- Preparation methods of revefenacin intermediate and revefenacin
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The invention relates to a synthesis method of a revefenacin intermediate, which specifically comprises the following steps: in a solvent, enabling piperidin-4-yl [1,1-biphenyl]-2-carbamate to react with methyl(2-oxyethyl) tert-butyl carbamate in the pres
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Paragraph 0073-0075
(2021/05/26)
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- Discovery of (R)-1-(3-((2-Chloro-4-(((2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-5-methoxyphenyl)amino)-3-oxopropyl)piperidin-4-yl [1,1′-biphenyl]-2-ylcarbamate (TD-5959, GSK961081, Batefenterol): First-in-Class dual pharmacology multivalent muscarinic antagonist and β2 agonist (MABA) for the treatment of chronic obstructive pulmonary disease (COPD)
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Through application of our multivalent approach to drug discovery we previously reported the first discovery of dual pharmacology MABA bronchodilators, exemplified by 1. Herein we describe the subsequent lead optimization of both muscarinic antagonist and β2 agonist activities, through modification of the linker motif, to achieve 24 h duration of action in a guinea pig bronchoprotection model. Concomitantly we targeted high lung selectivities, low systemic exposures and identified crystalline forms suitable for inhalation devices. This article culminates with the discovery of our first clinical candidate 12f (TD-5959, GSK961081, batefenterol). In a phase 2b trial, batefenterol produced statistical and clinically significant differences compared to placebo and numerically greater improvements in the primary end point of trough FEV1 compared to salmeterol after 4 weeks of dosing in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
- Hughes, Adam D.,Chen, Yan,Hegde, Sharath S.,Jasper, Jeffrey R.,Jaw-Tsai, Sarah,Lee, Tae-Weon,McNamara, Alexander,Pulido-Rios, M. Teresa,Steinfeld, Tod,Mammen, Mathai
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p. 2609 - 2622
(2015/04/14)
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- PROCESS FOR PREPARING A BIPHENYL-2-YLCARBAMIC ACID
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The invention provides a process of preparing an intermediate useful in the synthesis of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester, and a process of preparing a crystalline freebase of the ester.
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Page/Page column 9
(2012/02/01)
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- Compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity
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The invention is directed to compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7a, R7b, W, G1, G2, a, b, c, d and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.
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Page/Page column 41
(2008/06/13)
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