Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides

Jian Jin; Ming An; Anthony Sapienza; Nambi Aiyar; Diane Naselsky; Henry M Sarau; James J Foley; Kevin L Salyers; Steven D Knight; Richard M Keenan; Ralph A Rivero; Dashyant Dhanak; Stephen A Douglas

doi:10.1016/j.bmcl.2008.06.019

Urotensin-II receptor antagonists: synthesis and SAR of N-cyclic azaalkyl benzamides

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3950-4. doi: 10.1016/j.bmcl.2008.06.019. Epub 2008 Jun 10.

Authors

Jian Jin¹, Ming An, Anthony Sapienza, Nambi Aiyar, Diane Naselsky, Henry M Sarau, James J Foley, Kevin L Salyers, Steven D Knight, Richard M Keenan, Ralph A Rivero, Dashyant Dhanak, Stephen A Douglas

Affiliation

¹ Centers of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA. jian.jin@gsk.com

PMID: 18573659
DOI: 10.1016/j.bmcl.2008.06.019

Abstract

SAR exploration of the central diamine, benzyl, and terminal aminoalkoxy regions of the N-cyclic azaalkyl benzamide series led to the identification of very potent human urotensin-II receptor antagonists such as 1a with a K(i) of 4 nM. The synthesis and structure-activity relationships (SAR) of N-cyclic azaalkyl benzamides are described.

MeSH terms

Benzamides / chemistry*
Binding Sites
Chemistry, Pharmaceutical / methods
Diamines / chemistry
Drug Design
Humans
Inhibitory Concentration 50
Kinetics
Models, Chemical
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Benzamides
Diamines
Receptors, G-Protein-Coupled
UTS2R protein, human