Claims
- 1. A compound of formula 1, or a pharmaceutically acceptable salt thereof:
- 2. A compound of claim 1 wherein a represents double bond.
- 3. A compound of claim 2 wherein X is N, Y is N, and Z is O.
- 4. A compound of claim 3 wherein Ar1 is optionally substituted pyridyl.
- 5. A compound of claim 4 wherein Ar1 is optionally substituted 2-pyridyl.
- 6. A compound as defined in claim 3 wherein the substituent G is bonded to Ar2 and not Ar1.
- 7. A compound as defined in claim 6 wherein Ar2 is selected from the group consisting of: 5 member aryl; 6 member aryl; 5-member heteroaryl; and 6 member heteroaryl.
- 8. A compound of claim 7 wherein Ar2 is selected from the group consisting of: 6 member aryl and 6 member heteroaryl.
- 9. A compound of claim 8 wherein Ar2 is selected from the group consisting of: pyridyl and phenyl, wherein Ar2 is further substituted with one or more substituents selected from the group consisting of R2 and R4.
- 10. A compound of claim 9 wherein Ar2 is phenyl.
- 11. A compound of claim 9 wherein Ar2 is pyridyl.
- 12. A compound as defined in claim 9 wherein G is heteroaryl and wherein G is further substituted with one or more substitutents selected from the group consisting of R2, R3, and R4.
- 13. A compound as defined in claim 12 wherein G is selected from the group consisting of: pyridyl; thiophene; pyrimidine; and furan and G is further substituted with one or more substituents selected from the group consisting of R2 and R4.
- 14. A compound as defined in claim 13 wherein G is selected from the group consisting of 2-pyridine, 3-pyridine and 4-pyridine, wherein G is further substituted with one or more substituents selected from the group consisting of R2 and R4.
- 15. A compound as defined in claim 14 wherein G is 3-pyridine.
- 16. A compound as defined in claim 13 wherein G is 3-thiophene.
- 17. A compound as defined in claim 13 wherein G is pyrimidine.
- 18. A compound as defined in claim 13 wherein G is furan.
- 19. A compound as defined in claim 9 wherein G is substituted aryl, wherein the substituent is R4.
- 20. A compound as defined in claim 19 wherein G is substituted phenyl.
- 21. A compound as defined in claim 20 wherein G is substituted phenyl and R4 is selected from the group consisting of halo, NR2R3, CN, and alkoxy.
- 22. A compound of claim 9 wherein G is (CH2)m—NR2R3 and m is selected from 0 and 1 and R2 and R3 may be independently selected from the group consisting of: H; alkyl; haloalkyl; alkyloxy; alkylamine; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; alkylaryl; alkylheteroaryl; haloaryl; alkyloxyaryl; alkenylaryl; alkenyloxyaryl; and haloheteroaryl.
- 23. A compound as defined in claim 22 wherein R2 and R3 are independently selected from H and C1-3 alkyl.
- 24. A compound of claim 9 wherein G is alkenyl.
- 25. A compound as defined in claim 24 wherein G is selected from the group consisting of: —CH2═CH2 and —CH(CH3)═CH2.
- 26. A compound as defined in claim 9 wherein G is alkynyl.
- 27. A compound of claim 9 wherein G is selected from the group consisting of A-alkenyl and A-alkynyl.
- 28. A compound as defined in claim 27 wherein A is O.
- 29. A compound as defined in claim 28 wherein G is —O—CH2CH═CH2.
- 30. A compound as defined in claim 9 wherein G is —OCH2CH(Cl)CH2Cl.
- 31. A compound as defined in claim 9 wherein G is selected from the group consisting of alkyloxy and A-alkyloxy.
- 32. A compound as defined in claim 31 wherein G is —CH2CH2OH.
- 33. A compound as defined in claim 9 wherein G is —CH2OC(O)H.
- 34. A compound as defined in claim 9 wherein G is haloalkyl.
- 35. A compound as defined in claim 9 wherein G is cycloalkenyl.
- 36. A compound selected from the group consisting of compounds set forth in Table 2, or a pharmaceutically acceptable salt thereof.
- 37. A compound as defined in claim 36 wherein the compound is selected from the group consisting of:
3-(5-Methyl-pyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B57), 3-(5-Cyano-pyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B58), 3-(2-Pyridyl)-5-(5-bromo-2-methoxyphenyl)-1,2,4-oxadiazole (B62), 3-(2-Pyridyl)-5-(5-bromo-2-fluorophenyl)-1,2,4-oxadiazole (B63), 3-(2-Pyridyl)-5-(5-cyano-2-fluorophenyl)-1,2,4-oxadiazole (B64), 3-(2-Pyridyl)-5-(5-bromopyrid-3-yl)-1,2,4-oxadiazole (B65), 3-(2-Pyridyl)-5-(5-chloro-pyrid-3-yl)-1,2,4-oxadiazole (B66), 3-(5-Cyanopyrid-2-yl)-5-(5-bromo-pyrid-3-yl)-1,2,4-oxadiazole (B67), 3-(5-Fluoropyrid-2-yl)-5-(5-bromo-pyrid-3-yl-1,2,4-oxadiazole (B68), 3-(2-Pyridyl)-5-(2-thiomethoxy-pyrid-3-yl)]-1,2,4-oxadiazole (B69), 3-(2-Pyridyl)-5-(5-methylpyrid-3-yl)-1,2,4-oxadiazole (B70), 3-(2-Pyridyl)-5-(5-methoxypyrid-3-yl)-1,2,4-oxadiazole (B72), 3-(2-Pyridyl)-5-(3-cyano-5-methylphenyl)-1,2,4-oxadiazole (B73), 3-(2-Pyridyl)-5-(3-fluoro-5-bromophenyl)-1,2,4-oxadiazole (B74), 3-(2-Pyridyl)-5-(3-iodo-5-bromophenyl)-1,2,4-oxadiazole (B75), 3-(5-Fluoro-2-pyridyl)-5-(3-fluoro-5-bromophenyl)-1,2,4-oxadiazole (B76), 3-(2-Pyridyl)-5-(3-iodo-5-(methylphenylester)-1,2,4-oxadiazole (B78), 3-(2-Pyridyl)-5-(3-methoxy-5-(methoxycarbonyl)phenyl)-1,2,4-oxadiazole (B79), 3-(2-Pyridyl)-5-(3-bromo-5-cyanophenyl)-1,2,4-oxadiazole (B80), 3-(2-Pyridyl)-5-(5-cyano-3-iodophenyl)-1,2,4-oxadiazole (B81), 3-(5-Cyano-2-pyridyl)-5-(3-bromophenyl)-1,2,4-oxadiazole (B59), 3-(5-Cyano-2-pyridyl)-5-(3-cyano-5-fluorophenyl)-1,2,4-oxadiazole (B60), 3-(5-Cyano-2-pyridyl)-5-(3-bromo-5-fluorophenyl)-1,2,4-oxadiazole (B61), 3-(2-Pyridyl)-5-(5-cyano-2-methoxyphenyl)-1,2,4-oxadiazole (B97), 3-(2-Pyridyl)-5-(2-cyano-5-methoxyphenyl)-1,2,4-oxadiazole (B98), 3-(2-Pyridyl)-5-(5-cyano-pyrid-3-yl)-1,2,4-oxadiazole (B99), 3-(2-Pyridyl)-5-(3-cyano-5-(methoxycarbonyl)phenyl)-1,2,4-oxadiazole (B100), 3-(2-Pyridyl)-5-(5-phenyl-pyrid-3-yl)-1,2,4-oxadiazole (B118), 3-(2-Pyridyl)-5-(3-cyano-5-methoxyphenyl)-1,2,4-oxadiazole (B134), 3-(2-Pyridyl)-5-(3-cyano-5-hydroxyphenyl)-1,2,4-oxadiazole (B137), 3-(2-Pyridyl)-5-(3-cyano-5-propoxyphenyl)-1,2,4-oxadiazole (B141), 2-(3-Cyanophenyl)-4-(pyridin-2-yl)-1,3-thiazole (B146), 2-(3-Bromo-5-iodophenyl)-4-pyridin-2-yl)-1,3-oxazole (B147), 2-(2-Pyridyl)-5-(3-iodophenyl)-1,3,4-oxadiazole (B148), 2-(2-Pyridyl)-5-(3-cyanophenyl)-1,3,4-oxadiazole (B149), 2-(2-Pyridyl)-5-(3-cyanophenyl)-1,3,4-triazole (B150), 3-(5-Chloropyrid-2-yl)-5-(3-cyano-5-fluorophenyl)-1,2,4-oxadiazole (B83), 3-(5-Chloropyrid-2-yl)-5-(3-cyano-5-chlorophenyl)-1,2,4-oxadiazole (B84), 3-(5-Chloropyrid-2-yl)-5-(3-chloro-5-fluorophenyl)-1,2,4-oxadiazole (B85), 3-(5-Chloropyrid-2-yl)-5-(3-cyano-5-methoxyphenyl)-1,2,4-oxadiazole (B86), 3-(5-Fluoropyrid-2-yl)-5-(3-cyano-5-chlorophenyl)-1,2,4-oxadiazole (B87), 3-(5-Fluoropyrid-2-yl)-5-(3-fluoro-5-chlorophenyl)-1,2,4-oxadiazole (B88), 3-(5-Fluoropyrid-2-yl)-5-(3-cyano-5-methoxyphenyl)-1,2,4-oxadiazole (B89), 3-(5-Cyanopyrid-2-yl)-5-(3-cyano-5-chlorophenyl)-1,2,4-oxadiazole (B90), 3-(5-Cyanopyrid-2-yl)-5-(3-fluoro-5-chlorophenyl)-1,2,4-oxadiazole (B91) 3-(5-Cyanopyrid-2-yl)-5-(3-cyano-5-methoxyphenyl)-1,2,4-oxadiazole (B92), 3-(5-Fluoropyrid-2-yl)-5-(3,5-di-cyanophenyl)-1,2,4-oxadiazole (B93), 3-(3-(4-Dimethylaminobutoxy)-pyrid-2-yl)-5-(3-cyano-5-fluorophenyl)-1,2,4-oxadiazole (B94), 3-(3-(5-Dimethylaminopentyloxy)-pyrid-2-yl)-5-(3-Cyano-5-fluorophenyl)-1,2,4-oxadiazole (B95), and [3-(3-(6-Dimethylaminohexyloxy)-pyrid-2-yl)-5-(3-cyano-5-fluorophenyl)-1,2,4-oxadiazole (B96).
- 38. A compound as defined in claim 36 wherein the compound is selected from the group consisting of:
3-(2-Pyridyl)-5-(3-allyloxy-5-(methoxycarbonyl)phenyl)-1,2,4-oxadiazole (B77), 3-(2-Pyridyl)-5-(3-N,N-dimethylaminophenyl)-1,2,4-oxadiazole (B82), 3-(2-Pyridyl)-5-(3-cyano-5-(4-pyridyl)phenyl)-1,2,4-oxadiazole (B101), 3-(2-Pyridyl)-5-[2-methoxy-5-(4-pyridyl)phenyl]-1,2,4-oxadiazole (B102), 3-(2-pyridyl)-5-[2-fluoro-5-(4-pyridyl)phenyl]-1,2,4-oxadiazole (B103), 3-(2-Pyridyl)-5-(3-fluoro-5-(4-pyridyl)phenyl)-1,2,4-oxadiazole (B104), 3-(2-Pyridyl)-5-(3-fluoro-5-(3-pyridyl)phenyl)-1,2,4-oxadiazole (B105), 3-(2-Pyridyl)-5-[2-fluoro-5-(3-pyridyl)phenyl]-1,2,4-oxadiazole (B106), 3-(2-Pyridyl)-5-[2-methoxy-5-(3-pyridyl)phenyl]-1,2,4-oxadiazole (B107), 3-(2-Pyridyl)-5-(3-cyano-5-(3-pyridyl)phenyl)-1,2,4-oxadiazole (B108), 3-(5-Fluoro-2-pyridyl)-5-(3-fluoro-5-(3-pyridyl)phenyl)-1,2,4-oxadiazole (B109), 3-(2-Pyridyl)-5-[5-(3-pyridyl-pyrid-3-yl)]-]-1,2,4-oxadiazole (B111), 3-(5-Fluoropyrid-2-yl)]-5-[5-(3-pyridyl-pyrid-3-yl)]-]-1,2,4-oxadiazole (B110), 3-(5-Cyanopyrid-2-yl)-5-(3-(pyrid-3-yl)phenyl)-1,2,4-oxadiazole (B112), 3-(5-Cyanopyrid-2-yl)-5-(3-fluoro-5-(pyrid-3-yl)phenyl)-1,2,4-oxadiazole (B113), 3-(2-Pyridyl)-5-(3-cyano-5-(2-pyridyl)phenyl)-1,2,4-oxadiazole (B124), 3-(2-Pyridyl)-5-[2-methoxy-5-(2-pyridyl)phenyl]-1,2,4-oxadiazole (B125), 3-(2-Pyridyl)-5-[2-fluoro-5-(2-pyridyl)phenyl]-1,2,4-oxadiazole (B126), 3-(2-Pyridyl)-5-[(3-(3-fuorophenyl)-5-fluorophenyl)]-1,2,4-oxadiazole (B114), 3-(2-Pyridyl)-5-(3-cyano-5-(3-thiophene)phenyl)-1,2,4-oxadiazole (B115), 3-(2-Pyridyl)-5-[5-(3-thienyl)-pyrid-3-yl]-1,2,4-oxadiazole (B116), 3-(2-Pyridyl)-5-[5-(3-furyl)-pyrid-3-yl]-1,2,4-oxadiazole (B117), 3-(2-Pyridyl)-5-[5-(3-methoxyphenyl)-pyrid-3-yl]-1,2,4-oxadiazole (B119), 3-(2-Pyridyl)-5-(3-cyano-5-(5-pyrimidyl)phenyl)-1,2,4-oxadiazole (B120), 3-(2-Pyridyl)-5-(3-cyano-5-(3-aminophenyl)phenyl)-1,2,4-oxadiazole (B121), 3-(2-Pyridyl)-5-(3-cyano-5-(3-fluorophenyl) phenyl)-1,2,4-oxadiazole (B122), 3-(2-Pyridyl)-5-[5-(5-pyrimidyl)-pyrid-3-yl]-1,2,4-oxadiazole (B123), 3-(2-Pyridyl)-5-(3-aminomethyl-5-cyanophenyl)-1,2,4-oxadiazole (B127), 3-(2-Pyridyl)-5-[5[(2-propenyl)-pyrid-3-yl]-1,2,4-oxadiazole (B128), 3-(2-Pyridyl)-5-(3-cyano-5-vinylphenyl)-1,2,4-oxadiazole (B129), 3-(2-Pyridyl)-5-(3-cyano-5-(2-hydroxyethyl)phenyl)-1,2,4-oxadiazole (B130), 3-(2-Pyridyl)-5-(3-cyano-5-(2,3-dichloropropoxy)phenyl)-1,2,4-oxadiazole (B131), 3-(2-Pyridyl)-5-(3-allyloxy-5-carboxyphenyl)-1,2,4-oxadiazole (B135), 3-(2-Pyridyl)-5-(3-allyloxy-5-cyanophenyl)-1,2,4-oxadiazole (B136), 3-(2-Pyridyl)-5-(5-cyano-3-[3-hydroxypropyn-1-yl] phenyl)-1,2,4-oxadiazole (B142), 3-(2-Pyridyl)-5-(2-N-methylaminophenyl)-1,2,4-oxadiazole (B144), and 3-(2-Pyridyl)-5-[5-(3-N-benzyl-1,2,5,6,tetrahydropyridine)-pyrid-3-yl]-1,2,4-oxadiazole (B143).
- 39. A compound of Formula I, or a pharmaceutically acceptable salt thereof:
- 40. A compound as defined in claim 39 wherein represents a double bond.
- 41. The compound of claim 40, wherein X is N, Y is N, and Z is O.
- 42. The compound of claim 41 wherein Ar1 is 2-pyridyl and Ar2 is phenyl.
- 43 The compound of claim 42, wherein G is selected from the group consisting of —OCH3, —CF3, —Cl, —F, —Br, —CH3, —NO2, —OCF3, —SCH3, and —CN.
- 44. The compound of claim 42, wherein Ar1 is 2-pyridyl and substituted with one or more G, wherein G is selected from the group consisting of —OCH3, —CF3, —F, and —Cl.
- 45. The compound of claim 41, wherein Ar1 is 2-pyridyl and Ar2 is 1-naphthyl.
- 46. The compound of claim 39, wherein X is N, Y is C, and Z is O.
- 47. The compound of claim 46, wherein Ar1 is 2-pyridyl and is substituted with one or more G selected from the group consisting of —OCH3, —CF3, —F, and —Cl, and wherein Ar2 is phenyl and is substituted with one or more G selected from the group consisting of —OCH3, —CF3, —Cl, —F, —Br, —CH3, —NO2, —OCF3, —SCH3, and —CN.
- 48. A compound selected from the group consisting of compounds set forth in Table 1, or a pharmaceutically acceptable salt thereof, where the compound is not compound B4.
- 49. A compound as defined in claim 48, wherein the compound is selected from the group consisting of:
3-(2-pyridyl)-5-(3-methoxyphenyl)-1,2,4-oxadiazole (B1), 3-(2-pyridyl)-5-(3,5-dichlorophenyl)-1,2,4-oxadiazole (B2), 3-(2-pyridyl)-5-(3-chlorophenyl)-1,2,4-oxadiazole (B3), 3-(2-pyridyl)-5-(2-chlorophenyl)-1,2,4-oxadiazole (B5), 3-(2-pyridyl)-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (B6), 3-(2-pyridyl)-5-(3-methylphenyl)-1,2,4-oxadiazole (B9), 3-(2-pyridyl)-5-(1-naphthyl)-1,2,4-oxadiazole (B10), 3-(2-pyridyl)-5-[3-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole (B11), 3-(2-pyridyl)-5-(2,3-difluorophenyl)-1,2,4-oxadiazole (B16), 3-(2-pyridyl)-5-(2,5-difluorophenyl)-1,2,4-oxadiazole (B17), 3-(2-pyridyl)-5-(3,5-difluorophenyl)-1,2,4-oxadiazole (B18), 3-(2-pyridyl)-5-(3-nitrophenyl)-1,2,4-oxadiazole (B19), 3-(2-pyridyl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B21), 3-(2-pyridyl)-5-(3-bromophenyl)-1,2,4-oxadiazole (B22), 3-(2-pyridyl)-5-(3,5-dimethoxyphenyl)-1,2,4-oxadiazol (B23), 3-(2-pyridyl)-5-(2,3-dichlorophenyl)-1,2,4-oxadiazole (B25), 3-(2-pyridyl)-5-(3-chloro-5-cyanophenyl)-1,2,4-oxadiazole (B26), 3-(2-pyridyl)-5-(3-fluoro-5-cyanophenyl)-1,2,4-oxadiazole (B27), 3-(2-pyridyl)-5-(3-chloro-5-fluorophenyl)-1,2,4-oxadiazole (B28), 3-(5-chloropyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B29) 3-(5-fluoropyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B30), 3-(5-fluoropyrid-2-yl)-5-(3-cyano-5-fluorophenyl)-1,2,4-oxadiazole (B31), 3-(3-fluoropyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B32), 3-(5-fluoropyrid-2-yl)-5-(3,5-dimethoxyphenyl)-1,2,4-oxadiazole (B33), 3-(5-methoxypyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B34), 3-(2-quinolinyl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B35), 3-(3-chloro-5-trifluoromethylpyrid-2-yl)-5-(3-cyanophenyl)-1,2,4-oxadiazole (B36), 3-(2-pyridyl)-5-(5-chloro-2-methoxyphenyl)-1,2,4-oxadiazole (B37), 3-(2-pyridyl)-5-(2-chloro-5-methylthiophenyl)-1,2,4-oxadiazole (B39), 3-(2-pyridyl)-5-(2-bromo-5-methoxyphenyl)-1,2,4-oxadiazole (B42), 3-(2-pyridyl)-5-(2,5,6-trifluorophenyl)-1,2,4-oxadiazole (B45), 2-(3-chlorophenyl)-4-(2-pyridyl)-1,3-oxazole (B50), 2-(3-bromophenyl)-4-(2-pyridyl)-1,3-oxazole (B51), and 2-(3-cyanophenyl)-4-(2-pyridyl)-1,3-oxazole (B52).
- 50. A compound selected from the group consisting of:
2-(3,5-dichlorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-methoxyphenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2-chlorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-trifluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-methylphenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(1-naphthyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-trifluoromethoxyphenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2,3-difluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2,5-difluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3,5-difluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3,5-dimethoxyphenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2,3-dichlorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-chloro-5-cyanophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-fluoro-5-cyanophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-chloro-5-fluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-cyanophenyl)-4-(5-chloropyrid-2-yl)-1,3-oxazole, 2-(3-cyanophenyl)-4-(5-fluoropyrid-2-yl)-1,3-oxazole, 2-(3-cyano-5-fluorophenyl)-4-(5-fluoropyrid-2-yl)-1,3-oxazole, 2-(3-cyanophenyl)-4-(3-fluoropyrid-2-yl)-1,3-oxazole, 2-(3,5-dimethoxyphenyl)-4-(5-floropyrid-2-yl)-1,3-oxazole, 2-(3-cyanophenyl)-4-(5-methoxypyrid-2-yl)-1,3-oxazole, 2-(3-cyanophenyl)-4-(2-quinolinyl)-1,3-oxazole, 2-(3-cyanophenyl)-4-(3-chloro-5-trifluoromethylpyrid-2-yl)-1,3-oxazole, 2-(5-chloro-2-methoxyphenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2-chloro-5-methylthiophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2-bromo-5-methoxyphenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(2,5,6-trifluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-[3-chlorophenyl]-4-[pyridin-2-yl]-1,3-oxazole, 2-(2,5,6-trifluorophenyl)-4-(2-pyridyl)-1,3-oxazole, 2-(3-nitrophenyl)-4-(2-pyridyl-1,3-oxazole, and pharmaceutically acceptable salts thereof.
- 51. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective, non-toxic, amount of a compound of Formula I:
thereof: 599wherein represents a double or single bond; X, Y, and Z are independently selected from the group consisting of: N; O; S; and CR1 and at least one of X, Y, and Z is a heteroatom;
wherein R1 is selected from the group consisting of: H; alkyl; —CF3; —OR2; ——SR2; —NR2R3; ═O; ═S; ═NR2; and ═CR2R3; and
wherein R2 and R3 may be independently selected from the group consisting of: H; alkyl; haloalkyl; alkyloxy; alkylamine; cycloalkyl; heterocycloalkyl; aryl; heteroaryl; alkylaryl; alkylheteroaryl; haloaryl; alkyloxyaryl; alkenylaryl; alkenyloxyaryl; and haloheteroaryl; and Ar1 and Ar2 are independently selected from the group consisting of: aryl and heteroaryl and at least one of Ar1 and Ar2 is substituted with at least one substituent G;
wherein G is selected from the group consisting of: haloalkyl; heteroaryl; cycloalkene; alkenyl; alkynyl; A-alkenyl; A-alkynyl; alkyloxy; A-alkyloxy; —R2OR3; —R2OC(O)R3; (CH2)m—NR2R3; —OCH2CH(Cl)CH2Cl;
and substituted aryl wherein the aryl substituent is R4, and
wherein A is a linker selected from the group consisting of: CH2; O; NH; S; SO; SO2; NSO2; —OSO2; and —C(NR2)NR3; m is selected from 0 and 1; and R4 is selected from the group consisting of: halo; —OR2; —SR2; —SOR2; —SO2R2; —SO2NR2R3; —R2OR3; —R2SR3; —OCOR2; ——OCONR2R3; —NR2COR3; —NR2CO2R3; —CN; —NO2; —C(NR2)NR3; —CO2R2R3; —CONR2R3; —C(O)R2; —CH(OR2)R3; —CH2(OR2); —A—(CH2)m—NR2R3; NR2R3; aryl; aralkyl; heteroaryl; and heteroaralkyl; and Ar1, Ar2, and the substituent G are optionally further substituted with one or more substituents selected independently from the group consisting of R2 and R4,
with the proviso that when represents a double bond, then either of Ar1 or Ar2 is pyridyl and the compound is not:
3-(2-Pyridyl)-5-(2-chlorophenyl)-1,2,4-oxadiazole, 3-(4-Pyridyl)-5-(2-chlorophenyl)-1,2,4-oxadiazole, 3-(4-Pyridyl)-5-(2-chlorophenyl)-1,2,4-oxadiazole, 3-(4-Pyridyl)-5-(4-chlorophenyl)-1,2,4-oxadiazole, 3-(2-chlorophenyl)-5-(4-pyridyl)-1,2,4-oxadiazole, 3-(2-ethoxyphenyl)-5-(3-pyridyl)-1,2,4-oxadiazole, 3-styryl-5-(4-pyridyl)-1,2,4-oxadiazole, 3-(3-Pyridyl)-5-(4-aminophenyl)-1,2,4-oxadiazole, 3-(3-Pyridyl)-5-(4-chlorophenoxymethyl)-1,2,4-oxadiazole, 3-(4-Pyridyl)-5-(4-chlorophenoxymethyl)-1,2,4-oxadiazole, 3-(4-Pyridyl)-5-(3-pyridyl)-1,2,4-oxadiazole, 3-(4-Pyridyl)-5-(4-pyridyl)-1,2,4-oxadiazole, 3-(2-ethyl-4-pyridyl)-5-(2-hydroxyphenyl)-1,2,4-oxadiazole, 3-(2-ethyl-4-pyridyl)-5-(4-pyridyl)-1,2,4-oxadiazole, 3-(2-ethyl-4-pyridyl)-5-(2-ethyl-4-pyridyl)-1,2,4-oxadiazole, 3-(2-ethyl-4-pyridyl)-5-(4-chlorophenylmethyl)-1,2,4-oxadiazole, 3-(2-pyridyl)-5-(4-nitrophenyl)-1,2,4-oxadiazole, 3-(2-pyridyl)-5-(4-aminophenyl)-1,2,4-oxadiazole, 3-(3-pyridyl)-5-(4-nitrophenyl)-1,2,4-oxadiazole, 3-(3-pyridyl)-5-(4-aminophenyl)-1,2,4-oxadiazole, 3-(2-pyridyl)-5-{2-[2-(N,N,dimethylamino)-ethyl]oxyphenyl}-1,2,4-oxadiazole, 3-(4-pyridyl)-5-{2-[2-(N,N,dimethylamino)-ethyl]oxyphenyl}-1,2,4-oxadiazole2-(2-pyridyl)-5-[3-(3-methoxy-4-cyclopentoxy)phenyl]-furan, 2-(3-pyridyl)-5-[3-(3-methoxy-4-cyclopentoxy)phenyl]-furan, or 2-(4-pyridyl)-5-[3-(3-methoxy-4-cyclopentoxyphenyl)]-furan.
- 52. A method for treating a disease associated with Group I mGluR activation comprising the step of administering to a patient in need of such treatment a pharmaceutical composition as defined in claim 51.
- 53. A method according to claim 52 wherein the disease is a disease associated with mGluR activation.
- 54. A method according to claim 53 wherein the disease is a neurological disease.
- 55. A method according to claim 53 wherein the disease is a psychiatric disease.
- 56. A method according to claim 53 wherein the disease is selected from the group consisting of stroke, head trauma, anoxic injury, ischemic injury, hypoglycemia, epilepsy, pain, migraine headaches, Parkinson's disease, senile dementia, Huntington's Chorea, anxiety, and Alzheimer's disease.
- 57. A pharmaceutical composition comprising a therapeutically effective, non-toxic, amount of a compound of claim 39 and a pharmaceutically acceptable carrier.
- 58. A method for treating a disease associated with Group I mGluR activation comprising the step of administering to a patient in need of such treatment a pharmaceutical composition as defined in claim 57.
- 59. A method according to claim 58 wherein the disease is a disease associated with mGluR activation.
- 60. A method according to claim 59 wherein the disease is a neurological disease.
- 61. A method according to claim 59 wherein the disease is a psychiatric disease.
- 62. A method according to claim 59 wherein the disease is selected from the group consisting of stroke, head trauma, anoxic injury, ischemic injury, hypoglycemia, epilepsy, pain, migraine headaches, Parkinson's disease, senile dementia, Huntington's Chorea, anxiety, and Alzheimer's disease.
- 63. A method according to claim 59 wherein the disease is selected from the group consisting of schizophrenia and depression.
- 64. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of compounds as set forth in the following table:
- 65. A compound of formula II, or a pharmaceutically acceptable salt thereof:
- 66. A compound as defined in claim 65 wherein represents a double bond.
- 67. A compound as defined in claim 66 wherein X2 is N and Y2 is N.
- 68. A compound as defined in claim 67 wherein Ar3 and Ar4 are independently selected from the group consisting of optionally substituted pyridyl and optionally substituted phenyl wherein Ar3 and Ar4 are optionally substituted with a substituent selected from G2, R6, and R8.
- 69. A compound as defined in claim 68 wherein Ar3 and Ar4 are independently selected from the group consisting of 2-pyridyl, and optionally substituted phenyl wherein the substituent is selected from the group consisting of: aryl; heteroaryl; alkyl; halo, cyano, nitro, hydroxy, and alkoxy.
- 70. A compound selected from the group consisting of:
4-(3-Cyanophenyl)-1-(2-pyridyl)-1H-imidazole (B151) and 1-(3-Cyanophenyl)-4-(2-pyridyl)-1H-imidazole (B152).
- 71. A pharmaceutical composition comprising a therapeutically effective, non-toxic, amount of a compound of claim 65 and a pharmaceutically acceptable carrier.
- 72. A method for treating a disease associated with Group I mGluR acctivation comprising the step of administering to a patient in need of such treatment a pharmaceutical composition as defined in claim 71.
- 73. A method according to claim 72 wherein the disease is a disease associated with mGluR activation.
- 74. A method according to claim 73 wherein the disease is a neurological disease.
- 75. A method according to claim 73 wherein the disease is a psychiatric disease.
- 76. A method according to claim 73 wherein the disease is selected from the group consisting of stroke, head trauma, anoxic injury, ischemic injury, hypoglycemia, epilepsy, pain, migraine headaches, Parkinson's disease, senile dementia, Huntington's Chorea, anxiety, and Alzheimer's disease.
- 77. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective, non-toxic, amount of a compound of Formula I:
- 78. A method for treating a disease associated with Group I mGluR activation comprising the step of administering to a patient in need of such treatment a pharmaceutical composition as defined in claim 77.
- 79. A method according to claim 78 wherein the disease is a disease associated with mGluR activation.
- 80. A method according to claim 79 wherein the disease is a neurological disease.
- 81. A method according to claim 79 wherein the disease is a psychiatric disease.
- 82. A method according to claim 79 wherein the disease is selected from the group consisting of stroke, head trauma, anoxic injury, ischemic injury, hypoglycemia, epilepsy, pain, migraine headaches, Parkinson's disease, senile dementia, Huntington's Chorea, anxiety, and Alzheimer's disease.
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This application is a continuation-in-part of International Patent Application PCT US00/22618, filed on Aug. 18, 2000, which claims priority to U.S. Provisional Patent Application Ser. No. 60/149,464, filed on Aug. 19, 1999; and a continuation-in-part of U.S. Provisional Application Ser. No. 60/269,847, filed Feb. 21, 2001.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60149464 |
Aug 1999 |
US |
|
60269847 |
Feb 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
PCT/US00/22618 |
Aug 2000 |
US |
Child |
10076618 |
Feb 2002 |
US |