93609-84-8Relevant articles and documents
Discovery of β-arrestin-biased β2-adrenoceptor agonists from 2-amino-2-phenylethanol derivatives
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)
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
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Paragraph 0069, (2018/08/20)
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.
PROCESS FOR PREPARING ISOMERS OF CARMOTEROL
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, (2008/12/07)
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).
