Calcitonin gene-related peptide (CGRP) receptor antagonists: investigations of a pyridinone template.
In our effort to find potent, orally bioavailable CGRP receptor antagonists for the treatment of migraine, a novel series based on a pyridinone template was investigated. After optimizing the privileged structure and the placement of the attached phenyl ring, systematic SAR was carried out on both the N-alkyl and C-5 aryl substituents. Several analogs with good potency and pharmacokinetic profiles were identified.
Nguyen
Diem N
DN
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. diem_nguyen@merck.com
Paone
Daniel V
DV
Shaw
Anthony W
AW
Burgey
Christopher S
CS
Mosser
Scott D
SD
Johnston
Victor
V
Salvatore
Christopher A
CA
Leonard
Yvonne M
YM
Miller-Stein
Cynthia M
CM
Kane
Stefanie A
SA
Koblan
Kenneth S
KS
Vacca
Joseph P
JP
Graham
Samuel L
SL
Williams
Theresa M
TM
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006207:Half-Life; D011728:Pyridones / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D011728:Pyridones