Heterocyclic glucocorticoid receptor modulators with a 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl)propanamide core

Hai-Yun Xiao; Dauh-Rurng Wu; James E Sheppeck 2nd; Sium F Habte; Mark D Cunningham; John E Somerville; Joel C Barrish; Steven G Nadler; T G Murali Dhar

doi:10.1016/j.bmcl.2013.08.049

Heterocyclic glucocorticoid receptor modulators with a 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl)propanamide core

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5571-4. doi: 10.1016/j.bmcl.2013.08.049. Epub 2013 Aug 16.

Authors

Hai-Yun Xiao¹, Dauh-Rurng Wu, James E Sheppeck 2nd, Sium F Habte, Mark D Cunningham, John E Somerville, Joel C Barrish, Steven G Nadler, T G Murali Dhar

Affiliation

¹ Research and Development, Bristol-Myers Squibb Company, Princeton, NJ 08543-4000, United States.

PMID: 24011644
DOI: 10.1016/j.bmcl.2013.08.049

Abstract

A series of heterocyclic glucocorticoid receptor (GR) modulators with 2,2-dimethyl-3-phenyl-N-(thiazol or thiadiazol-2-yl)propanamide core are described. Structure-activity relationships suggest a combination of H-bond acceptor and a 4-fluorophenyl moiety as being important structural components contributing to the glucocorticoid receptor binding and functional activity for this series of GR modulators.

Keywords: Dissociated steroids; Glucocorticoid receptor; Non-steroidal glucocorticoid receptor agonists; Transactivation; Transrepression.

MeSH terms

Amides / chemistry*
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry*
Heterocyclic Compounds / metabolism
Protein Binding
Receptors, Glucocorticoid / agonists*
Receptors, Glucocorticoid / metabolism
Stereoisomerism
Structure-Activity Relationship
Thiadiazoles / chemistry*
Thiazoles / chemistry*

Substances

Amides
Heterocyclic Compounds
Receptors, Glucocorticoid
Thiadiazoles
Thiazoles