388080-67-9Relevant academic research and scientific papers
Identification, Structure-Activity Relationship, and Biological Characterization of 2,3,4,5-Tetrahydro-1 H-pyrido[4,3-b]indoles as a Novel Class of CFTR Potentiators
Brindani, Nicoletta,Gianotti, Ambra,Giovani, Simone,Giacomina, Francesca,Di Fruscia, Paolo,Sorana, Federico,Bertozzi, Sine Mandrup,Ottonello, Giuliana,Goldoni, Luca,Penna, Ilaria,Russo, Debora,Summa, Maria,Bertorelli, Rosalia,Ferrera, Loretta,Pesce, Emanuela,Sondo, Elvira,Galietta, Luis J. V.,Bandiera, Tiziano,Pedemonte, Nicoletta,Bertozzi, Fabio
supporting information, p. 11169 - 11194 (2020/10/09)
Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure-activity relationship studies led to the discovery of enantiomerically pure 39 endowed with a good efficacy in rescuing the gating defect of F508del-and G551D-CFTR and a promising in vitro druglike profile. The in vivo characterization of γ-carboline 39 showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.
COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CYSTIC FIBROSIS
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Page/Page column 43; 44; 48, (2020/02/06)
The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising the compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular to modulate CFTR protein or ABC protein activities.
New Heterocyclic compounds for therapeutic use
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, (2008/06/13)
A class of compounds particularly diaryl pyrazole of general formulas 1 and 2 where R and R′ represents alkyl, hydrogen, halogens, haloalkyl, cyano, nitro, formyl, carboxyl, alkoxycarbonyl, carboxyalkyl, alkoxycarbonylalkyl, hydroxyalkyl, alkylthio, alkylsulfinyl, alkylsulphonyl, N- alkylsulfamyl, N-arylsulfamyl, cyanoamido, amino, amidino, N-monoalkylamido, N-monoarylamido, N,N-dialkylamido, N-alkyl-N-arylamido, N, N-dialkylsulfamyl with the alkyl, or alkyl part of each such group containing 1-3 carbon atoms or mixtures thereof optionally their salts when they exist, and preparation thereof. The compounds of the present invention are antiinflammatory, antipyretic, antirheumatic, antiosteoarthritic agents with antibacterial activity. The particular class of compounds is given below (Formula 1 and Formula 2).
