title: Calcitonin gene-related peptide (CGRP) receptor antagonists: novel aspartates and succinates.
abstract: Novel aspartate and succinate CGRP full antagonists were identified through core modification of a potent lead CGRP antagonist, BMS-694153. While aspartates were much less active and had a flat SAR, some of the succinates were very potent CGRP full antagonists and matched the potency of BMS-694153. The most potency resides in the S enantiomer as demonstrated through an asymmetric synthesis.
authors.affiliation: Molecular Sciences and Candidate Optimization, Neuroscience Discovery 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: Sokhom S
authors.initials: SS
authors.lastname: Pin
authors.forename: Cen
authors.initials: C
authors.lastname: Xu
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: D001224:Aspartic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006801:Humans; D007191:Indazoles / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D052999:Quinazolinones / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013386:Succinates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C531228:4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007191:Indazoles; D052999:Quinazolinones; D013386:Succinates; D001224:Aspartic Acid