Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamine moieties

L L Brockunier; M R Candelore; M A Cascieri; Y Liu; L Tota; M J Wyvratt; M H Fisher; A E Weber; E R Parmee

doi:10.1016/s0960-894x(00)00669-7

Human beta3 adrenergic receptor agonists containing cyanoguanidine and nitroethylenediamine moieties

Bioorg Med Chem Lett. 2001 Feb 12;11(3):379-82. doi: 10.1016/s0960-894x(00)00669-7.

Authors

L L Brockunier¹, M R Candelore, M A Cascieri, Y Liu, L Tota, M J Wyvratt, M H Fisher, A E Weber, E R Parmee

Affiliation

¹ Department of Medicinal Chemistry, Biochemistry and Physiology, Merck Research Laboratories, Rahway, NJ 07065, USA.

PMID: 11212115
DOI: 10.1016/s0960-894x(00)00669-7

Abstract

Pyridineethanolamine derivatives containing cyanoguanidine or nitroethylenediamine moieties were examined as human beta3 adrenergic receptor (AR) agonists. Notably, indoline derivatives 6a and 11 were potent beta3 AR agonists (beta3 EC50 = 13 and 19 nM, respectively), which showed good selectivity over binding to and minimal activation of the beta1 and beta2 ARs.

Publication types

Comparative Study

MeSH terms

Adenylyl Cyclases / drug effects
Adenylyl Cyclases / metabolism
Adrenergic beta-3 Receptor Agonists*
Adrenergic beta-Agonists / chemical synthesis*
Adrenergic beta-Agonists / chemistry
Adrenergic beta-Agonists / pharmacology
Animals
CHO Cells
Cell Membrane / chemistry
Combinatorial Chemistry Techniques
Cricetinae
Diamines / chemistry
Ethane / analogs & derivatives
Ethane / chemistry
Guanidines / chemistry
Humans
Inhibitory Concentration 50
Nitroparaffins / chemistry
Radioligand Assay
Receptors, Adrenergic, beta / metabolism
Receptors, Adrenergic, beta-3 / metabolism
Structure-Activity Relationship

Substances

Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Diamines
Guanidines
Nitroparaffins
Receptors, Adrenergic, beta
Receptors, Adrenergic, beta-3
nitroethane
Adenylyl Cyclases
Ethane
dicyandiamido