Claims
- 1. A compound of Formula I
- 2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Y5, Y6, and Y8 are each C(R5), wherein each R5 is independently defined as above.
- 3. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein one of Y5, Y6, and Y8 is N and the other two of Y5, Y6, and Y8 are each C(R5), wherein each R5 is independently defined as above.
- 4. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Q is N(R6)C(O).
- 5. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Q is C≡C.
- 6. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Y3 is C(O).
- 7. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein Y3 and R4 is taken together to form a diradical group:
- 8. The compound according to any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R1 is independently selected from:
Phenyl-(C1-C8 alkylenyl); Substituted phenyl-(C1-C8 alkylenyl); 5- or 6-membered heteroaryl-(C1-C8 alkylenyl); Substituted 5- or 6-membered heteroaryl-(C1-C8 alkylenyl); 8- to 10-membered heterobiaryl-(C1-C8 alkylenyl); and Substituted 8- to 10-membered heterobiaryl-(C1-C8 alkylenyl); and R is independently selected from: Phenyl-(C1-C8 alkylenyl)m; Substituted phenyl-(C1-C8 alkylenyl)m; 5- or 6-membered heteroaryl-(C1-C8 alkylenyl)m; Substituted 5- or 6-membered heteroaryl-(C1-C8 alkylenyl)m; 8- to 10-membered heterobiaryl-(C1-C8 alkylenyl)m; and Substituted 8- to 10-membered heterobiaryl-(C1-C8 alkylenyl)m; wherein m is an integer of 0 or 1; and wherein each group and each substituent is independently selected.
- 9. The compound according to claim 1, selected from:
3-(4-Methanesulfonyl-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid (pyridin-4-ylmethyl)-amide; 3-(4-Methanesulfonyl-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid (pirimidin-5-ylmethyl)-amide; 3-(4-Methanesulfonyl-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid 4-methoxy-benzylamide; 3-(3-Chloro-4-fluoro-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid 4-methoxy-benzylamide; 4-[6-(4-Methoxy-benzylcarbamoyl)-1-methyl-2-oxo-1,4-dihydro-2H-quinazolin-3-ylmethyl]-benzoic acid; 3-(4-Bromo-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid (pyridin-4-ylmethyl)-amide; 1-Methyl-3-(4-methylsulfanyl-benzyl)-2-oxo-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid 3-methoxy-benzylamide; 3-(4-Methanesulfonyl-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrido[3,4-d]pyrimidine-6-carboxylic acid (pyridin-4-ylmethyl)-amide; 3-(3-Chloro-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrido[3,4-d]pyrimidine-6-carboxylic acid (2-methoxy-pyridin-4-ylmethyl)-amide; 3-(4-Cyano-benzyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrido[3,4-d]pyrimidine-6-carboxylic acid (pyridin-4ylmethyl)-amide; 4-[6-(4-Methoxy-benzylcarbamoyl)-1-methyl-2-oxo-1,4-dihydro-2H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-benzoic acid; 4-[6-(4-Methoxy-benzylcarbamoyl)-methyl-2-oxo-1,4-dihydro-2H-pyrido[2,3-d]pyrimidin-3-ylmethyl]-benzoic acid; 1-Methyl-3-(4-methylsulfanyl-benzyl)-2-oxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid (pyridin-3-ylmethyl)-amide; 3-(4-Isopropyl-benzyl)-methyl-2-oxo-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid (pyrimidin-5-ylmethyl)-amide; 1-Methyl-3-pyridin-3-ylmethyl-1,2,3,4-tetrahydro-quinazoline-6-carboxylic acid 4-methyl-benzylamide; {4-[6-Methoxy-benzylcarbamoyl)-1-methyl-1,4-dihydro-2H-pyrido[3,4-d]pyrimidin-3-ylmethyl]-phenyl}-acetic acid; 3-Benzyl-1-methyl-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid benzylamide; 3-Benzyl-3,4-dihydro-quinazoline-6-carboxylic acid 4-chloro-benzylamide; 3-Benzyl-3,4-dihydro-pyrido[3,4-d]pyrimidine-6-carboxylic acid (benzo[1,3]dioxo-5-ylmethyl)-amide; and 3-Benzyl-3,4-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid 3-fluoro-benzylamide; or a pharmaceutically acceptable salt thereof.
- 10. The compound according to claim 1, selected from:
3-(4-Methanesulfonyl-benzyl)-1-methyl-6-(3-phenyl-prop-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 6-(3-Imidazol-1-yl-prop-1-ynyl)-3-(4-methanesulfonyl-benzyl)-1-methyl-3,4-dihydro-1H-quinazolin-2-one; 6-[3-(4-Fluoro-phenyl)-prop-1-ynyl]-3-(4-methanesulfonyl-benzyl)-1-methyl-3,4-dihydro-1H-quinazolin-2-one; 6-[3-(4-Chloro-phenyl)-prop-1-ynyl]-3-(4-methanesulfonyl-benzyl)-1-methyl-3,4-dihydro-1H-quinazolin-2-one; 3-(4-Methanesulfonyl-benzyl)-1-methyl-6-(3-pyridin-4-yl-prop-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 3-(4-Methanesulfonyl-benzyl)-1-methyl-6-(4-phenyl-but-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 3-(4-Methanesulfonyl-benzyl)-1-methyl-6-(3-naphthalen-2-yl-prop-1-ynyl)-3,4-1H-quinazolin-2-one; 3-Benzyl-1-methyl-6-(3-phenyl-prop-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 4-[1-Methyl-2-oxo-6-(3-phenyl-prop-1-ynyl)-1,4-dihydro-2H-quinazolin-3-ylmethyl]-benzoic acid; 3-(4-Chloro-benzyl)-1-methyl-6-(3-phenyl-prop-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 3-(3,4-Difluoro-benzyl)-methyl-6-(3-phenyl-prop-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 3-(4-Methoxy-benzyl)-1-methyl-6-(3-phenyl-prop-1-ynyl)-3,4-dihydro-1H-quinazolin-2-one; 4-[1-Methyl-2-oxo-6-(3-phenyl-prop-1-ynyl) 1,4-dihydro-2H-quinazolin-3-ylmethyl]-benzonitrile; 5-[1-Methyl-2-oxo-6-(3-phenyl-prop-1-ynyl)-1,4-dihydro-2H-quinazolin-3-ylmethyl]furan-2-carboxylic acid; 4-[1-Methyl-6-(3-methyl-3-phenyl-but-1-ynyl)-2-oxo-1,4-dihydro-2H-pyrido[2,3-d]pyrimidin-3-ylmethyl]benzoic acid; 3-Benzyl-1-methyl-6-(3-phenyl-prop-1-ynyl)-1,2,3,4-tetrahydro-pyrido[2,3-d]pyrimidine; 3-[6-(3-Phenyl-prop-1-ynyl)-4H-pyrido[2,3-d]pyrimidin-3-ylmethyl]benzonitrile; and 4-[6-(3,3-Difluoro-3-phenyl-prop-1-ynyl)-4H-quinazolin-3-ylmethyl]-benzoic acid; or a pharmaceutically acceptable salt thereof.
- 11. A pharmaceutical composition, comprising a compound according to claim 1, or a pharmaceutically acceptable salt thereof, admixed with a pharmaceutically acceptable carrier, excipient, or diluent.
- 12. The pharmaceutical composition according to claim 11, comprising a compound according to claim 9 or 10, or a pharmaceutically acceptable salt thereof, admixed with a pharmaceutically acceptable carrier, excipient, or diluent.
- 13. A method for treating osteoarthritis or rheumatoid arthritis, comprising administering to a patient suffering from osteoarthritis or rheumatoid arthritis a nontoxic effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.
- 14. The method according to claim 11, wherein the compound administered is a compound according to claim 9 or 10, or a pharmaceutically acceptable salt thereof.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of priority from U.S. Provisional Patent Application No. 60/403,250, filed Aug. 13, 2002.
Provisional Applications (1)
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Number |
Date |
Country |
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60403250 |
Aug 2002 |
US |