74331-72-9Relevant academic research and scientific papers
Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition
R?hrig, Ute F.,Majjigapu, Somi Reddy,Grosdidier, Aurélien,Bron, Sylvian,Stroobant, Vincent,Pilotte, Luc,Colau, Didier,Vogel, Pierre,Van Den Eynde, Beno?t J.,Zoete, Vincent,Michielin, Olivier
, p. 5270 - 5290 (2012/08/28)
Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.
Vinyl Cation Intermediates in Solvolytic and Electrophilic Reactions. 1. Solvolysis of α-Arylvinyl Derivatives
Yates, Keith,Mandrapilias, George
, p. 3892 - 3902 (2007/10/02)
The solvolysis of 16 α-arylvinyl tosylates, bromides, and chlorides has been investigated in various alcohol-water mixtures and in acetic acid at several temperatures.All substrates were substituted with either 2-methyl or 2,6-dimethyl groups to accelerate the rates of reaction.The major or exclusive product isolated in most cases was the acetophenone arising from hydrolysis of the expected enol ethers or acetates during workup.The kinetics were simple first order in the vast majority of cases, with excess base added to prevent side reactions.Leaving group effects, Winstein-Grunwald m values, Schleyer Q values, and effects of solvent nucleophilicity all point to a limiting SN1 ionization generating a vinyl cation intermediate, in which there is little rear-side nucleophilic assistance by solvent.Substituent effects led to ρ values in the range -3.9 to -5.3 vs. ?+.Activation parameters are typical for an SN1 process, and ΔS% is insensitive to the presence of zero, one, or two o-methyl groups, as are the effects of solvent polarity on the rates.The results should therefore be directly comparable with other solvolytic or electrophilic reactions generating formally similar vinyl cation intermediates.
