Discovery of L-755,507: a subnanomolar human beta 3 adrenergic receptor agonist

E R Parmee; H O Ok; M R Candelore; L Tota; L Deng; C D Strader; M J Wyvratt; M H Fisher; A E Weber

doi:10.1016/s0960-894x(98)00170-x

Discovery of L-755,507: a subnanomolar human beta 3 adrenergic receptor agonist

Bioorg Med Chem Lett. 1998 May 5;8(9):1107-12. doi: 10.1016/s0960-894x(98)00170-x.

Authors

E R Parmee¹, H O Ok, M R Candelore, L Tota, L Deng, C D Strader, M J Wyvratt, M H Fisher, A E Weber

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, New Jersey 07065, USA.

PMID: 9871717
DOI: 10.1016/s0960-894x(98)00170-x

Abstract

A study of 4-acylaminobenzenesulfonamides in a cloned human beta 3 adrenergic receptor assay resulted in the discovery of n-hexylurea, L-755,507 (22). This 0.43 nM beta 3 agonist, which is > 440-fold selective over both beta 1 and beta 2 binding, is among the most potent human beta 3 agonists reported to date.

MeSH terms

Adrenergic beta-Agonists / chemical synthesis*
Adrenergic beta-Agonists / chemistry
Adrenergic beta-Agonists / pharmacology
Drug Design
Humans
Molecular Conformation
Molecular Structure
Receptors, Adrenergic, beta / drug effects*
Receptors, Adrenergic, beta / physiology
Receptors, Adrenergic, beta-1 / drug effects
Receptors, Adrenergic, beta-2 / drug effects
Receptors, Adrenergic, beta-3
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology*

Substances

Adrenergic beta-Agonists
L 755507
Receptors, Adrenergic, beta
Receptors, Adrenergic, beta-1
Receptors, Adrenergic, beta-2
Receptors, Adrenergic, beta-3
Sulfonamides