DERIVATIVES OF 1,4-DIAZABICYCLO3.2.1OCTANCARBONIC ACID, THEIR MANUFACTURING AND USE IN THERAPEUTICS

摘要

4-heterocyclylcarbonyl-1,4-diazacyclo-octane derivatives (I), as individual or mixed enantiomers, bases, solvates and acid addition salts are new. 4-heterocyclylcarbonyl-1,4-diazacyclo-octane derivatives of formula (I), as individual or mixed enantiomers, bases, solvates and acid addition salts are new. X : N or CR 2; P, Q, R and W : N or CR 3; R 1 and R 21-6C alkyl; R 3hydrogen, halo, 1-6C alkyl or alkoxy, nitro, amino, trifluoromethyl, cyano, NR 4R 5, NR 4COR 5, NR 4CONR 5R 6, NR 4COOR 5, NR 4SO 2NR 5R 6, OR 5, OCOR 5, OCOOR 5, OCO-ONR 4R 5. OCOSR 5, COOR 5, COR 5, CONR 4R 5, SR 5, SOR 5, SO 2R 5, SO 2NR 4R 6, or phenyl (optionally substituted by any of the groups indicated for R 3), or R 3 is any of a wide range of heterocyclic groups (het1); R 4, R 5 and R 6halo, 1-6C alkyl, 2-6C alkenyl or alkynyl, 3-8C cycloalkyl, 3-8C cycloalkyl(1-3C)alkyl, 4-8C cycloalkenyl or phenyl, and RNR 4R 5 or NR 5R 6 may complete a heterocycle (het2). The full definitions are given in the DEFINITIONS (Full Definitions) Field. [Image] ACTIVITY : Nootropic; Neuroprotective; Neuroleptic; Antiparkinsonian; Anticonvulsant; Tranquilizer; Antidepressant; Cardiant; Antiulcer; Antismoking. MECHANISM OF ACTION : (I) are ligands for nicotinic receptors, with high selectivity for receptors that include the alpha 7 subunit. The compound 3-(1,4-diazabicyclo[3,2,1]oct-4-yl-carbonyl)-6-methyl-1H-pyrazolo[3,4-b]pyridine hydrobromide had IC 50 for inhibition of binding of tritium-labeled alpha -bungarotoxin to nicotinic receptors that contained the alpha 7 subunit of 0.056 mu M.