New substituted 1-benzylcycloalkylcarboxylic acid compounds are soluble guanylate cyclase activators useful to treat and/or prevent e.g. heart failure, angina pectoris, hypertension, pulmonary hypertension and vascular disease

摘要

Substituted 1-benzylcycloalkylcarboxylic acid compounds (I) and their salts, solvates or solvates of the salts, are new. Substituted 1-benzylcycloalkylcarboxylic acid compounds of formula (I) and their salts, solvates or solvates of the salts, are new. R1aR1bC : cyclopropan-1,1-yl, 2,2-difluoro-cyclopropan-1,1-yl or cyclobutan-1,1-yl; R 2> : H, CH 3, C 2H 5, vinyl, OH, CH 3O, trideuteromethoxy, CF 3O, C 2H 5O or cyclopropyloxy; R 3> : H, CH 3, C 2H 5, isopropyl or cyclopropyl; R 4> : H, F, Cl, Br, CN, CH 3, CF 3, C 2H 5, isopropyl, cyclopropyl, cyclobutyl, CH 3O or CF 3O; R 5>, R 6> : H, F, Cl, CH 3, CF 3or CF 3O; either R7a : CH 3or C 2H 5; and R7b : CF 3; or R7aRbC : cyclopentane, 1,1-difluoro-cyclopentan-2-yl or 1,1-difluoro-cyclopentan-3-yl; R 8> : 1-4C-alkyl, 2-4C-alkenyl (both optionally substituted by 2 or 3 F), cyclopropyl or cyclobutyl (both optionally substituted by up to 2 F), F, Cl, Br, nitro, CN, CF 3O, acetyl or 2-cyanovinyl; and R 9> : H, F, Cl, CH 3, CF 3, C 2H 5, CH 3O or CF 3O. Independent claims are included for: (1) the preparation of (I); and (2) a medicament comprising (I) in combination with one or more inert, non-toxic auxiliary agent. [Image] ACTIVITY : Cardiant; Antianginal; Hypotensive; Respiratory-Gen.; Cerebroprotective; Vasotropic; Thrombolytic; Antiarteriosclerotic; Ophthalmological; Auditory; Neuroprotective; Cardiovascular-Gen.; Antiulcer; Dermatological; Fungicide; Antirheumatic; Nephrotropic; Antianemic; Osteopathic; Metabolic; Uropathic; Cytostatic; Endocrine-Gen.; Nootropic; Antiparkinsonian; Anticonvulsant; Tranquilizer; Antidepressant; Hypnotic; Antiaddictive; Analgesic; Antibacterial; Immunosuppressive; Antiinflammatory; Antiarthritic; Vulnerary. MECHANISM OF ACTION : Soluble guanylate cyclase activator. The ability of (I) to activate soluble guanylate cyclase was tested Chinese hamster ovary cell. The results showed that 1-(4-fluoro-3-{[(2S,3R)-4,4,4-trifluoro-2-(4-isopropylphenyl)-3-methylbutanoyl]amino}-benzyl)cyclopropane carboxylic acid exhibited a minimal effective concentration value of 0.1 nM.