4530-20-5Relevant articles and documents
Discovery of degradable niclosamide derivatives able to specially inhibit small cell lung cancer (SCLC)
He, XingGang,Li, MaoLin,Ye, WenChong,Zhou, Wen
, (2021)
Small cell lung cancer (SCLC) is exceedingly tough to treat and easy to develop resistance upon long use of the first-line drug carboplatin or radiotherapy. Novel medicines effective and specific against SCLC are greatly needed. Herein, we focused on the discovery of such a medicine by exploring a drug niclosamide with repurposing strategy. Initial screening efforts revealed that niclosamide, an anthelmintic drug, possessed the in vitro anticancer activity and an obvious sensitivity towards SCLC. This observation inspired the evaluation for two different kinds of niclosamide derivatives. 2 with a degradable ester as a linker exhibited the comparable activity but slightly inferior selectivity to SCLC, by contrast, the cytotoxicities of 4 and 5 with non-degradable ether linkages completely disappeared, clearly validating the importance of 2-free hydroxyl group or 2-hydroxyl group released in the antitumor activity. Mechanism study unfolded that, similar to niclosamide, 2 inhibited growth of cancer cells via p 53 activation and subsequent underwent cytochrome c dependent apoptosis. Further structural modification to afford phosphate sodium 8 with significantly enhanced aqueous solubility (22.1 mg/mL) and a good selectivity towards SCLC demonstrated more promising druggability profiles. Accordingly, niclosamide as an attractive lead hold a huge potential for developing targeted anti-SCLC drugs.
Substituted aza five-membered ring derivative and application thereof in medicine
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Paragraph 0466; 0471-0473, (2021/10/30)
The invention discloses a substituted aza-five-membered ring derivative and application thereof to medicines. , The invention provides a substituted aza five-membered ring compound or a stereoisomer, a tautomer, an oxynitride, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a pharmaceutical composition containing the compound of the present invention. The invention also discloses application of the compound or the pharmaceutical composition of the compound in preparation of a medicament for treating PDE4 related diseases such as atopic dermatitis (AD) or chronic obstructive pulmonary disease (COPD).
Vorinostat skeleton-based anthranilamide compound as well as preparation and application thereof
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Paragraph 0025, (2021/08/06)
The invention provides a vorinostat skeleton-based anthranilamide compound as well as preparation and application of the anthranilamide compound. The structural formula of the o-aminobenzamide compound based on a vorinostat skeleton is shown in the specification, wherein n is equal to 1-6, and R is methylamino, dimethylamino, hydroxyl, NH2 or the like. The anthranilamide compound based on the vorinostat skeleton has the effect of inhibiting gastric cancer cell proliferation through MTT method determination, and can be used for preparing anti-gastric cancer drugs.