35774-48-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole triazole derivatives as potent TRPV1 antagonists
Li, Jinyu,Nie, Cunbin,Qiao, Yue,Hu, Jing,Li, Qifei,Wang, Qiang,Pu, Xiaohui,Yan, Lin,Qian, Hai
, p. 433 - 445 (2019/06/18)
Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (6g), a potent TRPV1 antagonist. In vitro, using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo, 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs.
Iron-Catalyzed Intramolecular Aminations of C(sp3)?H Bonds in Alkylaryl Azides
Alt, Isabel T.,Guttroff, Claudia,Plietker, Bernd
supporting information, p. 10582 - 10586 (2017/08/22)
The nucleophilic iron complex Bu4N[Fe(CO)3(NO)] (TBA[Fe]) catalyzes the direct intramolecular amination of unactivated C(sp3)?H bonds in alkylaryl azides, which results in the formation of substituted indoline and tetrahydroquinoline derivatives.
1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of Estrogen-related receptor α
Xu, Shilin,Zhuang, Xiaoxi,Pan, Xiaofen,Zhang, Zhang,Duan, Lei,Liu, Yingxue,Zhang, Lianwen,Ren, Xiaomei,Ding, Ke
, p. 4631 - 4640 (2013/07/19)
Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure-activity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2, 3-triazoles as novel suppressors of ERRα
Rh2(II)-catalyzed intramolecular aliphatic C-H bond amination reactions using aryl azides as the N-atom source
Nguyen, Quyen,Sun, Ke,Driver, Tom G.
supporting information; experimental part, p. 7262 - 7265 (2012/06/16)
Rhodium(II) dicarboxylate complexes were discovered to catalyze the intramolecular amination of unactivated primary, secondary, or tertiary aliphatic C-H bonds using aryl azides as the N-atom precursor. While a strong electron-withdrawing group on the nitrogen atom is typically required to achieve this reaction, we found that both electron-rich and electron-poor aryl azides are efficient sources for the metal nitrene reactive intermediate.
Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent
Smith, Catherine J.,Smith, Christopher D.,Nikbin, Nikzad,Ley, Steven V.,Baxendale, Ian R.
supporting information; experimental part, p. 1927 - 1937 (2011/04/21)
Here we describe general flow processes for the synthesis of alkyl and aryl azides, and the development of a new monolithic triphenylphosphine reagent, which provides a convenient format for the use of this versatile reagent in flow. The utility of these new tools was demonstrated by their application to a flow Staudinger aza-Wittig reaction sequence. Finally, a multistep aza-Wittig, reduction and purification flow process was designed, allowing access to amine products in an automated fashion.
A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3- triazoles
Smith, Catherine J.,Nikbin, Nikzad,Ley, Steven V.,Lange, Heiko,Baxendale, Ian R.
supporting information; experimental part, p. 1938 - 1947 (2011/04/24)
Having demonstrated in the preceding publication the flow synthesis of aryl azides, we describe here a general protocol for the in-line purification of these versatile intermediates. As part of this investigation, we evaluated the use of ReactIR 45m as a
Transition-metal-free catalytic synthesis of 1,5-diaryl-1,2,3-triazoles
Kwok, Sen W.,Fotsing, Joseph R.,Fraser, Rebecca J.,Rodionov, Valentin O.,Fokin, Valery V.
supporting information; experimental part, p. 4217 - 4219 (2010/11/04)
Figure Presented. 1,5-Diarylsubstituted 1,2,3-triazoles are formed in high yield from aryl azides and terminal alkynes in DMSO in the presence of catalytic tetraalkylammonium hydroxide. The reaction is experimentally simple, does not require a transition-
