71787-43-4Relevant academic research and scientific papers
Merging Photoredox with Palladium Catalysis: Decarboxylative ortho-Acylation of Acetanilides with α-Oxocarboxylic Acids under Mild Reaction Conditions
Zhou, Chao,Li, Pinhua,Zhu, Xianjin,Wang, Lei
supporting information, p. 6198 - 6201 (2016/01/09)
A room temperature decarboxylative ortho-acylation of acetanilides with α-oxocarboxylic acids has been developed via a novel Eosin Y with Pd dual catalytic system. This dual catalytic reaction shows a broad substrate scope and good functional group tolera
Palladium-catalyzed direct oxidative ortho-acylation of anilides with toluene derivatives
Weng, Jianquan,Yu, Zhiqin,Liu, Xinghai,Zhang, Guofu
supporting information, p. 1205 - 1207 (2013/03/13)
Direct oxidative ortho-acylation reaction of anilides with toluene derivatives in the presence of palladium acetate using tert-butyl hydroperoxide as an oxidant was developed. A broad range of diaryl ketones was obtained in good to excellent yields (up to 95%). The plausible mechanism was also proposed.
Palladium-catalyzed direct ortho -acylation through an oxidative coupling of acetanilides with toluene derivatives
Yin, Zhangwei,Sun, Peipei
, p. 11339 - 11344 (2013/02/23)
A facile ortho-acylation of acetanilides by a Pd-catalyzed oxidative C-H activation was developed in which low toxic, stable, and commercially available toluene derivatives were first used as acylation reagents by a tandem reaction to form o-acylacetanili
Dihydroquinazolines as a novel class of Trypanosoma brucei trypanothione reductase inhibitors: Discovery, synthesis, and characterization of their binding mode by protein crystallography
Patterson, Stephen,Alphey, Magnus S.,Jones, Deuan C.,Shanks, Emma J.,Street, Ian P.,Frearson, Julie A.,Wyatt, Paul G.,Gilbert, Ian H.,Fairlamb, Alan H.
, p. 6514 - 6530 (2011/12/02)
Trypanothione reductase (TryR) is a genetically validated drug target in the parasite Trypanosoma brucei, the causative agent of human African trypanosomiasis. Here we report the discovery, synthesis, and development of a novel series of TryR inhibitors based on a 3,4-dihydroquinazoline scaffold. In addition, a high resolution crystal structure of TryR, alone and in complex with substrates and inhibitors from this series, is presented. This represents the first report of a high resolution complex between a noncovalent ligand and this enzyme. Structural studies revealed that upon ligand binding the enzyme undergoes a conformational change to create a new subpocket which is occupied by an aryl group on the ligand. Therefore, the inhibitor, in effect, creates its own small binding pocket within the otherwise large, solvent exposed active site. The TryR-ligand structure was subsequently used to guide the synthesis of inhibitors, including analogues that challenged the induced subpocket. This resulted in the development of inhibitors with improved potency against both TryR and T. brucei parasites in a whole cell assay.
Rational modification of a candidate cancer drug for use against chagas disease
Kraus, James M.,Verlinde, Christophe L. M. J.,Karimi, Mandana,Lepesheva, Galina I.,Gelb, Michael H.,Buckner, Frederick S.
experimental part, p. 1639 - 1647 (2010/01/07)
Chagas disease is one of the major neglected diseases of the world. Existing drug therapies are limited, ineffective, and highly toxic. We describe a novel strategy of drug discovery of adapting an existing clinical compound with excellent pharmaceutical properties to target a pathogenic organism. The protein farnesyltransferase (PFT) inhibitor tipifarnib, now in phase III anticancer clinical trials, was previously found to kill Trypanosoma cruzi by blocking sterol 14a-demethylase (14DM). We rationally developed tipifarnib analogues that display reduced affinity for human PFT to reduce toxicity while increasing affinity for parasite 14DM. The lead compound has picomolar activity against cultured T. cruzi and is efficacious in a mouse model of acute Chagas disease.
