Claims
- 1. A compound represented by the general formula II or III:
- 2. The compound of claim 1 wherein R is selected from the group consisting of halogen, C1 to C8 alkyl, CF3, OCF3, OCF2H, CH2CN, CN, SR2, (CR8R9)dC(O)OR2, (CR8R9)dC(O)N(R2)2, (CR8R9)dOR2, HNC(O)R2, HN—C(O)OR2, (CR8R9)6N(R2)2, SO2(CR8R9)dN(R2)2, OP(O)(OR2)2, OC(O)OR2, OCH2O, HN—CH═CH, —N(COR2)CH2CH2, HC═N—NH, N═CH—S, O(CR8R9)eR7, (CR8R9)dR7, —NR2(CR8R9)eR7 wherein R7 is selected from the group consisting of halogen, 3-fluoropyrrolidinyl, 3-fluoropiperidinyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyrrolinyl, pyrrolidinyl, piperidinyl, methyl isonipecotate, N-(2-methoxyethyl)-N-methylamyl, 1,2,3,6-tetrahydropyridinyl, morpholinyl, hexamethyleneiminyl, piperazinyl-2-one, piperazinyl, N-(2-methoxyethyl)ethylaminyl, thiomorpholinyl, heptamethyleneiminyl, 1-piperazinylcarboxaldehyde, 2,3,6,7-tetrahydro-(1H)-1,4-diazepinyl-5(4H)-one, N-methylhomopiperazinyl, (3-dimethylamino)pyrrolidinyl, N-(2-methoxyethyl)-N-propylaminyl, isoindolinyl, nipecotamidinyl, isonipecotamidinyl, 1-acetylpiperazinyl, 3-acetamidopyrrolidinyl, trans-decahydroisoquinolinyl, cis-decahydroisoquinolinyl, N-acetylhomopiperazinyl, 3-(diethylamino)pyrrolidinyl, 1,4-dioxa-8-azaspiro[4.5]decaninyl, 1-(2-methoxyethyl)-piperazinyl, 2-pyrrolidin-3-ylpyridinyl, 4-pyrrolidin-3-ylpyridinyl, 3-(methylsulfonyl)pyrrolidinyl, 3-picolylmethylaminyl, 2-(2-methylaminoethyl)pyridinyl, 1-(2-pyrimidyl)-piperazinyl, 1-(2-pyrazinyl)-piperazinyl, 2-methylaminomethyl-1,3-dioxolane, 2-(N-methyl-2-aminoethyl)-1,3-dioxolane, 3-(N-acetyl-N-methylamino)pyrrolidinyl, 2-methoxyethylaminyl, tetrahydrofurfurylaminyl, 4-aminotetrahydropyran, 2-amino-1-methoxybutane, 2-methoxyisopropylaminyl, 1-(3-aminopropyl)imidazole, histamyl, N,N-diisopropylethylenediaminyl, 1-benzyl-3-aminopyrrolidyl 2-(aminomethyl)-5-methylpyrazinyl, 2,2-dimethyl-1,3-dioxolane-4-methanaminyl, (R)-3-amino-1-N-BOC-pyrrolidinyl, 4-amino-1,2,2,6,6-pentamethylpiperidinyl, 4-aminomethyltetrahydropyran, ethanolamine and alkyl-substituted derivatives thereof; provided said alkyl or phenyl radicals may be substituted with one or two halo, hydroxy or lower alkyl amino radicals;
wherein R8 and R9 may be selected from the group consisting of H, halogen, hydroxy, and C1-C4 alkyl or CR8R9 may represent a carbocyclic ring of from 3 to 6 carbons.
- 3. The compound of claim 2 wherein R5 and R6 are hydrogen.
- 4. The compound of claim 3 wherein R3 and R4, together with the nitrogen atom, form a 5 or 6 member ring.
- 5. The compound of claim 4 wherein R3 and R4, together with the nitrogen atom, form a ring selected from the group consisting of morpholinyl or piperidinyl.
- 6. The compound of claim 3 wherein R3 is H and R4 is selected from the group consisting of alkyl or alkyloxyalkyl.
- 7. The compound of claim 3 wherein R1 is selected from the group consisting of halogen, C1 to C8 alkyl, phenyl, CF3, OCF3, OCF2H, CN, SR2, (CH2)dC(O)OR2, C(O)N(R2)2, (CH2)dOR2, H NC(O)R2, HN—C(O)OR2, (CH2)dN(R2)2, SO2N(R2)2, OP(O)(OR2)2, OC(O)OR2, OCH2O, HN—CH═CH, —N(COR2)CH2CH2HC═N—NH, N═CH—S, O(CH2)d—R7 and (CH2)c—R7 wherein R7 is selected from the group consisting of pyrrolidinyl, piperidinyl, pyrazinyl and morpholinyl and lower alkyl-substituted derivatives thereof; provided that R7 and/or said alkyl or phenyl radicals may be substituted with from one to three, halo, hydroxyl, lower alkyloxy or lower alkyl amino radicals.
- 8. The compound of claim 3 wherein Ar is selected from the group consisting of phenyl, naphthyl, pyridyl, pyrrolyl, furyl, thienyl and substituted derivatives thereof.
- 9. The compound of claim 8 wherein Ar is phenyl or pyrrolyl.
- 10. The compound of claim 3 wherein said compound is represented by formula II.
- 11. The compound of claim 10 wherein Ar is pyrrolyl.
- 12. The compound of claim 11 wherein a and b are 0.
- 13. The compound of claim 11 wherein a is 2 and R is methyl.
- 14. The compound of claim 11 wherein b is 1 and R1 is chloro.
- 15. The compound of claim 3 wherein said compound is represented by formula III.
- 16. The compound of claim 15 wherein X is 0 and Y is CH2.
- 17. The compound of claim 16 wherein a and b are 0.
- 18. The compound of claim 16 wherein a is 1 and R is dimethylamino.
- 19. The compound of claim 3 selected from the group consisting of
3-(5-Dimethylamino-3H-isobenzofuran-1-ylidene)-1-piperidin-1-ylmethyl-1,3-dihydro-indol-2-one and 5-Chloro-3-(5-dimethylamino-3H-isobenzofuran-1-ylidene)-1-piperidin-1-ylmethyl-1,3-dihydro-indol-2-one
- 20. A compound represented by the general formula I:
- 21. A method for treating diseases related to unregulated tyrosine kinase signal transduction, the method comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1.
- 22. The method of claim 21 wherein said disease is selected from the group consisting of cancer, blood vessel proliferative disorders, fibrotic disorders, mesangial cell proliferative disorders and metabolic diseases.
- 23. The method of claim 21 wherein the blood vessel proliferative disorder is selected from the group consisting of diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, arthritis and restenosis.
- 24. The method of claim 21 wherein the fibrotic disorder is selected from the group consisting of hepatic cirrhosis, atherosclerosis and surgical adhesions.
- 25. The method of claim 21 wherein the mesangial cell proliferative disorder is selected from the group consisting of glomerulonephritis, diabetic nephropathy, malignant nephrosclerosis, thrombotic microangiopathy syndromes, transplant rejection and glomerulopathies.
- 26. The method of claim 21 wherein the metabolic disorder is selected from the group consisting of psoriasis, diabetes mellitus, wound healing, inflammation and neurodegenerative diseases.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This patent application is a continuation of U.S. patent application Ser. No. 10/389,416, filed Mar. 13, 2003, which a continuation of U.S. patent application Ser. No. 10/306,975, filed Nov. 27, 2002.
Continuations (2)
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Number |
Date |
Country |
Parent |
10389416 |
Mar 2003 |
US |
Child |
10829139 |
Apr 2004 |
US |
Parent |
10306975 |
Nov 2002 |
US |
Child |
10389416 |
Mar 2003 |
US |