Synthesis and structure-activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists.
A series of N(3)-pyridylpyrazinones was investigated as corticotropin-releasing factor-1 receptor antagonists. It was observed that the binding affinity of analogues containing a pyridyl group was influenced not only by the substitution pattern on the pyridyl group, but also by the pK(a) of the pyridyl nitrogen. Analogues containing a novel 6-(difluoromethoxy)-2,5-dimethylpyridin-3-amine group were among the most potent N(3)-pyridylpyrazinones synthesized. The synthesis and SAR of N(3)-pyridylpyrazinones is described herein.
Hartz
Richard A
RA
Neuroscience Discovery Chemistry, Research and Development, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA. richard.hartz@bms.com
Ahuja
Vijay T
VT
Schmitz
William D
WD
Molski
Thaddeus F
TF
Mattson
Gail K
GK
Lodge
Nicholas J
NJ
Bronson
Joanne J
JJ
Macor
John E
JE
D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
D011719:Pyrazines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1