Patent EA-004602-B1 (EA)
Title: Diaryl-enynes
Inventor: EGLE IAN
IPC: C07C323/32
Filed: 2000-11-01
Abstract: 1. A compound of Formula I: wherein: Ar1 and Ar2 are independently selected aryl groups, optionally substituted with up to five substituents independently selected from the group consisting of alkyl, alkoxy, cycloalkyl, cycloalkyloxy, heterocycloalkyl, heterocycloalkyloxy, alkanoyl, thioalkyl, aralkyl, aralkyloxy, aryloxyalkyl, aryloxyalkoxy, cycloalkyl, substituted alkyl, cycloalkyloxy-substituted alkyl, cycloalkyl-substituted alkoxy, cycloalkyloxy-substituted alkoxy, heterocycloalkyl-substituted alkyl, heterocycloalkyloxy-substituted alkyl, heterocycloalkyl-substituted alkoxy, heterocycloalkyloxy-substituted alkoxy, thioaryl, aralkylthio, thioaryl-alkyl, aralkylthioalkyl, halo, NO2, CF3, CN, OH, alkylenedioxy, SO2NRR', NRR', CO2R (where R and R' are independently selected from the group consisting of H and alkyl), and a second aryl group, which may be substituted as above; R1 is selected from the group consisting of H and alkyl; R2 is selected from the group consisting of H, alkyl and; R3 is selected from the group consisting of CO2R, CONRR', CONH (OH), COSR, SO2NRR', PO (OR) (OR') and tetrazolyl, wherein R and R' are independently selected from the group consisting of H and alkyl; wherein said alkyl and cycloalkyl groups comprise from 1 to 6 and from 3 to 8 carbon atoms respectively, and a heterocycloalkyl group is a ring comprising from 3 to 8 members; and a salt, solvate or hydrate thereof. 2. A compound according to claim 1, wherein Ar1 is an aryl group, optionally substituted with up to three substituents independently selected from halo, NO2, CF3, CN, OH, SO2NRR', NRR', CO2R (where R and R' are independently selected from the group consisting of H and alkyl), and a substituent of the formula R"-(X)n- wherein n is 0 or 1; X is CH2 or a heteroatom; R" is H, alkyl and aryl substituted optionally with up to three substituents selected from alkyl, halo, NO2, CF3, CN, OH, SO2NRR', NRR' and CO2R, wherein R and R' are independently selected from the group consisting of H and alkyl. 3. A compound according to claim 2, wherein Ar1 is phenyl. 4. A compound according to claim 2, wherein Ar1 is substituted phenyl. 5. A compound according to claim 2, wherein Ar1 is phenyl substituted by an optionally substituted five-membered aryl group. 6. A compound according to claim 5, wherein said five-membered aryl group incorporates at least one heteroatom. 7. A compound according to claim 6, wherein Ar1 said five membered aryl group is a 3-furyl group. 8. A compound according to claim 7, wherein Ar1 is -(3-furyl) phenyl. 9. A compound according to claim 7, wherein Ar1 is 4-(3-thienyl) phenyl. 10. A compound according to claim 7, wherein Ar1 is 4-(1-pyrrolyl) phenyl. 11. A compound according to claim 4, wherein Ar1 is lower alkyl substituted phenyl. 12. A compound according to claim 11, wherein Ar1 is 4-(alkyl)-phenyl. 13. A compound according to claim 12, wherein said alkyl group is selected from methyl, ethyl, n-propyl, isopropyl and n-butyl. 14. A compound according to claim 1, wherein Ar1 is alkylenedioxy-phenyl. 15. A compound according to claim 14, wherein Ar1 is methylendioxy-phenyl. 16. A compound according to claim 15, wherein Ar1 is 3,4-methylenedioxy-phenyl. 17. A compound according to claim1, wherein Ar1 is a benzo-fused aromatic group. 18. A compound according to claim 17, wherein Ar1 is carbocyclic. 19. A compound according to claim 18, wherein Ar1 is naphthyl. 20. A compound according to claim 19, wherein Ar1 is 2-naphthyl. 21. A compound according to any one of claims 1-20, wherein Ar2 is an aryl group optionally substituted with up to three substituents independently selected from halo, haloalkyl, alkyl, haloalkoxy, and alkoxy. 22. A compound according to claim 21 in which Ar2 is unsubstituted aryl. 23. A compound according to claim 22 in which Ar2 is phenyl. 24. A compound according to claim 21, wherein Ar2 is substituted phenyl. 5. A compound according to claim 24, wherein Ar2 is halo-substituted phenyl. 26. A compound according to claim 25, wherein Ar2 is phenyl substituted by chloro or fluoro. 27. A compound according to any one of claims 1-26, wherein R1 is H. 28. A compound according to any one of claims 1-27, wherein R2 is H. 29. A compound according to claim 28, wherein R3 is methyl. 30. A compound according to any one of claims 1-28, wherein R3 is COOR. 31. A compound according to claim 30, wherein R3 is COOH. 32. A compound according to claim1, selected from: N-(5-(4-Fluorophenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(2-Fluorophenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(2,4-Difluorophenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(3-Nitrophenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Nitrophenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(3-Phenyl-5-(2-thiomethylphenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Chlorophenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(3,5-Bis (trifluoromethyl) phenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(3,5-Diphenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-diphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-trifluoromethylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-benzylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-ethylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-n-propylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-n-butylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-n-pentylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-phenoxyphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(1-naphthyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-methyphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(3-isopropylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(2-naphthyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(3,4-dimethylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(2-isopropylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(3,4-methylenedioxyphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-pyrrolylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-trifluoromethoxyphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(3,4-dimethoxyphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(3-Phenyl-5-(4-thiomethylphenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Methylphenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(3-Phenyl-5-(3-thiophene)-2-penten-4-yn-1-yl)-sarcosine N-(3-Phenyl-5-(4-tbutylphenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-(3-furyl)-phenyl)-3-phenyl-2-penten-4yn-1-yl)-sarcosine N-(5-(4-(3-thiophene)-phenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(4-(trifluoromethyl) phenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(4-fluorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(2-fluorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-t-Butylphenyl)-3-(2-fluorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(4-chlorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-t-Butylphenyl)-3-(4-chlorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(2-chlorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-t-Butylphenyl)-3-(2-chlorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(3-fluorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(3-thienyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Isopropylphenyl)-3-(4-methoxyphenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(3,4-Methylenedioxyphenyl)-3-(3-fluorophenyl)-2-penten-4-yn-1-yl)-sarcosine N-(5-(4-Ethylphenyl)-3-(2-chlorophenyl)-2-penten-4-yn-1-yl)-sarcosine, and N-(5-(4-Propylphenyl)-3-(2-chlorophenyl)-2-penten-4-yn-1-yl)-sarcosine. 33. The compound N-(5-(4-(3-Furyl)-phenyl)-3-phenyl-2-penten-4-yn-1-yl)-sarcosine. 34. A composition comprising a compound according to any one of claims 1-33, and a carrier. 35. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1-33, and a pharmaceutically acceptable carrier. 36. A method for treating a patient having a medical condition for which a glycine transport inhibitor is indicated, comprising the step of administering to the patient a pharmaceutical composition as defined in claim 35. 37. A method according to claim 36 in which the medical condition is schizophrenia. 38. A method according to claim 36 in which the medical condition is cognitive dysfunction. 39. A method according to claim 9 in which the medical condition is Alzheimer's disease.