23126-68-3Relevant articles and documents
Antitumor activity of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, is highly dependent on its primary structure and steric configuration
Zhao, Jiuyang,Ling, Xiang,Cao, Shousong,Liu, Xiaojun,Wan, Shengbiao,Jiang, Tao,Li, Fengzhi
, p. 457 - 467 (2014)
We recently reported the identification and characterization of a novel small chemical molecule designated FL118. FL118 selectively inhibits multiple cancer survival and proliferation-associated antiapoptotic proteins (survivin, Mcl-1, XIAP, cIAP2) and eliminates small and large human tumor xenografts in animal models (Ling et al., PLoS One 2012, 7, e45571). Here, we report a follow-up study on the structure-activity relationship (SAR) of the hydroxyl group in the lactone ring of FL118. We found that the superior antitumor efficacy of FL118 heavily depends on its steric configuration through comparing the antitumor activity of FL118 with FL113 (the racemic mixture of FL118). Consistently, FL118 proved much more effective in inhibiting the expression of survivin, Mcl-1, and cIAP2, both in vitro and in vivo, compared to FL113. Additionally, Tet-on controlled induction of survivin or forced expression of Mcl-1 protects cancer cells from FL118-mediated growth inhibition and cell death. To further explore the SAR, we synthesized seven position 20-esterifiable FL118 and FL113 derivatives. Studies on these seven new compounds revealed that keeping a free hydroxyl group of FL118 is also important for high antitumor efficacy. Together, these studies confirm the superior anticancer activity of FL118 and narrow the window for further SAR studies to generate novel analogues based on FL118 core structure on its other potential chemical positions.
Piperidine compound and preparation method and medical application thereof
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Paragraph 0533-0536, (2021/04/07)
The invention discloses a piperidine compound shown as a formula (I) and a preparation method and medical application thereof, and particularly relates to a piperidine USP7 inhibitor compound or pharmaceutically acceptable salt or ester or solvate thereof and a preparation method and application of the piperidine USP7 inhibitor compound or pharmaceutically acceptable salt or ester or solvate thereof. The compound provided by the invention can inhibit the activity of USP7 enzyme, has very good selectivity and druggability, and can be used for preparing medicines for preventing or treating tumor diseases or virus infectious diseases.
Preparation method of medical intermediate 6-amino heliotropin
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Paragraph 0036-0095, (2020/07/06)
The invention discloses a preparation method of a medical intermediate 6-amino heliotropin, wherein the method comprises the following steps: S1, adding heliotropin into concentrated nitric acid to react, and pouring into water; S2, extracting with an organic solvent, and collecting an organic phase; S3, adding potassium permanganate into the organic phase, reacting at the temperature of 90-120 DEG C, filtering to remove solids, and collecting filtrate; and S4, adding a palladium-carbon catalyst into the filtrate, reducing at the temperature of 80-100 DEG C in the presence of a mixed gas of hydrogen and inert gas to obtain a crude product, and recrystallizing the crude product. Compared with the prior art, the preparation method has the advantages that the purification step of an intermediate product is omitted; the yield of the final product 6-amino heliotropin is about 40-50%, so that the raw material utilization rate is remarkably improved, the operation efficiency of enterprises isimproved, the time cost and the material cost are saved for the enterprises, and the method has a wide industrial prospect.
