title: Synthesis and pharmacological characterisation of a conformationally restrained series of indole-2-carboxylates as in vivo potent glycine antagonists.
abstract: After the identification of GV150526, the indole-2-carboxylate template was further explored in order to identify novel potential anti-stroke agents. In particular, the SAR of the side chain present at the C-3 position of the indole nucleus was widely studied. In this paper, the synthesis and the pharmacological profile of a further class of conformationally restricted analogues of GV150526 as in vitro and in vivo potent glycine antagonists is reported. In particular, a pyrazolidinone derivative was identified as a potent neuroprotective agent in animal models of cerebral ischaemia.
authors.affiliation: GlaxoSmzithKline Group, GlaxoWellcome SpA, Medicines Research Centre, Verona, Italy. rdf26781@glaxowellcome.co.uk
authors.forename: R D
authors.initials: RD
authors.lastname: Fabio
authors.forename: G
authors.initials: G
authors.lastname: Araldi
authors.forename: D
authors.initials: D
authors.lastname: Baraldi
authors.forename: A
authors.initials: A
authors.lastname: Cugola
authors.forename: D
authors.initials: D
authors.lastname: Donati
authors.forename: P
authors.initials: P
authors.lastname: Gastaldi
authors.forename: S A
authors.initials: SA
authors.lastname: Giacobbe
authors.forename: F
authors.initials: F
authors.lastname: Micheli
authors.forename: G
authors.initials: G
authors.lastname: Pentassuglia
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D005998:Glycine / Q000037:antagonists & inhibitors*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000517:prevention & control; D020521:Stroke / Q000517:prevention & control; D013329:Structure-Activity Relationship
chemical_list: C105319:3-(2-((phenylamino)carbonyl)ethenyl)-4,6-dichloroindole-2-carboxylic acid; D007211:Indoles; D018696:Neuroprotective Agents; D005998:Glycine