Yuan, Shuo; Wang, Bo; Dai, Qing-Qing; Zhang, Xiao-Nan; Zhang, Jing-Ya; Zuo, Jia-Hui; Liu, Hui; Chen, Zhe-Sheng; Li, Guo-Bo; Wang, Shaomeng; Liu, Hong-Min; Yu, Bin published an article in 2021. The article was titled 《Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.Reference of 4-Cyanobenzyl bromide The information in the text is summarized as follows:
The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clin. stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors. In the experiment, the researchers used 4-Cyanobenzyl bromide(cas: 17201-43-3Reference of 4-Cyanobenzyl bromide)
4-Cyanobenzyl bromide(cas: 17201-43-3) is an important intermediate for pharmaceutical production. It can be used for the synthesis of a series of piperidine-linked aromatic diimidazolines, which have been synthesized as conformationally restricted congeners of the anti-Pneumocystis carinii (PCP) drug, Pentamidine.Reference of 4-Cyanobenzyl bromide
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts