Aminoalkoxybenzyl pyrrolidines as novel human urotensin-II receptor antagonists.
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.
Jin
Jian
J
High Throughput Chemistry, GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, PA 19426, USA. jian.jin@gsk.com
Dhanak
Dashyant
D
Knight
Steven D
SD
Widdowson
Katherine
K
Aiyar
Nambi
N
Naselsky
Diane
D
Sarau
Henry M
HM
Foley
James J
JJ
Schmidt
Dulcie B
DB
Bennett
Carl D
CD
Wang
Bing
B
Warren
Gregory L
GL
Moore
Michael L
ML
Keenan
Richard M
RM
Rivero
Ralph A
RA
Douglas
Stephen A
SA
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
D011759:Pyrrolidines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human