Claims
- 1. A compound of Formula I
- 2. A compound of Formula I′
- 3. Compound of claim 2 wherein R1 is selected from unsubstituted or substituted 9-10 membered bicyclic saturated or partially saturated heterocyclyl; and wherein Ra is H; and pharmaceutically acceptable derivatives thereof.
- 4. Compound of claim 3 wherein R1 is selected from 1,2-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 2,3-dihydro-1H-indolyl, tetrahydroquinolinyl, and 1,4-benzodioxanyl; wherein R1 is unsubstituted or substituted with one or more substituents selected from bromo, chloro, fluoro, iodo, nitro, amino, cyano, aminoethyl, Boc-aminoethyl, hydroxy, oxo, aminosulfonyl, 4-methylpiperazinylsulfonyl, cyclohexyl, phenyl, phenylmethyl, morpholinylmethyl, 1-methylpiperazin-4-ylmethyl, 1-methylpiperazin-4-ylpropyl, morpholinylpropyl, piperidin-1-ylmethyl, 1-methylpiperidin-4-ylmethyl, 2-methyl-2-(1-methylpiperidin-4-yl)ethyl, morpholinylethyl, 1-(4-morpholinyl)-2,2-dimethylpropyl, piperidin-4-ylethyl, 1-Boc-piperidin-4-ylethyl, piperidin-1-ylethyl, 1-Boc-piperidin-4-ylethyl, piperidin-4-ylmethyl, 1-Boc-piperidin-4-ylmethyl, piperidin-4-ylpropyl, 1-Boc-piperidin-4-ylpropyl, piperidin-1-ylpropyl, pyrrolidin-1-yl-propyl, pyrrolidin-2-ylpropyl, 1-Boc-pyrrolidin-2-yl-propyl, pyrrolidin-1-ylmethyl, pyrrolidin-2-ylmethyl, 1-Boc-pyrrolidin-2-ylmethyl, pyrrolidinylpropenyl, pyrrolidinylbutenyl, fluorosulfonyl, methylsulfonyl, methylcarbonyl, Boc, piperidin-1-ylmethylcarbonyl, 4-methylpiperazin-1-ylcarbonylethyl, methoxycarbonyl, aminomethylcarbonyl, dimethylaminomethylcarbonyl, 3-ethoxycarbonyl-2-methyl-fur-5-yl, 4-methylpiperazin-1-yl, 4-methyl-1-piperidyl, 1-Boc-4-piperidyl, piperidin-4-yl, 1-methylpiperidin-4-yl, 1-methyl-(1,2,3,6-tetrahydropyridyl), imidazolyl, morpholinyl, 4-trifluoromethyl-1-piperidinyl, hydroxybutyl, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, trifluoromethyl, pentafluoroethyl, nonafluorobutyl, dimethylaminopropyl, 1,1-di(trifluoromethyl)-1-hydroxymethyl, 1,1-di(trifluoromethyl)-1-(piperidinylethoxy)methyl, 1,1-di(trifluoromethyl)-1-(methoxyethoxyethoxy)methyl, 1-hydroxyethyl, 2-hydroxyethyl, trifluoromethoxy, 1-aminoethyl, 2-aminoethyl, 1-(N-isopropylamino)ethyl, 2-(N-isopropylamino)ethyl, dimethylaminoethoxy, 4-chlorophenoxy, phenyloxy, azetidin-3-ylmethoxy, 1-Boc-azetidin-3-yl-methoxy, pyrrol-2-ylmethoxy, 1-Boc-pyrrol-2-ylmethoxy, pyrrol-lylmethoxy, 1-methyl-pyrrol-2-ylmethoxy, 1-isopropyl-pyrrol2-yl-methoxy, 1-Boc-piperdin-4-ylmethoxy, piperdin-4-yl-methoxy, 1-methylpiperdin-4-yloxy, isopropoxy, methoxy and ethoxy; and pharmaceutically acceptable derivatives thereof.
- 5. Compound of claim 4 wherein R1 is selected from 4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinol-7-yl, 4,4-dimethyl-1,2,3,4-tetrahydro-isoquinol-7-yl, 2-acetyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinol-7-yl, 2,3-dihydro-1H-indolyl, 3,3-dimethyl-2,3-dihydro-1H-indol-6-yl, 1-ethyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl, and 1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl; and pharmaceutically acceptable derivatives thereof.
- 6. Compound of claim 5 wherein R1 is 3,3-dimethyl-2,3-dihydro-1H-indol-6-yl; and pharmaceutically acceptable derivatives thereof.
- 7. Compound of claim 5 wherein R1 is 4,4-dimethyl-1,2,3,4-tetrahydro-isoquinol-7-yl; and pharmaceutically acceptable derivatives thereof.
- 8. Compound of claim 2 wherein R1 is selected from phenyl substituted with a substituent selected from optionally substituted 4-6 membered heterocyclyl-C1-C4-alkyl, optionally substituted 4-6 membered heterocyclyl-C2-C4alkenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted 4-6 membered heterocyclyloxy, optionally substituted 4-6 membered heterocyclyl-C1-4-alkoxy, optionally substituted 4-6 membered heterocyclylsulfonyl, optionally substituted 4-6 membered heterocyclylamino, optionally substituted 4-6 membered heterocyclylcarbonyl, chloro, C3-C4-alkyl and optionally substituted 4-6 membered heterocyclyl-C1-4-alkylcarbonyl; and wherein Ra is H; and pharmaceutically acceptable derivatives thereof; provided R3 is not aryl or heteroaryl when R1 is phenyl substituted with chloro or alkyl and when R2 is H.
- 9. Compound of claim 8 wherein R1 is selected from 4-chlorophenyl, 4-tert-butylphenyl, and 4-[1-methyl-1-(1-methyl-piperidin-4-yl)-ethyl]phenyl; and pharmaceutically acceptable derivatives thereof.
- 10. Compound of claim 2 wherein R2 is selected from H, chloro, fluoro, bromo, amino, hydroxy, methyl, ethyl, propyl, oxo, dimethylamino, aminosulfonyl, cyclopropyl, cyano, hydroxymethyl, nitro, propenyl, trifluoromethyl, methoxy, ethoxy, trifluoromethoxy, carboxymethyl, morpholinylethylamino, propynyl, unsubstituted or substituted phenyl and unsubstituted or substituted heteroaryl selected from thienyl, furanyl, pyridyl, imidazolyl, and pyrazolyl;
and pharmaceutically acceptable derivatives thereof.
- 11. Compound of claim 10 wherein R2 is H; and
pharmaceutically acceptable derivatives thereof.
- 12. Compound of claim 2 wherein R is —(CH2)—R3; and wherein R3 is selected from phenyl substituted with one or more substituents independently selected from halo, amino, C1-3-alkoxy, hydroxyl, C1-3-alkyl and C1-2-haloalkyl; and pharmaceutically acceptable derivatives thereof.
- 13. Compound of claim 2 wherein R is selected from unsubstituted or substituted 9- or 10-membered fused nitrogen-containing heterocyclyl; and pharmaceutically acceptable derivatives thereof.
- 14. Compound of claim 13 wherein R is selected from optionally substituted indazolyl, quinolinyl, [1,7]napthyridinyl, quinazolinyl and isoquinolinyl; and pharmaceutically acceptable derivatives thereof.
- 15. Compound of claim 14 wherein R is selected from [1,7]napthyridin-2-yl, quinazolin-6-yl and 7-isoquinolinyl; and pharmaceutically acceptable derivatives thereof.
- 16. Compound of claim 2 wherein R is —(CH2)1-2—R3; and wherein R3 is selected from substituted or unsubstituted 5-6 membered nitrogen-containing heteroaryl, and substituted or unsubstituted fused 9-, or 10-membered nitrogen-containing heteroaryl; and pharmaceutically acceptable derivatives thereof.
- 17. Compound of claim 16 wherein R is selected from (3-pyridyl)-(CH2)2—, (4-pyridyl)-CH2—, (4-pyrimidinyl)-CH2—, (5-pyrimidinyl)-CH2—, (6-pyrimidinyl)-CH2—, (4-pyridazinyl)-CH2— and (6-pyridazinyl)-CH2—; wherein R is unsubstituted or substituted with one or more substituents selected from chloro, fluoro, amino, methylamino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, methoxy and ethoxy; and pharmaceutically acceptable derivatives thereof.
- 18. Compound of claim 16 wherein R is selected from 5-indazolyl-CH2—, 4-quinolinyl-CH2—, (1H-pyrrolo[2,3-b]pyridin-3-yl)-CH2—, 5-quinoxalinyl-CH2—, 5-isoquinolinyl-CH2— and 4-quinazolinyl-CH2—; and pharmaceutically acceptable derivatives thereof.
- 19. Compound of claim 2 wherein R is selected from (4-pyridyl)-CH2—, (4-fluorphenyl)-CH2—, (2-methylamino-4-pyrimidinyl)-CH2—, (4-quinolinyl)-CH2—, 5-quinoxalinyl-CH2—, (4-pyridazinyl)-CH2—, (1H-pyrrolo[2,3-b]pyridin-3-yl)-CH2—, (2-methoxy-4-pyridyl)-CH2—, (4-pyridazinyl)-CH2—, (2-amino-4-pyrimidinyl)-CH2—, quinazolin-6-yl and 7-isoquinolinyl; and pharmaceutically acceptable derivatives thereof.
- 20. Compound of claim 2 wherein R is —(CHCH3)—R3; wherein R3 is selected from unsubstituted or substituted 6-membered nitrogen-containing heteroaryl; and wherein substituted R3 is substituted with one or more substituents independently selected from halo, amino, C1-3-alkoxy, hydroxyl, C1-3-alkyl and C1-2-haloalkyl; and pharmaceutically acceptable derivatives thereof.
- 21. Compound of claim 20 wherein R is selected from (4-pyridyl)-(CHCH3)—, (4-pyrimidinyl)-(CHCH3)—, (5-pyrimidinyl)-(CHCH3)—, (6-pyrimidinyl)-(CHCH3)—, (4-pyridazinyl)-(CHCH3)— and (6-pyridazinyl)-(CHCH3)—; wherein R is unsubstituted or substituted with one or more substituents selected from chloro, fluoro, amino, hydroxy, methyl, ethyl, propyl, trifluoromethyl, methoxy and ethoxy; and pharmaceutically acceptable derivatives thereof.
- 22. Compound of claim 21 wherein R is (2-methylamino-4-pyrimidinyl)-CHCH3— or (2-amino-4-pyrimidinyl)-CHCH3—; and pharmaceutically acceptable derivatives thereof.
- 23. Compound of claim 2 wherein R5 is selected from H, piperidinylethyl and methoxyethoxyethyl; wherein Ra is H; and wherein Rb and Rc are independently selected from H and trifluoromethyl; and pharmaceutically acceptable derivatives thereof.
- 24. Compound of claim 2 wherein R is (4-pyridyl)-CH2—; and pharmaceutically acceptable derivatives thereof.
- 25. Compound of claim 2 wherein R is (4-fluorophenyl)-CH2—; and pharmaceutically acceptable derivatives thereof.
- 26. Compound of claim 2 wherein R is (4-quinolyl)-CH2— ; and pharmaceutically acceptable derivatives thereof.
- 27. Compound of claim 2 wherein R is (1H-pyrrolo[2,3-b]pyridin-3-yl)-CH2—; and pharmaceutically acceptable derivatives thereof.
- 28. Compound of claim 2 wherein R is (2-amino-pyrimidin-4-yl)-CHCH3— or (2-methylaminopyrimidin-4-yl)-CHCH3—; and pharmaceutically acceptable derivatives thereof.
- 29. Compound of claim 2 wherein R2 is H or fluoro; and pharmaceutically acceptable derivatives thereof.
- 30. Compound of claim 2 and pharmaceutically acceptable salts thereof selected from
N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)-amino]-benzamide; N-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)-amino]-benzamide; N-(4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-7-yl)-2-(quinazolin-6-ylamino)-benzamide; N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(2-methylamino-pyrimidin-4-ylmethyl)-amino]-benzamide; (R)—N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[1-(2-methylamino-pyrimidin-4-yl)-ethylamino]-benzamide; N-(1-Ethyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)-amino]-benzamide; N-(3,3-Dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(quinolin-4-ylmethyl)-amino]-benzamide; N-(4-tert-Butyl-phenyl)-2-(isoquinolin-7-ylamino)-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(2-methoxy-pyridin-4-ylmethyl)-amino]-benzamide; N-{4-[1-Methyl-1-(1-methyl-piperidin-4-yl)-ethyl]-phenyl}-2-[(pyridin-4-ylmethyl)-amino]-benzamide; N-(1-Acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(quinolin-4-ylmethyl)-amino]-benzamide; N-(3,3-Dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(1-oxy-pyridin-4-ylmethyl)-amino]-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-fluoro-6-[(2-methoxy-pyridin-4-ylmethyl)-amino]-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-3-fluoro-6-[(2-methoxy-pyridin-4-ylmethyl)-amino]-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-quinolin-7-yl)-2-[(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amino]-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(pyridazin-4-ylmethyl)-amino]-benzamide; 2-[1-(2-Amino-pyrimidin-4-yl)-ethylamino]-N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[1-(2-methylamino-pyrimidin-4-yl)-ethylamino]-benzamide; 2-(4-Fluoro-benzylamino)-N-{4-[1-methyl-1-(1-methyl-piperidin-4-yl)-ethyl]-phenyl}-benzamide; N-{4-[1-Methyl-1-(1-methyl-piperidin-4-yl)-ethyl]-phenyl}-2-[(quinolin-4-ylmethyl)-amino]-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-(4-fluoro-benzylamino)-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-fluoro-2-(4-fluoro-benzylamino)-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-3-fluoro-2-(4-fluoro-benzylamino)-benzamide; N-(4,4-Dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-4-fluoro-6-[(2-methoxy-pyridin-4-ylmethyl)-amino]-benzamide; and N-(4,4-Dimethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-2-[(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amino]-benzamide.
- 31. Compound of claim 2, and pharmaceutically acceptable salts thereof, comprising N-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)-amino]-benzamide.
- 32. Compound of claim 2, and pharmaceutically acceptable salts thereof, comprising N-(1-acetyl-3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)-amino]-benzamide.
- 33. Compound of claim 2, and pharmaceutically acceptable salts thereof, comprising N-(4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-7-yl)-2-(quinazolin-6-ylamino)-benzamide.
- 34. Compound of claim 2, and pharmaceutically acceptable salts thereof, comprising N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[(2-methylamino-pyrimidin-4-ylmethyl)-amino]-benzamide.
- 35. Compound of claim 2, and pharmaceutically acceptable salts thereof, comprising (R)—N-(4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-2-[1-(2-methylamino-pyrimidin-4-yl)-ethylamino]-benzamide.
- 36. A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of claim 1.
- 37. A method of treating cancer in a subject, said method comprising administering an effective amount of a compound of claim 1.
- 38. The method of claim 37 comprising a combination with a compound selected from antibiotic-type agents, alkylating agents, antimetabolite agents, hormonal agents, immunological agents, interferon-type agents and miscellaneous agents.
- 39. A method of treating angiogenesis in a subject, said method comprising administering an effective amount of a compound of claim 1.
- 40. A method of treating VEGF receptor-related disorders in a mammal, said method comprising administering an effective amount of a compound of claim 1.
- 41. A method of treating proliferation-related disorders in a mammal, said method comprising administering an effective amount of a compound of claim 1.
- 42. The method of claim 41 wherein the disorder is inflammation or an inflammation-related disorder.
- 43. A method of reducing blood flow in a tumor in a subject, said method comprising administering an effective amount of a compound of claim 1.
- 44. A method of reducing tumor size in a subject, said method comprising administering an effective amount of a compound of claim 1.
- 45. A method of treating diabetic retinopathy in a subject, said method comprising administering an effective amount of a compound of claim 1.
Parent Case Info
[0001] This application claims the benefit of U.S. Provisional Application No. 60/395,144 filed Jul. 9, 2002, which is hereby incorporated by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60395144 |
Jul 2002 |
US |