Patent DE-10010425-A1 (DE)
Title: Medicaments for treating anemia, containing new or known 6-(4-(acylamino)-phenyl)-5-methyl-dihydropyridazinones having erythropoietin sensitizing and erythropoiesis stimulating activity
Inventor: BRAEUNLICH GABRIELE
IPC: C07D405/12
Filed: 2000-03-03
Abstract: The use of 6-(4-(acylamino)-phenyl)-5-methyl-dihydropyridazinone derivatives (I) as medicaments for the treatment or prophylaxis of anemia is new. Some compounds (I) are new.  The use of pyridazinone derivatives of formula (I) (including their tautomers and salts) is claimed for production of medicaments or pharmaceutical compositions for the prophylaxis and/or treatment of anemia. A, D, E, G  = H, alkyl, OH, NO2, halo or alkoxy;  R1  = H or 1-4C alkyl;  R2  = (a) 2-methyl-tetrahydrofuran-2-yl, 1,2-dithian-4-yl, 5-methyl-1,3-dioxan-5-yl, 5,5-dimethyl-2-oxo-tetrahydrofuran-4-yl, 2,5-dihydrothienyl, 2-oxo-tetrahydrofuran-5-yl, 2-oxo-pyrrolidin-5-yl, 4-methyl-2-oxo-pyrrolidin-5-yl, tetrahydrofuran-5-yl, -CHPh2, 4-(5-methyl-4,5-dihydropyridazin-3(2H)-on-6-yl)-anilino or (1-4C) alkylbenzamidomethyl; (b) cycloalkyl (optionally substituted (os) by 1-4 of alkyl, alkoxy, alkoxycarbonyl, OH, COOH or aryl (itself os by 1-3 halo)); (c) aryl, aryloxy, arylthio, dihydropyridinone or Het (all os by 1-3 of CF3, NO2, OH, CN, cycloalkyl, halo, mono-, di- or trihalophenoxyalkyl, phenoxy, alkoxy, alkoxycarbonyl, COOH, arylcarbonyl or NR3R4; or by phenyl (itself os by 1-3 of alkyl or alkoxy)); (d) 1-10C alkyl (os by 1-3 of halo, alkoxycarbonyl, COOH, 1-6C acyloxy, NR5R6, S(C(S)NR7R8 or OR9); (e) alkoxycarbonyl or NR13R14; or (f) alkenyl (os by aryl);  Het  = 5- or 6-membered aromatic heterocycle, containing 1-3 of O, S and/or N as heteroatom(s);  R9  = H, alkyl or alkenyl (os by aryl); or 1-10C alkyl (os by 3-8C cycloalkyl, aryl or Het' (where the ring systems are os by 1-3 of OH, CN, cycloalkyl, halo, CF3, alkyl, aryl, OPh, 1-8C alkoxy, alkoxycarbonyl, COOH or NR11R12; or aryl (itself os by halo)));  R3 - R8, R11, R12  = H, alkyl or 1-6C acyl;  Het'  = optionally benzo-fused, aromatic or saturated, 5- or 6-membered heterocycle containing 1-3 of O, S, N and/or NR10 as heteroatom(s); R10  = H, Ph or alkyl;  R13, R14  = H, alkyl or 1-6C acyl; 3-8C cycloalkyl, aryl or 5- or 6-membered heterocycle containing 1-3 of O, S and/or N as heteroatom(s) (all os by 1 or 2 of OH, alkyl, alkoxycarbonyl, alkoxy, halo, CONR15R16 or SO2NR17R18); or alkyl (os by phenyl, itself os by 1-3 halo);  R15-R18  = H, aryl or alkyl; Unless specified otherwise alkyl moieties have 1-6C, cycloalkyl moieties 3-6C, alkenyl moieties 2-6C and aryl moieties 6-10C. Independent claims are included for 26 specific new compounds (I) (including tautomers and salts), i.e. 6-(4-(N-(QCO)-amino)-phenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-ones and 6-(4-(N-(Q'CO)-amino)-2-methylphenyl)-5-methyl-4,5-dihydropyridazin-3( 2H)-ones, where:  Q  = 3-(2-chloro-4-fluorophenyl)-5-methyl-isoxazol-4-yl, 2-carbamoyl-3-thienylamino, 2-(2-fluorophenyl)-ethylamino, 2-sulfamoylphenylamino, 2-fluorophenylamino, 3,5-dichloro-2-pyridinyl, 3-isoquinolinyl, 6-methyl-2-pyridinyl, 4-chloro-2-pyridinyl, 4-(methoxycarbonyl)-2-pyridinyl, 3-pyridinylmethyl, 2,6-dichlorobenzyl, 2-phenylethyl, 3-fluorophenyl, 2-fluorophenyl, 2-(trifluoromethyl)-phenyl, 6-fluoro-2-pyridinyl or 3-methyl-2-pyridinyl; and Q'  = 2-pyridinyl, 3,5-dichloro-2-pyridinyl, 2-pyridinylmethyl, 6-methyl-2-pyridinyl, 6-fluoro-2-pyridinyl, 3-pyridinylmethyl, 2-fluorophenyl or 3-propoxy-2-pyridinyl.