title: Evolution of a series of peptidoleukotriene antagonists: synthesis and structure-activity relationships of 1,6-disubstituted indoles and indazoles.
abstract: A perception of structural similarities between two independent series of leukotriene antagonists (one emanating from FPL 55712 and one based upon the leukotrienes themselves) led to the discovery of a novel class of indole and indazole derived antagonists of peptidoleukotrienes. A systematic exploration of C-6 substituted 4-(indol-1-ylmethyl)-3-methoxybenzoic acids identified cyclopentylacetamide and cyclopentylurethane as preferred substituents. The corresponding indazoles were equipotent. These compounds are selective leukotriene antagonists with pKB values of 7.5-7.8 vs LTE4 on guinea pig trachea.
authors.affiliation: Department of Medicinal Chemistry, ICI Pharmaceuticals Group, Wilmington, Delaware 19897.
authors.forename: F J
authors.initials: FJ
authors.lastname: Brown
authors.forename: Y K
authors.initials: YK
authors.lastname: Yee
authors.forename: L A
authors.initials: LA
authors.lastname: Cronk
authors.forename: K C
authors.initials: KC
authors.lastname: Hebbel
authors.forename: R D
authors.initials: RD
authors.lastname: Krell
authors.forename: D W
authors.initials: DW
authors.lastname: Snyder
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007191:Indazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D011720:Pyrazoles / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D007191:Indazoles; D007211:Indoles; D011720:Pyrazoles; D013189:SRS-A