Synthesis and evaluation of carbamate and aryl ether substituted pyrazinones as corticotropin releasing factor-1 (CRF1) receptor antagonists. Issue 9 (1st May 2016)

• Record Type: Journal Article
• Authors: Ahuja, Vijay T.; Hartz, Richard A.; Molski, Thaddeus F.; Mattson, Gail K.; Lentz, Kimberley A.; Grace, James E.; Lodge, Nicholas J.; Bronson, Joanne J.; Macor, John E.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 9(2016)
• Page Start: 2184
• Page End: 2187
• Publication Date: 2016-05-01
• Subjects: CRF1 receptor antagonists -- CRF -- Depression -- Neuroscience -- Pyrazinones; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.067
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of pyrazinone-based compounds incorporating either carbamate or aryl ether groups was synthesized and evaluated as corticotropin-releasing factor-1 (CRF1 ) receptor antagonists. Structure–activity relationship studies led to the identification of highly potent CRF1 receptor antagonists14a (IC50 = 0.74 nM) and14b (IC50 = 1.9 nM). The synthesis, structure–activity relationships and in vitro metabolic stability properties of compounds in this series will be described.