742675-58-7Relevant academic research and scientific papers
Highly Enantioselective Construction of Fluoroalkylated Quaternary Stereocenters via Organocatalytic Dehydrated Mannich Reaction of Unprotected Hemiaminals with Ketones
Zhang, Sheng,Li, Lijun,Hu, Yanbin,Li, Yanan,Yang, Yu,Zha, Zhenggen,Wang, Zhiyong
, p. 5036 - 5039 (2015/11/03)
A general organocatalytic asymmetric dehydrated Mannich reaction of fluoroalkyl hemiaminals with ketones is reported. In this Mannich reaction, previously less explored aryl ketones showed great reactivity. By virtue of this efficient method, a wide range of biologically active β-amino ketones were directly obtained. More importantly, two different intermediates involved in the reaction were detected and identified by 19F NMR and HRMS analysis. Furthermore, the synthetic utility of the products was demonstrated by the synthesis of the biologically active fluoroalkyl β-amino alcohols.
Synthesis of peptide aldehyde derivatives as selective inhibitors of human cathepsin L and their inhibitory effect on bone resorption
Yasuma, Tsuneo,Oi, Satoru,Choh, Nobuo,Nomura, Toshiyuki,Furuyama, Naoki,Nishimura, Atsushi,Fujisawa, Yukio,Sohda, Takashi
, p. 4301 - 4308 (2007/10/03)
Cathepsin L, a lysosomal cysteine protease, is secreted by osteoclasts and participates in bone collagen degradation. In a search for cathepsin L inhibitors as antiosteoporotic agents, a series of peptide aldehyde derivatives were prepared by two synthetic approaches, DMSO oxidation of the corresponding alcohol derivatives and DIBAL-H reduction of the corresponding N,O-dimethylhydroxylamide derivatives, and evaluated for inhibitory activity against human cathepsin L and for inhibitory effects on bone resorption. Some of the peptide aldehyde derivatives including α-acylamino aldehyde derivatives showed potent activities. Among these compounds, N-(1- naphthalenylsulfonyl-L-isoleucyl-L-tryptophanal (12) was selected as a candidate for further investigation. Compound 12, a potent, selective, and reversible inhibitor of human cathepsin L with an IC50 of 1.9 nM, inhibited the release of Ca2+ and hydroxyproline from bone in in vitro bone culture system and also prevented bone loss in ovariectomized mice at an oral dose of 50 mg/kg.
