title: Synthesis and SAR of 3- and 4-substituted quinolin-2-ones: discovery of mixed 5-HT(1B)/5-HT(2A) receptor antagonists.
abstract: Quinolin-2-ones bearing a heteroaryl-piperazine linked by a two carbon chain at the 3- or 4-position were synthesised and evaluated as mixed 5-HT(1B)/5-HT(2A) receptor antagonists. Potent mixed antagonists were obtained with thieno[3,2-c]pyridine derivatives. In this series, compound 2.1 (SL 65.0472) proved to be functional antagonist at both the 5-HT(2A) receptor (rat in vivo 5-HT-induced hypertension model) and the 5-HT(1B) receptor (dog in vitro saphenous vein assay).
authors.affiliation: Department of Cardiovascular/Thrombosis Medicinal Chemistry, Sanofi-Synthélabo Recherche, Chilly-Mazarin Cedex, France. gary.mccort@sanofi-synthelabo.com
authors.forename: G
authors.initials: G
authors.lastname: McCort
authors.forename: C
authors.initials: C
authors.lastname: Hoornaert
authors.forename: M
authors.initials: M
authors.lastname: Aletru
authors.forename: C
authors.initials: C
authors.lastname: Denys
authors.forename: O
authors.initials: O
authors.lastname: Duclos
authors.forename: C
authors.initials: C
authors.lastname: Cadilhac
authors.forename: E
authors.initials: E
authors.lastname: Guilpain
authors.forename: G
authors.initials: G
authors.lastname: Dellac
authors.forename: P
authors.initials: P
authors.lastname: Janiak
authors.forename: A M
authors.initials: AM
authors.lastname: Galzin
authors.forename: M
authors.initials: M
authors.lastname: Delahaye
authors.forename: F
authors.initials: F
authors.lastname: Guilbert
authors.forename: S
authors.initials: S
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D004285:Dogs; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C416534:7-fluoro-2-oxo-4-(2-(4-(thieno(3,2-c)pyridin-4-yl)piperazin-1-yl)ethyl)-1,2-dihydroquinoline-1-acetamide; D010879:Piperazines; D011804:Quinolines; D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists