Guanidine compounds and use of same as binding partners for 5-HT5 receptors

摘要

Guanidine compounds (I), their enantiomers, diastereomers and/or tautomers and salts are new. Guanidine compounds of formula (I), their enantiomers, diastereomers and/or tautomers and salts are new. Q-N(R 2>)-C(=NR 3>)-N(R 1>)-Z-W (I) W : substituted phenyl or thienyl; Z : -(CR 1> zR 2> z) a-(V z) b-(CR 3> zR 4> z) c-; a and c : 0-4; b : 0 or 1, and the sum of a, b and c = 1-5; R 1> z to R 4> z : hydrogen, halo, hydroxy, 1-6C alkyl, 2-6C alkenyl or alkynyl, 1-6C alkylene(3-7C)cycloalkyl, 3-7C cycloalkyl, (hetero)aryl, 1-4C alkylene(hetero)aryl or R 1> z/R 2> z and/or R 3> z/R 4> z together complete a 3-7 membered, optionally substituted, (un)saturated carbo- or heterocyclic group, containing up to 3 heteroatoms (O, N or S); V z : CO, CONR 5> z, NR 5> zCO, O, S, SO, SO 2, SO 2NR 5> z, NR 5> zSO 2, CS, CSNR 5> z, NR 5> zCS, CSO, OCS, COO, OCO, O, ethylnylene, C(=CR 6> zR 7> z), CR 6> z=CR 7> z, NR 5> zCONR 5>, OCONR 5> z or NR 5> z; R 1>-R 3> : hydrogen or substituents; Q : disubstituted 5-membered heteroaryl. Full definitions are given in the DEFINITIONS (Full Definitions) field. ACTIVITY : Antimigraine; Neuroprotective; Nootropic; Cerebroprotective; Anticonvulsant; Neuroleptic; Tranquilizer; Antidepressant; Cytostatic; Analgesic; Antialcoholic. No details of tests for these activities are given. MECHANISM OF ACTION : 5-Hydroxytryptamine (5HT) class 5 receptor non-competitive inhibitor. (I) bind to 5-hydroxytryptamine (5HT) class 5 receptors as non-competitive inhibitors, so cause (ultimately) an increase in intracellular calcium ion concentration. The compound N-(2-methoxybenzyl)-N'-(1,3-thiazol-2-yl)guanidine (Ia) had binding affinity (inhibition constant) for human 5-HT 5 receptors of below 50 nM.