405058-54-0Relevant academic research and scientific papers
Discovery of trans-3-(pyridin-3-yl)acrylamide-derived sulfamides as potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors for the potential treatment of cancer
Zhang, Kuojun,Ni, Yong,Chen, Jiaxuan,Tu, Zhengchao,Wu, Xiaoxing,Chen, Dong,Yao, Hequan,Jiang, Sheng
, p. 1502 - 1506 (2019/04/17)
Nicotinamide phosphoribosyltransferase (NAMPT) has emerged as a promising target for the discovery of anticancer drugs. Based on NAMPT inhibitor FK866 that has been advanced into phase II trial, we identified a trans-3-(pyridin-3-yl)acrylamide compound 13 incorporating with a biarylsulfanilamide moiety as a new NAMPT inhibitor. Further structure-activity relationship (SAR) exploration led to additional biarylsulfanilamide-derived compounds with high in vitro NAMPT inhibitory potency and antiproliferative activity. In particular, compound 23, the most potent NAMPT inhibitor (IC50 = 5.08 nM), showed single-digit nanomolar antiproliferative activity against DU145, Hela, and H1975 cells with IC50 values of 2.90 nM, 2.34 nM, and 2.24 nM, respectively, and even subnanomolar level against K562, MCF-7, and HUH7 cells with IC50 values of 0.46 nM, 0.23 nM and 0.53 nM, respectively. Our findings provided promising lead compounds for the discovery of more potent NAMPT inhibitors as anticancer drugs.
Synthesis method of belinostat
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Paragraph 0043; 0044; 0045; 0046, (2016/11/14)
The invention discloses a synthesis method of belinostat. The method comprises the following steps: by using benzoic acid as an initial material, performing six reaction steps of chlorosulfonation, aniline condensation, reduction, oxidation, Witting-Horner condensation and hydrolysis, acylating chlorination and hydroxylamine condensation to prepare a target compound. The initial material benzoic acid of the method is cheap and easy to obtain, the sulfonylation and acylating chlorination reaction are realized through one step, the preparation time is shortened, and the yield is improved. In the oxidation process, an oxidizing reagent which is cheap and does not contains metal ion is adopted so that the active ingredients easily achieve the requirement of heavy metal ion limitation, and the pollution to the environment is reduced. All reaction intermediates of the method are solid and can be purified through a salt formation or recrystallization method, the time-consuming and labor-consuming column chromatography purification is avoided, and the method is suitable for industrial production.
A he belli department is suitable for industrial production of synthetic method
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Paragraph 0011; 0034; 0035, (2016/10/08)
The invention provides an improved belinostatsynthesis method. According to the method, sodium m-carboxyl benzenesulfonate is taken as a starting material, and belinostat is prepared through six steps of esterification, acylation and aniline condensation, reduction, oxidation, Wittig-Horner condensation and hydrolysis as well as acylation and hydroxylamine condensation. With the adoption of the method, the production time is shortened, the reaction yield is increased, the production safety is enhanced, the environmental pollution is reduced, and the method is more suitable for industrial production.
CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS
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, (2008/06/13)
Tertiary amines containing a multiplicity of heteroaromatic substituents are useful as chemokine receptor modulators.
