- Intramolecular Crossed [2+2] Photocycloaddition through Visible Light-Induced Energy Transfer
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Herein, we present the intramolecular [2+2] cycloadditions of dienones promoted through sensitization, using a polypyridyl iridium(III) catalyst, to form bridged cyclobutanes. In contrast to previous examples of straight [2+2] cycloadditions, these efficient crossed additions were achieved under irradiation with visible light. The reactions delivered desired bridged benzobicycloheptanone products with excellent regioselectivity in high yields (up to 96%). This process is superior to previous syntheses of benzobicyclo[3.1.1]heptanones, which are readily converted to B-norbenzomorphan analogues of biological significance. Electrochemical, computational, and spectroscopic studies substantiated the mechanism of triplet energy transfer and explained the unusual regiocontrol.
- Zhao, Jiannan,Brosmer, Jonathan L.,Tang, Qingxuan,Yang, Zhongyue,Houk,Diaconescu, Paula L.,Kwon, Ohyun
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supporting information
p. 9807 - 9810
(2017/08/03)
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- Asymmetric Synthesis of the Major Metabolite of a Calcitonin Gene-Related Peptide Receptor Antagonist and Mechanism of Epoxide Hydrogenolysis
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An asymmetric synthesis of the major metabolite of the calcitonin gene-related peptide recepotor antagonist BMS-846372 is presented. The variously substituted cyclohepta[b]pyridine ring system represents an underexplored ring system and showed some unexpe
- Luo, Guanglin,Chen, Ling,Conway, Charles M.,Kostich, Walter,Johnson, Benjamin M.,Ng, Alicia,Macor, John E.,Dubowchik, Gene M.
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p. 3710 - 3720
(2017/04/11)
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- Discovery of BMS-846372, a potent and orally active human CGRP receptor antagonist for the treatment of migraine
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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.
- Luo, Guanglin,Chen, Ling,Conway, Charles M.,Denton, Rex,Keavy, Deborah,Gulianello, Michael,Huang, Yanling,Kostich, Walter,Lentz, Kimberley A.,Mercer, Stephen E.,Schartman, Richard,Signor, Laura,Browning, Marc,MacOr, John E.,Dubowchik, Gene M.
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supporting information; experimental part
p. 337 - 341
(2012/06/01)
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- CGRP Receptor Antagonists
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The disclosure generally relates to the novel compounds of formula I, including their salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).
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Page/Page column 24-25
(2009/10/21)
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- Conjugate addition of 2- and 4-pyridylcuprates: An expeditious asymmetric synthesis of natural (-)-evoninic acid
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(Chemical Equation Presented) The scope and limitations of the conjugate addition of 2- and the first 4-pyridyl Gilman homocuprates to various α,β-unsaturated Michael acceptors are delineated. The conjugate addition of the cuprate of 2-bromo-3-methylpyridine to (E)-methyl crotonate then diastereoselective enolate alkylation and lipase-mediated enantioselective ester hydrolysis have enabled an efficient four-step first asymmetric synthesis of the Celastraceae sesquiterpenoid esterifying ligand (-)-(1′S,2′S) -evoninic acid.
- Spivey, Alan C.,Shukla, Lena,Hayler, Judy F.
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p. 891 - 894
(2007/10/03)
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