New substituted annellated pyrimidine compounds are guanylate cyclase stimulators useful to treat and/or prevent heart failure, hypertension, ischemia, vascular disease, renal failure, thromboembolic disorders and fibrotic diseases

摘要

Substituted annellated pyrimidine compounds are new. Substituted annellated pyrimidine compounds and/or their N-oxides, salts, solvates, and salts and solvates of the N-oxides are new. L : a1-CR7aR7b-(CR8aR8b) m-a2; a1 : connection point to carbonyl group; a2 : connection point to pyrimidine ring; R7a : e.g. H or F; R7b : e.g. H, F or CHF 2; R8a : H, F, (1-4C)alkyl or OH; R8b : H, F, (1-4C)alkyl or CF 3; ring Q : 8- or 9-membered heteroaryl; R3 : e.g. -OR4; R4 : e.g. (1-6C)alkyl; R1 : F, Cl, CN, CHF 2, CF 3, (1-4C)alkyl, (3-7C)cycloalkyl or (1-4C)alkoxy; n : 0-2; and R2 : CF 3, (1-6C)alkyl (substituted by CHF 2or CF 3, and optionally substituted by 1-3 F), (3-8C)cycloalkyl (optionally substituted by 1 or 2 F, CH 3or CH 3O), phenyl (substituted by 1-3 F and optionally substituted by 1-2 CH 3or CH 3O) or 5 or 6 membered heteroaryl (optionally substituted by 1 or 2 F, CF 3or CH 3). Full Definitions are given in the DEFINITIONS (Full Definitions) Field. 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.