Patent DE-10010067-A1 (DE)
Title: New 2-phenyl-imidazo (5,1-f) (1,2,4) triazin-4-one derivatives, are phosphodiesterase inhibitors useful for treating cardiovascular, cerebrovascular or urogenital disorders
Inventor: NIEWOEHNER ULRICH
IPC: A61P7/02
Filed: 2000-03-02
Abstract: 5-Alkyl-7-(cyclo)alkyl-2-(2-oxy-5-substituted-phenyl)-3H-imidazo (5,1-f) (1,2,4) triazin-4-ones (I) are new. Imidazo-triazinones of formula (I) and their tautomers, salts, hydrates and pro-drugs are new. [Image] R1, R3alkyl; R21-12C alkyl or 3-8C cycloalkyl; R4-NHSO2R5 or -N(SO2R6)SO2R7; COOH, -NH-CH(Ph)-P(O)(OR11)(OR12), 2-hydroxy-4-methyl-2-morpholinyl, oxiranyl, COR13 or OR14; NHCONR17R18; NHCOR24; 1-12C alkyl (optionally substituted (os) by 1-3 of OH, N3, Ph, NR28R29, OCOR30 or P(O)(O-alkyl)2; or by triazolyl (itself os by 1 or 2 of halo, Ph, tetrahydrofuranyl, tetrahydropyranyl, alkoxycarbonyl, CONH2 or alkyl (os by OH, alkoxy, NR34R35 or OCOR36))); COR37; or a 5-membered heterocycle containing 1-3 of S, N and/or O as heteroatom(s) (os by 1-3 of halo, CF3, phenyl (os by one or more of halo or CF3), 3-6C cycloalkyl, pyrrolyl, 1-12C alkyl (os by CN, CF3, alkoxycarbonyl, alkoxy, NH2, Ph or nitrophenyl), NR43R44, NHCOCOR45, NHCOR46, NHCOCH2R47, COR48 or NHC(=NH)NH2); R5 - R7vinyl or alkyl ((os) by 1-3 of CF3, halo, alkoxy, OC2F5, C2F5, -CH(CF3)2, N-(R8)-piperazino or morpholino; or 6-12C aryl (os by 1-3 of halo, CF3, NO2, CN, COOH, alkyl or alkoxy); or R5 may also : quinolyl; 5- or 6-membered aromatic or saturated heterocycle containing 1-3 of S, O and N as heteroatom(s) (os by 1-3 of halo or alkyl); 6-chloro-imidazo (2,1-b) thiazol-5-yl; benzofurazan-4-yl; or NR9R10; R8, R11, R12H or 1-4C alkyl; R9, R10H, alkyl or Ph; R13alkyl; R14alkyl (os by 1-3 of OH, Ph or NR15R16); R15, R16H, Ph or 1-4C alkyl (os by Ph); R17, R18H, alkyl (os by 5-methyl-tetrahydrofuran-2-yl, tetrahydrofuran-3-yl or NR19R20) or 6-12C aryl (os by halo, trifluoroethyl or SCF3); or R18 may also = SO2R23 if R17 = H; or NR17R18N-(R21)-piperazino, morpholino, R22-substituted pyrrolidino or R22-substituted piperidino; R19, R20H, Ph or alkyl; R21H or alkyl; R22OH or alkyl (os by OH); R23alkyl or aryl (os by halo); or morpholino or N-methyl-piperazino; R241-(R26)-4-(R25)-piperazin-2-yl; alkyl (os by 6-12C aryl, itself os by OH or alkoxy); or alkyl (os by R27 or SO2R27); R25, R26H, alkyl or alkoxycarbonyl; R27morpholino, morpholinomethyl or N-methylpiperazino; R28, R29H, Ph or alkyl (os by OH, alkoxy or Ph); or R28R294-(5,6-dihydro-1,4,2-dioxazin-3-yl)-piperidino, 4-hydroxypiperidino, 4-(NR31R32)-piperidino or 4-(R33)-piperazino; R30alkyl; R31, R32H or alkyl; R33alkyl, benzyl, alkoxycarbonyl, COOH, pyridyl, pyrimidyl or phenyl (os by alkoxy); R34, R35H or alkyl; R36alkyl; R37CH2CN, morpholino, 4-(R36)-piperazino, morpholinomethyl, N-(R36)-piperazinomethyl. NR39R40, CH2NR39R40 or CH2P(O)(OR41)OR42; R38H or alkyl; R39, R40H or alkyl (os by OH); R41, R42alkyl; R43, R44H, benzyl, alkyl or Ph (os by halo or CF3); R45alkoxy; R46alkyl or Ph; R47OH, alkoxy or OCOR49; R48CH2CN or Ph (os by halo, CF3 or alkoxy); and R491-4C alkyl; alkyl moieties have 1-6C unless specified otherwise. An independent claim is included for the preparation of (I). - ACTIVITY : Hypotensive; antianginal; antiarrhythmic; vasotropic; cardiant; thrombolytic; anticoagulant; cerebroprotective; nootropic; neuroprotective; cytostatic; uropathic. - MECHANISM OF ACTION : Cyclic guanosine monophosphate (cGMP)-metabolizing phosphodiesterase (PDE) inhibitor. (I) inhibit one or more of PDE I, PDE II and PDE V.