21236-97-5Relevant articles and documents
Aryl spiro compound containing formamidine as well as preparation method and application of aryl spiro compound
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Paragraph 0073-0076, (2021/08/14)
The invention belongs to the field of medicinal chemistry, and particularly relates to an aryl spiro compound containing formamidine as well as a preparation method and application of the aryl spiro compound. The invention relates to three aryl spiro compounds as shown in general formulas I-III and pharmaceutically acceptable salts, enantiomers, non-isomers, tautomers, solvates, polymorphic substances or prodrugs thereof. On the basis that SHP099 is used as a lead compound, a brand new compound with guanidyl at the tail end is prepared, and the problems that an existing SHP2 inhibitor is single in structural framework and the like are solved. The aryl spiro compound has the important significance of providing many modification sites and providing a basis for later structural modification. Meanwhile, the embodiment of the invention proves that the compound has an allosteric inhibition effect on SHP2 phosphatase, and a skeleton support is provided for subsequent development of an SHP2 phosphatase inhibitor.
Synthesis and biological evaluation of novel xanthine derivatives as potential apoptotic antitumor agents
Hisham, Mohamed,Youssif, Bahaa G.M.,Osman, Essam Eldin A.,Hayallah, Alaa M.,Abdel-Aziz, Mohamed
, p. 117 - 128 (2019/05/21)
A series of novel xanthine/NO donor hybrids containing 1,3,8-trisubstituted or 1,8-disubstituted xanthine derivatives were designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 90% cell viability at a concentration of 50 μM. The oxime containing compounds 7a-b and 17-24 were more active as antiproliferative agents than their non-oxime congeners 6a-b and 9-16. Hydroxyimino-phenethyl scaffold compounds 17-24 were more active than the hydroxyimino-ethyl phenyl acetamide 7a-b derivatives. Compounds 18–20 and 22-24 exhibited inhibition of EGFR with IC50 ranging from 0.32 to 2.88 μM. Compounds 18-20 and 22-24 increased the level of active caspase 3 by 4–8 folds, compared to the control cells in Panc-1 cell lines compared to doxorubicin as a reference drug. Compounds 18, 22 and 23 were the most caspase-3 inducers. Compounds 22 and 23 increased the levels of caspase-8 and 9 indicating activation of both intrinsic and extrinsic pathways and showed potent induction of Bax, down-regulation of Bcl-2 protein levels and over-expression of cytochrome c levels in Panc-1 human pancreas cancer cells. Compound 23 exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases in the cell cycle analysis of Panc-1 cell line. The drug likeness profiles of compounds 18-20 and 22-24 were predicted to have good to excellent drug likeness profiles specially compounds 18-20 and 23. Finally molecular docking study was performed at the EGFR active site to suggest thier possible binding mode. The hydroxyimino-phenethyl scaffold compounds 17-24 represent an interesting starting point to optimize their pharmacokinetics and pharmacodynamics profiles.
MARKER COMPOUNDS OF LEPTOSPERMUM HONEYS AND METHODS OF ISOLATION AND ASSAYING THEREOF
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Page/Page column 8; 28, (2017/07/06)
Described herein are novel isolated compounds from Leptospermum honey and methods of assay thereof for use in the verification of the place of origin, authenticity and content of Leptospermum honeys such as mānuka honey. The inventors screened flower nectar and honeys of various floral types found in New Zealand to identify chemicals that were either unique to or in significantly higher concentrations in mānuka nectar and mono-floral mānuka honey compared to other predominantly mono-floral nectars and honeys. As a result of the screening exercise, the inventors discovered a marker compounds that could distinguish Leptospermum honey nectar and honey from other floral sources.
