title: Discovery of BMS-846372, a Potent and Orally Active Human CGRP Receptor Antagonist for the Treatment of Migraine.
abstract: Calcitonin gene-related peptide (CGRP) receptor antagonists have been clinically shown to be effective in the treatment of migraine, but identification of potent and orally bioavailable compounds has been challenging. Herein, we describe the conceptualization, synthesis, and preclinical characterization of a potent, orally active CGRP receptor antagonist 5 (BMS-846372). Compound 5 has good oral bioavailability in rat, dog, and cynomolgus monkeys and overall attractive preclinical properties including strong (>50% inhibition) exposure-dependent in vivo efficacy in a marmoset migraine model.
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Luo
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Conway
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Rex
authors.initials: R
authors.lastname: Denton
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Deborah
authors.initials: D
authors.lastname: Keavy
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Gulianello
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Walter
authors.initials: W
authors.lastname: Kostich
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Lentz
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Mercer
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Schartman
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Signor
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Marc
authors.initials: M
authors.lastname: Browning
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Biology, Bristol-Myers Squibb Research & Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
keywords: CGRP; CGRP receptor; antagonist; migraine