New diazeniumdiolate derivatives are angiotensin-II receptor antagonists, useful as a medicament to treat e.g. hypertension, cardiovascular disease, retinopathy, stroke, dementia, left ventricular hypertrophy, heart failure and nephropathy

摘要

Diazeniumdiolate derivatives (I) and their enantiomers and diastereomers are new. Diazeniumdiolate derivatives of formula G-(CH 2) n-A-(CH 2) m-(CR 1R 2) p-(CH 2) o-R 3 (I) and their enantiomers and diastereomers are new. R 1, R 2H or 1-6C alkyl (where the -CH 2- or CR 1R 2 groups of (I) is replaced by phenylene group, -PhC(O)- or -PhC(O)O-, where Ph is phenyl radical); A : -CH 2-C(=O)-O-CH 2-, CH 2-O-C(=O)-CH 2-, 4-methyl-piperazine-1-carboxylic acid methyl ester, -N(R 4)-C(=O)-O- or -O-C(=O)-N(R 4)-, preferably -C(O)O- ; R 4H or 1-6C alkyl; R 3-O-N=N +>(O ->)-N(R 5)(R 6) (preferred) or -(O ->)N( +>)=N-O-R 7; either R 5, R 6, R 7H or 1-6C alkyl; or R 5R 61-6C alkylene; G : bis(N-methyl benzoimidazole) compound of formula (II); n : 0-3; m : 0-3; p : 0 or 1; and o : 0-2. [Image] ACTIVITY : Hypotensive; Cardiovascular-Gen; Ophthalmological; Cerebroprotective; Vasotropic; Nootropic; Cardiant; Antianginal; Nephrotropic; Antiinflammatory; Anticoagulant; Antidiabetic; Anorectic; Cytostatic; Metabolic. MECHANISM OF ACTION : Angiotensin-II receptor antagonist. The ability of (I) to inhibit angiotensin-II receptor antagonist was tested in spinalized rats. The result showed that the 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzimidazol-3'-yl)methyl]biphenyl-2-carboxylate of {[(Z)-2-oxido-2-pyrrolidin-1-yldiazenyl]oxy}methyl exhibited an IC 5 0 value of 0.83 mu M.