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.
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. diem_nguyen@merck.com
Diem N
DN
Nguyen
Daniel V
DV
Paone
Anthony W
AW
Shaw
Christopher S
CS
Burgey
Scott D
SD
Mosser
Victor
V
Johnston
Christopher A
CA
Salvatore
Yvonne M
YM
Leonard
Cynthia M
CM
Miller-Stein
Stefanie A
SA
Kane
Kenneth S
KS
Koblan
Joseph P
JP
Vacca
Samuel L
SL
Graham
Theresa M
TM
Williams
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