2. Academic Validation
  3. Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated glucocorticoid receptor agonists

Dimethyl-diphenyl-propanamide derivatives as nonsteroidal dissociated glucocorticoid receptor agonists

  • J Med Chem. 2010 Dec 9;53(23):8241-51. doi: 10.1021/jm100957a.
Bingwei V Yang 1,  David S Weinstein,  Lidia M Doweyko,  Hua Gong,  Wayne Vaccaro,  Tram Huynh,  Hai-Yun Xiao,  Arthur M Doweyko,  Lorraine McKay,  Deborah A Holloway,  John E Somerville,  Sium Habte,  Mark Cunningham,  Michele McMahon,  Robert Townsend,  David Shuster,  John H Dodd,  Steven G Nadler,  Joel C Barrish
Affiliations

Affiliation

  • 1 Bristol-Myers Squibb Company, Research and Development, Princeton, New Jersey 08543-4000, United States.
PMID: 21073190 DOI: 10.1021/jm100957a
Abstract

A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel Glucocorticoid Receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactivation assays. Compounds 17 and 30 showed anti-inflammatory activity comparable to prednisolone in the rat carrageenan-induced paw edema model, with markedly decreased side effects with regard to increases in blood glucose and expression of hepatic tyrosine aminotransferase. A hypothetical binding mode accounting for the induction of the functional activity by a 4-hydroxyl group is proposed.

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