Category: 886496-91-9

Yamada, Ken published the artcileDiscovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma, Formula: C8H5BrClF3, the main research area is CETP inhibition piperidine analog hypertriglyceridemic plasma activity; piperidine analog preparation hypertriglyceridemic plasma activity.

Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead mol. with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound I (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclin. efficacy and safety profile, the compound was advanced into clin. trials.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 886496-91-9 belongs to class chlorides-buliding-blocks, name is 1-(Bromomethyl)-3-chloro-5-(trifluoromethyl)benzene, and the molecular formula is C8H5BrClF3, Formula: C8H5BrClF3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Dhungana, Roshan K. published the artcileNi-catalyzed regioselective 1,2-dialkylation of alkenes enabled by the formation of two C(sp3)-C(sp3) bonds, Application In Synthesis of 886496-91-9, the main research area is alkene regioselective dialkylation benzyl halide alkylzinc reagent nickel catalysis.

The authors disclosed a Ni-catalyzed vicinal difunctionalization of alkenes with benzyl halides and alkylzinc reagents, which produces products with two new alkyl-alkyl bonds. This alkene dialkylation is effective in combining secondary benzyl halides and secondary alkylzinc reagents with internal alkenes, which furnishes products with three contiguous all-carbon secondary stereocenters. The products can be readily elaborated to access complex tetraene, benzosuberene, and bicyclodecene cores. The reaction also features as the most efficient alkene difunctionalization process to date with catalyst loadings down to 500 ppm and the catalytic turnover number (TON) and turnover frequency (TOF) registering up to 2 x 103 and 165 h-1 at rt, resp.

Journal of the American Chemical Society published new progress about Alkenes Role: RCT (Reactant), RACT (Reactant or Reagent). 886496-91-9 belongs to class chlorides-buliding-blocks, name is 1-(Bromomethyl)-3-chloro-5-(trifluoromethyl)benzene, and the molecular formula is C8H5BrClF3, Application In Synthesis of 886496-91-9.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics