93609-84-8

Usage

Uses

Used in Pharmaceutical Industry:
5-Acetyl-8-(phenylmethoxy)-2-quinolinone is used as a key intermediate in the synthesis of phenylethanolamine derivatives, which are known as β2 adrenoreceptor agonists. These agonists play a crucial role in the treatment of various respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD), by relaxing the smooth muscles in the airways and improving lung function.
In the preparation of phenylethanolamine derivatives, 5-Acetyl-8-(phenylmethoxy)-2-quinolinone serves as a valuable building block, enabling the development of new and effective medications with improved pharmacological properties. Its unique structure and reactivity make it an essential component in the design and synthesis of innovative therapeutic agents targeting the β2 adrenoreceptor pathway.

Upstream product

• 100-44-7 benzyl chloride 
• 62978-73-8 5-acetyl-8-hydroxy-2(1H)-quinolinone 
• 1127-45-3 8-Hydroxyquinoline-N-oxide 
• 148-24-3 8-quinolinol 
• 15450-72-3 2-oxo-1,2-dihydroquinolin-8-yl acetate 
• 26872-48-0 1-(8-benzyloxyquinolin-5-yl)ethanone 
• 2598-31-4 5-acetyl-8-hydroxyquinoline 
• 100331-93-9 5-Acetyl-8-benzyloxyquinoline-N-oxide 
• 22614-69-3 8-methoxy-1H-quinolin-2-one 
• 100-39-0 benzyl bromide 
• 62978-76-1 acetyl-5 methoxy-8 carbostyrile 
• 15450-76-7 8-Hydroxy-1H-quinolin-2-one 

Downstream Products

• 93609-85-9 oxime de (benzyloxy-8 carbostyrile-5)-1-ethanone 
• 100331-89-3 8-benzyloxy-5-(2-bromoacetyl)-1H-quinolin-2-one 
• 63404-86-4 8-benzyloxy-5-[2-chloroacetyl]-1H-quinolin-2-one 
• 100331-91-7 5-(2,2-Dihydroxyacetyl)-8-(benzyloxy)-carbostyril 
• 956234-40-5 8-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)quinolin-2(1H)-one 
• 1613593-47-7 2-(4-((((R)-2-Hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl)amino)methyl)-2-methylphenoxy)ethyl 4-((3-((S)-phenyl((((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)phenoxy)methyl)benzoate 

Relevant academic research and scientific papers

CLASS OF BIFUNCTIONAL COMPOUNDS WITH QUATERNARY AMMONIUM SALT STRUCTURE

The invention provides a class of compounds represented by formula (I), having bifunctional active quaternary ammonium salt structure of a β2-adrenoreceptor agonist and an M receptor antagonist, a pharmaceutically acceptable salt, solvate, and optical isomer thereof. A pharmaceutical composition comprising such a compound with quaternary ammonium salt structure, a method for preparing such a compound with quaternary ammonium salt structure and an intermediate thereof, and uses thereof in treating pulmonary disorders are also provided. The compounds of the invention have high selectivity to the M receptor subtype, and have less adverse reaction and lower toxic and side effects in the treatment of pulmonary diseases such as COPD and asthma.

Discovery of β-arrestin-biased β2-adrenoceptor agonists from 2-amino-2-phenylethanol derivatives

β-Arrestins are a small family of proteins important for signal transduction at G protein-coupled receptors (GPCRs). β-Arrestins are involved in the desensitization of GPCRs. Recently, biased ligands possessing different efficacies in activating the G protein- versus the β-arrestin-dependent signals downstream of a single GPCR have emerged, which can be used to selectively modulate GPCR signal transduction in such a way that desirable signals are enhanced to produce therapeutic effects while undesirable signals of the same GPCR are suppressed to avoid side effects. In the present study, we evaluated agonist bias for compounds developed along a drug discovery project of β2-adrenoceptor agonists. About 150 compounds, including derivatives of fenoterol, 2-amino-1-phenylethanol and 2-amino-2-phenylethanol, were obtained or synthesized, and initially screened for their β-adrenoceptor-mediated activities in the guinea pig tracheal smooth muscle relaxation assay or the cardiomyocyte contractility assay. Nineteen bioactive compounds were further assessed using both the HTRF cAMP assay and the PathHunter β-arrestin assay. Their concentration-response data in stimulating cAMP synthesis and β-arrestin recruitment were applied to the Black–Leff operational model for ligand bias quantitation. As a result, three compounds (L-2, L-4, and L-12) with the core structure of 5-(1-amino-2-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one were identified as a new series of β-arrestin-biased β2-adrenoceptor agonists, whereas salmeterol was found to be Gs-biased. These findings would facilitate the development of novel drugs for the treatment of both heart failure and asthma.

A Process for Preparing Indacaterol and Salts Thereof

The present invention relates to a process for preparing indacaterol or salts thereof. The process comprises of forming compound of Formula 1 by reacting compound of Formula 2 and compound of Formula 3 in the presence of a solvent to Form compound of Formula 4, which on removal of the protecting groups forms compound of Formula 1.

QUATERNARY AMMONIUM SALT COMPOUNDS

[Problem] The object of the present invention is to provide a novel compound having 132 adrenergic receptor agonist activity and muscarinic receptor antagonist activity. [Means for Solving the Problem] The present invention is a quaternary ammonium salt compounds represented by formula (I), or a pharmaceutically acceptable salt thereof, with superior β32 adrenergic receptor agonist activity and muscarinic receptor antagonist activity.

PROCESS FOR PREPARING ISOMERS OF CARMOTEROL

A process for preparing a compound of formula (III) comprising condensing an oxiranyl compound of formula (I) with an amine of formula (II) or a salt thereof wherein: R1 is a group selected from alkyl, aryl, allyl, alkoxy, cycloalkyl, heterocyclic, alkenyl, benzocycloalkyl, aralkyl, haloarylalkyl, heteroaralkyl, haloalkyl, alkoxyaralkyl, substituted silyl and benzyl; and R2 is hydrogen, optionally substituted silyl or optionally substituted benzyl. Formula (I), (II) and (III): There is also described a process for preparing (R,R)-carmoterol from compound (III).

Compounds having beta adrenergic receptor agonist and muscarinic receptor antagonist activity

This invention provides compounds of formula I: wherein R1, R2, R4, R5, R6, R7, R8a, R8b, W, a, b, c and m are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Accordingly, such compounds are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

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.

COMPOUNDS HAVING β2 ADRENERGIC RECEPTOR AGONIST AND MUSCARINIC RECEPTOR ANTAGONIST ACTIVITY

This invention provides compounds of formula I wherein R1, R2, R3, R4, R5, R6, R7, R8a, R8b, W, a and b are as defined in the specification, or a pharmaceutically acceptable salt or solvate or stereoisomer thereof. The compounds of this invention possess both β2 adrenergic receptor agonist and muscarinic receptor antagonist activity. Accordingly, such compounds are expected to be useful as therapeutic agents for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.

ORGANIC COMPOUNDS

A process for preparing 8-substituted oxy-5-((R)-2-halo-l-hydroxy-ethyl)-(1 H)-quinolin-2-ones or acceptable solvates thereof. The process involves reacting a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one with a reducing agent in the presence of a chiral agent and a base to form a 8-(substituted oxy)-5-((R)-2-halo-l-hydroxy-ethyl)-(1H)-quinolin-2-one, said chiral agent having a formula (I) or (II), wherein M, L, X, R1, R2 and R3 have the meanings as indicated in the specification.

Crystalline form of a biphenyl compound

The invention provides a crystalline naphthalene-1,5-disulfonic acid salt of biphenyl-2-ylcarbamic acid 1-{9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydro-quinolin-5-yl)ethylamino]nonyl}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.