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Serendipitous oxidation product of BIBN4096BS: a potent CGRP receptor antagonist.
Dasgupta, Bireshwar; Kozlowski, Edward; Schroeder, Daniel R; Torrente, John R; Xu, Cen; Pin, Sokhom; Conway, Charlie M; Dubowchik, Gene M; Macor, John E; Vrudhula, Vivekananda M.
Afiliação
  • Dasgupta B; Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: Bireshwar.Dasgupta@bms.com.
  • Kozlowski E; Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Schroeder DR; Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Torrente JR; Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Xu C; Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Pin S; Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Conway CM; Neuroscience Discovery Biology, Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Dubowchik GM; Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Macor JE; Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States.
  • Vrudhula VM; Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, United States. Electronic address: Vivekananda.Vrudhula@bms.com.
Bioorg Med Chem Lett ; 24(12): 2744-8, 2014 Jun 15.
Article em En | MEDLINE | ID: mdl-24794104
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Quinazolinas / Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Quinazolinas / Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina Idioma: En Ano de publicação: 2014 Tipo de documento: Article