171722-92-2

Usage

Uses

Used in Pharmaceutical Synthesis:
Piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate is used as an intermediate in the synthesis of Des-4''(methylpiperidine-4-carboxamide)-4''-hydroxymethyl Revefenacin (D119860), which is an impurity of Revefenacin (R279600). Revefenacin is a pharmaceutical drug utilized for the treatment of chronic obstructive pulmonary diseases (COPD). The compound plays a significant role in the development of effective treatments for respiratory conditions by contributing to the synthesis of the active pharmaceutical ingredient.
In the pharmaceutical industry, piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate is used as a key building block for the creation of Revefenacin, a drug that targets the management and treatment of chronic obstructive pulmonary diseases. Its application in this context is crucial, as it helps in the development of medications that can improve the quality of life for patients suffering from these respiratory conditions.

Physical Form

Solid

InChI:InChI=1/C18H20N2O2/c21-18(22-15-10-12-19-13-11-15)20-17-9-5-4-8-16(17)14-6-2-1-3-7-14/h1-9,15,19H,10-13H2,(H,20,21)

Upstream product

• 4727-72-4 1-benzyl-4-hydroxypiperidine 
• 17337-13-2 [1,1'-biphenyl]-2-yl-isocyanate 
• 90-41-5 2-phenylaniline 
• 1225223-05-1 C₁₄H₂₁N₃O₄ 
• 171723-80-1 1-benzyl-4-piperidylbiphenyl-2-ylcarbamate 
• 947-84-2 2-Biphenylcarboxylic acid 

Downstream Products

• 171723-10-7 biphenyl-2-yl-carbamic acid 1-(4-nitro-benzyl)-piperidin-4-yl ester 
• 171723-09-4 1-(3-nitrobenzyl)-4-piperidyl biphenyl-2-ylcarbamate 
• 953394-10-0 biphenyl-2-ylcarbamic acid 1-[2-(4-[1,3]dioxolan-2-yl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester 
• 953394-16-6 biphenyl-2-ylcarbamic acid 1-[2-(4-iodo-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester 
• 743461-40-7 biphenyl-2-ylcarbamic Acid 1-[2-Fluoro-3-(4-hydroxymethylpiperidin-1-ylmethyl)-benzyl]piperidin-4-yl Ester 
• 852291-44-2 biphenyl-2-ylcarbamic acid 1-(9-hydroxynonyl)piperidin-4-yl ester 
• 743461-45-2 biphenyl-2-ylcarbamic Acid 1-{3-[4-(2-Hydroxyethyl)phenoxy]propyl}piperidin-4-yl Ester 
• 743460-49-3 biphenyl-2-ylcarbamic acid 1-[2-((benzyloxycarbonyl)-N-methylamino)ethyl]piperidin-4-yl ester 
• 743461-12-3 biphenyl-2-ylcarbamic Acid 1-[2-(5-tert-Butoxycarbonylaminopentylsulfamoyl)-ethyl]piperidin-4-yl Ester 
• 743461-50-9 Methyl (4-{4-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]butyl}phenyl)acetate 
• 876126-21-5 methyl 4-{3-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionylamino}-5-chloro-2-methoxybenzoate 
• 743460-98-2 biphenyl-2-ylcarbamic Acid 1-[2-(4-(tert-Butoxycarbonylaminomethyl)-2-chlorophenylcarbamoyl)ethyl]piperidin-4-yl Ester 
• 852291-49-7 biphenyl-2-ylcarbamic acid 1-[2-(4-hydroxymethylphenylcarbamoyl)ethyl]-piperidin-4-yl ester 
• 743461-33-8 biphenyl-2-ylcarbamic Acid 1-[(E)-3-(4-Nitrophenyl)allyl]piperidin-4-yl Ester 

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).

PROCESS FOR PREPARING A BIPHENYL-2-YLCARBAMIC ACID

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.

Discovery of muscarinic acetylcholine receptor antagonist and beta 2 adrenoceptor agonist (MABA) dual pharmacology molecules

We sought to design dual pharmacology bronchodilators targeting both the M3 muscarinic acetylcholine and beta-2 adrenergic (β2) receptors by applying our multivalent approach to drug discovery. Herein, we describe our initial discovery and the SAR of the first such compounds with matched potencies at both receptors.

Crystalline forms of a biphenyl compound

The invention provides crystalline forms of biphenyl-2-ylcarbamic acid 1-[2-({3-[2-(4-hydroxybenzylamino)ethylcarbamoyl]benzoyl}methylamino)ethyl]piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The crystalline form can be a freebase (Form I or II), a salt such as a hemiedisylate salt or a heminapadisylate salt, or a solvate of a salt such as a heminapadisylate methanolate or a heminapadisylate ethanolate. The invention also provides pharmaceutical compositions comprising these crystalline compounds or prepared using these compounds; processes and intermediates for preparing the crystalline compounds; and methods of using these compounds to treat a pulmonary disorder.

Crystalline forms of a dimethylphenyl compound

The invention relates to crystalline free base forms of biphenyl-2-ylcarbamic acid 1-[2-(4-{[(R)-2-(3-formylamino-4-hydroxyphenyl)-2-hydroxyethylamino]methyl}-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester or a solvate thereof. This invention also relates to pharmaceutical compositions containing or prepared from such crystalline forms; processes and intermediates useful for preparing such crystalline forms; and methods of using such crystalline forms to, for example, treat a pulmonary disorder.

Dialkylphenyl compounds having beta2 adrenergic receptor agonist and muscarinic receptor antagonist activity

This invention relates to compounds of formula I: wherein R1 and R2 are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The invention also relates to pharmaceutical compositions and combinations comprising such compounds, processes and intermediates for preparing such compounds, and methods of using such compound to, for example, treat pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

Biphenyl compounds useful as muscarinic receptor antagonists

The invention provides compounds of formula I: wherein a, b, c, d, f, W, Q, Y, R1, R2, and R3 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.

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.

Crystalline forms of a biphenyl compound

The invention provides crystalline naphthalene-1,5-disulfonic acid salts of biphenyl-2-ylcarbamic acid 1-{2-[5-(4-hydroxybenzylamino)pentylcarbamoyl]ethyl}piperidin-4-yl ester, and pharmaceutically acceptable solvates thereof. The invention also provides pharmaceutical compositions comprising the crystalline compounds or prepared using such compounds; processes and intermediates for preparing the crystalline compounds; and methods of using the compounds to treat pulmonary disorders.