743461-62-3

Upstream product

• 876126-21-5 methyl 4-{3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-5-chloro-2-methoxybenzoate 
• 743461-60-1 methyl 4-Acryloylamino-5-chloro-2-methoxybenzoate 
• 171723-80-1 1-benzyl-4-piperidylbiphenyl-2-ylcarbamate 
• 20896-27-9 methyl 4-amino-5-chloro-2-methoxybenzoate 
• 171722-92-2 4-piperidyl N-(2-biphenyl)carbamate 
• 17337-13-2 [1,1'-biphenyl]-2-yl-isocyanate 
• 4727-72-4 1-benzyl-4-hydroxypiperidine 
• 1225223-05-1 C₁₄H₂₁N₃O₄ 
• 90-41-5 2-phenylaniline 

Downstream Products

• 743461-63-4 biphenyl-2-ylcarbamic Acid 1-[2-(2-Chloro-4-formyl-5-methoxyphenylcarbamoyl)-ethyl]piperidin-4-yl Ester 
• 743461-64-5 biphenyl-2-ylcarbamic Acid 1-[2-(4-{[(R)-2-(tert-Butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-2-chloro-5-methoxy-phenylcarbamoyl)ethyl]piperidin-4-yl Ester 
• 743461-65-6 (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 

Relevant academic research and scientific papers

GSK961081 and its intermediate synthesis method

The invention relates to a new method for preparing a medicine GSK961081 and an intermediate thereof. Compared with an existing synthetic method, the new method not only avoids the use of a hypertoxic isocyanate reagent, but also is simple in synthetic ro

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)

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).

Crystalline form of a biphenyl compound

The invention provides a crystalline 1,2-ethanedisulfonic acid salt of biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also provides pharmaceutical compositions comprising such a salt or prepared using such a salt; processes and intermediates for preparing such a salt; and methods of using such a salt to treat a pulmonary disorder.

Biphenyl derivatives

This invention provides biphenyl derivatives of formula I: wherein R1, R2, R3, R4, R5, R6, R7, W, a, b and c are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The biphenyl derivatives of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity and therefore, such biphenyl derivatives are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.