New quinuclidine N-phenylcarbamate derivatives, are selective muscarinic receptor antagonists useful e.g. for treating urinary incontinence, irritable bowel syndrome or respiratory disorders

摘要

3-Quinuclidinyl N-(arylmethyl, cycloalkylmethyl or heteroarylmethyl)-N-phenylcarbamates (I) are new. Carbamates of formula (I) and their N-(1-4C alkyl)-quinuclidinium salt or quinuclidine-N-oxide derivatives, stereoisomers, stereoisomer mixtures, salts and solvates are new. [Image] R 1 - R 3H, OH, SH, CN, F, Cl, Br, I, ST, OT (optionally substituted by one or more F), NHCONH 2 or T (optionally substituted by one or more of F and OH); or R 1 + R 2 or R 2 + R 3(CH 2) 3 or (CH 2) 4; T : 1-4C alkyl; R 43-6C cycloalkyl, cyclohexenyl, norbornenyl, bicyclo (2.2.1) heptanyl, 2- or 3-thienyl, 2- or 3-furyl, 2-, 3- or 4-pyridyl, 1- or 2-naphthyl, 1- or 2-benzodioxolanyl, 1- or 2-benzodioxanyl or phenyl (optionally substituted by one or more of OH, SH, CN, F, Cl, Br, I, NHCONH 2, COOH, COOT, ST, OT (optionally substituted by one or more F) or T (optionally substituted by one or more of F and OH)); the quinuclidinyl group preferably has 3(R)-configuration. ACTIVITY : Uropathic; antiinflammatory; antiasthmatic; antiallergic; ophthalmological MECHANISM OF ACTION : Muscarinic receptor antagonist. In particular (I) are selective M 3 receptor antagonists. 3(R)-Quinuclidinyl N-(cyclohexylmethyl)-N-(4-fluorophenyl)-carbamate (Ia) had K i 0.025 nM for M 3 receptors and a selectivity for the M 3 relative to the M 2 receptor of 300.