title: P2T purinoceptor antagonists. A QSAR study of some 2-substituted ATP analogues.
abstract: FPL67085MX represents the first in a class of novel, highly potent and selective P2T purinoceptor antagonists which are inhibitors of adenosine diphosphate (ADP)-induced platelet aggregation in-vitro. In an early series of compounds we studied the effect of variation of the adenine 2-substituent on potency and derived quantitative structure-activity relationships (QSARs) between the properties of the molecules and their biological activity. This work has recently been revisited using comparative molecular-field analysis (CoMFA) and the comparison of the predictions from the two methods is discussed along with their relative merits in terms of compound design. The model suggests that the receptor for these molecules has a narrow lipophilic cleft, which is occupied by the adenine 2-substituent.
authors.affiliation: Pharmaceutical Division, Fisons plc, Loughborough, Leicestershire, UK.
authors.forename: N P
authors.initials: NP
authors.lastname: Tomkinson
authors.forename: D P
authors.initials: DP
authors.lastname: Marriott
authors.forename: P A
authors.initials: PA
authors.lastname: Cage
authors.forename: D
authors.initials: D
authors.lastname: Cox
authors.forename: A M
authors.initials: AM
authors.lastname: Davis
authors.forename: D R
authors.initials: DR
authors.lastname: Flower
authors.forename: N P
authors.initials: NP
authors.lastname: Gensmantel
authors.forename: R G
authors.initials: RG
authors.lastname: Humphries
authors.forename: A H
authors.initials: AH
authors.lastname: Ingall
authors.forename: N D
authors.initials: ND
authors.lastname: Kindon
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D016014:Linear Models; D013329:Structure-Activity Relationship
chemical_list: C096709:FPL 67085; D000255:Adenosine Triphosphate