title: Aminoalkoxybenzyl pyrrolidines as novel human urotensin-II receptor antagonists.
abstract: High throughput screening of the corporate compound collection led to the discovery of a novel series of substituted aminoalkoxybenzyl pyrrolidines as human urotensin-II receptor antagonists. The synthesis, initial structure-activity relationships, and optimization of the initial hit that led to the identification of a truncated sub-series, represented by SB-436811 (1a), are described.
authors.affiliation: High Throughput Chemistry, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. jian.jin@gsk.com
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.forename: Dashyant
authors.initials: D
authors.lastname: Dhanak
authors.forename: Steven D
authors.initials: SD
authors.lastname: Knight
authors.forename: Katherine
authors.initials: K
authors.lastname: Widdowson
authors.forename: Nambi
authors.initials: N
authors.lastname: Aiyar
authors.forename: Diane
authors.initials: D
authors.lastname: Naselsky
authors.forename: Henry M
authors.initials: HM
authors.lastname: Sarau
authors.forename: James J
authors.initials: JJ
authors.lastname: Foley
authors.forename: Dulcie B
authors.initials: DB
authors.lastname: Schmidt
authors.forename: Carl D
authors.initials: CD
authors.lastname: Bennett
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Warren
authors.forename: Michael L
authors.initials: ML
authors.lastname: Moore
authors.forename: Richard M
authors.initials: RM
authors.lastname: Keenan
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Rivero
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Douglas
mesh_terms: D004353:Drug Evaluation, Preclinical; D006801:Humans; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011759:Pyrrolidines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human