title: Serendipitous oxidation product of BIBN4096BS: a potent CGRP receptor antagonist.
abstract: An oxidation product (5) formed during the synthesis of BIBN-4096BS (1) was found to be a potent CGRP antagonist (IC50=0.11nM). While 5 was found to be ten-fold less potent than 1, another analog 8 with lower molecular weight containing the oxidized fragment demonstrated twenty-fold higher activity than its parent 7. Alternative conditions which preclude the formation of the oxidation product are described. The activities of 1, 5, 7 and 8 in functional cAMP assay are also discussed.
authors.affiliation: Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: Bireshwar.Dasgupta@bms.com.
authors.forename: Bireshwar
authors.initials: B
authors.lastname: Dasgupta
authors.affiliation: Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Kozlowski
authors.affiliation: Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Schroeder
authors.affiliation: Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: John R
authors.initials: JR
authors.lastname: Torrente
authors.affiliation: Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Cen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Sokhom
authors.initials: S
authors.lastname: Pin
authors.affiliation: Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Charlie M
authors.initials: CM
authors.lastname: Conway
authors.affiliation: Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
authors.affiliation: Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.affiliation: Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: Vivekananda.Vrudhula@bms.com.
authors.forename: Vivekananda M
authors.initials: VM
authors.lastname: Vrudhula
mesh_terms: D001681:Biological Assay; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010879:Piperazines; D011799:Quinazolines; C406305:olcegepant
keywords: Antagonists; BIBN4096BS; CGRP