- Novel Quinolone Derivatives: Synthesis and Antioxidant Activity
-
Abstract: Novel quinolone derivatives have been designed and readily synthesized according to a simple protocol including O-alkylation and Claisen rearrangement processes. Structures of the synthesized compounds have been confirmed by IR, 1H and 13C NMR, and mass spectra. The new products have been tested for their antioxidant activity, and two of those demonstrate high antioxidant activity.
- Chennupalli, Venkata Suryanarayana,Prasad, Mutyala Veera Venkata Vara,Rao, Radha Hunasenahalli Raghavendra,Sathish, Byrappa,Veeranna, Vadde
-
p. 2522 - 2526
(2022/01/22)
-
- 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.
- Woo, Anthony Yiu-Ho,Ge, Xin-yue,Pan, Li,Xing, Gang,Mo, Yong-mei,Xing, Rui-juan,Li, Xiao-ran,Zhang, Yu-yang,Wainer, Irving W.,Cheng, Mao-sheng,Xiao, Rui-ping
-
p. 1095 - 1105
(2019/01/19)
-
- 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.
- -
-
Paragraph 0157
(2019/11/11)
-
- 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.
- -
-
Page/Page column 20
(2012/03/10)
-
- 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.
- -
-
Page/Page column 25
(2008/06/13)
-
- 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.
- -
-
Page/Page column 13
(2008/06/13)
-
- 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.
- -
-
Page/Page column 64
(2008/06/13)
-
- 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.
- -
-
Page/Page column 32-33
(2008/06/13)
-
- 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.
- -
-
Page/Page column 11
(2010/02/13)
-
- 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.
- -
-
Page/Page column 32
(2008/06/13)
-
- DIARYLMETHYL AND RELATED COMPOUNDS
-
This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, R6, R7, Ar1, Ar2, E, a, b, c, and z 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. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
- -
-
-
- A PROCESS FOR THE PREPARATION OF 5-(HALOACETYL)-8-(SUBSTITUTED OXY)-(1H)-QUINOLIN-2-ONES
-
The invention relates to a process for preparing 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-ones. The process involves (i) reacting (a) 8-hydroxy-(1H)-quinolin-2-one with an acylating agent and a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (b) 8-hydroxy-(lH)-quinolin-2-one with an acylating agent to form 8-acetoxy-(lH)-quinolin-2-one, and treating, in-situ, the 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(1H)-quinolin-2-one; or (c) 8-acetoxy-(1H)-quinolin-2-one with a Lewis acid to form 5-acetyl-8-hydroxy-(lH)-quinolin-2-one; (ii) reacting the 5-acetyl-8-hydroxy-(1H)-quinolin-2-one prepared in Step (i) with a compound having the Formula RL in the presence of a base and a solvent to form 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one, wherein R is a protecting group and L is a leaving group; and (iii) reacting the 5-acetyl-8-substituted oxy-(1H)-quinolin-2-one with a halogenating agent in the presence of a solvent to form a 5-(α-haloacetyl)-8-substituted oxy-(1H)-quinolin-2-one.
- -
-
-
- Crystalline form of aryl aniline beta-2 adrenergic receptor agonist
-
The invention provides crystalline solvate forms of a salt of a novel β2 adrenergic receptor agonist. The invention also provides pharmaceutical compositions comprising the solvate forms, formulations containing the pharmaceutical compositions,
- -
-
-
- Azabicycloalkane compounds
-
This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, R6 and R7 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. Such compounds are useful for treating pulmonary disorders, such as chronic obstructive pulmonary disease and asthma.
- -
-
-
- Aryl aniline beta2 adrenergic receptor agonists
-
The invention provides novel β2 adrenergic receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with β2 adrenergic
- -
-
-
- Aryl aniline beta2 adrenergic receptor agonists
-
The invention provides novel β2 adrenergic receptor agonist compounds of formula (I): wherein R1-R13 and w have any of the values described in the specification. The invention also provides combinations of such compounds and other therapeutic agents, pharmaceutical compositions comprising such compounds and combinations, methods of using such compounds to treat diseases associated with β2 adrenergic receptor activity, and processes and intermediates useful for preparing such compounds.
- -
-
-
- Ethers of oximes with a carbostyril ring. IV. Syntheses and β-blocking activities
-
Syntheses of 12-O-(1-alkylamino-2-propanol)(8-hydroxy or alkoxycarbostyril)-5 methylketone oxime are reported. The beta-adrenergic blocking activity of the 12 compounds was determined in vitro on the trachea and atria of the guinea pig. Structure-activity relationships are discussed.
- Amlaiky,Leclerc,Decker,Schwartz
-
p. 341 - 346
(2007/10/02)
-
