New amidomethyl substituted 1-(carboxyalkyl)-cyclopentylcarbonylamino-benzazepine-n-acetic acid derivatives useful to treat cardiovascular disorders or diseases; hypertension; sexual dysfunction; or neurodegenerative disorders

摘要

Amidomethyl substituted 1-(carboxyalkyl)-cyclopentylcarbonylamino-benzazepine-n-acetic acid derivatives (I) and their salts are new. Amidomethyl substituted 1-(carboxyalkyl)-cyclopentylcarbonylamino-benzazepine-n-acetic acid derivatives of formula (I) and their salts are new. [Image] R 1>, R 4>H or a group forming a biolabile ester; and either R 2>H, 1-4C alkyl or 1-4C hydroxyalkyl (where the OH is optionally esterified with 2-4C alkanoyl or an amino acid residue); and R 3>1-4C alkyl, 1-4C alkoxy-1-4C alkyl; 1-4C hydroxyalkyl (optionally substituted by a second hydroxyl group and the hydroxyl groups of which are each optionally esterified with 2-4C alkanoyl or an amino acid residue); (0-4C alkyl) 2amino-1-6C alkyl, 3-7C cycloalkyl(1-4C alkyl), phenyl-1-4C alkyl or phenylcarbonylmethyl (where the phenyl group is optionally substituted 1-2 times by 1-4C alkyl, 1-4C alkoxy and/or halo), naphthyl-1-4C alkyl, 3-6C oxoalkyl or 2-oxoazepanyl; or R 2> + R 3>4-7C alkylene (where the methylene groups are optionally replaced 1-2 times by carbonyl, nitrogen, oxygen and/or sulfur and/or which are optionally substituted once by OH, which is optionally esterified with 2-4C alkanoyl or an amino acid residue), 1-4C alkyl; 1-4C hydroxyalkyl (where the OH group is optionally esterified with 2-4C alkanoyl or an amino acid residue); phenyl or benzyl. Independent claims are also included for: (1) preparation of (I); and (2) a carboxyalkyl-cyclopentylcarbonylamino-benzazepine-n-acetic acid derivatives of formula (II). [Image] R 1> 0> 1>, R 4> 0> 1>an acid-protecting group. ACTIVITY : Cardiovascular-Gen.; Hypotensive; Nephrotropic; Respiratory-Gen.; Endocrine-Gen.; Vasotropic; Neuroprotective; Cerebroprotective; Antiinflammatory; Nootropic; Antiarteriosclerotic; Anti-HIV; Muscular-Gen.; Anticonvulsant; Vulnerary; Antiparkinsonian; Antiinflammatory; Hepatotropic; Antibacterial; Virucide; CNS-Gen.; Dermatological; Antiemetic; Cytostatic; Gastrointestinal-Gen.; Antiulcer; Antimicrobial; Immunosuppressive; Antialcoholic; Antiarthritic; Osteopathic; Immunostimulant; Hemostatic; Antirheumatic; Cardiant; Antithyroid; Anabolic; Hypertensive; Antidiabetic; Antipsoriatic; Gynecological; Antiallergic; Auditory; Antianemic; Antiseborrheic; Keratolytic; Vasotropic; Anticoagulant; Vulnerary; Ophthalmological; Metabolic; Protozoacide; Fungicide; Antidote; Antirheumatic. MECHANISM OF ACTION : Neutral endopeptidase (NEP) inhibitor; Human soluble endopeptidase (hSEP) inhibitor. The ability of (I) to inhibit (NEP) was assessed in vitro. The results showed that median inhibitory concentration (IC 5 0) value of (I) was less than 1 nM.