title: Molecular modelling and conformational analysis of novel glycoprotein (Gp) IIb/IIIa antagonists. Molecular orbital calculation and the condensed heterocyclic derivatives.
abstract: A naphthalene compound was chosen as lead compound to develop a new series of fibrinogen receptor antagonists. Eight new compounds with different condensed heterocyclic parts were prepared and their in vitro activities were evaluated. 5-Amidinobenzofuran compound 2, 6-amidinobenzothiophene 7, and 5-amidinofuro[2,3-b]pyridine 8 were more active than lead compound 1. Molecular orbital calculation studies suggested the presence of a preferred spatial orientation between the amidine and the carboxylic acid.
authors.affiliation: Exploratory Reseach II, Drug Discovery Laboratories, Welfide Corporation, 2-25-1 Shodai-Ohtani, Hirakata, 573-1153, Osaka, Japan. onos@welfide.co.jp
authors.forename: S
authors.initials: S
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Kosaka
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Imada
authors.forename: C
authors.initials: C
authors.lastname: Fukaya
authors.forename: N
authors.initials: N
authors.lastname: Nakamura
mesh_terms: D000085:Acetates / Q000737:chemistry* / Q000494:pharmacology*; D000578:Amidines / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: C412594:2-(((5-amidinobenzofuran-2-yl)formamido)phenyloxy)acetic acid; C412593:2-(((5-amidinofuro(2,3-b)pyridin-2-yl)formamido)phenyloxy)acetic acid; C412592:2-(((6-amidinobenzothiophene-2-yl)formamido)phenyloxy)acetic acid; D000085:Acetates; D000578:Amidines; D006571:Heterocyclic Compounds; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex