التفاصيل البيبلوغرافية
| العنوان: |
PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONISTS |
| Document Number: |
20090062358 |
| تاريخ النشر: |
March 5, 2009 |
| Appl. No: |
11/828446 |
| Application Filed: |
July 26, 2007 |
| مستخلص: |
The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts, solvates and hydrates thereof, [chemical expression included] R1 is a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-2-alkyl, heteroaryl-C0-2-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl. X is a C2-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH2)nCOOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, arylC0-C4alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl. |
| Inventors: |
Cano, Ivan Collado (Alcobendas, ES); Dominianni, Samuel James (Indianapolis, IN, US); Etgen, JR., Garret Jay (Carmel, IN, US); Garcia-Paredes, Cristina (Alcobendas, ES); Johnston, Richard Duane (Greenfield, IN, US); Letourneau, Michael Edward (Indianapolis, IN, US); Mantlo, Nathan Bryan (Brownsburg, IN, US); Martinelli, Michael John (Zionsville, IN, US); Mayhugh, Daniel Ray (Carmel, IN, US); Saeed, Ashraf (Framingham, MA, US); Thompson, Richard Craig (Frankfort, IN, US); Wang, Xiaodong (Carmel, IN, US); Coffey, David Scott (Indianapolis, IN, US); Schmid, Christopher Randall (Indianapolis, IN, US); Vicenzi, Jeffrey Thomas (Brownsburg, IN, US); Xu, Yanping (Fishers, IN, US) |
| Claim: |
1. A compound represented by the following structural Formula I: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R1 is selected from the group consisting of hydrogen, substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl, and —CH2—C(O)—R17-R18, wherein R17 is O or NH and R18 is optionally substituted benzyl; (b) W is O or S; (c) R2 is H or a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, sulfonamide, amide, OR10 and C3-C6 cycloalkyl; (d) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (e) Y is C, O, S, NH or a single bond; and (f) E is selected from the group consisting of hydrogen, C(R3)(R4)A, A, substituted or unsubstituted selected from the group consisting of (CH2)n COOR19, C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-4alkoxyaryl, C1-4alkoxy C1-4alkyl, aminoaryl, and aminoC1-4alkyl, and wherein (i) n is 0, 1, 2 or 3, (ii) A is an functional group selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole; (iii) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy, and (iv) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, aryl C0-C4 alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (v) R19 is selected from the group consisting of hydrogen, optionally substituted arylmethyl and optionally substituted C1-C4alkyl; (g) R8 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo; (h) R9 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, substituted or unsubstituted aryl, substituted or unsubstituted aryl-C1-C4 alkyl, substituted or unsubstituted heteroaryl, C1-C6 allyl, and OR10; and (i) R10 is independently selected from the group consisting of hydrogen and C1-C4 alkyl. |
| Claim: |
2. (canceled) |
| Claim: |
3. A compound as claimed by any one of claims 1 or 2 wherein W is O. |
| Claim: |
4. A compound as claimed by any one of claims 1, 2 or 3 wherein E is A. |
| Claim: |
5. A compound as claimed by any one of claims 1, 2, 3 or 4 wherein A is COOH. |
| Claim: |
6. A compound as claimed by any one of claims 1, 2, 3, 4 or 5 wherein Y is O. |
| Claim: |
7. A compound as claimed by any one of claims 1, 2, 3, 4 or 5 wherein Y is C. |
| Claim: |
8. A compound of claim 7 wherein E is selected from the group consisting of aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-4alkoxyaryl, C1-4alkoxyalkyl, aminoaryl, and aminoC1-4alkyl. |
| Claim: |
9. A compound as claimed by any one of claims 1, 2, 3, 6, or 7 wherein E is a group of the formula: [chemical expression included] wherein R14 is selected from the group consisting of CF3, substituted or unsubstituted phenyl, substituted or unsubstituted aryl-C0-4-alkyl, and C1-6-alkyl. |
| Claim: |
10. A compound as claimed by any one of claims 1, 2, 3, 6, or 7 wherein E is a group of the formula: [chemical expression included] wherein R14 is selected from the group consisting of CF3, substituted or unsubstituted phenyl, substituted or unsubstituted aryl-C0-4-alkyl, and C1-6-alkyl. |
| Claim: |
11. A compound as claimed by any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 wherein X is optionally substituted C2-C5 alkylene. |
| Claim: |
12. A compound as claimed by any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 wherein X is propylene. |
| Claim: |
13. A compound of claim 1 which is Propanoic Acid, 2-[4-[3-[2,5-dihydro-1-[(4-methylphenyl)methyl]-5-oxo-1H-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methyl-. |
| Claim: |
14. A compound of claim 13 which is Crystalline Propanoic Acid, 2-[4-[3-[2,5-dihydro-1-[(4-methylphenyl)methyl]-5-oxo-1H-1,2,4-triazol-3-yl]propyl]phenoxy]-2-methyl- having an X-ray diffraction pattern which comprises at least one of the following peaks: 13.2+/−0.2, 15.9+/−0.2, 20.7+/−0.2, and 24.1+/−0.2 in 20 when obtained from a copper radiation source. |
| Claim: |
15. A compound as claimed by any one of claims 1, 2, 5, 11 or 12 that is represented by the following structural formula: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R1 is selected from the group consisting of hydrogen, substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl, and —CH2—C(O)—R17-R18, wherein R17 is O or NH and R18 is optionally substituted benzyl; (b) R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl; (c) X is a C2-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (d) Q is C, O or S; (e) A is a functional group selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole; (f) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy; and (g) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl. |
| Claim: |
16. A compound as claimed by claim 15 wherein A is COOH. |
| Claim: |
17. A compound as claimed by any one of claims 15, or 16 wherein R3 is methyl. |
| Claim: |
18. A compound as claimed by any one of claims 15, 16 or 17 wherein R4 is methyl. |
| Claim: |
19. A compound as claimed by any one of claims 1, 2, 11 or 12 that is represented by the following structural formula: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R1 is selected from the group consisting of hydrogen, substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl, and —CH2—C(O)—R17-R18, wherein R17 is O or NH and R18 is optionally substituted benzyl; (b) R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl; (c) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (d) Q is C, O or S; (e) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy; and (f) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl. |
| Claim: |
20. A compound as claimed by any one of claims 1-12, 15, 16, 17, 18, or 19 wherein R1 selected from the group consisting of a substituted or unsubstituted C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, and C3-C6 cycloalkylaryl-C0-2-alkyl. |
| Claim: |
21. A compound as claimed by any one of claims 1-12, 15, 16, 17, 18, 19 or 20 wherein R1 is substituted aryl. |
| Claim: |
22. A compound as claimed by any one of claims 1, 2, 11, or 12 that is represented by the following structural formula: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl; (b) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (c) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy; (d) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (e) V is a bond or a unsubstituted or substituted C1-C3 alkylene group; and (f) R5 is substituted or unsubstituted group selected from aryl, heteroaryl and cycloalkyl groups. |
| Claim: |
23. A compound as claimed by any one of claims 1, 2, 11 or 12 that is represented by the following structural formula: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl (delete heteroaryl); (b) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (c) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy; (d) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (e) V is a bond or a unsubstituted or substituted C1-C3 alkylene group; and (f) R6 is H, OH, C1-C5 alkyl, alkoxy, halo, haloalkyl, haloalkoxy, nitro, phenyl, aryloxy, SO2R7, SR7, cyano, benzyloxy, phenoxy, alkylcarboxamido or COOH wherein R7 is an alkyl or a haloalkyl. |
| Claim: |
24. A compound of claim 23 wherein V is methylene. |
| Claim: |
25. A compound as claimed by any one of claims 23 or 24 wherein X is propylene. |
| Claim: |
26. A compound as claimed by any one of claims 23, 24 or 25 wherein R3 is methyl. |
| Claim: |
27. A compound as claimed by any one of claims 23, 24, 25 or 26 wherein R4 is methyl. |
| Claim: |
28. A compound as claimed by any one of claims 1 or 2 that is represented by the following structural formula: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl (delete heteroaryl); (b) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy; (c) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; and (d) R6 is independently selected from the group consisting of H, OH, C1-C5 alkyl, alkoxy, halo, haloalkyl, haloalkoxy, nitro, phenyl, aryloxy, SO2R7, SR7, cyano, benzyloxy, phenoxy, alkylcarboxamido or COOH wherein R7 is an alkyl or a haloalkyl. |
| Claim: |
29. A compound as claimed by any one of claims 1, 2, or 4-28, that is represented by the following structure: [chemical expression included] wherein R6 is independently selected from the group consisting of H, OH, C1-C5 alkyl, alkoxy, halo, haloalkyl, haloalkoxy, nitro, phenyl, aryloxy, SO2R7, SR7, cyano, benzyloxy, phenoxy, alkylcarboxamido or COOH wherein R7 is an alkyl or a haloalkyl. |
| Claim: |
30. A compound as claimed by any one of claims 1, 2, or 4-29 wherein there are two R6 substituents independently selected from the group consisting of hydrogen, C1-C5 alkyl, Cl, F, OCH3, CF3, and SCF3. |
| Claim: |
31. A compound as claimed by any one of claims 1, 2, or 4-30 wherein EY is [chemical expression included] |
| Claim: |
32. A compound represented by the following structural formula: [chemical expression included] and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein: (a) R1 is selected from the group consisting of hydrogen, substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl, and —CH2—C(O)—R17-R18, wherein R17 is O or NH and R18 is optionally substituted benzyl; (b) W is O or S; (c) R2 is H or a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, sulfonamide, amide, OR10 and C3-C6 cycloalkyl; (d) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (e) Y is C, O, S, NH or a single bond; and (f) E is selected from the group consisting of hydrogen, C(R3)(R4)A, A, substituted or unsubstituted selected from the group consisting of (CH2)n COOR19, C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-4alkoxyaryl, C1-4alkoxy C1-4alkyl, aminoaryl, and aminoC1-4alkyl, and wherein (i) n is 0, 1, 2 or 3, (ii) A is a functional group selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole; (iii) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy, and (iv) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, aryl C0-C4 alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (v) R19 is selected from the group consisting of hydrogen, optionally substituted arylmethyl and optionally substituted C1-C4 alkyl; (g) R8 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo; (h) R9 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, substituted or unsubstituted aryl, substituted or unsubstituted aryl-C1-C4 alkyl, substituted or unsubstituted heteroaryl, C1-C6 allyl, and OR10; (i) R10 is independently selected from the group consisting of hydrogen and C1-C4 alkyl; (j) Z is C0-C3 alkylene, O, S, N, O—(C0-C2 alkylene), S—(C0-C2 alkylene), and N—(C0-C2 alkylene); and (k) — is an optional bond to form a double bond. |
| Claim: |
33. A compound of claim 32 having the formula: [chemical expression included] |
| Claim: |
34. A compound of 33 represented by the structural formula: [chemical expression included] |
| Claim: |
35. A compound of claim 32 represented by the structural formula: [chemical expression included] |
| Claim: |
36. A compound of claim 32 represented by the following structure: [chemical expression included] |
| Claim: |
37. A compound of claim 32 represented by the following structure: [chemical expression included] |
| Claim: |
38. A compound as claimed by 32 wherein A is COOH. |
| Claim: |
39. A compound as claimed by claim 32 wherein W is O. |
| Claim: |
40. A compound as claimed by claim 39 wherein R2 is C1-C4 alkyl. |
| Claim: |
41. A compound as claimed by claim 40, wherein X is C2-C3 alkylene. |
| Claim: |
42. A compound as claimed by claim 41 wherein R1 is optionally substituted phenyl or benzyl. |
| Claim: |
43. A compound as claimed by claim 32, wherein R1 is a substituted or unsubstituted group selected from the group consisting of C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl and phenyl. |
| Claim: |
44. A compound as claimed by claim 32 wherein said compound is radiolabeled. |
| Claim: |
45. A compound as claimed by claim 44 wherein said compound is tritiated. |
| Claim: |
46. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and at least one compound as claimed by any one of claim 42, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
47. A method of modulating a peroxisome proliferator activated receptor, comprising the step of contacting the receptor with at least one compound as claimed by any one of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
48. The method of claim 47, wherein the peroxisome proliferator activated receptor is an α receptor. |
| Claim: |
49. A method of treating diabetes mellitus in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
50. A method of preventing diabetes mellitus in a mammal, comprising the step of administering to the mammal an effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
51. The method of any one of claims 49 or 50 wherein the compound lowers blood glucose levels. |
| Claim: |
52. A method of treating cardiovascular disease in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
53. A method of preventing cardiovascular disease in a mammal, comprising the step of administering to the mammal an effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
54. The method of any one of claims 52 or 53 wherein the compound lowers triglycerides in the mammal. |
| Claim: |
55. The method of any one of claims 52, 53, or 54 wherein the compound lowers low density lipoproteins in the mammal. |
| Claim: |
56. The method of claims 52, 53 or 54 wherein the compound increases high density lipoproteins in a mammal. |
| Claim: |
57. A method of treating Syndrome X in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
58. A method of preventing Syndrome X in a mammal, comprising the step of administering to the mammal an effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
59. The method of claim 58 wherein the compound lowers blood glucose levels. |
| Claim: |
60. The method of any one of claims 58 or 59 wherein the compound lowers serum concentration of triglycerides in the mammal. |
| Claim: |
61. The method of any one of claims 58, 59 or 60 wherein the compound lowers serum concentration of low density lipoproteins in the mammal. |
| Claim: |
62. The method of any one of claims 58, 59, 60 or 61 wherein the compound increases serum concentration of high density lipoproteins in a mammal. |
| Claim: |
63. A method of treating obesity in a mammal, comprising the step of administering to the mammal a therapeutically effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
64. A method of preventing obesity in a mammal, comprising the step of administering to the mammal an effective amount of at least one compound of claims 1-43, or a pharmaceutically acceptable salt, solvate or hydrate thereof. |
| Claim: |
65. The method of any one of claims 47-64 wherein the mammal is a human. |
| Claim: |
66. A compound for use in therapy for a disorder modulated by a peroxisome proliferator activated receptor, wherein the compound, or pharmaceutically acceptable salt, solvate or hydrate thereof, is a compound of claims 1-43. |
| Claim: |
67. Use of a compound for the manufacture of a medicament for the treatment of a condition modulated by a peroxisome proliferator activated receptor, wherein the compound, or pharmaceutically acceptable salt, solvate or hydrate thereof, is a compound of claims 1-43. |
| Claim: |
68. (canceled) |
| Claim: |
69. A process for preparing a triazolone from an acyl semicarbazide comprising contacting said acyl semicarbazide with an acid. |
| Claim: |
70. A process as claimed by claim 69 wherein the acid is a sulfonic acid. |
| Claim: |
71. A process as claimed by claim 69 wherein the acid is pyridinium hydrochloride. |
| Claim: |
72. A process as claimed by any one of claims 69, 70, or 71 wherein the triazalone is represented by Formula I. |
| Claim: |
73. A compound of the formula: [chemical expression included] wherein (a) R1 is hydrogen or is selected from the group consisting of a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, and C3-C6 cycloalkylaryl-C0-2-alkyl; (b) R2 is H or a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, sulfonamide, amide, OR10 and C3-C6 cycloalkyl; (c) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (d) Y is C, O, S, NH or a single bond; and (e) E is selected from the group consisting of hydrogen, (CH2)nCOOR19, C(R3)(R4)A, substituted or unsubstituted selected from the group consisting of C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-4alkoxyaryl, C1-4alkoxy C1-4alkyl, aminoaryl, and aminoC1-4alkyl, and wherein (i) n is 0, 1, 2 or 3, (ii) A is a functional group selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole; (iii) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy, and (iv) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, aryl C0-C4 alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (v) R19 is selected from the group consisting of hydrogen, optionally substituted C1-C4alkyl and optionally substituted arylmethyl; (f) R8 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo; (g) R9 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, substituted or unsubstituted aryl, substituted or unsubstituted aryl-C1-C4 alkyl, substituted or unsubstituted heteroaryl, C1-C6 allyl, and OR10; and (h) R10 is independently selected from the group consisting of hydrogen and C1-C4 alkyl; and (i) R15 is selected from the group consisting of hydrogen and an optionally substituted substituent selected from the group consisting of C1-C4 alkyl, aryl, and benzyl. |
| Claim: |
74. A compound of claim 73 having the formula: [chemical expression included] |
| Claim: |
75. A compound as claimed by any one of claims 73 and 74 wherein X is C2-C5 alkylene. |
| Claim: |
76. A compound as claimed by any one of claims 73, 74, or 75 wherein A is selected from the group consisting of COOH, and C1-C3alkylnitrile. |
| Claim: |
77. A compound as claimed by any one of claims 73, 74, 75, or 76 wherein R2 is C1-C4 alkyl. |
| Claim: |
78. A compound as claimed by any one of claims 73, 74, 75, 76 or 77, wherein X is C2-C3 alkylene. |
| Claim: |
79. A compound as claimed by any one of claims 73, 74, 75, 76, 77, or 78 wherein R1 is optionally substituted phenyl or benzyl. |
| Claim: |
80. A compound as claimed by any one of claims 73, 74, 75, 76, 77, 78, or 79 wherein R1 is a substituted or unsubstituted group selected from the group consisting of C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl and phenyl. |
| Claim: |
81. A compound of the formula: [chemical expression included] wherein (a) R1 is hydrogen or is selected from the group consisting of a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, and C3-C6 cycloalkylaryl-C0-2-alkyl; (b) R2 is H or a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, sulfonamide, amide, OR10 and C3-C6 cycloalkyl; (c) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (d) Y is C, O, S, NH or a single bond; and (e) E is selected from the group consisting of hydrogen, substituted or unsubstituted selected from the group consisting of (CH2)nCOOR19, C(R3)(R4)A, C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-4alkoxyaryl, C1-4alkoxy C1-4alkyl, aminoaryl, and aminoC1-4alkyl, and wherein (i) n is 0, 1, 2 or 3, (ii) A is an acidic functional group selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole; (iii) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy, and (iv) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, aryl C0-C4 alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (v) R19 is selected from the group consisting of hydrogen, optionally substituted C1-C4alkyl and optionally substituted arylmethyl; (f) R8 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo; (g) R9 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, substituted or unsubstituted aryl, substituted or unsubstituted aryl-C1-C4 alkyl, substituted or unsubstituted heteroaryl, C1-C6 allyl, and OR10; and (h) R10 is independently selected from the group consisting of hydrogen and C1-C4 alkyl. |
| Claim: |
82. A compound as claimed by claim 81 wherein X is C2-C5 alkylene. |
| Claim: |
83. A compound as claimed by any one of claims 81 or 82 wherein A is selected from the group consisting of COOH, and C1-C3alkylnitrile. |
| Claim: |
84. A compound as claimed by any one of claims 81, 82, or 83 wherein R2 is C1-C4 alkyl. |
| Claim: |
85. A compound as claimed by any one of claims 81, 82, 83, or 84, wherein X is C2-C3 alkylene. |
| Claim: |
86. A compound as claimed by any one of claims 81, 82, 83, 84, or 85 wherein R1 is optionally substituted phenyl or benzyl. |
| Claim: |
87. A compound of the formula: [chemical expression included] wherein (a) R1 is hydrogen or is selected from the group consisting of a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, and C3-C6 cycloalkylaryl-C0-2-alkyl; (b) R2 is H or a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, sulfonamide, amide, OR10 and C3-C6 cycloalkyl; (c) X is an optionally substituted C1-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S; (d) Y is C, O, S, NH or a single bond; and (e) E is selected from the group consisting of hydrogen, substituted or unsubstituted selected from the group consisting of (CH2)nCOOR19, C(R3)(R4)A, C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-4alkoxyaryl, C1-4alkoxy C1-4alkyl, aminoaryl, and aminoC1-4alkyl, and wherein (i) n is 0, 1, 2 or 3, (ii) A is an acidic functional group selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole; (iii) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy, and (iv) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, aryl C0-C4 alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl; (v) R19 is selected from the group consisting of hydrogen, optionally substituted C1-C4 alkyl and optionally substituted arylmethyl; (f) R8 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo; (g) R9 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, substituted or unsubstituted aryl, substituted or unsubstituted aryl-C1-C4 alkyl, substituted or unsubstituted heteroaryl, C1-C6 allyl, and OR10; and (h) R10 is independently selected from the group consisting of hydrogen and C1-C4 alkyl. |
| Claim: |
88. A compound as claimed by claim 87 wherein X is C2-C5 alkylene. |
| Claim: |
89. A compound as claimed by any one of claims 87 or 88 wherein A is selected from the group consisting of COOH, and C1-C3alkylnitrile. |
| Claim: |
90. A compound as claimed by any one of claims 87, 88, or 89 wherein R2 is C1-C4 alkyl. |
| Claim: |
91. A compound as claimed by any one of claims 87, 88, 89, or 90, wherein X is C2-C3 alkylene. |
| Claim: |
92. A compound as claimed by any one of claims 87, 88, 89, 90, or 91 wherein R1 is optionally substituted phenyl or benzyl. |
| Claim: |
93. A compound as claimed by claim 32 wherein E is selected from the group consisting of hydrogen, C(R3)(R4)A, substituted or unsubstituted selected from the group consisting of (CH2)n COOH, C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, thio-C1-4-alkyl, thioaryl, C1-14alkoxyaryl, C1-4alkoxy C1-4alkyl, aminoaryl, and aminoC1-4-alkyl. |
| Claim: |
94. (canceled) |
| Current U.S. Class: |
514/384 |
| Current International Class: |
61; 07; 07 |
| رقم الانضمام: |
edspap.20090062358 |
| قاعدة البيانات: |
USPTO Patent Applications |