Synthesis and evaluation of 2-anilino-3-phenylsulfonyl-6-methylpyridines as corticotropin-releasing factor1 receptor ligands.
A novel series of 2-anilino-3-phenylsulfonyl-6-methylpyridines was synthesized and evaluated as corticotropin-releasing factor receptor ligands. Structure-activity relationship studies focused primarily on optimization of the 3-phenylsulfonyl group. Compounds within this series were identified which showed potent binding affinity for the CRF1 receptor. Selected compounds were examined in a rat pharmacokinetic study and were found to have oral bioavailabilities ranging from 16 to 35%.
Hartz
Richard A
RA
Discovery Chemistry, Bristol-Myers Squibb Company, Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. richard.hartz@bms.com
Arvanitis
Argyrios G
AG
Arnold
Charles
C
Rescinito
Joseph P
JP
Hung
Kimberly L
KL
Zhang
Ge
G
Wong
Harvey
H
Langley
David R
DR
Gilligan
Paul J
PJ
Trainor
George L
GL
D000284:Administration, Oral; D000818:Animals; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D000099052:CRF Receptor, Type 1
D008024:Ligands; D011725:Pyridines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1