title: Calcitonin gene-related peptide (CGRP) receptor antagonists: pyridine as a replacement for a core amide group.
abstract: In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good Caco-2 cell permeability.
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development, Wallingford, CT 06492, USA. guanglin.luo@bms.com
authors.forename: Guanglin
authors.initials: G
authors.lastname: Luo
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Rita
authors.initials: R
authors.lastname: Civiello
authors.forename: Sokhom S
authors.initials: SS
authors.lastname: Pin
authors.forename: Cen
authors.initials: C
authors.lastname: Xu
authors.forename: Walter
authors.initials: W
authors.lastname: Kostich
authors.forename: Michelle
authors.initials: M
authors.lastname: Kelley
authors.forename: Charles M
authors.initials: CM
authors.lastname: Conway
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: D000577:Amides / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006801:Humans; D020128:Inhibitory Concentration 50; D008881:Migraine Disorders / Q000188:drug therapy; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000577:Amides; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D011725:Pyridines