Hyatt, Janice L. published the artcileSelective Inhibition of Carboxylesterases by Isatins, Indole-2,3-diones, Application In Synthesis of 1677-47-0, the main research area is isatin inhibitor carboxylesterase structure activity relationship drug metabolism.
Carboxylesterases (CE) are ubiquitous enzymes thought to be responsible for the metabolism and detoxification of xenobiotics. Numerous clin. used drugs including Demerol, lidocaine, capecitabine, and CPT-11 are hydrolyzed by these enzymes. Hence, the identification and application of selective CE inhibitors may prove useful in modulating the metabolism of esterified drugs in vivo. Having recently identified benzil (diphenylethane-1,2-dione) as a potent selective inhibitor of CEs, we sought to evaluate the inhibitory activity of related 1,2-diones toward these enzymes. Biochem. assays and kinetic studies demonstrated that isatins (indole-2,3-diones), containing hydrophobic groups attached at a variety of positions within these mols., could act as potent, specific CE inhibitors. Interestingly, the inhibitory potency of the isatin compounds was related to their hydrophobicity, such that compounds with clogP values of <1.25 were ineffective at enzyme inhibition. Conversely, analogs demonstrating clogP values >5 routinely yielded Ki values in the nM range. Furthermore, excellent 3D QSAR correlates were obtained for 2 human CEs, hCE1 and hiCE. While the isatin analogs were generally less effective at CE inhibition than the benzils, the former may represent valid lead compounds for the development of inhibitors for use in modulating drug metabolism in vivo.
Journal of Medicinal Chemistry published new progress about Drug metabolism. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, Application In Synthesis of 1677-47-0.
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Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles