Category: 324769-07-5

Yamada, Ken published the artcileDiscovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma, Application of 1-N-Boc-2-Ethylpiperidin-4-one, 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. 324769-07-5 belongs to class piperidines, name is 1-N-Boc-2-Ethylpiperidin-4-one, and the molecular formula is C12H21NO3, Application of 1-N-Boc-2-Ethylpiperidin-4-one.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wanner, Benedikt published the artcileCatalytic Kinetic Resolution of Disubstituted Piperidines by Enantioselective Acylation: Synthetic Utility and Mechanistic Insights, Application of 1-N-Boc-2-Ethylpiperidin-4-one, the main research area is piperidine nonracemic preparation; kinetic resolution piperidine acylation nonracemic indanooxazinol hydrocinnamate; dependence acylation enantioselectivity stereochem disubstituted piperidine; transition state model enantioselective acylation piperidine nonracemic indanooxazinol hydrocinnamate; nitrophenylsulfonyl benzylethylpiperidine mol crystal structure.

Resolution of 2,3-, 2,4-, and 2,5-disubstituted piperidines using either a nonracemic hydroxamate ester I (R = 4-MeOC6H4) or using an unsaturated α-hydroxy-α’,β’-unsaturated ketone in the presence of a nonracemic hydroxamate and a pyrrolotriazolium N-heterocyclic carbene precursor yielded N-acylated piperidines and nonracemic piperidines with practical selectivity factors (s, up to 52). The selectivity of resolution depended strongly on the conformation of the piperidine reactants, with cis-2,3- and 2,5-disubstituted piperidines and trans-2,4-disubstituted piperidines being resolved more effectively than trans-2,3- and 2,5-disubstituted and cis-2,4-disubstituted piperidines. The method was also used for the resolution of 2-substituted 4-methylenepiperidines and 2-substituted 4-piperidinone ethylene and propylene ketals. Detailed exptl. and computational studies of the kinetic resolution of various disubstituted piperidines revealed a strong preference for the acylation of conformers in which the α-substituent occupies the axial position. This work provides further exptl. and computational support for the concerted 7-membered transition state model for acyl transfer reagents and expands the scope and functional group tolerance of the secondary amine kinetic resolution The structure of a nonracemic (nitrophenylsulfonyl)benzylethylpiperidine was determined by X-ray crystallog.

Journal of the American Chemical Society published new progress about Acylation catalysts (stereoselective). 324769-07-5 belongs to class piperidines, name is 1-N-Boc-2-Ethylpiperidin-4-one, and the molecular formula is C12H21NO3, Application of 1-N-Boc-2-Ethylpiperidin-4-one.

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem