Patent DE-102011082041-A1 (DE)
Title: New substituted fused pyrimidine compounds are guanylate cyclase stimulators useful to treat and/or prevent e.g. heart failure, hypertension, ischemia, vascular disease, renal failure, thromboembolic disorders and fibrotic diseases
IPC: C07D487/04
Filed: 2011-09-02
Abstract: Substituted fused pyrimidine compounds (I) are new. Substituted fused pyrimidine compounds of formula (I) and their N-oxides, salts, solvates, salts of N-oxides, solvates of the N-oxides or salts are new. L : a1-CR7aR7b-(CR8aR8b) m-a2; a1 : connection point to carbonyl group; a2 : connection point to pyrimidine ring; m : 0-2; either R7a : H, F, (1-4C)alkyl (optionally substituted by 1-3 F, CF 3, OH, hydroxycarbonyl, (1-4C)alkoxycarbonyl or amino), OH or amino; and R7b : H, F, (1-4C)-alkyl (optionally substituted by 1-3 F, CF 3, OH, hydroxycarbonyl, (1-4C)alkoxycarbonyl or amino), CF 3, (1-4C)alkoxycarbonylamino or phenyl; or R7aR7b : 3-6-membered carbocyclic group, 4-7-membered heterocycle (both optionally substituted by 1 or 2 F or (1-4C)alkyl), (2-4C)alkenyl group or oxo; R8a : H, F, (1-4C)alkyl or OH; R8b : H, F, (1-4C)alkyl or CF 3; ring Q : 8-9-membered heteroaryl; R3 : -OR4 or -NR5R6; R4 : (1-6C)alkyl, (3-7C)cycloalkyl, 4-7-membered heterocyclyl or 5 or 6 membered heteroaryl (all optionally substituted by 1-3 F, difluoromethyl, trifluoromethyl, (3-6C)cycloalkyl, difluoromethoxy, trifluoromethoxy, -(C=O) p-OR9, -C(=O) p-NR9R10, -NR9-(C=O)-R10, -NR9-(C=O)-OR10, -NR9-(C=O)-NR10R11, -NR9-SO 2-R10, -S(O) q-R12 or -SO 2-NR9R10) or H; p : 0 or 1; q : 0-2; either R9-R11 : (1-6C)alkyl (optionally substituted by 1 or 2 F, difluoromethyl, trifluoromethyl, OH, (1-6C)alkoxy, difluoromethoxy, trifluoromethoxy, (1-6C)alkoxycarbonyl, amino, mono-(1-6C)alkylamino, di-(1-6C)alkylamino or 4-7-membered substituted heterocyclyl), H or (3-8C)cycloalkyl; or R9R10, R10R11 : 4-7 membered heterocycle optionally substituted by 1 or 2 F, CF 3, (1-6C)alkyl, OH, oxo, (1-6C)alkoxy, trifluoromethoxy, (1-6C)alkoxycarbonyl, amino, mono-(1-6C)alkylamino or di-(1-6C)alkylamino); R12 : (1-6C)alkyl or (3-7C)cycloalkyl; either R5 : H or (1-4C)alkyl; and R6 : (1-4C)alkyl, (3-7C)cycloalkyl, 4-7 membered heterocycle or 5 or 6 membered heteroaryl (all optionally substituted by F, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, -(C=O) p-OR9, -C(=O) p-NR9R10, -NR9-(C=O)-R10, -NR9-(C=O)-OR10, -NR9-(C=O)-NR10R11, -NR9-SO 2-R10, -S(O) q-R12 or -SO 2-NR9R10); or R5R6N : 4-7 membered heterocycle (optionally substituted by 1 or 2 F, CF 3, (1-6C)alkyl, OH, oxo, (1-6C)alkoxy, trifluoromethoxy, (1-6C)alkoxycarbonyl, amino, mono-(1-6C) alkylamino or di-(1-6C)alkylamino); R1 : F, Cl or CH 3; n : 0-2; and R2 : (1-6C)alkyl ((substituted by CF 3and optionally substituted by 1-3 F), (3-8C)-cycloalkyl, phenyl (substituted by 1-3 F) or 5- or 6-membered heteroaryl (optionally substituted by 1 or 2 F or CH 3). Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with an inert, non-toxic excipient. [Image] ACTIVITY : Cardiant; Antianginal; Hypotensive; Respiratory-Gen.; Vasotropic; Nephrotropic; Thrombolytic; Antiarteriosclerotic; Immunosuppressive; Antiinflammatory; Antibacterial; Cerebroprotective; Endocrine-Gen.; Antilipemic; Hemostatic; Anorectic; Cardiovascular-Gen.; Ophthalmological; Dermatological; Antirheumatic; Uropathic; Antiasthmatic; Anti-HIV; Antianemic; Antisickling; CNS-Gen.; Nootropic; Neuroprotective; Antiparkinsonian; Anticonvulsant; Tranquilizer; Antidepressant; Analgesic; Auditory; Gastrointestinal-Gen.; Hepatotropic; Vulnerary; Cytostatic; Virucide; Osteopathic. MECHANISM OF ACTION : Guanylate cyclase stimulator.