58662-50-3Relevant articles and documents
Discovery and Characterization of Potent Dual P-Glycoprotein and CYP3A4 Inhibitors: Design, Synthesis, Cryo-EM Analysis, and Biological Evaluations
Bu, Yahao,Lau, Johnson Y. N.,Locher, Kaspar P.,Nasief, Nader N.,Nosol, Kamil,Said, Ahmed M.,Smolinski, Michael P.,Urgaonkar, Sameer
, (2022/01/03)
Targeted concurrent inhibition of intestinal drug efflux transporter P-glycoprotein (P-gp) and drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is a promising approach to improve oral bioavailability of their common substrates such as docetaxel, while avoiding side effects arising from their pan inhibitions. Herein, we report the discovery and characterization of potent small molecule inhibitors of P-gp and CYP3A4 with encequidar (minimally absorbed P-gp inhibitor) as a starting point for optimization. To aid in the design of these dual inhibitors, we solved the high-resolution cryo-EM structure of encequidar bound to human P-gp. The structure guided us to prudently decorate the encequidar scaffold with CYP3A4 pharmacophores, leading to the identification of several analogues with dual potency against P-gp and CYP3A4. In vivo, dual P-gp and CYP3A4 inhibitor 3a improved the oral absorption of docetaxel by 3-fold as compared to vehicle, while 3a itself remained poorly absorbed.
3-heterocycle substituted quinoline derivatives as well as preparation method and applications thereof
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Paragraph 0211-0212, (2017/04/29)
The invention relates to new quinoline derivatives shown in a general formula I and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof, and wherein substituent R1, R2, R3 and n contain meanings shown in the specification. The invention also relates to an enhanced effect of the compounds shown in formula I for inhibiting DNA duplication of HBV, and also relates to applications of the compounds and pharmaceutically acceptable salts, hydrates, solvates or prodrugs thereof to preparation of medicaments for treating diseases due to infection of HBV, and especially relates to applications of medicaments for treating and/or preventing viral hepatitis B.
Facile and efficient oxidation of quinazolines into quinazolin-4(3 H)-ones by peracetic acid
Jin, Jian-Wen,Zhang, Lin,Meng, Guang-Rong,Zhu, Jian-Hua,Zhang, Qian
, p. 346 - 351 (2014/01/06)
A new approach to synthesize quinazoline-4(3H)-ones was achieved by oxidation of quinazolines using peracetic acid, which possesses some advantages of economic reagents, simplified operation, high efficiency, and environmental friendliness. Application of this method allowed us to synthesize a series of quinazolin-4(3H)-ones with different substituents at 6 and 7 positions in good to excellent yields, including the key intermediates of tyrosine kinase inhibitors such as PD153035, Erlotinib, and Gefitinib. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
