title: Synthesis and structure-activity relationships of N3-pyridylpyrazinones as corticotropin-releasing factor-1 (CRF1) receptor antagonists.
abstract: 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.
authors.affiliation: Neuroscience Discovery Chemistry, Research and Development, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA. richard.hartz@bms.com
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hartz
authors.forename: Vijay T
authors.initials: VT
authors.lastname: Ahuja
authors.forename: William D
authors.initials: WD
authors.lastname: Schmitz
authors.forename: Thaddeus F
authors.initials: TF
authors.lastname: Molski
authors.forename: Gail K
authors.initials: GK
authors.lastname: Mattson
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Lodge
authors.forename: Joanne J
authors.initials: JJ
authors.lastname: Bronson
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
mesh_terms: 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
chemical_list: D011719:Pyrazines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1