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.
The 4-tert-butylphenyl group as a simple tag for solution phase synthesis
Blodgett, Jordan,Li, Tingyu
, p. 6649 - 6652 (2004)
A solution phase synthesis strategy was investigated using 4-tert-butylphenyl group as the tag and a beta-cyclodextrin column as the affinity chromatographic support for the isolation of compounds containing the tag. It was found that compounds containing the tag have significantly longer retention times on the beta-cyclodextrin column than those compounds that do not have such a tag. The tag is chemically inert and can be introduced onto and removed from target compounds readily. This solution phase synthesis method was applied to the synthesis of some simple amino acid derivatives.
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).
Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin
Bassetto, Marcella,Brancale, Andrea,Pasqualetto, Gaia,Pileggi, Elisa,Rozanowska, Malgorzata,Schepelmann, Martin,Varricchio, Carmine
supporting information, (2021/09/24)
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.
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.
PRODRUGS OF ABIRATERONE
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Page/Page column 20, (2021/05/29)
The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers, or pharmaceutically acceptable salt(s) thereof as prodrugs of abiraterone. The present invention also describes method of making such compounds, pharmaceutical compositions comprising such compounds and the use of the compounds of formula (I).
TRPV1 agonist, preparation method and application thereof
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Paragraph 0160-0164, (2021/03/31)
The present invention relates to a compound represented by a formula I, a stereoisomer, a tautomer, a solvate, a polymorph or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound, and a preparation method and a medical use of the compound, wherein the structure of the formula I is shown in the specification.
PHOTOLYTIC COMPOUNDS AND TRIPLET-TRIPLET ANNIHILATION MEDIATED PHOTOLYSIS
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Paragraph 0026; 00203, (2021/04/17)
The invention provides novel photolytic compounds and prodrugs, nanoparticles and compositions thereof, and methods of conducting photolysis mediated by triplet-triplet annihilation.
Composition for promoting differentiation of skin keratinocyte comprising a SAC derivatives or a SMC derivatives
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Paragraph 0028-0031; 0041-0043; 0057-0060; 0070-0072, (2021/02/02)
The present invention relates to a composition for promoting keratinocyte differentiation. More specifically, SAC derivative or SMC derivatives as an active ingredient promotes differentiation of keratinocytes to promote skin keratinocyte differentiation, has excellent anti-wrinkling effect, skin barrier recovery effect, and is applicable to pharmaceutical, cosmetic, soap, body, shampoo and pack.
Amino acid substrate and preparation method and purpose thereof
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Paragraph 0019, (2019/02/10)
The invention discloses an amino acid substrate. A structural formula of the substrate is shown in Figure 1. By means of development and innovation of a synthetic process of dipeptide in the amino acid substrate and a coupling process of the dipeptide and chromogen and innovation and application verification of an extraction and purification process, the reaction yield of each step of a product isgreatly improved, the color is close to white, the influence of the substrate color in the identification process is reduced, and the sensitivity and the accuracy of the aerobic flora vaginitis detection process are improved to a greater extent. The substrate is in the form of hydrochloride, and the solubility of the substrate can be greatly improved when the detection is carried out in the formof the hydrochloride. In a detection application, the corresponding preparation work is conducted according to the preparation requirement of the aerobic flora vaginitis detection, and the color rendering performance of the synthetic substrate is compared with the color rendering performance of the existing aerobic flora vaginitis detection in the market according to a detection standard. The color rendering performance is better than that of an aerobic flora vaginitis detection reagent in the market.
