864760-29-2

Upstream product

• 743460-61-9 biphenyl-2-ylcarbamic acid 1-(2-aminoethyl)piperidin-4-yl ester 
• 619-66-9 4-Carboxybenzaldehyde 
• 743460-60-8 biphenyl-2-ylcarbamic Acid 1-(2-tert-Butoxycarbonylaminoethyl)piperidin-4-yl Ester 
• 4727-72-4 1-benzyl-4-hydroxypiperidine 
• 17337-13-2 [1,1'-biphenyl]-2-yl-isocyanate 
• 171722-92-2 4-piperidyl N-(2-biphenyl)carbamate 
• 171723-80-1 1-benzyl-4-piperidylbiphenyl-2-ylcarbamate 

Relevant academic research and scientific papers

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).

Biphenyl compounds useful as muscarinic receptor antagonists

The invention provides compounds of formula I: wherein a, b, c, m, s, t, W, Z, Ar, R1, R2, R3, R6, and R7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.

Biphenyl compounds useful as muscarinic receptor antagonists

This invention provides compounds of formula I: wherein a, b, c, m, p, s, t, W, Ar1, X1, R1, R2, R3, R4, R6, and R7 are as defined in the specification. The compounds of formula I are muscarinic receptor antagonists. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing such compounds and methods of using such compounds to treat pulmonary disorders.