-7.95 (m, 1H), 8.57 (q, J=5.3 Hz, 1H), 10.53 (brs, 1H).

Example 1-293

[1044] MS ESI m/e: 447 (M+H), 445 (MH).

[1045] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 0.99-1.08 (m, 2H), 2.59 (s, 3H), 2.62-2.73 (m, 1H), 3.00 (dt, J=25.2, 6.0 Hz, 2H), 4.67 (dt, J=47.1, 6.4 Hz, 2H), 5.46 (s, 1H), 7.23-7.29 (m, 2H), 7.33-7.39 (m, 2H), 7.40-7.56 (m, 5H), 10.51 (brs, 1H).

Example 1-294

[1046] MS ESI m/e: 590, 592 (M+H), 588, 590 (MH).

[1047] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.00-1.09 (m, 2H), 2.42 (s, 3H), 2.58-2.70 (m, 4H), 5.37 (s, 1H), 7.45-7.54 (m, 2H), 7.70-7.80 (m, 3H), 7.82-7.88 (m, 2H), 10.51 (s, 1H).

Example 1-295

[1048] MS ESI m/e: 604, 606 (M+H), 602, 604 (MH).

[1049] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.79 (m, 2H), 0.96 (t, J=6.0 Hz, 3H), 1.01-1.08 (m, 2H), 2.58-2.71 (m, 4H), 2.74-2.84 (m, 2H), 5.37 (s, 1H), 7.46-7.55 (m, 2H), 7.69-7.79 (m, 4H), 7.84-7.90 (m, 2H), 10.51 (s, 1H).

Example 1-296

[1050] MS ESI m/e: 504 (M+H), 502 (MH).

[1051] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.91 (m, 2H), 1.12-1.23 (m, 2H), 1.26 (t, J=7.5 Hz, 3H), 2.16 (s, 3H), 2.66 (q, J=7.6 Hz, 2H), 2.72-2.82 (m, 1H), 2.86 (s, 3H), 5.59 (d, J=1.5 Hz, 1H), 6.95-7.08 (m, 3H), 7.22-7.32 (m, 1H), 7.33-7.55 (m, 3H), 7.70 (s, 1H), 10.18 (s, 1H).

Example 1-297

[1052] MS ESI m/e: 602 (M+H), 600 (MH).

[1053] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.68-0.79 (m, 2H), 0.98-1.09 (m, 2H), 2.04 (s, 3H), 2.63-2.71 (m, 1H), 2.66 (s, 3H), 5.38 (d, J=1.5 Hz, 1H), 7.04-7.10 (m, 1H), 7.29-7.38 (m, 1H), 7.38-7.46 (m, 1H), 7.60-7.72 (m, 3H), 7.81 (dd, J=1.8, 10.2 Hz, 1H), 10.15 (s, 1H), 10.55 (s, 1H).

Example 1-298

[1054] MS ESI m/e: 532 (M+H), 530 (MH).

[1055] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.80 (m, 2H), 0.98-1.09 (m, 2H), 1.18 (t, J=7.3 Hz, 3H), 2.61-2.72 (m, 1H), 2.65 (s, 3H), 3.13 (q, J=7.5 Hz, 2H), 4.18 (s, 1H), 5.65 (s, 1H), 7.08-7.15 (m, 1H), 7.24-7.31 (m, 1H), 7.31-7.38 (m, 3H), 7.41-7.49 (m, 1H), 7.51-7.57 (m, 2H), 10.04 (s, 1H), 10.70 (s, 1H).

Example 1-299

[1056] MS ESI m/e: 667, 669 (M+H), 665, 667 (MH).

[1057] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.77 (m, 2H), 0.83 (t, J=7.4 Hz, 3H), 0.98-1.07 (m, 2H), 1.19-1.29 (m, 2H), 1.39-1.49 (m, 2H), so 2.04 (t, J=7.5 Hz, 2H), 2.45-2.53 (m, 2H), 2.63-2.70 (m, 1H), 2.66 (s, 3H), 3.27-3.35 (m, 2H), 5.35 (d, J=1.1 Hz, 1H), 7.05-7.11 (m, 1H), 7.42 (t, J=8.1 Hz, 1H), 7.47-7.52 (m, 2H), 7.60-7.67 (m, 1H), 7.70-7.77 (m, 2H), 7.87-7.94 (m, 1H), 10.17 (brs, 1H), 10.54 (brs, 1H).

Example 1-300

[1058] MS ESI m/e: 457 (M+H), 455 (M1).

[1059] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.80-0.90 (m, 2H), 1.10-1.30 (m, 2H), 1.34 (s, 9H), 2.77 (m, 1H), 2.81 (s, 3H), 5.79 (s, 1H), 7.20 (d, J=8.5 Hz, 2H), 7.30-7.35 (m, 2H), 7.35-7.55 (m, 5H), 10.29 (S, 1H).

Example 1-301

[1060] MS ESI m/e: 580 (M+H), 578 (M1).

[1061] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.75 (brs, 2H), 1.05 (m, 2H), 2.68 (s, 4H), 3.03 (s, 3H), 3.32 (s, 3H), 5.68 (s, 1H), 7.15 (d, J=8.9 Hz, 1H), 7.27 (d, J=8.1 Hz, 1H), 7.47 (t, J=8.0 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 7.75-7.90 (m, 2H), 10.01 (s, 1H), 10.95 (s, 1H).

Example 1-302

[1062] MS ESI m/e: 620 (M+H), 618 (MH).

[1063] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.71-0.78 (m, 2H), 0.99-1.07 (m, 2H), 2.62-2.69 (m, 1H), 2.65 (s, 3H), 3.02 (s, 3H), 5.54 (s, 1H), 7.10-7.19 (m, 3H), 7.23-7.28 (m, 1H), 7.29-7.32 (m, 1H), 7.42-7.49 (m, 1H), 7.74-7.80 (m, 2H), 10.00 (s, 1H), 10.57 (s, 1H).

Example 1-303

[1064] MS ESI m/e: 625, 627 (M+H), 623, 625 (MH).

[1065] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.78 (m, 2H), 0.99-1.09 (m, 2H), 2.34-2.56 (m, 6H), 2.61-2.71 (m, 1H), 2.74 (s, 3H), 3.08-3.19 (m, 2H), 3.50-3.62 (m, 4H), 5.36 (s, 1H), 5.77 (brs, 1H), 6.53-6.70 (m, 3H), 7.18 (dd, J=9.0, 6.0 Hz, 1H), 7.40-7.50 (m, 2H), 7.74 (d, J=9.0 Hz, 1H), 10.56 (brs, 1H).

Example 1-304

[1066] MS ESI m/e: 572, 574 (M+H), 570, 572 (MH).

[1067] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.74-0.79 (m, 2H), 1.00-1.08 (m, 2H), 2.62-2.68 (m, 4H), 3.02 (s, 3H), 5.53 (s, 1H), 7.12-7.14 (m, 1H), 7.22-7.35 (m, 4H), 7.42-7.44 (m, 1H), 7.60-7.62 (m, 2H), 10.00 (brs, 1H), 10.57 (brs, 1H).

Example 1-305

[1068] MS ESI m/e: 584, 586 (M+H), 582, 584 (MH).

[1069] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.80 (m, 2H), 0.97-1.08 (m, 2H), 2.47 (t, J=7.2 Hz, 2H), 2.62-2.71 (m, 1H), 2.67 (s, 3H), 3.70 (q, J=5.9 Hz, 2H), 4.69 (t, J=5.1 Hz, 1H), 5.36 (d, J=1.1 Hz, 1H), 7.07 (dd, J=2.6, 7.9 Hz, 1H), 7.42 (t, J=8.1 Hz, 1H), 7.48-7.55 (m, 2H), 7.62-7.69 (m, 1H), 7.71-7.77 (m, 2H), 10.13 (brs, 1H), 10.54 (brs, 1H).

Example 1-306

[1070] MS ESI m/e: 611, 613 (M+H), 609, 611 (MH).

[1071] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.98-1.08 (m, 2H), 2.16 (s, 6H), 2.39-2.48 (m, 2H), 2.51-2.59 (m, 2H), 2.63-2.72 (m, 1H), 2.67 (s, 3H), 5.35 (d, J=1.1 Hz, 1H), 7.05-7.11 (m, 1H), 7.42 (t, J=8.1 Hz, 1H), 7.47-7.55 (m, 2H), 7.61-7.67 (m, 1H), 7.69-7.77 (m, 2H), 10.22 (brs, 1H), 10.54 (brs, 1H).

Example 1-307

[1072] MS ESI m/e: 583, 585 (M+H), 581, 583 (MH).

[1073] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.98-1.08 (m, 2H), 1.04 (t, J=7.2 Hz, 3H), 2.62-2.74 (m, 1H), 2.68 (s, 3H), 3.09 (quint, J=6.8 Hz, 2H), 5.35 (d, J=1.1 Hz, 1H), 6.16 (t, J=5.8 Hz, 1H), 6.88-6.95 (m, 1H), 7.32 (t, J=7.9 Hz, 1H), 7.36-7.42 (m, 1H), 7.45-7.57 (m, 3H), 7.71-7.77 (m, 1H), 8.73 (brs, 1H), 10.55 (brs, 1H).

Example 1-308

[1074] MS ESI m/e: 584, 586 (M+H), 582, 584 (MH).

[1075] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.78 (m, 2H), 0.98-1.08 (m, 2H), 1.24 (t, J=7.2 Hz, 3H), 2.61-2.72 (m, 1H), 2.66 (s, 3H), 4.12 (q, J=6.9 Hz, 2H), 5.36 (d, J=1.1 Hz, 1H), 7.00-7.05 (m, 1H), 7.39 (t, J=7.9 Hz, 1H), 7.43-7.55 (m, 3H), 7.60-7.65 (m, 1H), 7.70-7.78 (m, 1H), 9.85 (brs, 1H), 10.54 (brs, 1H).

Example 1-309

[1076] MS ESI m/e: 619, 621 (M+H), 617, 619 (MH).

[1077] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.68-0.80 (m, 2H), 0.98-1.07 (m, 2H), 2.60-2.71 (m, 1H), 2.63 (s, 3H), 2.67 (s, 6H), 5.35 (d, J=1.1 Hz, 1H), 7.09-7.15 (m, 1H), 7.21-7.27 (m, 2H), 7.43 (t, J=8.5 Hz, 1H), 7.47-7.54 (m, 2H), 7.70-7.76 (m, 1H), 10.11 (brs, 1H), 10.54 (brs, 1H).

Example 1-310

[1078] MS ESI m/e: 500 (M+H), 498 (MH).

[1079] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.98-1.08 (m, 2H), 2.05 (s, 3H), 2.63-2.72 (m, 1H), 2.67 (s, 3H), 4.32 (s, 1H), 5.51 (brs, 1H), 7.04-7.12 (m, 1H), 7.35-7.46 (m, 2H), 7.50-7.61 (m, 2H), 7.62-7.67 (m, 1H), 7.67-7.72 (m, 1H), 10.16 (s, 1H), 10.75 (s, 1H).

Example 1-311

[1080] MS ESI m/e: 666 (M+H), 664 (MH).

[1081] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.71-0.77 (m, 2H), 0.92 (t, J=7.5 Hz, 3H), 1.00-1.07 (m, 2H), 1.59-1.71 (m, 2H), 2.62-2.70 (m, 1H), 2.64 (s, 3H), 3.09 (t, J=7.4 Hz, 2H), 5.38 (d, J=1.2 Hz, 1H), 7.08-7.14 (m, 1H), 7.23-7.37 (m, 3H), 7.41-7.48 (m, 1H), 7.61-7.66 (m, 1H), 7.79-7.84 (m, 1H), 10.54 (s, 1H).

Example 1-312

[1082] MS ESI m/e: 753, 755 (M+H), 751, 753 (MH).

[1083] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.81-0.89 (m, 2H), 1.14-1.22 (m, 2H), 2.70-2.79 (m, 1H), 2.81 (s, 3H), 3.21-3.32 (m, 2H), 3.57-3.68 (m, 2H), 5.07 (s, 2H), 5.57-5.67 (m, 1H), 5.65 (d, J=1.1 Hz, 1H), 7.04-7.09 (m, 1H), 7.21-7.40 (m, 11H), 7.74-7.80 (m, 1H), 10.34 (brs, 1H).

Example 1-313

[1084] MS ESI m/e: 619, 621 (M+H), 617, 619 (MH).

[1085] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.79 (m, 2H), 0.99-1.09 (m, 2H), 2.63-2.70 (m, 1H), 2.66 (s, 3H), 3.09-3.19 (m, 2H), 3.37-3.49 (m, 2H), 5.36 (d, J=0.9 Hz, 1H), 7.17-7.24 (m, 1H), 7.30-7.39 (m, 2H), 7.47-7.54 (m, 3H), 7.73-7.77 (m, 1H), 7.93-8.14 (m, 3H), 10.39 (brs, 1H), 10.52 (brs, 1H).

Example 1-314

[1086] MS ESI m/e: 703, 705 (M+H), 701, 703 (MH).

[1087] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.78 (m, 2H), 0.82 (t, J=7.2 Hz, 3H), 0.99-1.08 (m, 2H), 1.15-1.27 (m, 1H), 1.37-1.47 (m, 2H), 2.01 (t, J=7.5 Hz, 2H), 2.62-2.70 (m, 1H), 2.65 (s, 3H), 3.17-3.25 (m, 2H), 3.33-3.43 (m, 2H), 5.36 (d, J=1.1 Hz, 1H), 7.11-7.18 (m, 1H), 7.25-7.30 (m, 1H), 7.33-7.36 (m, 1H), 7.42-7.54 (m, 3H), 7.72-7.77 (m, 1H), 7.87-7.94 (m, 1H), 10.08 (brs, 1H), 10.53 (brs, 1H).

Example 1-315

[1088] MS ESI m/e: 659, 661 (M+H), 657, 659 (MH).

[1089] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.72-0.79 (m, 2H), 1.01-1.09 (m, 2H), 2.14 (s, 3H), 2.32-2.39 (m, 4H), 2.60-2.72 (m, 4H), 2.83-2.97 (m, 4H), 5.37 (s, 1H), 7.46-7.55 (m, 2H), 7.71-7.87 (m, 5H), 10.51 (s, 1H).

Example 1-316

[1090] MS ESI m/e: 646, 648 (M+H), 644, 646 (MH).

[1091] .sup.1H-NMR DMSO-d.sub.6, 300 MHz) 0.72-0.79 (m, 2H), 1.01-1.10 (m, 2H), 2.60-2.71 (m, 4H), 2.81-2.94 (m, 4H), 3.58-3.67 (m, 4H), 5.38 (s, 1H), 7.47-7.55 (m, 2H), 7.71-7.88 (m, 5H), 10.50 (s, 1H).

Example 1-317

[1092] MS ESI m/e: 644, 646 (M+H), 642, 644 (MH).

[1093] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.00-1.09 (m, 2H), 1.32-1.41 (m, 2H), 1.47-1.58 (m, 4H), 2.58-2.73 (m, 4H), 2.82-2.92 (m, 4H), 5.37 (s, 1H), 7.46-7.54 (m, 2H), 7.71-7.84 (m, 5H), 10.51 (s, 1H).

Example 1-318

[1094] MS ESI m/e: 630, 632 (M+H), 628, 630 (MH).

[1095] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.79 (m, 2H), 1.01-1.10 (m, 2H), 1.59-1.69 (m, 4H), 2.58 (s, 3H), 2.63-2.71 (m, 1H), 3.03-3.22 (m, 4H), 5.37 (s, 1H), 7.46-7.55 (m, 2H), 7.71-7.82 (m, 3H), 7.87-7.92 (m, 2H), 10.51 (s, 1H).

Example 1-319

[1096] MS ESI m/e: 666 (M+H), 664 (MH).

[1097] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.99-1.08 (m, 2H), 1.23 (d, J=6.6 Hz, 6H), 2.61-2.71 (m, 1H), 2.64 (s, 3H), 5.38 (s, 1H), 7.08-7.15 (m, 1H), 7.27-7.38 (m, 3H), 7.39-7.47 (m, 1H), 7.60-7.66 (m, 1H), 7.78-7.84 (m, 1H), 9.99 (brs, 1H), 10.54 (s, 1H).

Example 1-320

[1098] MS ESI m/e: 564 (M+H), 562 (MH).

[1099] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.70-0.79 (m, 2H), 0.92 (t, J=7.3 Hz, 3H), 0.99-1.09 (m, 2H), 1.58-1.74 (m, 2H), 2.62-2.72 (m, 1H), 2.66 (s, 3H), 3.05-3.14 (m, 2H), 4.32 (s, 1H), 5.51 (s, 1H), 7.09-7.16 (m, 1H), 7.24-7.34 (m, 2H), 7.35-7.50 (m, 2H), 7.50-7.61 (m, 2H), 10.04 (brs, 1H), 10.73 (s, 1H).

Example 1-321

[1100] MS ESI m/e: 564 (M+H), 562 (MH).

[1101] .sup.1H-NMR (DMSO-d, 300 MHz) 0.70-0.79 (m, 2H), 0.99-1.08 (m, 2H), 1.23 (d, J=6.6 Hz, 6H), 2.62-2.71 (m, 1H), 2.65 (s, 1H), 3.18-3.30 (m, 1H), 4.31 (s, 1H), 5.51 (s, 1H), 7.08-7.14 (m, 1H), 7.26-7.35 (m, 2H), 7.35-7.48 (m, 2H), 7.50-7.61 (m, 2H), 10.00 (brs, 1H), 10.73 (s, 1H).

Example 1-322

[1102] MS ESI m/e: 655 (M+H), 653 (MH).

[1103] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.99-1.09 (m, 2H), 2.61-2.71 (m, 4H), 3.02 (s, 3H), 5.49 (s, 1H), 7.15 (d, J=9.0 Hz, 1H), 7.25-7.31 (m, 2H), 7.38-7.49 (m, 2H), 7.74-7.77 (m, 1H), 8.00 (s, 1H), 9.99 (brs, 1H), 10.76 (brs, 1H).

Example 1-323

[1104] MS ESI m/e: 625, 627 (M+H), 623, 625 (MH).

[1105] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.70-0.79 (m, 2H), 0.98-1.09 (m, 2H), 1.70 (quint, J=7.2 Hz, 2H), 2.11 (s, 6H), 2.21 (t, J=7.2 Hz, 2H), 2.33 (t, J=7.3 Hz, 2H), 2.62-2.72 (m, 1H), 2.66 (s, 3H), 5.35 (d, J=1.1 Hz, 1H), 7.04-7.11 (m, 1H), 7.41 (t, J=8.1 Hz, 1H), 7.45-7.54 (m, 2H), 7.60-7.67 (m, 1H), 7.69-7.78 (m, 2H), 10.13 (brs, 1H), 10.54 (brs, 1H).

Example 1-324

[1106] MS ESI m/e: 583, 585 (M+H), 581, 583 (MH).

[1107] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.97-1.08 (m, 2H), 2.62-2.74 (m, 1H), 2.69 (s, 3H), 2.92 (s, 6H), 5.35 (d, J=1.1 Hz, 1H), 6.94-7.01 (m, 1H), 7.34 (t, J=8.1 Hz, 1H), 7.46-7.54 (m, 2H), 7.54-7.61 (m, 2H), 7.70-7.77 (m, 1H), 8.51 (brs, 1H), 10.54 (brs, 1H).

Example 1-325

[1108] MS ESI m/e: 569, 571 (M+H), 567, 569 (MH).

[1109] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.80 (m, 2H), 0.98-1.09 (m, 2H), 2.63 (d, J=4.9 Hz, 3H), 2.65-2.73 (m, 1H), 2.68 (s, 3H), 5.35 (d, J=1.1 Hz, 1H), 6.00-6.08 (m, 1H), 6.89-6.95 (m, 1H), 7.33 (t, J=7.9 Hz, 1H), 7.38-7.45 (m, 1H), 7.46-7.52 (m, 2H), 7.52-7.56 (m, 1H), 7.69-7.77 (m, 1H), 8.77 (brs, 1H), 10.55 (brs, 1H).

Example 1-326

[1110] MS ESI m/e: 465 (M+H), 463 (MH).

[1111] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.80 (m, 2H), 0.99-1.08 (m, 2H), 2.59 (s, 3H), 2.62-2.72 (m, 1H), 3.21 (dt, J=4.5, 18.3 Hz, 2H), 5.50 (s, 1H), 6.27 (tt, J=4.3, 56.3 Hz, 1H), 7.26-7.34 (m, 2H), 7.34-7.56 (m, 7H), 10.55 (brs, 1H).

Example 1-327

[1112] MS ESI m/e: 585, 587 (M+H), 583, 585 (M1).

[1113] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.75 (brs, 2H), 1.03 (m, 2H), 2.68 (s, 4H), 3.61 (s, 3H), 5.36 (s, 1H), 7.00-7.10 (m, 1H), 7.38 (t, J=8.1 Hz, 1H), 7.45-7.55 (m, 2H), 7.65-7.80 (m, 3H), 9.12 (s, 1H), 9.63 (s, 1H), 10.54 (s, 1H).

Example 1-328

[1114] MS ESI m/e: 457 (M+H), 455 (MH).

[1115] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.74-0.81 (m, 2H), 1.01-1.10 (m, 2H), 2.60 (s, 3H), 2.65-2.74 (m, 1H), 5.50 (s, 1H), 7.32 (dd, J=1.9, 8.7 Hz, 1H), 7.40-7.56 (m, 6H), 7.82-7.87 (m, 2H), 8.07 (d, J=8.3 Hz, 1H), 10.63 (brs, 1H).

Example 1-329

[1116] MS ESI m/e: 437 (M+H), 435 (MH).

[1117] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 2.89 (s, 3H), 7.15-7.55 (m, 5H), 10.35 (S, 1H).

Example 1-330

[1118] MS ESI m/e: 347 (M+H), 345 (MH).

[1119] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 3.41 (s, 3H), 3.53 (s, 3H), 3.56 (s, 3H), 7.15-7.23 (m, 2H), 7.32-7.38 (m, 2H), 10.45 (s, 1H).

Example 1-331

[1120] MS ESI m/e: 458 (M+H), 456 (MH).

[1121] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.40-0.57 (m, 4H), 1.24-1.37 (m, 1H), 2.81 (s, 3H), 2.97 (s, 6H), 3.91 (d, J=7.0 Hz, 2H), 5.61 (s, 1H), 6.70-6.77 (m, 2H), 7.10-7.17 (m, 2H), 7.33-7.54 (m, 5H), 10.22 (s, 1H).

Example 1-332

[1122] MS ESI m/e: 495 (M+H), 496, 493 (MH), 494.

[1123] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 2.70 (s, 3H), 3.84 (s, 3H), 5.88 (s, 1H), 7.36-7.55 (m, 10H), 7.46 (d, J=9.0 Hz, 2H), 7.99 (d, J=9.0 Hz, 2H), 10.85 (brs, 1H).

Example 1-333

[1124] MS ESI m/e: 604, 606 (M+H), 602, 604 (MH).

[1125] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.66-0.74 (m, 2H), 0.98-1.06 (m, 2H), 1.56 (s, 3H), 2.60-2.69 (m, 1H), 2.74 (s, 3H), 3.03 (s, 3H), 6.80(t, J=8.9 Hz, 1H), 7.10-7.15 (m, 1H), 7.25-7.36 (m, 3H), 7.46 (t, J=8.0 Hz, 1H), 7.59-7.64 (m, 1H), 9.99 (s, 1H), 10.17 (s, 1H).

Example 1-334

[1126] MS ESI m/e: 556(M+H), 554(MH).

[1127] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.78 (m, 2H), 0.99-1.08 (m, 2H), 2.74(s, 38), 2.61-2.72 (m, 1H), 2.69-2.79 (m, 2H), 2.98-3.09 (m, 2H), 5.36 (s, 1H), 5.92 (brs, 1H), 6.51-6.68 (m, 3H), 7.15-7.20 (m, 1H), 7.49-7.50 (m, 2H), 7.72-7.75 (m, 1H), 10.60 (brs, 1H).

Example 1-335

[1128] MS ESI m/e: 654(M+H), 652(MH).

[1129] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.67-0.81 (m, 2H), 0.96-1.09 (m, 2H), 2.36 (s, 3H), 2.61-2.69 (m, 1H), 5.35 (s, 1H), 7.08(d, J=9.0 Hz, 1H), 7.16(d, J=9.0 Hz, 1H), 7.31-7.39 (m, 2H), 7.48-7.53 (m, 2H), 7.57-7.62 (m, 1H), 7.74 (d, J=9.0 Hz, 1H), 8.10(d, J=9.0 Hz, 1H), 8.77-8.80 (m, 1H), 8.88-8.90 (m, 1H), 10.52 (brs, 1H), 10.69 (brs, 1H).

Example 1-336

[1130] MS ESI m/e: 532(M+H), 530(MH).

[1131] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.71-0.80 (m, 2H), 0.99-1.09 (m, 2H), 2.25 (s, 3H), 2.61-2.73 (m, 1H), 2.64 (s, 3H), 3.01 (s, 3H), 4.17 (s, 1H), 5.27 (s, 1H), 7.14-7.48 (m, 7H), 9.98 (brs, 1H), 10.50 (brs, 1H).

Example 1-337

[1132] MS ESI m/e: 552(M+H), 550(MH).

[1133] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.68-0.78 (m, 2H), 0.99-1.10 (m, 2H), 2.66 (s, 3H), 2.61-2.76 (m, 1H), 3.01 (s, 3H), 4.31 (s, 1H), 5.61 (s, 1H), 7.13 (d, J=12.0 Hz, 1H), 7.22-7.32 (m, 2H), 7.41-7.51 (m, 2H), 7.61 (d, J=6.0 Hz, 1H), 7.74 (s, 1H), 9.98 (brs, 1H), 10.90 (brs, 1H).

Example 1-338

[1134] MS ESI m/e: 558 (M+H), 556 (MH).

[1135] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.81 (m, 2H), 0.99-1.08 (m, 2H), 2.61-2.71 (m, 1H), 2.65 (s, 3H), 3.02(dt, J=18.8, 3.4 Hz, 2H), 3.02 (s, 3H), 4.69(dt, J=47.1, 3.0 Hz, 2H), 5.28 (s, 1H), 7.10-7.16 (m, 1H), 7.17-7.23 (m, 1H), 7.23-7.29 (m, 1H), 7.29-7.39 (m, 2H), 7.41-7.50 (m, 2H), 10.00 (brs, 1H), 10.43 (s, 1H).

Example 1-339

[1136] MS ESI m/e: 690(M+H), 688(MH).

[1137] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.98-1.09 (m, 2H), 2.22-2.32 (m, 4H), 2.64 (s, 3H), 2.60-2.71 (m, 3H), 3.25-3.41 (m, 2H), 3.41-3.51 (m, 4H), 5.34 (s, 1H), 7.09(d, J=6.0 Hz, 1H), 7.23-7.35 (m, 2H), 7.40-7.51 (m, 3H), 7.73(d, J=12.0 Hz, 1H), 10.08 (brs, 1H), 10.52 (brs, 1H).

Example 1-340

[1138] MS ESI m/e: 634(M+H), 632(MH).

[1139] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.79 (m, 2H), 0.98-1.09 (m, 2H), 2.22 (s, 3H), 2.60-2.69 (m, 1H), 2.63 (s, 3H), 3.01 (s, 3H), 5.14 (s, 1H), 7.13(d, J=9.0 Hz, 2H), 7.22-7.30 (m, 2H), 7.41-7.48 (m, 1H), 7.61-7.64 (m, 1H), 7.74 (s, 1H), 9.98 (brs, 1H), 10.32 (brs, 1H).

Example 1-341

[1140] MS ESI m/e: 522 (M+H), 520 (MH).

[1141] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.70-0.80 (m, 2H), 0.97-1.09 (m, 2H), 2.06 (s, 3H), 2.54 (s, 3H), 2.63-2.72 (m, 1H), 2.66 (s, 3H), 5.23-5.26 (m, 1H), 7.05-7.20 (m, 2H), 7.28-7.49 (m, 3H), 7.61-7.73 (m, 2H), 10.17 (brs, 1H), 10.41 (brs, 1H).

Example 1-342

[1142] MS ESI m/e: 522 (M+H), 520 (MH).

[1143] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.69-0.79 (m, 2H), 0.97-1.10 (m, 2H), 2.04 (s, 3H), 2.60-2.73 (m, 1H), 2.65 (s, 3H), 3.02(dt, J=25.2, 2.8 Hz, 2H), 4.69(dt, J=47.1, 3.2 Hz, 2H), 5.27 (s, 1H), 7.02-7.11 (m, 1H), 7.16-7.23 (m, 1H), 7.29-7.49 (m, 3H), 7.61-7.71 (m, 2H), 10.16 (brs, 1H), 10.44 (brs, 1H).

Example 1-343

[1144] MS ESI m/e: 475 (M+H), 473 (MH).

[1145] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.85-0.94 (m, 2H), 1.16-1.24 (m, 2H), 2.75-2.83 (m, 1H), 2.82 (s, 3H), 5.54-5.58 (m, 1H), 7.30-7.38 (m, 3H), 7.43-7.54(m, 5H), 7.63-7.69 (m, 1H), 10.28 (brs, 1H).

Example 2-1

[1146] MS ESI m/e: 472 (M+H), 470 (MH).

[1147] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 2.68 (s, 3H), 7.34-7.39 (m, 2H), 7.41-7.61 (m, 10H), 7.80-7.87 (m, 2H), 11.34 (s, 1H).

Example 2-2

[1148] MS ESI m/e: 592 (M+H), 590 (MH).

[1149] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.70-0.82 (m, 2H), 1.01-1.13 (m, 2H), 2.64-2.75 (m, 1H), 2.67 (s, 3H), 3.05 (s, 3H), 7.19-7.27 (m, 1H), 7.27-7.34 (m, 1H), 7.35-7.39 (m, 1H), 7.45-7.54 (m, 2H), 7.71 (dd, J=3.0, 12.0 Hz, 1H), 8.51 (t, J=9.0 Hz, 1H), 10.05 (s, 1H), 11.61 (d, J=3.0 Hz, 1H).

Example 3-1

[1150] MS ESI m/e: 493, 495 (M+H), 491, 493 (MH).

[1151] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.77-0.82 (m, 2H), 1.09-1.15 (m, 2H), 1.36 (s, 3H), 2.72-2.74 (m, 1H), 3.20 (s, 3H), 6.86 (d, 2H), 7.28-7.32 (m, 2H), 7.34-7.51 (m, 5H), 11.36 (s, 1H).

Example 3-2

[1152] MS ESI m/e: 479, 481 (M+H), 477, 479 (MH).

[1153] .sup.1H-NMR (CDCl.sub.3, 400 MHz) 0.83-0.90 (m, 2H), 1.10-1.18 (m, 2H), 2.67-2.76 (m, 1H), 3.11 (s, 3H), 5.00 (s, 1H), 7.02 (d, J=8.6 Hz, 2H), 7.10-7.15 (m, 2H), 7.19-7.25 (m, 1H), 7.34-7.41 (m, 2H), 7.63-7.70 (m, 2H), 11.71 (s, 1H).

Example 3-3

[1154] MS ESI m/e: 479, 481 (M+H), 477, 479 (MH).

[1155] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.83-0.92 (m, 2H), 1.09-1.19 (m, 2H), 2.67-2.78 (m, 1H), 3.13 (s, 3H), 5.06 (s, 1H), 6.87-6.94 (m, 2H), 7.21-7.28 (m, 2H), 7.45-7.60 (m, 5H), 11.68 (s, 1H).

Example 3-4

[1156] MS ESI m/e: 604 (M+H), 606, 602 (MH), 604.

[1157] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.69 (m, 2H), 0.93-0.98 (m, 2H), 1.25 (s, 3H), 2.59-2.64 (m, 1H), 3.01 (s, 3H), 3.08 (s, 3H), 7.08-7.13 (m, 2H), 7.21-7.25 (m, 2H), 7.39-7.43 (m, 2H), 7.70-7.74 (m, 1H), 9.90 (brs, 1H), 11.09 (brs, 1H).

Example 3-5

[1158] MS ESI m/e: 618 (M+H), 620, 616 (MH), 618.

[1159] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.92-0.98 (m, 2H), 1.19 (t, J=9.8 Hz, 3H), 1.24 (s, 3H), 2.58-2.64 (m, 1H), 3.11 (q, J=9.8 Hz, 2H), 3.08 (s, 3H), 7.07-7.13 (m, 2H), 7.21-7.25 (m, 2H), 7.37-7.42 (m, 2H), 7.70-7.74 (m, 2H), 9.95 (brs, 1H), 11.09 (brs, 1H).

Example 3-6

[1160] MS ESI m/e: 604 (M+H), 606, 602 (MH), 604.

[1161] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.92-0.99 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.08 (s, 3H), 7.01-7.13 (m, 2H), 7.33-7.43 (m, 2H), 7.58-7.60 (m, 2H), 7.70-7.74 (m, 1H), 10.10 (brs, 1H), 11.09 (brs, 1H).

Example 3-7

[1162] MS ESI m/e: 652 (M+H), 650 (MH).

[1163] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.25 (s, 3H), 2.57-2.67 (m, 1H), 3.01 (s, 3H), 3.08 (s, 3H), 6.92 (t, J=9.0 Hz, 1H), 7.09-7.14 (m, 1H), 7.20-7.26 (m, 2H), 7.37-7.45 (m, 1H), 7.52-7.58 (m, 1H), 7.79 (dd, J=1.8, 9.0 Hz, 1H), 9.89 (s, 1H), 11.08 (s, 1H).

Example 3-8

[1164] MS ESI m/e: 550 (M+H), 548 (MH).

[1165] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.71 (m, 2H), 0.90-1.01 (m, 2H), 1.26 (s, 3H), 2.56-2.66 (m, 1H), 3.01 (s, 3H), 3.10 (s, 3H), 4.30 (s, 1H), 7.05-7.16 (m, 2H), 7.20-7.27 (m, 2H), 7.32 (dd, J=1.7, 9.0 Hz, 1H), 7.37-7.45 (m, 1H), 7.52 (dd, J=1.7, 12.0 Hz, 1H), 9.90 (s, 1H), 11.10 (s, 1H).

Example 3-9

[1166] MS ESI m/e: 639 (M+H), 638, 637 (MH).

[1167] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.73 (m, 2H), 0.93-0.98 (m, 2H), 1.26 (s, 3H), 2.58-2.65 (m, 1H), 3.05 (s, 3H), 3.08 (s, 3H), 7.11 (dd, J=10.1 Hz, 13.0 Hz, 1H), 7.32 (d, J=11.6 Hz, 1H), 7.42 (d, J=10.1 Hz, 1H), 7.48 (s, 1H), 7.63 (d, J=11.6 Hz, 1H), 7.72 (d, J=13.0 Hz, 1H), 9.65 (brs, 1H), 11.08 (brs, 1H).

Example 4-1

[1168] MS ESI m/e: 616 (M+H), 614 (MH).

[1169] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.70 (m, 2H), 0.91-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 6.92 (t, J=8.8 Hz, 1H), 7.00-7.05 (m, 1H), 7.36(t, J=8.2 Hz, 1H), 7.52-7.63 (m, 3H), 7.79(dd, J=2.0, 10.4 Hz, 1H), 10.10 (s, 1H), 11.08 (s, 1H).

Example 4-2

[1170] MS ESI m/e: 666 (M+H), 664 (MH).

[1171] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.71 (m, 2H), 0.91-1.01 (m, 2H), 1.19(t, J=7.2 Hz, 3H), 1.24 (s, 3H), 2.56-2.67 (m, 1H), 3.08 (s, 3H), 3.11(q, J=7.2 Hz, 2H), 6.92(t, J=8.7 Hz, 1H), 7.09 (d, J=8.1 Hz, 1H), 7.21-7.28 (m, 2H), 7.40(t, J=8.3 Hz, 1H), 7.55(d, J=8.1 Hz, 1H), 7.79(dd, J=1.8, 10.5 Hz, 1H), 9.94 (s, 1H), 11.08 (s, 1H).

Example 4-3

[1172] MS ESI m/e: 514 (M+H), 512 (MH).

[1173] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.70 (m, 2H), 0.91-0.99 (m, 2H), 1.26 (s, 3H), 2.04 (s, 3H), 2.58-2.66 (m, 1H), 3.10 (s, 3H), 4.30 (s, 1H), 7.01-7.06 (m, 1H), 7.09(t, J=8.4 Hz, 1H), 7.31(dd, J=1.6, 8.4 Hz, 1H), 7.36(t, J=7.8 Hz, 1H), 7.52 (dd, J=1.6, 11.6 Hz, 1H), 7.57-7.63 (m, 2H), 10.10(s, 1H), 11.10 (s, 1H)

Example 4-4

[1174] MS ESI m/e: 568, 570(M+H), 566, 568(MH)

[1175] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.65 (m, 2H), 0.90-0.95 (m, 2H), 1.20 (s, 3H), 2.04 (s, 3H), 2.56-2.61 (m, 1H), 3.04 (s, 3H), 7.07(dd, J=8.6, 10.7 Hz, 1H), 7.25(d, J=8.8 Hz, 2H), 7.38(d, J=10.7 Hz, 1H), 7.60(d, J=8.8 Hz, 2H), 7.69(d, J=8.6 Hz, 1H), 10.07 (s, 1H), 11.05 (s, 1H)

Example 4-5

[1176] MS ESI m/e: 556, 558(M+1).

[1177] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.67 (m, 2H), 0.91-0.96 (m, 2H), 1.17 (s, 3H), 2.56-2.62 (m, 1H), 3.05 (s, 3H), 7.11 (dd, J=8.6, 10.4 Hz, 1H), 7.40(d, J=8.6 Hz, 1H), 7.66 (d, J=9.3 Hz, 2H), 7.69 (dd, J=2.1, 10.4 Hz, 1H), 8.30(d, J=9.3 Hz, 2H), 10.94 (s, 1H)

Example 4-6

[1178] MS ESI m/e: 564 (M+H), 562 (MH).

[1179] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.64-0.70 (m, 2H), 0.92-0.99 (m, 2H), 1.19(t, J=7.4 Hz, 3H), 1.25 (s, 3H), 2.57-2.65 (m, 1H), 3.10 (s, 3H), 3.11(q, J=7.4 Hz, 2H), 4.31 (s, 1H), 7.06-7.12 (m, 2H), 7.22-7.27 (m, 2H), 7.32(dd, J=1.6, 8.0 Hz, 1H), 7.40(t, J=8.0 Hz, 1H), 7.52 (dd, J=1.6, 11.6 Hz, 1H), 9.95 (s, 1H), 11.10 (s, 1H).

Example 4-7

[1180] MS ESI m/e: 490 (M+H), 488 (MH).

[1181] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.64-0.71 (m, 2H), 0.91-0.99 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.60-2.67 (m, 1H), 3.05 (s, 3H), 7.02-7.06 (m, 1H), 7.13-7.19 (m, 1H), 7.20-7.29 (m, 2H), 7.33-7.41 (m, 2H), 7.57-7.63 (m, 2H), 10.10 (s, 1H), 11.23 (s, 1H).

Example 4-8

[1182] MS ESI m/e: 604, 606(M+H), 602, 604(MH).

[1183] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.69 (m, 2H), 0.92-0.99 (m, 2H), 1.23 (s, 3H), 2.57-2.67 (m, 1H), 3.04 (s, 3H), 3.07 (s, 3H), 7.08-7.14 (m, 1H), 7.26 (d, J=9.0 Hz, 2H), 7.34(d, J=9.0 Hz, 2H), 7.39-7.44 (m, 1H), 7.70-7.75 (m, 1H), 9.96 (s, 1H), 11.08 (s, 1H)

Example 4-9

[1184] MS ESI m/e: 518 (M+H), 516 (MH).

[1185] .sup.1H-NMR (DMSO-ds, 400 MHz) 0.64-0.71 (m, 2H), 0.92-1.00 (m, 2H), 1.19(t, J=7.6 Hz, 3H), 1.24 (s, 3H), 2.04 (s, 3H), 2.59-2.67 (m, 1H), 2.62(q, J=7.6 Hz, 2H), 3.03 (s, 3H), 7.01-7.11 (m, 3H), 7.23(d, J=11.6 Hz, 1H), 7.36(t, J=8.2 Hz, 1H), 7.56-7.63 (m, 2H), 10.10 (s, 1H), 11.23 (s, 1H).

Example 4-10

[1186] MS ESI m/e: 603, 605 (M+H), 601, 603 (MH).

[1187] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.77-0.84 (m, 2H), 1.11-1.18 (m, 2H), 1.32 (t, J=7.3 Hz, 3H), 1.33 (s, 3H), 2.70-2.78 (m, 1H), 3.15(q, so J=7.5 Hz, 2H), 3.20 (s, 3H), 6.89 (t, J=8.3 Hz, 1H), 7.28-7.32 (m, 1H), 7.36 (dd, J=2.3, 9.8 Hz, 1H), 7.60-7.69 (m, 2H), 7.86-7.93 (m, 2H), 11.28 (s, 1H).

Example 4-11

[1188] MS ESI m/e: 516 (M+H), 514 (MH).

[1189] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.64-0.71 (m, 2H), 0.92-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.59-2.67 (m, 1H), 3.07 (s, 3H), 5.32(d, J=11.1 Hz, 1H), 5.89(d, J=17.6 Hz, 1H), 6.73(dd, J=10.9, 17.6 Hz, 1H), 7.01-7.06 (m, 1H), 7.11(t, J=8.6 Hz, 1H), 7.28-7.33 (m, 1H), 7.33-7.40 (m, 1H), 7.51-7.57 (m, 1H), 7.57-7.63(m, 2H), 10.10 (s, 1H), 11.22 (s, 1H).

Example 4-12

[1190] MS ESI m/e: 729 (M+H), 727 (MH).

[1191] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.68 (m, 2H), 0.83 (t, J=7.3 Hz, 3H), 0.93-0.97 (m, 2H), 1.23-1.26 (m, 5H), 1.40-1.50 (m, 2H), 2.04 (t, J=7.5 Hz, 2H), 2.48-2.50 (m, 2H), 2.59-2.64 (m, 1H), 3.08 (s, 3H), 3.28-3.33 (m, 2H), 6.92 (t, J=8.7 Hz, 1H), 7.03 (d, J=7.9 Hz, 1H), 7.36 (t, J=8.1 Hz, 1H), 7.56-7.59 (m, 2H), 7.64-7.66 (m, 1H), 7.79 (dd, J=10.4, 1.7 Hz, 1H), 7.90 (t, J=5.7 Hz, 1H), 10.10 (s, 1H), 11.08 (s, 1H).

Example 4-13

[1192] MS ESI m/e: 603 (M+H), 601 (MH).

[1193] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.66-0.69 (m, 2H), 0.83 (t, J=7.2 Hz, 3H), 0.93-0.98 (m, 2H), 1.17-1.29 (m, 5H), 1.40-1.50 (m, 2H), 2.04 (t, J=0.7.3 Hz, 2H), 2.47-2.51 (m, 2H), 2.61-2.65 (m, 1H), 3.05 (s, 3H), 3.29-3.33 (m, 2H), 7.04 (d, J=9.0 Hz, 1H), 7.19-7.34 (m, 5H), 7.59 (d, J=8.7 Hz, 1H), 7.66 (s, 1H), 7.91 (t, J=5.3 Hz, 1H), 10.10 (s, 1H), 11.23 (s, 1H).

Example 4-14

[1194] MS ESI m/e: 685 (M+H), 683 (MH).

[1195] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.82(t, J=7.3 Hz, 3H), 0.90-0.98 (m, 2H), 1.14-1.28 (m, 4H), 1.25 (s, 3H), 1.37-1.49 (m, 2H), 1.45 (s, 6H), 2.04 (t, J=7.3 Hz, 2H), 2.58-2.65 (m, 1H), 3.07 (s, 3H), 3.27-3.34 (m, 2H), 5.49 (brs, 1H), 6.99-7.11 (m, 2H), 7.18-7.25 (m, 1H), 7.31-7.42 (m, 2H), 7.55-7.67 (m, 2H), 7.85-7.93 (m, 1H), 10.09 (s, 1H), 11.14 (s, 1H).

Example 4-15

[1196] MS ESI m/e: 590 (M+H), 588 (MH).

[1197] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.42 (s, 3H), 2.16 (s, 3H), 3.21 (s, 3H), 3.37 (s, 3H), 6.69(t, J=8.3 Hz, 1H), 7.04-7.10 (m, 1H), 7.31-7.55 (m, 5H), 7.70 (s, 1H), 11.41 (s, 1H).

Example 4-16

[1198] MS ESI m/e: 626 (M+H), 624 (MH).

[1199] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.26 (s, 3H), 3.01 (s, 3H), 3.09 (s, 3H), 3.21 (s, 3H), 6.93(t, J=8.3 Hz, 1H), 7.11-7.15 (m, 1H), 7.20-7.28 (m, 2H), 7.42(t, J=8.3 Hz, 1H), 7.52-7.57 (m, 1H), 7.76-7.81 (m, 1H), 9.94 (br, 1H), 11.21 (br, 1H).

Example 4-17

[1200] MS ESI m/e: 630 (M+H), 628 (MH).

[1201] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.81 (m, 2H), 1.05-1.15 (m, 5H), 1.41 (s, 3H), 2.15 (s, 3H), 2.68-2.77 (m, 1H), 3.90-4.00 (m, 2H), 6.72(t, J=8.3 Hz, 1H), 6.97-7.03 (m, 1H), 7.30-7.54 (m, 5H), 7.65-7.69(m, 1H), 11.07 (s, 1H).

Example 4-18

[1202] MS ESI m/e: 666 (M+H), 664 (MH).

[1203] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.81 (m, 2H), 1.06-1.15 (m, 5H), 1.39 (s, 3H), 2.68-2.76 (m, 1H), 3.02 (s, 3H), 3.90-4.00 (m, 2H), 6.74(t, J=8.3 Hz, 1H), 6.93-6.99 (m, 1H), 7.07-7.13 (m, 1H), 7.20-7.26 (m, 2H), 7.38-7.54 (m, 3H), 11.07 (s, 1H).

Example 4-19

[1204] MS ESI m/e: 654 (M+H), 652 (MH).

[1205] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.13(t, J=6.8 Hz, 3H), 1.20(t, J=7.2 Hz, 3H), 1.25 (s, 3H), 3.08 (s, 3H), 3.12(q, J=7.4 Hz, 2H), 3.87(d, J=7.1 Hz, 2H), 6.94(t, J=8.6 Hz, 1H), 7.12(d, J=8.0 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 7.29 (s, 1H), 7.41(t, J=8.0 Hz, 1H), 7.55(d, J=8.5 Hz, 1H), 7.79 (d, J=10.5 Hz, 1H), 9.98 (s, 1H), 11.24 (s, 1H).

Example 4-20

[1206] MS ESI m/e: 640 (M+H), 638 (MH).

[1207] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.13(t, J=6.8 Hz, 3H), 1.26 (s, 3H), 3.02 (s, 3H), 3.09 (s, 3H), 3.88(q, J=6.8 Hz, 2H), 6.95 (t, J=8.5 Hz, 1H), 7.11-7.18 (m, 1H), 7.21-7.30 (m, 2H), 7.43(t, J=7.7 Hz, 1H), 7.55(d, J=9.0 Hz, 1H), 7.76-7.82 (m, 1H), 9.94 (brs, 1H), 11.24 (brs, 1H).

Example 4-21

[1208] MS ESI m/e: 604 (M+H), 602 (MH).

[1209] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.13(t, J=6.8 Hz, 3H), 1.26 (s, 3H), 2.04 (s, 3H), 3.08 (s, 3H), 3.87(q, J=7.5 Hz, 2H), 6.94(t, J=8.5 Hz, 1H), 7.05-7.11 (m, 1H), 7.37(t, J=7.9 Hz, 1H), 7.51-7.60 (m, 2H), 7.65-7.71 (m, 1H), 7.78(d, J=10.2 Hz, 1H), 10.10 (brs, 1H), 11.23 (brs, 1H).

Example 4-22

[1210] MS ESI m/e: 666 (M+H), 664 (MH).

[1211] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.47(t, J=7.2 Hz, 3H), 0.63-0.69 (m, 2H), 0.90-0.97 (m, 2H), 1.76-1.94 (m, 2H), 2.57-2.63 (m, 1H), 3.00 (s, 3H), 3.07 (s, 3H), 6.93(t, J=8.8 Hz, 1H), 7.12-7.16 (m, 1H), 7.23-7.30 (m, 2H), 7.42 (t, J=8.0 Hz, 1H), 7.53-7.58 (m, 1H), 7.79(dd, J=1.6, 10.0 Hz, 1H), 9.91 (s, 1H), 11.07 (s, 1H).

Example 4-23

[1212] MS ESI m/e: 680 (M+H), 678 (MH).

[1213] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.47 (t, J=7.4 Hz, 3H), 0.61-0.70 (m, 2H), 0.89-0.98 (m, 2H), 1.20(t, J=7.4 Hz, 3H), 1.74-1.95 (m, 2H), 2.55-2.65 (m, 1H), 3.07 (s, 3H), 3.11(q, J=7.4 Hz, 2H), 6.92(t, J=8.6 Hz, 1H), 7.11(d, J=7.8 Hz, 1H), 7.22-7.31 (m, 2H), 7.40(t, J=7.9 Hz, 1H), 7.56(d, J=8.7 Hz, 1H), 7.79(d, J=10.2 Hz, 1H), 9.97 (s, 1H), 11.07 (s, 1H).

Example 4-24

[1214] MS ESI m/e: 630 (M+H), 628 (MH).

[1215] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.47(t, J=7.2 Hz, 3H), 0.60-0.69 (m, 2H), 0.87-0.98 (m, 2H), 1.79-1.93 (m, 2H), 2.04 (s, 3H), 2.56-2.66 (m, 1H), 3.07 (s, 3H), 6.92 (t, J=8.6 Hz, 1H), 7.07(d, J=8.4 Hz, 1H), 7.37(t, J=8.1 Hz, 1H), 7.53-7.69 (m, 3H), 7.79(d, J=10.2 Hz, 1H), 10.09 (s, 1H), 11.07 (s, 1H).

Example 4-25

[1216] MS ESI m/e: 554 (M+H), 552 (MH).

[1217] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.64-0.73 (m, 2H), 0.91-1.01 (m, 2H), 1.19(t, J=7.5 Hz, 3H), 1.24 (s, 3H), 2.57-2.68 (m, 1H), 2.62(q, J=7.4 Hz, 2H), 3.01 (s, 3H), 3.03 (s, 3H), 7.03-7.15 (m, 3H), 7.19-7.27 (m, 3H), 7.41(t, J=8.1 Hz, 1H), 9.89 (s, 1H), 11.24 (s, 1H).

Example 4-26

[1218] MS ESI m/e: 568 (M+H), 566 (MH).

[1219] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.73 (m, 2H), 0.91-1.01 (m, 2H), 1.18 (t, J=7.5 Hz, 3H), 1.19 (t, J=7.2 Hz, 3H), 1.23 (s, 3H), 2.57-2.68 (m, 1H), 2.62(q, J=7.5 Hz, 2H), 3.03 (s, 3H), 3.11(q, J=7.2 Hz, 2H), 7.03-7.13 (m, 3H), 7.19-7.27 (m, 3H), 7.40 (t, J=8.1 Hz, 1H), 9.94 (s, 1H), 11.24 (s, 1H).

Example 4-27

[1220] MS ESI m/e: 528 (M+H), 526 (MH).

[1221] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.48 (t, J=7.4 Hz, 3H), 0.60-0.70 (m, 2H), 0.88-0.98 (m, 2H), 1.77-1.92 (m, 2H), 2.04 (s, 3H), 2.55-2.66 (m, 1H), 3.10 (s, 3H), 4.30 (s, 1H), 7.04-7.14 (m, 2H), 7.28-7.41 (m, 2H), 7.52(d, J=11.7 Hz, 1H), 7.58-7.68 (m, 2H), 10.09 (s, 1H), 11.08 (s, 1H).

Example 4-28

[1222] MS ESI m/e: 564 (M+H), 562 (MH).

[1223] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.48(t, J=7.2 Hz, 3H), 0.63-0.69 (m, 2H), 0.90-0.97 (m, 2H), 1.78-1.93 (m, 2H), 2.56-2.64 (m, 1H), 3.01 (s, 3H), 3.10 (s, 3H), 4.31 (s, 1H), 7.09 (t, J=8.4 Hz, 1H), 7.13-7.17 (m, 1H), 7.23-7.34 (m, 3H), 7.42 (t, J=8.0 Hz, 1H), 7.52(dd, J=2.0, 11.6 Hz, 1H), 9.92 (s, 1H), 11.08 (s, 1H).

Example 4-29

[1224] MS ESI m/e: 578 (M+N), 576 (MH).

[1225] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.47(t, J=7.1 Hz, 3H), 0.61-0.70 (m, 2H), 0.88-0.98 (m, 2H), 1.20(t, J=7.2 Hz, 3H), 1.75-1.95 (m, 2H), 2.55-2.64 (m, 1H), 3.10 (s, 3H), 3.11(q, J=7.2 Hz, 2H), 4.30(s, 1H), 7.04-7.14 (m, 2H), 7.23-7.35 (m, 3H), 7.40(t, J=7.8 Hz, 1H), 7.52 (d, J=11.4 Hz, 1H), 9.97 (s, 1H), 11.08 (s, 1H).

Example 4-30

[1226] MS ESI m/e: 532 (M+H), 530 (MH).

[1227] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.46(t, J=7.4 Hz, 3H), 0.64-0.70 (m, 2H), 0.90-0.97 (m, 2H), 1.19(t, J=7.6 Hz, 3H), 1.80-1.90 (m, 2H), 2.04 (s, 3H), 2.57-2.67 (m, 1H), 2.63(q, J=7.6 Hz, 2H), 3.02 (s, 3H), 7.04-7.13 (m, 3H), 7.23 (d, J=12.0 Hz, 1H), 7.37(t, J=8.0 Hz, 1H), 7.61 (d, J=7.6 Hz, 1H), 7.64(t, J=2.0 Hz, 1H), 10.09 (s, 1H), 11.24 (s, 1H).

Example 4-31

[1228] MS ESI m/e: 568 (M+H), 566 (MH).

[1229] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.47 (t, J=7.2 Hz, 3H), 0.63-0.71 (m, 2H), 0.90-0.98 (m, 2H), 1.19(t, J=7.4 Hz, 3H), 1.74-1.96 (m, 2H), 2.57-2.67 (m, 1H), 2.63(q, J=7.4 Hz, 2H), 3.01 (s, 3H), 3.02 (s, 3H), 7.06-7.11 (m, 2H), 7.12-7.17 (m, 1H), 7.20-7.30 (m, 3H), 7.42(t, J=8.0 Hz, 1H), 9.91 (s, 1H), 11.24 (s, 1H).

Example 4-32

[1230] MS ESI m/e: 582 (M+H), 580 (MH).

[1231] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.46(t, J=7.2 Hz, 3H), 0.64-0.70 (m, 2H), 0.90-0.98 (m, 2H), 1.19(t, J=7.6 Hz, 3H), 1.20(t, J=7.6 Hz, 3H), 1.75-1.93 (m, 2H), 2.58-2.68 (m, 1H), 2.63(q, J=7.6 Hz, 2H), 3.02 (s, 3H), 3.10(q, J=7.6 Hz, 2H), 7.05-7.14 (m, 3H), 7.20-7.31 (m, 3H), 7.40(t, J=8.0 Hz, 1H), 9.97 (s, 1H), 11.23 (s, 1H).

Example 4-33

[1232] MS ESI m/e: 681(M+H), 679(MH).

[1233] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.69 (m, 2H), 0.90-1.00 (m, 2H), 1.22 (s, 3H), 2.52-2.63 (m, 1H), 2.67 (s, 6H), 3.06 (s, 3H), 6.88-6.94 (m, 1H), 7.02-7.09 (m, 1H), 7.18-7.21 (m, 2H), 7.31-7.39 (m, 1H), 7.51-7.56 (m, 1H), 7.75-7.81 (m, 1H), 10.01 (brs, 1H), 11.06 (brs, 1H).

Example 4-34

[1234] MS ESI m/e: 723(M+H), 721(MH).

[1235] .sup.1H-NMR (DMSO-d, 300 MHz) 0.61-0.70 (m, 2H), 0.90-0.99 (m, 2H), 1.24 (s, 3H), 2.55-2.64 (m, 1H), 3.06 (s, 3H), 2.99-3.10 (m, 4H), 3.43-3.53 (m, 4H), 6.88-6.92 (m, 1H), 7.05-7.09 (m, 2H), 7.14-7.22 (m, 1H), 7.31-7.40 (m, 1H), 7.51-7.59 (m, 1H), 7.75-7.81 (m, 1H), 10.21 (brs, 1H), 11.08 (brs, 1H).

Example 4-35

[1236] MS ESI m/e: 519 (M+H), 517 (MH).

[1237] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.71 (m, 2H), 0.92-1.00 (m, 2H), 1.26 (s, 3H), 2.59-2.67 (m, 1H), 2.73(t, J=7.0 Hz, 2H), 3.02-3.12 (m, 2H), 3.05 (s, 3H), 7.04-7.43 (m, 6H), 7.58-7.63 (m, 1H), 7.67 (s, 1H), 7.77-7.88 (m, 3H), 10.39 (s, 1H), 11.23 (s, 1H).

Example 4-36

[1238] MS ESI m/e: 645 (M+H), 643 (MH).

[1239] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.70 (m, 2H), 0.92-0.98 (m, 2H), 1.26 (s, 3H), 2.59-2.66 (m, 1H), 2.72 (t, J=7.2 Hz, 2H), 3.03-3.13 (m, 2H), 3.08 (s, 3H), 6.93(t, J=8.4 Hz, 1H), 7.03-7.08 (m, 1H), 7.39(t, J=8.4 Hz, 1H), 7.53-7.68 (m, 3H), 7.72-7.85 (m, 4H), 10.37 (s, 1H), 11.08 (s, 1H).

Example 4-37

[1240] MS ESI m/e: 650(M+H), 648(MH).

[1241] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.92-0.99 (m, 2H), 1.31 (s, 3H), 2.06 (s, 3H), 2.57-2.64 (m, 1H), 3.08 (s, 3H), 6.93(dd, J=9.3, 11.1 Hz, 1H), 7.19 (s, 1H), 7.46 (s, 1H), 7.55 (d, J=9.3 Hz, 1H), 7.79 (d, J=11.1 Hz, 1H), 7.83 (s, 1H), 10.27 (s, 1H), 11.03 (s, 1H)

Example 4-38

[1242] MS ESI m/e: 564 (M+H), 562 (MH).

[1243] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.81 (m, 2H), 1.06-1.16 (m, 5H), 1.40 (s, 3H), 2.69-2.76 (m, 1H), 3.03 (s, 3H), 3.13 (s, 1H), 3.92-4.01 (m, 2H), 6.77-6.84 (m, 1H), 6.92(t, J=8.1 Hz, 1H), 7.08-7.13 (m, 1H), 7.18-7.33 (m, 4H), 7.42(t, J=8.1 Hz, 1H), 11.11 (s, 1H).

Example 4-39

[1244] MS ESI m/e: 568 (M+H), 566 (MH).

[1245] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.83 (m, 2H), 1.02 (t, J=7.0 Hz, 3H), 1.07-1.15 (m, 2H), 1.24(t, J=7.7 Hz, 3H), 1.38 (s, 3H), 2.60-2.76 (m, 3H), 3.02 (s, 3H), 3.90-4.00 (m, 2H), 6.77 (s, 1H), 6.94-7.03 (m, 3H), 7.08-7.13 (m, 1H), 7.19-7.27 (m, 2H), 7.41(t, J=7.7 Hz, 1H), 11.19 (s, 1H).

Example 4-40

[1246] MS ESI m/e: 552 (M+H), 550 (MH).

[1247] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.13(t, J=6.9 Hz, 3H), 1.20(t, J=7.3 Hz, 3H), 1.26 (s, 3H), 3.11 (s, 3H), 3.12(q, J=7.4 Hz, 2H), 3.87(q, J=7.1 Hz, 2H), 4.30 (s, 1H), 7.05-7.15 (m, 2H), 7.20-7.35 (m, 3H), 7.41(t, J=8.0 Hz, 1H), 7.52 (d, J=11.6 Hz, 1H), 9.99 (s, 1H), 11.25 (s, 1H).

Example 4-41

[1248] MS ESI m/e: 556 (M+H), 554 (MH).

[1249] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.10-1.25 (m, 12H), 2.62(q, J=7.6 Hz, 2H), 3.03 (s, 3H), 3.12(q, J=7.3 Hz, 2H), 3.88(q, J=6.9 Hz, 2H), 7.05-7.15 (m, 3H), 7.20-7.30 (m, 3H), 7.41(t, J=8.0 Hz, 1H), 9.98 (s, 1H), 11.41 (s, 1H).

Example 4-42

[1250] MS ESI m/e: 538 (M+H), 536 (MH).

[1251] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.13 (t, J=7.2 Hz, 3H), 1.27 (s, 3H), 3.03 (s, 3H), 3.11 (s, 3H), 3.87(q, J=6.8 Hz, 2H), 4.30 (s, 1H), 7.05-7.18 (m, 2H), 7.20-7.35 (m, 3H), 7.43(t, J=7.9 Hz, 1H), 7.52(d, J=11.3 Hz, 1H), 9.94 (brs, 1H), 11.25 (brs, 1H).

Example 4-43

[1252] MS ESI m/e: 502 (M+H), 500 (MH).

[1253] .sup.1H-NMR (DMSO-d, 300 MHz) 1.13(t, J=7.0 Hz, 3H), 1.27 (s, 3H), 2.05 (s, 3H), 3.11 (s, 3H), 3.87(q, J=7.1 Hz, 2H), 4.30 (s, 1H), 7.04-7.15 (m, 2H), 7.28-7.34 (m, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.49-7.60 (m, 2H), 7.66-7.70 (m, 1H), 10.10 (brs, 1H), 11.24 (brs, 1H).

Example 4-44

[1254] MS ESI m/e: 542 (M+H), 540 (MH).

[1255] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.14(t, J=7.2 Hz, 3H), 1.19(t, J=7.5 Hz, 3H), 1.25 (s, 3H), 2.63(q, J=7.5 Hz, 2H), 3.02 (s, 3H), 3.03 (s, 3H), 3.89(q, J=7.0 Hz, 2H), 7.04-7.18 (m, 3H), 7.20-7.30 (m, 3H), 7.42 (t, J=8.1 Hz, 1H), 9.93 (brs, 1H), 11.41 (brs, 1H).

Example 4-45

[1256] MS ESI m/e: 506 (M+H), 504 (MH).

[1257] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.14(t, J=6.2 Hz, 3H), 1.19(t, J=7.5 Hz, 3H), 1.25 (s, 3H), 2.05 (s, 3H), 2.63(q, J=7.5 Hz, 2H), 3.03 (s, 3H), 3.89(q, J=6.8 Hz, 2H), 7.04-7.15 (m, 3H), 7.23(d, J=12.0 Hz, 1H), 7.37(t, J=8.1 Hz, 1H), 7.53-7.60 (m, 1H), 7.65-7.70 (m, 1H), 10.10 (brs, 1H), 11.41 (brs, 1H).

Example 4-46

[1258] MS ESI m/e: 528 (M+H), 526 (MH).

[1259] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.82 (m, 2H), 1.06-1.16 (m, 5H), 1.42 (s, 3H), 2.17 (s, 3H), 2.68-2.78 (m, 1H), 3.13 (s, 1H), 3.92-4.01 (m, 2H), 6.90 (t, J=7.9 Hz, 1H), 6.99-7.06 (m, 1H), 7.22-7.46 (m, 5H), 7.63-7.68 (m, 1H), 11.10 (s, 1H).

Example 4-47

[1260] MS ESI m/e: 532 (M+H), 530 (MH).

[1261] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.83 (m, 2H), 1.02 (t, J=7.0 Hz, 3H), 1.08-1.16 (m, 2H), 1.24(t, J=7.5 Hz, 3H), 1.40 (s, 3H), 2.16 (s, 3H), 2.61-2.77 (m, 3H), 3.91-4.00 (m, 2H), 6.93-7.05 (m, 4H), 7.26-7.48 (m, 3H), 7.59-7.64 (m, 1H), 11.19 (s, 1H).

Example 4-48

[1262] MS ESI m/e: 488 (M+H), 486 (MH).

[1263] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.42 (s, 3H), 2.15 (s, 3H), 3.13 (s, 1H), 3.23 (s, 3H), 3.38 (s, 3H), 6.86 (t, J=8.7 Hz, 1H), 7.03-7.10 (m, 1H), 7.22-7.41 (m, 5H), 7.70 (s, 1H), 11.46 (s, 1H).

Example 4-49

[1264] MS ESI m/e: 524 (M+H), 522 (MH).

[1265] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.41 (s, 3H), 3.04 (s, 3H), 3.14 (s, 1H), 3.23 (s, 3H), 3.38 (s, 3H), 6.75 (s, 1H), 6.89(t, J=8.5 Hz, 1H), 7.11-7.17 (m, 1H), 7.18-7.33 (m, 4H), 7.43 (t, J=8.1 Hz, 1H), 11.47 (s, 1H).

Example 4-50

[1266] MS ESI m/e: 492 (M+H), 490 (MH).

[1267] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.24 (t, J=7.5 Hz, 3H), 1.41 (s, 3H), 2.15 (s, 3H), 2.65(q, J=7.7 Hz, 2H), 3.18 (s, 3H), 3.38 (s, 3H), 6.88-7.11 (m, 4H), 7.32-7.46 (m, 3H), 7.63-7.69 (m, 1H), 11.45 (s, 1H).

Example 4-51

[1268] MS ESI m/e: 528 (M+H), 526 (MH).

[1269] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 1.24(t, J=7.5 Hz, 3H), 1.39 (s, 3H), 2.65(q, J=7.3 Hz, 2H), 3.03 (s, 3H), 3.18 (s, 3H), 3.38 (s, 3H), 6.84 (s, 1H), 6.90-7.03 (m, 3H), 7.11-7.17 (m, 1H), 7.19-7.30 (m, 2H), 7.42(t, J=8.1 Hz, 1H), 11.46 (s, 1H).

Example 4-52

[1270] MS ESI m/e: 528 (M+H), 526 (MH).

[1271] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.64-0.70 (m, 2H), 0.91-0.99 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.05 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 7.01-7.10 (m, 2H), 7.20-7.25 (m, 1H), 7.32-7.43 (m, 2H), 7.57-7.63 (m, 2H), 10.10 (s, 1H), 11.14 (s, 1H).

Example 4-53

[1272] MS ESI m/e: 532 (M+H), 530 (MH).

[1273] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.64-0.71 (m, 2H), 0.89 (t, J=7.4 Hz, 3H), 0.92-0.99 (m, 2H), 1.24 (s, 3H), 1.54-1.65 (m, 2H), 2.04 (s, 3H), 2.57(t, J=7.5 Hz, 2H), 2.60-2.67 (m, 1H), 3.02 (s, 3H), 7.01-7.12 (m, 3H), 7.18-7.24 (m, 1H), 7.33-7.39 (m, 1H), 7.58-7.62 (m, 2H), 10.10 (s, 1H), 11.24 (s, 1H).

Example 4-54

[1274] MS ESI m/e: 653(M+H), 651(MH).

[1275] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.60-0.71 (m, 2H), 0.90-1.01 (m, 2H), 1.27 (s, 3H), 2.58-2.67 (m, 1H), 3.08 (s, 3H), 6.89-7.01 (m, 2H), 7.09-7.23 (m, 4H), 7.30-7.39 (m, 1H), 7.51-7.59 (m, 1H), 7.73-7.83 (m, 1H), 9.69 (brs, 1H), 11.09 (brs, 1H).

Example 4-55

[1276] MS ESI m/e: 637 (M+H), 635 (MH).

[1277] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.69 (m, 2H), 0.96 (m, 2H), 1.17 (s, 3H), 2.62 (m, 1H), 3.09 (s, 3H), 3.26 (s, 3H), 6.95 (t, J=8.6 Hz, 1H), 7.56 (d, J=8.7 Hz, 1H), 7.70-7.85 (m, 3H), 7.90-8.00 (m, 2H), 11.04 (s, 1H).

Example 4-56

[1278] MS ESI m/e: 504 (M+H), 502 (MH).

[1279] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.65-0.71 (m, 2H), 0.92-0.99 (m, 2H), 1.24 (s, 3H), 2.04 (s, 3H), 2.32 (s, 3H), 2.58-2.67 (m, 1H), 3.02 (s, 3H), 7.00-7.10 (m, 3H), 7.20(d, J=12.0 Hz, 1H), 7.36(t, J=8.2 Hz, 1H), 7.56-7.63 (m, 2H), 10.10 (s, 1H), 11.24 (s, 1H).

Example 4-57

[1280] MS ESI m/e: 558 (M+H), 556 (MH).

[1281] .sup.1H-NMR (DMSO-ds, 400 MHz) 0.64-0.71 (m, 2H), 0.90-0.99 (m, 2H), 1.24 (s, 3H), 1.46-1.57 (m, 2H), 1.58-1.69 (m, 2H), 1.71-1.83 (m, 2H), 1.97-2.07 (m, 2H), 2.04 (s, 3H), 2.58-2.68 (m, 1H), 2.93-3.06 (m, 1H), 3.03 (s, 3H), 7.00-7.14 (m, 3H), 7.24 (dd, J=1.2, 12.0 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 7.57-7.63 (m, 1H), 10.10 (s, 1H), 11.22 (s, 1H).

Example 4-58

[1282] MS ESI m/e: 651 (M+H), 649 (MH).

[1283] .sup.1H-NMR (DMSO-d, 300 MHz) 0.65-0.71 (m, 2H), 0.93-1.00 (m, 2H), 1.10 (t, J=7.3 Hz, 3H), 1.17 (s, 3H), 2.56-2.66 (m, 1H), 3.09(s, 3H), 3.29-3.40 (m, 2H), 6.95 (t, J=8.7 Hz, 1H), 7.52-7.58 (m, 1H), 7.73-7.82 (m, 3H), 7.88-7.95 (m, 2H), 11.04 (s, 1H).

Example 4-59

[1284] MS ESI m/e: 721(M+H), 719(MH).

[1285] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.71 (m, 2H), 0.91-1.01 (m, 2H), 1.26 (s, 3H), 1.35-1.60 (m, 6H), 2.59-2.67 (m, 1H), 2.99-3.12 (m, 4H), 3.07 (s, 3H), 6.89-6.94 (m, 1H), 7.04-7.06 (m, 1H), 7.13-7.17 (m, 2H), 7.34-7.39 (m, 1H), 7.54-7.57 (m, 1H), 7.77-7.80 (m, 1H), 10.06 (brs, 1H), 11.06 (brs, 1H).

Example 4-60

[1286] MS ESI m/e: 630(M+H), 628(MH).

[1287] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.63-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.09(t, J=7.5 Hz, 3H), 1.27 (s, 3H), 2.34(q, J=7.0 Hz, 2H), 2.59-2.70 (m, 1H), 3.09 (s, 3H), 6.91-7.08 (m, 2H), 7.34-7.40 (m, 1H), 7.56-7.69 (m, 3H), 7.78-7.82 (m, 1H), 10.03 (brs, 1H), 11.09 (brs, 1H).

Example 4-61

[1288] MS ESI m/e: 533 (M+H), 531 (MH).

[1289] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.73 (m, 2H), 0.91-1.01 (m, 2H), 1.22 (s, 3H), 2.04 (s, 3H), 2.58-2.68 (m, 1H), 2.92 (s, 6H), 2.98 (s, 3H), 6.55(dd, J=3.0, 9.1 Hz, 1H), 6.62(dd, J=2.6, 14.3 Hz, 1H), 6.99-7.11 (m, 2H), 7.35(t, J=7.9 Hz, 1H), 7.55-7.62 (m, 2H), 10.09 (brs, 1H), 11.27 (brs, 1H).

Example 4-62

[1290] MS ESI m/e: 673(M+H), 671(MH) .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.69 (m, 2H), 0.91-0.98 (m, 2H), 1.33 (s, 3H), 2.03 (s, 6H), 3.08 (s, 3H), 6.91(dd, J=10.5, 9.6 Hz, 1H), 7.28 (s, 2H), 7.55(d, J=9.6 Hz, 1H), 7.78(d, J=10.5 Hz, 1H), 10.09 (s, 1H), 7.92 (s, 1H), 11.09 (s, 1H)

Example 4-63

[1291] MS ESI m/e: 646.0(M+H), 644.0(MH).

[1292] .sup.1H-NMR (DMSO-d, 300 MHz) 0.63-0.69 (m, 2H), 0.91-0.98 (m, 2H), 1.28 (s, 3H), 2.08 (s, 3H), 2.57-2.65 (m, 1H), 3.07 (s, 3H), 3.89 (s, 3H), 6.91 (dd, J=12.0, 9.0 Hz, 1H), 7.07 (s, 2H), 7.55 (d, J=9.0 Hz, 1H), 7.79(d, J=12.0 Hz, 1H), 7.95 (s, 1H), 9.27 (s, 1H), 11.12 (s, 1H)

Example 4-64

[1293] MS ESI m/e: 685.9, 687.9, 684.0, 685.9

[1294] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.92-0.99 (m, 2H), 1.31 (s, 3H), 2.57-2.63 (m, 1H), 3.08 (s, 6H), 6.94 (dd, J=9.0, 12.0 Hz, 1H), 7.22-7.22 (m, 1H), 7.27-7.27 (m, 2H), 7.56(d, J=9.0 Hz, 1H), 7.79(d, J=12.0 Hz, 1H), 10.16 (s, 1H), 11.04 (s, 1H)

Example 4-65

[1295] MS ESI m/e: 571.1 (M+H), 569.2 (MH).

[1296] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.93-1.00 (m, 2H), 1.35 (s, 3H), 2.04 (s, 6H), 2.59-2.67 (m, 1H), 3.11 (s, 3H), 4.32 (s, 1H), 7.09(dd, J=9.0, 12.0 Hz, 1H), 7.30 (s, 2H), 7.33(d, J=9.0 Hz, 1H), 7.53(d, J=12.0 Hz, 1H), 7.94 (s, 1H), 10.11 (s, 2H), 11.12 (s, 1H)

Example 4-66

[1297] MS ESI m/e: 616.0(M+H), 614.0(MH).

[1298] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.68 (m, 2H), 0.92-0.99 (m, 2H), 1.23 (s, 3H), 2.07 (s, 3H), 2.58-2.66 (m, 1H), 3.07 (s, 3H), 6.92 (dd, J=9.0, 9.0 Hz, 1H), 7.28(d, J=9.0 Hz, 2H), 7.55(d, J=9.0 Hz, 1H), 7.64(d, J=9.0 Hz, 2H), 7.79(d, J=9.0 Hz, 1H), 10.10 (s, 1H), 11.06 (s, 1H)

Example 4-67

[1299] MS ESI m/e: 530 (M+H), 528 (MH).

[1300] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.76 (m, 4H), 0.90-1.03 (m, 4H), 1.24 (s, 3H), 1.88-2.02 (m, 1H), 2.04 (s, 3H), 2.58-2.68 (m, 1H), 3.01 (s, 3H), 6.92-7.11 (m, 4H), 7.35 (t, J=8.6 Hz, 1H), 7.55-7.64 (m, 2H), 10.09 (s, 1H), 11.23 (s, 1H).

Example 4-68

[1301] MS ESI m/e: 660 (M+H), 658 (MH).

[1302] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.56-0.64 (m, 2H), 0.85-0.95 (m, 2H), 1.26 (s, 3H), 2.04 (s, 3H), 2.46-2.60 (m, 1H), 3.20 (brs, 3H), 3.46-3.55 (m, 2H), 4.01-4.11 (m, 2H), 6.91(t, J=8.5 Hz, 1H), 6.97-7.07 (m, 1H), 7.35(t, J=7.8 Hz, 1H), 7.45(d, J=8.4 Hz, 1H), 7.54-7.67 (m, 2H), 7.73 (d, J=9.9 Hz, 1H), 10.09 (s, 1H), 10.13 (s, 1H).

Example 4-69

[1303] MS ESI m/e: 696 (M+H), 694 (MH).

[1304] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.56-0.66 (m, 2H), 0.81-0.97 (m, 2H), 1.26 (s, 3H), 2.50-2.59 (m, 1H), 3.00 (s, 3H), 3.19 (s, 3H), 3.50(t, J=5.3 Hz, 2H), 4.05(t, J=5.1 Hz, 2H), 6.90 (t, J=8.9 Hz, 1H), 7.07-7.15 (m, 1H), 7.18-7.27 (m, 2H), 7.35-7.50 (m, 2H), 7.69-7.78 (m, 1H), 9.90 (brs, 1H), 10.16 (brs, 1H).

Example 4-70

[1305] MS ESI m/e: 652.0 (M+H), 650.0(MH).

[1306] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.60-0.64 (m, 2H), 0.89-0.94 (m, 2H), 1.19 (s, 3H), 2.55-2.62 (m, 1H), 2.99 (s, 3H), 3.03 (s, 3H), 6.88(dd, J=8.0, 8.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.29(d, J=8.0 Hz, 2H), 7.51(d, J=8.0 Hz, 1H), 7.75 (d, J=8.0 Hz, 1H), 9.91 (s, 1H), 11.02 (s, 1H)

Example 4-71

[1307] MS ESI m/e: 514.1(M+H), 512.2 (MH).

[1308] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.69 (m, 2H), 0.91-0.99 (m, 2H), 1.24 (s, 3H), 2.07 (s, 3H), 2.59-2.66 (m, 1H), 3.10 (s, 3H), 4.30 (s, 1H), 7.09(dd, J=8.7, 8.4 Hz, 1H), 7.28 (d, J=8.4 Hz, 2H), 7.31(d, J=8.7 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.64(d, J=8.4 Hz, 2H), 10.10 (s, 1H), 11.08 (s, 1H)

Example 4-72

[1309] MS ESI m/e: 559 (M+H), 557 (MH).

[1310] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.90-1.01 (m, 2H), 1.18 (s, 3H), 2.57-2.67 (m, 1H), 3.07 (s, 3H), 6.93(t, J=8.5 Hz, 1H), 7.34-7.50 (m, 5H), 7.52-7.58 (m, 1H), 7.79 (dd, J=1.5, 10.2 Hz, 1H), 11.06 (brs, 1H).

Example 4-73

[1311] MS ESI m/e: 668(M+H), 666(MH).

[1312] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.92-1.01 (m, 2H), 1.30 (s, 3H), 2.60-2.69 (m, 1H), 3.10 (s, 3H), 6.91-6.99 (m, 1H), 7.06-7.11 (m, 1H), 7.38-7.42 (m, 1H), 7.52-7.60 (m, 1H), 7.75-7.95 (m, 5H), 9.98 (brs, 1H), 11.09 (brs, 1H), 12.68 (brs, 1H).

[1313] MS ESI m/e: 681(M+H), 679(MH).

[1314] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.72 (m, 2H), 0.90-1.02 (m, 2H), 1.31 (s, 3H), 2.60-2.69 (m, 1H), 3.09 (s, 3H), 3.89 (s, 3H), 6.09-6.11 (m, 1H), 6.90-6.97 (m, 1H), 7.01-7.11 (m, 3H), 7.37-7.42 (m, 1H), 7.52-7.60 (m, 1H), 7.73-7.84 (m, 3H), 9.90 (brs, 1H), 11.10 (brs, 1H).

Example 4-74

[1315] MS ESI m/et 647 (M+H), 645 (MH).

[1316] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.92-0.99 (m, 2H), 1.27 (s, 3H), 2.58-2.66 (m, 1H), 3.08 (s, 3H), 3.62 (s, 3H), 6.92 (t, J=8.6 Hz, 1H), 6.99-7.02 (m, 1H), 7.33(t, J=8.1 Hz, 1H), 7.54-7.57 (m, 1H), 7.61-7.66 (m, 2H), 7.79 (dd, J=1.8, 10.2 Hz, 1H), 9.05 (s, 1H), 9.58 (s, 1H), 11.08 (s, 1H).

Example 4-75

[1317] MS ESI m/e: 518.0 (M+H), 516.0(MH).

[1318] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.92-1.00 (m, 2H), 1.19(t, J=7.8 Hz, 3H), 1.23 (s, 3H), 2.07 (s, 3H), 2.57-2.65 (m, 1H), 2.63(q, J=7.8 Hz, 2H), 3.02 (s, 3H), 7.07-7.09 (m, 2H), 7.21-7.25 (m, 1H), 7.28 (d, J=9.0 Hz, 2H), 7.63 (d, J=8.7 Hz, 2H), 10.10 (s, 1H), 11.22 (s, 1H)

Example 4-76

[1319] MS ESI m/e: 550.1 (M+H), 548.1(MH)

[1320] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.69 (m, 2H), 0.91-0.99 (m, 2H), 1.24 (s, 3H), 2.07 (s, 3H), 2.59-2.66 (m, 1H), 3.10 (s, 3H), 4.30 (s, 1H), 7.09(dd, J=8.7, 8.4 Hz, 1H), 7.28(d, J=8.4 Hz, 2H), 7.31 (d, J=8.7 Hz, 1H), 7.52 (d, J=8.4 Hz, 1H), 7.64(d, J=8.4 Hz, 2H), 10.10 (s, 1H), 11.08 (s, 1H)

Example 4-77

[1321] MS ESI m/e: 666.0 (M+H), 664.0 (MH).

[1322] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.69 (m, 2H), 0.92-0.99 (m, 2H), 1.21(t, J=7.4 Hz, 3H), 1.23 (s, 3H), 2.58-2.65 (m, 1H), 3.14(q, J=7.4 Hz, 2H), 6.92(dd, J=7.5, 10.5 Hz, 1H), 7.26(d, J=9.0 Hz, 2H), 7.32 (d, J=9.0 Hz, 2H), 7.55 (d, J=7.5 Hz, 1H), 7.79(d, J=10.5 Hz, 1H), 9.98 (s, 1H), 11.06 (s, 1H)

Example 4-78

[1323] MS ESI m/e: 554.2 (M+H), 552.1 (MH)

[1324] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.92-0.99 (m, 2H), 1.19 (t, J=7.5 Hz, 3H), 1.22 (s, 3H), 2.55-2.63 (m, 1H), 2.63(q, J=7.5 Hz, 2H), 3.02 (s, 3H), 3.04 (s, 3H), 7.07-7.09 (m, 2H), 7.21-7.25 (m, 1H), 7.25(d, J=9.3 Hz, 2H), 7.34(d, J=9.3 Hz, 2H), 9.95 (s, 1H), 11.22 (s, 1H)

Example 4-79

[1325] MS ESI m/e: 664 (M+H), 662 (MH).

[1326] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.28-0.34 (m, 2H), 0.69-0.77 (m, 2H), 1.06 (brs, 3H), 2.30-2.37 (m, 1H), 2.99 (s, 3H), 4.21(t, J=9.2 Hz, 2H), 4.72(t, J=8.6 Hz, 2H), 6.50-6.57 (m, 1H), 7.06-7.11 (m, 1H), 7.14-7.24 (m, 3H), 7.29-7.35 (m, 1H), 7.35-7.41 (m, 1H), 9.91 (brs, 1H).

Example 4-80

[1327] MS ESI m/e: 661 (M+H), 659 (MH).

[1328] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.69 (m, 2H), 0.93-0.98 (m, 2H), 1.27 (s, 3H), 2.60-2.65 (m, 1H), 3.05 (s, 3H), 3.08 (s, 3H), 3.67 (s, 3H), 6.92(t, J=8.5 Hz, 1H), 7.00-7.03 (m, 1H), 7.34 (t, J=7.9 Hz, 1H), 7.54-7.57 (m, 1H), 7.61-7.67 (m, 2H), 7.77-7.81 (m, 1H), 9.24 (s, 1H), 11.08 (s, 1H).

Example 4-81

[1329] MS ESI m/e: 617 (M+H), 615 (MH).

[1330] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.70 (m, 2H), 0.92-0.98 (m, 2H), 1.28 (s, 3H), 2.59-2.66 (m, 1H), 3.08 (s, 3H), 5.89 (s, 2H), 6.87-6.94 (m, 2H), 7.28(t, J=7.9 Hz, 1H), 7.35-7.45 (m, 2H), 7.53-7.56 (m, 1H), 7.75-7.81 (m, 1H), 8.71 (s, 1H), 11.09 (s, 1H).

Example 4-82

[1331] MS ESI m/e: 632 (M+H), 630 (MH).

[1332] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.92-0.98 (m, 2H), 1.25 (s, 3H), 2.60-2.64 (m, 1H), 3.08 (s, 3H), 3.99(d, J=6.0 Hz, 2H), 5.64(t, J=6.0 Hz, 11), 6.92(t, J=8.5 Hz, 1H), 7.05-7.08 (m, 1H), 7.37(t, J=7.9 Hz, 1H), 7.53-7.56 (m, 1H), 7.71-7.81 (m, 3H), 9.83 (s, 1H), 11.07 (s, 1H).

Example 4-83

[1333] MS ESI m/e: 511, 513 (M+H), 509, 511 (MH).

[1334] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.20 (s, 3H), 3.08 (s, 3H), 3.22 (s, 3H), 3.50 (t, J=6.2 Hz, 2H), 4.04(t, J=6.2 Hz, 2H), 7.07(d, J=8.7 Hz, 2H), 7.35-7.51 (m, 5H), 7.55(d, J=8.7 Hz, 2H), 11.06 (s, 1H).

Example 4-84

[1335] MS ESI m/e: 511, 513 (M+H), 509, 511 (MH).

[1336] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.22 (s, 3H), 3.08 (s, 3H), 4.50 (s, 2H), 7.08 (d, J=8.7 Hz, 2H), 7.38-7.52 (m, 5H), 7.55(d, J=8.7 Hz, 2H), 10.89 (s, 1H).

Example 4-85

[1337] MS ESI m/e: 497, 499 (M+H), 495, 497 (MH).

[1338] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.20 (s, 3H), 3.08 (s, 3H), 3.53(q, J=6.3 Hz, 2H), 3.94 (t, J=6.4 Hz, 2H), 4.77(t, J=5.8 Hz, 1H), 7.06(d, J=9.0 Hz, 2H), 7.37-7.51 (m, 5H), 7.55(d, J=9.0 Hz, 2H), 11.10 (s, 1H).

Example 4-86

[1339] MS ESI m/e: 524, 526 (M+H), 522, 524 (MH).

[1340] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.20 (s, 3H), 2.16 (s, 6H), 2.42(t, J=6.8 Hz, 2H), 3.08 (s, 3H), 3.94(t, J=7.2 Hz, 2H), 7.07 (d, J=9.0 Hz, 2H), 7.37-7.51 (m, 5H), 7.56(d, J=8.7 Hz, 2H), 11.07 (s, 1H).

Example 4-87

[1341] MS ESI m/e: 681(M+H), 679(MH).

[1342] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.72 (m, 2H), 0.90-1.02 (m, 2H), 1.31 (s, 3H), 2.60-2.69 (m, 1H), 3.09 (s, 3H), 3.89 (s, 3H), 6.09-6.11 (m, 1H), 6.90-6.97 (m, 1H), 7.01-7.11 (m, 3H), 7.37-7.42 (m, 1H), 7.52-7.60 (m, 1H), 7.73-7.84 (m, 3H), 9.90 (brs, 1H), 11.10 (brs, 1H).

Example 4-88

[1343] MS ESI m/e: 614(M+H), 612(MH).

[1344] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.31 (s, 3H), 2.55-2.68 (m, 1H), 3.09 (s, 3H), 3.57 (s, 2H), 6.87-6.96 (m, 3H), 7.25-7.28 (m, 1H), 7.55-7.58 (m, 1H), 7.78-7.81 (m, 1H), 10.49 (brs, 1H), 11.08 (brs, 1H).

Example 4-89

[1345] MS ESI m/e: 668(M+H), 666(MH).

[1346] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.71 (m, 2H), 0.91-1.01 (m, 2H), 1.29 (s, 3H), 2.60-2.70 (m, 1H), 3.08 (s, 3H), 6.93(dd, J=9.0, 9.0 Hz, 1H), 7.08(d, J=9.0 Hz, 1H), 7.40(dd, J=9.0, 9.0 Hz, 1H), 7.56(d, J=9.0 Hz, 1H), 7.70 (s, 1H), 7.80 (d, J=9.0 Hz, 2H), 8.05 (s, 1H), 8.38 (s, 1H), 9.96 (brs, 1H), 11.08 (brs, 1H), 13.27 (brs, 1H).

Example 4-90

[1347] MS ESI m/e: 603 (M+H), 601 (MH).

[1348] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.71 (m, 2H), 0.93-1.00 (m, 2H), 1.19 (s, 3H), 2.58-2.66 (m, 1H), 3.08 (s, 3H), 6.95(t, J=8.5 Hz, 1H), 7.46-7.58 (m, 3H), 7.79(dd, J=1.5, 10.2 Hz, 1H), 8.01(d, J=8.7 Hz, 2H), 11.01 (s, 1H), 13.14 (br, 1H).

Example 4-91

[1349] MS ESI m/e: 602 (M+H), 600 (MH).

[1350] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.71 (m, 2H), 0.92-1.00 (m, 2H), 1.19 (s, 3H), 2.59-2.65 (m, 1H), 3.08 (s, 3H), 6.94 (t, J=8.7 Hz, 1H), 7.42-7.49 (m, 3H), 7.53-7.58 (m, 1H), 7.76-7.81 (m, 1H), 7.94 (d, J=8.7 Hz, 2H), 8.07 (brs, 1H), 11.02 (s, 1H).

Example 4-92

[1351] MS ESI m/e: 616 (M+H), 614 (MH).

[1352] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.92-1.00 (m, 2H), 1.18 (s, 3H), 2.58-2.66 (m, 1H), 2.81(d, J=4.5 Hz, 3H), 3.08 (s, 3H), 6.94 (t, J=8.7 Hz, 1H), 7.47 (d, J=8.6 Hz, 2H), 7.52-7.58 (m, 1H), 7.76-7.82 (m, 1H), 7.90(d, J=8.6 Hz, 2H), 8.51-8.56 (m, 1H), 11.02 (brs, 1H).

Example 4-93

[1353] MS ESI m/e: 630 (M+H), 628 (MH).

[1354] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.92-1.00 (m, 2H), 1.22 (s, 3H), 2.59-2.66 (m, 1H), 2.93 (brs, 3H), 3.00 (brs, 3H), 3.08 (s, 3H), 6.94 (t, J=8.5 Hz, 1H), 7.42-7.49 (m, 4H), 7.53-7.57 (m, 1H), 7.77-7.81 (m, 1H), 11.04 (s, 1H).

Example 4-94

[1355] MS ESI m/e: 617 (M+H), 615 (MH).

[1356] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.69 (m, 2H), 0.92-0.99 (m, 2H), 1.19 (s, 3H), 2.58-2.65 (m, 1H), 3.07 (s, 3H), 3.63 (s, 2H), 6.92(t, J=8.7 Hz, 1H), 7.28-7.36 (m, 4H), 7.53-7.57 (m, 1H), 7.75-7.81 (m, 1H), 11.07 (br, 1H), 12.39 (br, 1H).

Example 4-95

[1357] MS ESI m/e: 661 (M+H), 659 (MH).

[1358] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.71 (m, 2H), 0.90-1.00 (m, 2H), 1.28 (s, 3H), 2.55-2.68 (m, 1H), 3.08 (s, 3H), 3.14(q, J=5.6 Hz, 2H), 3.43(q, J=5.6 Hz, 2H), 4.74(t, J=5.6 Hz, 1H), 6.20(t, J=5.6 Hz, 1H), 6.83-6.97 (m, 2H), 7.22-7.38 (m, 2H), 7.48 (s, 1H), 7.54(d, J=9.0 Hz, 1H), 7.78(d, J=10.5 Hz, 11), 8.75 (s, 1H), 11.08 (s, 1H).

Example 4-96

[1359] MS ESI m/e: 784 (M+H), 782 (MH).

[1360] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.71 (m, 2H), 0.90-1.02 (m, 2H), 1.24 (s, 3H), 2.57-2.69 (m, 1H), 3.00(q, J=6.7 Hz, 4H), 3.07 (s, 3H), 3.35(q, J=6.7 Hz, 2H), 3.89 (t, J=6.7 Hz, 2H), 4.60(t, J=5.7 Hz, 1H), 6.86-7.05 (m, 3H), 7.10-7.21 (m, 2H), 7.35(t, J=7.8 Hz, 1H), 7.55(d, J=7.8 Hz, 1H), 7.71(t, J=5.7 Hz, 1H), 7.79(dd, J=1.8, 9.6 Hz, 1H), 9.88 (s, 1H), 11.09 (s, 1H).

Example 4-97

[1361] MS ESI m/e: 530 (M+H), 528 (MH).

[1362] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.71 (m, 2H), 0.91-1.00 (m, 2H), 1.25 (s, 3H), 2.04 (s, 3H), 2.10 (s, 3H), 2.58-2.68 (m, 1H), 3.07 (s, 3H), 5.16 (s, 1H), 5.52 (s, 1H), 7.04(d, J=6.9 Hz, 1H), 7.11(t, J=8.6 Hz, 1H), 7.32-7.40 (m, 2H), 7.51 (dd, J=1.8, 12.6 Hz, 1H), 7.56-7.63 (m, 2H), 10.10 (s, 1H), 11.22 (s, 1H).

Example 4-98

[1363] MS ESI m/e: 532 (M+H), 530 (MH).

[1364] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.60-0.73 (m, 2H), 0.89-1.00 (m, 2H), 1.20(d, J=6.4 Hz, 6H), 1.24 (s, 3H), 2.04 (s, 3H), 2.56-2.68 (m, 1H), 2.84-2.97 (m, 1H), 3.03 (s, 3H), 6.97-7.16 (m, 3H), 7.19-7.29 (m, 1H), 7.35(t, J=8.0 Hz, 1H), 7.53-7.66 (m, 2H), 10.10 (s, 1H), 11.22 (s, 1H).

Example 4-99

[1365] MS ESI m/e: 634.0 (M+H), 632.1 (MH).

[1366] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.69 (m, 2H), 0.91-0.98 (m, 2H), 1.28 (s, 3H), 2.09 (s, 3H), 2.57-2.66 (m, 1H), 3.07 (s, 3H), 6.92(dd, J=9.0, 8.7 Hz, 1H), 7.14-7.19 (m, 1H), 7.33 (dd, J=8.7, 10.5 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.79(d, J=12.0 Hz, 1H), 7.88-7.92 (m, 1H), 9.87 (s, 1H), 11.09 (s, 1H)

Example 4-100

[1367] MS ESI m/e: 646 (M+H), 644 (MH).

[1368] .sup.1H-NMR (DMSO-ds, 300 MHz) 0.52-0.62 (m, 2H), 0.82-0.96 (m, 2H), 1.28 (s, 3H), 2.04 (s, 3H), 2.44-2.59 (m, 1H), 3.58-3.65 (m, 2H), 4.01-4.08 (m, 2H), 5.58(t, J=4.5 Hz, 1H), 6.91(t, J=8.6 Hz, 1H), 6.99-7.08 (m, 1H), 7.30-7.45 (m, 2H), 7.57-7.65 (m, 2H), 7.66-7.75 (m, 1H), 10.09 (brs, 1H), 10.12 (brs, 1H).

Example 4-101

[1369] MS ESI m/e: 670.0 (M+H), 668.0 (MH)

[1370] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.60-0.67 (m, 2H), 0.89-0.96 (m, 2H), 1.35 (s, 3H), 2.56-2.62 (m, 1H), 2.60 (s, 3H), 3.09 (s, 3H), 6.49-6.56 (m, 1H), 6.84-6.99 (m, 3H), 7.22(dd, J=2.4, 7.5 Hz, 1H), 7.46-7.52(m, 1H)

Example 4-102

[1371] MS ESI m/e: 532.1 (M+H), 530.2 (MH).

[1372] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.69 (m, 2H), 0.92-0.94 (m, 2H), 1.29 (s, 3H), 2.09 (s, 3H), 2.59-2.63 (m, 1H), 3.10 (s, 3H), 4.29 (s, 1H), 7.06-7.54 (m, 5H), 7.90 (d, 1H, J=6.6 Hz), 9.86 (s, 1H), 11.11 (s, 1H).

Example 4-103

[1373] MS ESI m/e: 615.1 (M+H), 613.1 (MH)

[1374] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.71 (m, 2H), 0.91-0.98 (m, 2H), 1.23 (s, 3H), 2.57-2.65 (m, 1H), 3.07 (s, 3H), 6.88-6.96 (m, 4H), 7.55 (d, J=8.7 Hz, 1H), 7.78(d, J=10.5 Hz, 1H), 10.76 (s, 1H), 10.79 (s, 1H), 11.10 (s, 1H)

Example 4-104

[1375] MS ESI m/e: 638 (M+H), 636 (MH).

[1376] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.70 (m, 2H), 0.93-0.99 (m, 2H), 1.19 (s, 3H), 2.57-2.65 (m, 1H), 3.08 (s, 3H), 6.90-6.98 (m, 1H), 7.48 (s, 2H), 7.52-7.61 (m, 3H), 7.75-7.82 (m, 1H), 7.89(d, J=8.6 Hz, 2H), 11.00 (s, 1H).

Example 4-105

[1377] MS ESI m/e: 536 (M+H), 534 (MH).

[1378] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.71 (m, 2H), 0.91-1.00 (m, 2H), 1.24 (s, 3H), 2.04 (s, 3H), 2.51 (s, 3H), 2.59-2.65 (m, 1H), 3.04 (s, 3H), 7.00-7.14 (m, 3H), 7.27-7.40 (m, 2H), 7.56-7.62 (m, 2H), 10.09 (brs, 1H), 11.22 (brs, 1H).

Example 4-106

[1379] MS ESI m/e: 572 (M+H), 570 (MH).

[1380] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.24 (s, 3H), 2.51 (s, 3H), 2.60-2.67 (m, 1H), 3.01 (s, 3H), 3.04 (s, 3H), 7.05-7.15 (m, 3H), 7.20-7.34 (m, 3H), 7.40 (t, J=4.1 Hz, 1H), 9.88 (s, 1H), 11.22 (s, 1H).

Example 4-107

[1381] MS ESI m/e: 599(M+H), 597(MH).

[1382] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.66-0.72 (m, 2H), 0.93-0.98 (m, 2H), 1.12(d, J=3.0 Hz, 3H), 2.60-2.67 (m, 1H), 3.08 (s, 3H), 6.90-6.97 (m, 1H), 7.15-7.25 (m, 1H), 7.54-7.57 (m, 2H), 7.64-7.69 (m, 1H), 7.77-7.81 (m, 1H), 8.31(d, J=3.8 Hz, 1H), 11.12 (d, J=3.4 Hz, 1H), 12.60(d, J=14.3 Hz, 1H).

Example 4-108

[1383] MS ESI m/e: 657 (M+H), 655 (MH).

[1384] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.74 (m, 2H), 0.90-1.01 (m, 2H), 1.26 (s, 3H), 2.58-2.70 (m, 1H), 3.08 (s, 3H), 4.06 (s, 2H), 6.92(t, J=8.6 Hz, 1H), 7.36-7.47 (m, 3H), 7.51-7.60 (m, 2H), 7.78 (dd, J=1.8, 10.2 Hz, 1H), 8.31 (s, 1H), 11.04 (s, 1H).

Example 4-109

[1385] MS ESI m/e: 657 (M+H), 655 (MH).

[1386] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.71 (m, 2H), 0.90-0.99 (m, 2H), 1.26 (s, 3H), 2.56-2.67 (m, 1H), 3.08 (s, 3H), 4.44 (s, 2H), 6.93(t, J=8.7 Hz, 1H), 7.13 (d, J=7.5 Hz, 1H), 7.45 (t, J=8.1 Hz, 1H), 7.50-7.58 (m, 2H), 7.71-7.82 (m, 2H), 11.10 (s, 1H), 11.23 (s, 1H).

Example 4-110

[1387] MS ESI m/e: 643 (M+H), 641 (MH).

[1388] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.90-1.00 (m, 2H), 1.27 (s, 3H), 2.58-2.67 (m, 1H), 3.08 (s, 3H), 3.60-3.86 (m, 2H), 4.16-4.32 (m, 2H), 6.84-6.97 (m, 2H), 7.28 (t, J=7.8 Hz, 1H), 7.40-7.73 (m, 2H), 7.55(d, J=8.4 Hz, 1H), 0.7.78(dd, J=1.5, 10.2 Hz, 1H), 9.15-9.51 (brs, 1H), 11.09 (s, 1H).

Example 4-111

[1389] MS ESI m/e: 613 (M+H), 611 (MH).

[1390] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.74 (m, 2H), 0.91-1.01 (m, 2H), 1.11 (s, 3H), 2.58-2.69 (m, 1H), 3.08 (s, 3H), 3.89 (s, 3H), 6.94(t, J=8.4 Hz, 1H), 7.26-7.34 (m, 1H), 7.51-7.58 (m, 1H), 7.59-7.67 (m, 2H), 7.74-7.84 (m, 1H), 8.27 (s, 1H), 11.10 (brs, 1H).

Example 4-112

[1391] MS ESI m/e: 613 (M+H), 611 (MH).

[1392] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.74 (m, 2H), 0.91-1.02 (m, 2H), 1.13 (s, 3H), 2.57-2.69 (m, 1H), 3.08 (s, 3H), 4.09 (s, 3H), 6.94 (t, J=8.5 Hz, 1H), 7.39-7.47 (m, 1H), 7.51-7.60 (m, 1H), 7.66-7.74 (m, 2H), 7.75-7.83 (m, 1H), 8.09 (s, 1H), 11.10 (brs, 1H).

Example 4-113

[1393] MS ESI m/e: 602 (M+H), 600 (MH).

[1394] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz, 120 C.) 0.72 (m, 2H), 0.95 (m, 2H), 1.30 (s, 3H), 2.67 (m, 1H), 3.12 (s, 3H), 6.88(t, J=8.4 Hz, 1H), 7.07(dd, J=1.8, 8.8 Hz, 1H), 7.36(t, J=7.9 Hz, 1H), 7.40-7.55 (m, 3H), 7.67(dd, J=1.8, 10.3 Hz, 1H), 8.39 (brs, 1H), 9.84 (brs, 1H), 10.90 (s, 1H).

Example 4-114

[1395] MS ESI m/e: 679 (M+H), 677 (MH).

[1396] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.62-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.25 (s, 3H), 2.59-2.66 (m, 1H), 3.08 (s, 3H), 3.48-3.56 (m, 2H), 3.84(t, J=6.4 Hz, 2H), 6.92(t, J=8.6 Hz, 1H), 7.09 (d, J=8.0 Hz, 1H), 7.16-7.26 (m, 2H), 7.44(t, J=8.2 Hz, 1H), 7.55(d, J=8.0 Hz, 1H), 7.74-7.83 (m, 2H), 11.10 (s, 1H).

Example 4-115

[1397] MS ESI m/e: 599 (M+H), 597 (MH).

[1398] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.73 (m, 2H), 0.91-1.00 (m, 2H), 1.14 (s, 3H), 2.59-2.67 (m, 1H), 3.09 (s, 3H), 6.92(t, J=4.1 Hz, 1H), 7.11-7.16 (m, 1H), 7.53-7.59 (m, 2H), 7.76-7.83 (m, 2H), 8.14 (s, 1H), 11.10 (s, 1H), 13.20 (s, 1H).

Example 4-116

[1399] MS ESI m/e: 685.9 (M+H), 684.0 (MH).

[1400] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.70 (m, 2H), 0.92-0.98 (m, 2H), 1.26 (s, 3H), 2.57-2.65 (m, 1H), 3.08 (s, 3H), 3.09 (s, 3H), 6.94(dd, J=9.0, 8.7 Hz, 1H), 7.38(dd, J=2.3, 8.6 Hz, 1H), 7.51-7.57 (m, 3H), 7.63(d, J=2.3 Hz, 1H), 7.78 (dd, J=1.5, 10.2 Hz, 1H), 9.59 (s, 1H), 11.01 (s, 1H)

Example 4-117

[1401] MS ESI m/e: 666.0 (M+H), 664.1 (MH).

[1402] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.68 (m, 2H), 0.90-0.97 (m, 2H), 1.23 (s, 3H), 2.30 (s, 3H), 2.5.5-2.63 (m, 1H), 3.09 (s, 3H), 6.88-6.95 (m, 1H), 7.15-7.34 (m, 3H), 7.47-7.57 (m, 2H), 7.70-7.80(m, 2H).

Example 4-118

[1403] MS ESI m/e: 630 (M+H), 628 (MH).

[1404] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.75-0.81 (m, 2H), 1.09-1.15 (m, 2H), 1.47 (s, 3H), 2.70-2.77 (m, 1H), 3.20 (s, 3H), 4.66 (s, 2H), 6.70 (t, J=8.5 Hz, 1H), 6.81-6.88 (m, 2H), 7.00(d, J=8.3 Hz, 1H), 7.43-7.55 (m, 2H), 8.12 (s, 1H), 11.31 (s, 1H).

Example 4-119

[1405] MS ESI m/e: 612 (M+H), 610 (MH).

[1406] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.21 (s, 3H), 3.09 (s, 3H), 3.21 (s, 3H), 6.96(t, J=8.5 Hz, 1H), 7.48 (s, 2H), 7.53-7.64 (m, 3H), 7.76-7.81 (m, 1H), 7.90 (d, J=8.3 Hz, 2H), 11.13 (s, 1H).

Example 4-120

[1407] MS ESI m/e: 573 (M+H), 571 (MH).

[1408] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.66-0.69 (m, 2H), 0.94-0.98 (m, 2H), 1.26 (s, 3H), 2.50 (s, 3H), 2.61-2.66 (m, 1H), 3.04 (s, 3H), 6.98 (d, J=7.3 Hz, 1H), 7.10-7.19 (m, 6H), 7.31-7.33 (m, 2H), 9.66 (s, 1H), 11.23 (s, 1H).

Example 4-121

[1409] MS ESI m/e: 600 (M+H), 598 (MH).

[1410] .sup.1H-NMR (CDCl.sub.3, 300 MHz) 0.80-0.90 (m, 2H), 1.11-1.20 (m, 2H), 1.27 (s, 3H), 2.74-2.83 (m, 1H), 3.24 (s, 3H), 6.75(t, J=8.3 Hz, 1H), 7.37(dd, J=1.9, 8.7 Hz, 1H), 7.45-7.57 (m, 2H), 7.80 (brs, 3H), 11.37 (s, 1H).

Example 4-122

[1411] MS ESI m/e: 671 (M+H), 669 (MH).

[1412] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.60-0.67 (m, 2H), 0.87-0.95 (m, 2H), 1.21 (s, 13H), 2.24 (brs, 3H), 2.54-2.61 (m, 1H), 2.69 (brs, 2H), 3.04 (s, 3H), 3.07 (brs, 2H), 3.62 (brs, 2H), 6.89 (t, J=8.7 Hz, 1H), 7.24-7.29 (m, 1H), 7.30-7.35 (m, 2H), 7.40-7.46 (m, 1H), 7.48-7.53 (m, 1H), 7.72-7.77 (m, 1H), 11.01 (s, 1H).

Example 4-123

[1413] MS ESI m/e: 628(M+H), 626(MH).

[1414] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.61-0.71 (m, 2H), 0.90-1.00 (m, 2H), 1.30 (s, 3H), 2.50 (t, J=7.5 Hz, 2H), 2.55-2.67 (m, 1H), 2.95(t, J=7.5 Hz, 2H), 3.09 (s, 3H), 6.87-6.95 (m, 3H), 7.24 (d, J=9.0 Hz, 1H), 7.57(d, J=9.0 Hz, 1H), 7.80(d, J=9.0 Hz, 1H), 10.11 (brs, 1H), 11.07 (brs, 1H).

Example 4-124

[1415] MS ESI m/e: 643 (M+H), 641 (MH).

[1416] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.63-0.72 (m, 2H), 0.90-1.00 (m, 2H), 1.27 (s, 3H), 2.58-2.67 (m, 1H), 3.08 (s, 3H), 3.41(t, J=8.3 Hz, 2H), 3.85 (t, J=8.3 Hz, 2H), 6.92(t, J=8.5 Hz, 1H), 6.98(d, J=7.8 Hz, 1H), 7.05 (s, 1H), 7.37(t, J=8.1 Hz, 1H), 7.49(d, J=8.1 Hz, 1H), 7.55(d, J=8.4 Hz, 1H), 7.67-7.71 (m, 1H), 7.79(dd, J=1.8, 10.5 Hz, 1H), 11.11 (s, 1H).

Example 4-125

[1417] MS ESI m/e: 644 (M+H), 642 (MH).

[1418] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.72 (m, 2H), 0.89-1.01 (m, 2H), 1.25 (s, 3H), 2.56-2.68 (m, 1H), 3.08 (s, 3H), 4.07 (t, J=8.4 Hz, 2H), 4.45(t, J=8.4 Hz, 2H), 6.92 (t, J=8.3 Hz, 1H), 7.14 (d, J=8.1 Hz, 1H), 7.46(t, J=8.1 Hz, 1H), 7.51-7.60 (m, 2H), 7.65-7.69 (m, 1H), 7.78(d, J=9.3 Hz, 1H), 11.10 (s, 1H).

Example 4-126

[1419] MS ESI m/e: 616 (M+H), 614 (MH).

[1420] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.73 (m, 2H), 0.90-1.00 (m, 2H), 1.24 (s, 3H), 2.57-2.67 (m, 1H), 3.08 (s, 3H), 6.93 (t, J=8.6 Hz, 1H), 7.08(dd, J=2.4, 8.7 Hz, 1H), 7.18 (d, J=2.1 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.79(dd, J=1.5, 10.5 Hz, 1H), 11.08 (s, 1H), 11.80 (s, 1H).

Example 4-127

[1421] MS ESI m/e: 638 (M+H), 636 (MH).

[1422] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.64-0.72 (m, 2H), 0.90-1.01 (m, 2H), 1.19 (s, 3H), 2.57-2.66 (m, 1H), 3.09 (s, 3H), 6.94(t, J=8.7 Hz, 1H), 7.51 (brs, 2H), 7.53-7.58 (m, 1H), 7.61-7.70 (m, 2H), 7.76-7.88 (m, 3H), 11.05 (brs, 1H).

Example 4-128

[1423] MS ESI m/e: 642 (M+H), 640 (MH).

[1424] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.59-0.72 (m, 2H), 0.88-1.01 (m, 2H), 1.27 (s, 3H), 1.29 (s, 6H), 2.55-2.67 (m, 1H), 3.07 (s, 3H), 6.86-6.97 (m, 2H), 7.34 (d, J=7.9 Hz, 1H), 7.55(dd, J=1.1, 7.9 Hz, 1H), 7.78 (dd, J=1.1, 10.6 Hz, 1H), 10.44 (brs, 1H), 11.07 (s, 1H).

Example 4-129

[1425] MS ESI m/e: 574(M+H), 572(MH).

[1426] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.59-0.69 (m, 2H), 0.89-0.99 (m, 2H), 1.35 (s, 3H), 2.52-2.66 (m, 1H), 3.07 (s, 3H), 5.25 (brs, 2H), 6.46(d, J=6.0 Hz, 1H), 6.53 (s, 1H), 6.55(d, J=9.0 Hz, 1H), 6.90(dd, J=9.0, 9.0 Hz, 1H), 7.06(dd, J=9.0, 9.0 Hz, 1H), 7.55(d, J=9.0 Hz, 1H), 7.78(d, J=9.0 Hz, 1H), 11.06 (brs, 1H).

Example 4-130

[1427] MS ESI m/e: 640 (M+H), 638 (MH).

[1428] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.60-0.71 (m, 2H), 0.89-1.00 (m, 2H), 1.29 (s, 3H), 1.47-1.55 (m, 2H), 1.58-1.68 (m, 2H), 2.55-2.68 (m, 1H), 3.07 (s, 3H), 6.87-6.96 (m, 3H), 7.02(d, J=7.9 Hz, 1H), 7.52-7.58 (m, 1H), 7.78 (dd, J=1.9, 10.2 Hz, 1H), 10.66 (brs, 1H), 11.07 (brs, 1H).

Example 4-131

[1429] MS ESI m/e: 472 (M+H), 470 (MH).

[1430] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.59-0.70 (m, 2H), 0.89-1.01 (m, 2H), 1.36 (s, 3H), 2.56-2.67 (m, 1H), 3.10 (s, 3H), 4.28 (s, 1H), 5.24 (s, 2H), 6.42-6.62 (m, 3H), 6.99-7.14 (m, 2H), 7.26-7.36 (m, 1H), 7.46-7.57 (m, 1H), 11.08 (s, 1H).

Example 4-132

[1431] MS ESI m/e: 716(M+H), 714(MH).

[1432] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.62-0.74 (m, 2H), 0.91-1.04 (m, 2H), 1.28 (s, 3H), 1.36 (s, 9H), 2.48 (s, 3H), 2.59-2.69 (m, 1H), 3.08 (s, 3H), 6.94(t, J=8.6 Hz, 1H), 7.17-7.24 (m, 2H), 7.38-7.57 (m, 3H), 7.79 (d, J=10.3 Hz, 1H), 11.0(brs, 1H).

Example 4-133

[1433] MS ESI m/e: 694(M+H), 692(MH).

[1434] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.62-0.71 (m, 2H), 0.92-1.01 (m, 2H), 1.17 (s, 3H), 1.95 (s, 3H), 2.59-2.69 (m, 1H), 3.08 (s, 3H), 3.54 (s, 3H), 6.94(d, J=9.0 Hz, 1H), 7.52-7.60 (m, 5H), 7.79(d, J=10.4 Hz, 1H), 11.0(brs, 1H).

Example 4-134

[1435] MS ESI m/e: 620(M+H), 618(MH).

[1436] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.27 (s, 3H), 2.06 (s, 3H), 3.10 (s, 3H), 3.49-3.60 (m, 2H), 3.89-4.01 (m, 2H), 4.78 (brs, 1H), 6.95(t, J=8.7 Hz, 1H), 7.03-7.10 (m, 1H), 7.41 (t, J=8.0 Hz, 1H), 7.51-7.60 (m, 2H), 7.68 (s, 1H), 7.78-7.82 (m, 1H), 10.1(brs, 1H), 11.3(brs, 1H).

Example 4-135

[1437] MS ESI m/e: 634(M+H), 632(MH).

[1438] .sup.1H-NMR (DMSO-d, 300 MHz) 1.27 (s, 3H), 2.65-2.79 (m, 2H), 2.06 (s, 3H), 3.09 (s, 3H), 3.39-3.50 (m, 2H), 3.82-3.94 (m, 2H), 4.46 (brs, 1H), 6.95(t, J=8.7 Hz, 1H), 7.07-7.10 (m, 1H), 7.38(t, J=8.0 Hz, 1H), 7.55-7.58 (m, 2H), 7.68 (s, 1H), 7.78-7.81 (m, 1H), 10.1(brs, 1H), 11.3(brs, 1H).

Example 4-136

[1439] MS ESI m/e: 650 (M+H), 648 (M1).

[1440] .sup.1H-NMR (DMSO-d, 300 MHz) 1.27 (s, 3H), 2.05 (s, 3H), 3.09 (s, 3H), 3.70-3.90 (m, 2H), 4.02(q, J=7.8 Hz 1H), 4.55(t, J=5.7 Hz, LH), 4.77(d, J=5.4 Hz, 1H), 6.94 (t, J=8.7 Hz, 1H), 7.05(d, J=7.5 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.56 (d, J=8.7 Hz, 2H), 7.68 (s, 1H), 7.79(dd, J=1.5, 10.2 Hz, 1H), 10.10 (s, 1H), 11.30 (s, 1H).

Example 4-137

[1441] MS ESI m/e: 650 (M+H), 648 (M1).

[1442] .sup.1H-NMR (DMSO-ds, 300 MHz) 1.27 (s, 3H), 2.05 (s, 3H), 3.09 (s, 3H), 3.70-3.90 (m, 2H), 4.02(q, J=7.1 Hz, 1H), 4.55 (brs, 1H), 4.77 (d, J=3.9 Hz, 1H), 6.94 (t, J=8.5 Hz, 1H), 7.04(d, J=8.7 Hz, 1H), 7.37(t, J=8.1 Hz, 1H), 7.56(d, J=8.7 Hz, 2H), 7.68 (s, 1H), so 7.79 (dd, J=2.4, 10.8 Hz, 1H), 10.10 (s, 1H), 11.30 (s, 1H).

Example 4-138

[1443] MS ESI m/e: 723(M+H), 721(MH).

[1444] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 0.65-0.72 (m, 2H), 0.91-1.01 (m, 2H), 1.27 (s, 3H), 1.91 (s, 3H), 2.59-2.69 (m, 1H), 2.93 (s, 6H), 3.10 (s, 3H), 6.98(t, J=8.6 Hz, 1H), 7.43-7.60 (m, 5H), 7.80(d, J=10.3 Hz, 1H), 11.0(brs, 1H).

Example 4-139

[1445] MS ESI m/e: 630 (M+H), 628 (MH).

[1446] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.63-0.71 (m, 2H), 0.92-1.00 (m, 2H), 1.26 (s, 3H), 1.82 (brs, 3H), 2.58-2.67 (m, 1H), 3.08 (s, 3H), 3.16 (brs, 3H), 6.94(t, J=8.7 Hz, 1H), 7.30-7.46 (m, 3H), 7.47-7.60 (m, 2H), 7.76-7.82 (m, 1H), 11.02 (s, 1H).

Example 4-140

[1447] MS ESI m/e: 658 (M+H), 656 (MH).

[1448] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 0.61-0.72 (m, 2H), 0.92-1.01 (m, 2H), 1.28 (s, 3H), 2.20 (s, 6H), 2.58-2.66 (m, 1H), 3.08 (s, 3H), 6.94(t, J=8.6 Hz, 1H), 7.29-7.35 (m, 1H), 7.36-7.40 (m, 1H), 7.42-7.48 (m, 1H), 7.51-7.58 (m, 2H), 7.75-7.82 (m, 1H), 11.00 (s, 1H).

Example 4-141

[1449] MS ESI m/e: 633 (M+H), 631 (MH).

[1450] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.27 (s, 3H), 1.81-1.93 (m, 2H), 2.05 (s, 3H), 2.75-2.87 (m, 2H), 3.09 (s, 3H), 3.91(t, 2H, J=6.2 Hz), 6.93(t, 1H, J=8.5 Hz), 7.04-7.10 (m, 1H), 7.38(t, 1H, J=8.1 Hz), 7.48-7.59 (m, 2H), 7.69-7.86 (m, 5H), 10.18 (s, 1H), 11.21 (s, 1H).

Example 4-142

[1451] MS ESI m/e: 664 (M+H), 662 (MH).

[1452] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.26 (s, 3H), 1.46-1.57 (m, 1H), 1.65-1.80 (m, 1H), 2.05 (s, 3H), 3.08 (s, 3H), 3.15-3.36 (m, 2H), 3.40-3.51 (m, 1H), 3.78-3.91 (m, 1H), 3.98-4.11 (m, 1H), 4.46-4.56 (m, 2H), 6.94 (t, 1H, J=8.7 Hz), 7.04-7.10 (m, 1H), 7.37(t, 1H, J=8.1 Hz), 7.52-7.59 (m, 2H), 7.65-7.69 (m, 1H), 7.79(dd, 1H, J=1.9, 10.5 Hz), 10.10 (s, 1H), 11.28(s, 1H).

Example 4-143

[1453] MS ESI m/e: 664 (M+H), 662 (MH).

[1454] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.26 (s, 3H), 1.43-1.59 (m, 1H), 1.67-1.79 (m, 1H), 2.04 (s, 3H), 3.08 (s, 3H), 3.15-3.32 (m, 2H), 3.40-3.50 (m, 1H), 3.78-3.91 (m, 1H), 3.97-4.10 (m, 1H), 4.45-4.54 (m, 2H), 6.94(t, 1H, J=8.7 Hz), 7.04-7.09 (m, 1H), 7.37(t, 1H, J=8.1 Hz), 7.53-7.59 (m, 2H), 7.65-7.69 (m, 1H), 7.79(dd, 1H, J=1.9, 10.2 Hz), 10.10 (s, 1H), 11.27 (s, 1H).

Example 4-144

[1455] MS ESI m/e: 648 (M+H), 646 (MH).

[1456] .sup.1H-NMR (CDCL3, 300 MHz) 1.42 (s, 3H), 1.53-1.82 (m, 4H), 2.17 (s, 3H), 3.21 (s, 3H), 3.68 (t, 2H, J=6.2 Hz), 3.96-4.04 (m, 2H), 6.70 (t, 1H, J=8.3 Hz), 7.05-7.12 (m, 1H), 7.22-7.56 (m, 6H), 7.70 (s, 1H), 11.47 (s, 1H).

Example 4-145

[1457] MS ESI m/e: 670 (M+H), 668 (MH).

[1458] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.26 (s, 3H), 1.66-1.75 (m, 2H), 3.02 (s, 3H), 3.08 (s, 3H), 3.42 (q, 2H, J=5.9 Hz), 3.88-3.91 (m, 2H), 4.45 (t, 1H, J=5.1 Hz), 6.94 (t, 1H, J=8.6 Hz), 7.12-7.15 (m, 1H), 7.23-7.29 (m, 2H), 7.42 (t, 1H, J=7.9 Hz), 7.54-7.57 (m, 1H), 7.78 (dd, 1H, J=10.5, 1.7 Hz), 9.92 (s, 1H), 11.26 (s, 1H).

Example 4-146

[1459] MS ESI m/e: 634 (M+H), 632 (MH).

[1460] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) 1.25 (s, 3H), 1.66-1.75 (m, 2H), 3.08 (s, 3H), 3.42(q, 2H, J=4.5 Hz), 3.86-3.93 (m, 2H), 4.46(t, 1H, J=3.8 Hz), 6.95 (t, 1H, J=6.4 Hz), 7.11(dd, 1H, J=1.7, 6.4 Hz), 7.22 (d, 1H, J=1.6 Hz), 7.35(d, 1H, J=6.4 Hz), 7.53-7.58 (m, 1H), 7.79(dd, 1H, J=1.4, 7.8 Hz), 11.27 (s, 1H), 11.84 (s, 1H).

Example 4-147

[1461] MS ESI m/e: 577 (M+H), 575 (MH).

[1462] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.19 (s, 3H), 1.65-1.76 (m, 2H), 3.08 (s, 3H), 3.43(q, 2H, J=5.9 Hz), 3.86-3.94 (m, 2H), 4.46(t, 1H, J=5.3 Hz), 6.95(t, 1H, J=8.7 Hz), 7.38-7.51 (m, 5H), 7.52-7.58 (m, 1H), 7.79 (dd, 1H, J=1.9, 10.2 Hz), 11.25 (s, 1H).

Example 4-148

[1463] MS ESI m/e: 650 (M+H), 648 (MH).

[1464] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) 1.26 (s, 3H), 1.70-1.72 (m, 2H), 3.08 (s, 3H), 3.42 (q, 2H, J=5.7 Hz), 3.89-3.91 (m, 2H), 3.99 (d, 2H, J=5.9 Hz), 4.44 (t, 1H, J=5.3 Hz), 5.64 (t, 1H, J=6.1 Hz), 6.94 (t, 1H, J=8.6 Hz), 7.11 (d, 1H, J=7.0 Hz), 7.39 (t, 1H, J=8.3 Hz), 7.55 (d, 1H, J=8.1 Hz), 7.70-7.81 (m, 3H), 9.83 (s, 1H), 11.25 (s, 1H).

INDUSTRIAL APPLICABILITY

[1465] The compound of the present invention shows superior p15 protein inducing action and/or p27 protein inducing action and/or MEK inhibitory action.

[1466] In addition, the compound of the present invention shows superior antitumor activity, and anti-rheumatism activity.

[1467] Therefore, the compound can be a pharmaceutical agent effective for the prophylaxis or treatment of a disease caused by undesirable cell proliferation, particularly, tumor or rheumatism.

[1468] This application is based on patent application Nos. 174770/2004 and 327111/2004 filed in Japan, the contents of which are hereby incorporated by reference.