NETZ, ASTRID,AMBERG, WILHELM,LANGE, UDO,OCHSE, MICHAEL,HUTCHINS, CHARLES, W.,GARCIA-LADONA, FRANCISCO-XAVIER,WERNET, WOLFGANG,KLING, ANDREAS
申请号：
EP05707406.4
公开号：
EP1716127B1
申请日:
2005.02.15
申请国别(地区):
EP
年份:
2014
代理人:
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.
