Patent EA-002816-B1 (EA)
Title: Carbazol derivatives
Inventor: ANDERSON BENJAMIM ALAN
IPC: C07D209/88
Filed: 1999-04-16
Abstract: 1. A compound selected from the group consisting of [9-benzyl-5-carbainoyl-l-fluorocarbazol-4-yl]oxyacetic acid, sodium salt{9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ether {9-[(3-fluorophenyl)niethyl]-5-carbamoylcarbazol-4-yl} oxyacetic acid, {9-[(3-chlorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt {9-[(3-trifluoromethylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt {9-[(2-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt {9-[(3-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt {9-[(3-trifluoromethoxyphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, [9-benzyl-5-carbamoyl-l-chlorocarbazol-4-yl]oxyacetic acid, [9-[(cyclohexyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid, and [9-[(cyclopentyl)methyl]-5-carbamoylcarbazol-4-yl] oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 2. A compound of Claim 1 which is sodium salt {9-[(phenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, or methyl ether [9-benzyl-5-carbamoyl-l-fluorocarbazol-4-yl]oxyacetic acid. 3. A compound of Claim 1 which is of [9-benzyl-5-carbamoyl-l-fluorocarbazol-4-yl]oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 4. A compound of Claim 1 which is {9-[(3-fluorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 5. A compound of Claim 1 which is {9-[(3-chlorophenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 6. A compound of Claim 1 which is of [9-benzyl-5-carbamoyl-l-chlorocarbazol-4-yl]oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 7. A compound of Claim 1 which is [9-[(cyclohexyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 8. A compound of Claim 1 which is [9-[(cyclopentyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 9. A compound as claimed in any one of Claims 1 to 8 wherein the salt is sodium. 10. A compound of Claim 1 which is sodium salt {9-[(3-trifluoromethylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer or prodrug derivative. 11. A compound of Claim 1 which is sodium salt {9-[(2-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer, prodrug derivative or salt, thereof. 12. A compound of Claim 1 which is sodium salt {9-[(3-methylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer or a prodrug derivative. 13. A compound of Claim 1 which is sodium salt {9-[(3-trifluoromethoxyphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, sodium salt or a pharmaceutically acceptable racemate, solvate, tautomer, optical isomer or a prodrug derivative. 14. A compound as claimed in any one of Claims 1 to 13 wherein the prodrug derivative is a methyl, ethyl, propyl, isopropyl, butyl, morpholinoethyl or diethylglycolamide ester. 15. [9-[(cyclohexyl)methyl]-5-carbamoylcarbazol-4-yl]oxyacetic acid represented by a structural formula   16. A pharmaceutical formulation comprising a compound as claimed in any one of Claims 1 to 15 together with a pharmaceutically acceptable carrier or diluent therefor. 17. A pharmaceutical formulation adapted for the treatment of a condition associated with inhibiting sPLA2, containing a compound as claimed in any one of Claims 1 to 15 together with a pharmaceutically acceptable carrier or diluent therefor. 18. A method of selectively inhibiting sPLA2 in a mammal in need of such treatment comprising administering to said mammal a therapeutically effective amount of a compound of any one of Claims 1 to 15. 19. A method of Claim 18 wherein the mammal is a human. 20. A method of alleviating the pathological effects of sPLA2 related diseases which comprises administering to a mammal in need of such treatment a compound as claimed in any one of Claims 1 to 15 in an amount sufficient to inhibit sPLA2 mediated release of fatty acid and to thereby inhibit or prevent the arachidonic acid cascade and its deleterious products. 21. The use of a compound of formula I as claimed in any one of Claims 1 to 15 for the manufacture of a medicament for alleviating the pathological effects of sPLA2 related diseases which comprises administering to a mammal in need of such treatment a compound of formula I. 22. A method of inhibiting sPLA2 which comprises contacting the sPLA2 with a compound as claimed in any one of Claims 1 to 15. 23. A method of treating sepsis, septic shock, rheumatoid arthritis, osteoarthritis, stroke, apoptosis, asthma, chronic bronchitis, acute bronchitis, cystic fibrosis, inflammatory bowel disease, or pancreatitis which comprises administering to a subject in need of such treatment, a therapeutically effective amount of a compound as claimed in any one of Claims 1 to 15. 24. A method of Claim 20 of alleviating the pathological effects of sepsis, septic shock, adult respiratory distress syndrome, pancreatitis, trauma-induced shock, bronchial asthma, allergic rhinitis, rheumatoid arthritis, cystic fibrosis, stroke, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, spondylarthropathris, ankylosing spondylitis, Reiter's syndrome, psoriatic arthropathy, enterapathric spondylitis. Juvenile arthropathy or juvenile ankylosing spondylitis, reactive arthropathy, infectious or post-infectious arthritis, gonoccocal arthritis, tuberculous arthritis, viral arthritis, fungal arthritis, syphilitic arthritis, Lyme disease, arthritis associated with ""vasculitic syndromes", polyarteritis nodosa, hypersensitivity vasculitis, Luegenec's granulomatosis, polymyalgin rheumatica, joint cell arteritis, calcium crystal deposition arthropathris, pseudo gout, non-articular rheumatism, bursitis, tenosynomitis, epicondylitis (tennis elbow), carpal tunnel syndrome, repetitive use injury (typing), miscellaneous forms of arthritis, neuropathic joint disease (charco and joint), hemarthrosis (hemarthrosic), Henoch-Schonlein Purpura, hypertrophic osteoarthropathy, multicentric reticulohistiocytosis, arthritis associated with certain diseases, surcoilosis, hemochromatosis, sickle cell disease and other hemoglobinopathries, hyperlipoproteineimia, hypogammaglobulinemia, hyperparathyroidism, acromegaly, familial Mediterranean fever, Behat's Disease, systemic lupus erythrematosis, or relapsing polychondritis and related diseases.