Patent EA-004066-B1 (EA)
Title: Bridged indenopyrrolocarbazoles, pharmaceutical compositions and methods
Inventor: SINGH JASBIR
IPC: A61P25/14
Filed: 1999-06-04
Abstract: 1. Indenopyrrolocarbazoles of Formula II: wherein: R<1>, R<4>, R<6>, R<7> are H; Y is O; n is 1; m is 1 or 2; R<2> is H, OH or alkyl having 1 to 4 carbon atoms; R<3> is H, halo, C1-C4alkoxy, 3-(3` -NH2-Ph); R<5> is H, C1-C4alkoxy: R<8> is H, C1-C4alkyl, CO2Et, CH2OH; Z is a bond or O; A<1> and A<2>, B<1> and B<2> are selected from the group consisting of H and H or together form a moiety =O. 2. The compound of claim 1 having diastereomers of formula: 3. The compound of claim 2 having enantiomers of formula: 4. The compound of claim 1 wherein R<1> is H. 5. The compound of claim 1 wherein R<2> is hydroxyl or C1-C4alkyl. 6. The compound of claim 1 having the formula: 7. The compound of claim 1 having the formula: 8. The compound of claim 7 having enantiomers of formula: 9. The compound of claim 8 having diastereomers of formula: 10. A pharmaceutical composition having inhibiting trk kinase activity, comprising an active compound according to claim 1 and a pharmaceutically acceptable carrier. 11. A pharmaceutical composition according to claim 10, comprising a compound according to claim 7 and a pharmaceutically acceptable carrier. 12. A pharmaceutical composition for treating or preventing prostate disorders comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 13. The pharmaceutical composition according to claim 12 wherein the prostate disorder is prostate cancer or benign prostate hyperplasia. 14. A pharmaceutical composition for treating or preventing angiogenic disorders comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 15. The pharmaceutical composition according to claim 14 wherein the angiogenic disorder is cancer of solid tumors, endometriosis, diabetic retinopathy, psoriasis, hemangioblastoma, ocular disorders or macular degeneration. 16. A pharmaceutical composition for treating or preventing neoplasia, rheumatoid arthritis, pulmonary fibrosis, myelofibrosis, abnormal wound healing, atherosclerosis, or restenosis comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 17. A pharmaceutical composition for treating or preventing Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, stroke, ischaemia, Huntington's disease, AIDS dementia, epilepsy, multiple sclerosis, peripheral neuropathy, or injuries of the brain or spinal chord comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 18. A method for inhibiting trk kinase activity comprising providing a compound according to claim 1 in an amount sufficient to result in effective inhibition. 19. The method of claim 18 wherein the trk kinase is trk A. 20. The method of claim 18 wherein the compound of claim 1 is provided to treat inflammation. 21. A method for treating or preventing prostate disorders which comprises administering to a host in need of such treatment or prevention a therapeutically effective amount of a compound according to claim 1. 22. The method of claim 21 wherein the prostate disorder is prostate cancer or benign prostate hyperplasia. 23. A method for treating or preventing angiogenic disorders which comprises administering to a host in need of such treatment or prevention a therapeutically effective amount of a compound according to claim 1. 24. A pharmaceutical composition for treating or preventing prostate disorders comprising a compound according to claim 1 and a pharmaceutically acceptable carrier. 25. A method for treating or preventing disorders where PDGFR activity contributes to pathological conditions comprising providing a compound of claim 1 in an amount sufficient to result in the platelet derived growth factor receptor being contacted with an effective inhibitory amount of the compound. 26. A method for treating or preventing neoplasia, rheumatoid arthritis, pulmonary fibrosis, myelofibrosis, abnormal wound healing, atherosclerosis, or restenosis which comprises administering to a host in need of such treatment or prevention a therapeutically effective amount of a compound according to claim 1. 27. A method for treating or preventing disorders characterized by the aberrant activity of trophic factor responsive cells comprising providing a compound according to claim 1 in an amount sufficient to result in the trophic factor cell receptor being contacted with an effective activity inducing amount of the compound. 28. A method for treating or preventing Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, stroke, ischaemia, Huntington's disease, AIDS dementia, epilepsy, multiple sclerosis, peripheral neuropathy, or injuries of the brain or spinal chord which comprises administering to a host in need of such treatment or prevention a therapeutically effective amount of a compound according to claim 1.