179688-29-0Relevant articles and documents
Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors
Chen, Zhe-Sheng,Dai, Qing-Qing,Li, Guo-Bo,Liu, Hong-Min,Liu, Hui,Wang, Bo,Wang, Shaomeng,Yu, Bin,Yuan, Shuo,Zhang, Jing-Ya,Zhang, Xiao-Nan,Zuo, Jia-Hui
, p. 14895 - 14911 (2021/10/12)
The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical 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.
Catalytic cyclization preparation method and application of erlotinib key intermediate
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Paragraph 0022; 0033-0042, (2021/11/06)
The invention relates to a catalytic cyclization preparation method and application of an erlotinib key intermediate. By using 2-nitro-4, 5-bis (2-methoxyethoxy) ethyl benzoate as a raw material and adopting a polysaccharide-loaded nano-palladium catalyst, the erlotinib key intermediate 6, 7-bis (2-methoxyethoxy)-4-quinazolinone is prepared through a one-pot method. The erlotinib key intermediate is applied to preparation of quinazoline ring compounds. The method is carried out by adopting a catalytic one-pot method, the catalyst can be recycled for more than 10 times, the post-treatment is simple, the product purity is high, the next reaction can be directly carried out, the operation is simple, the pollution is less, and the cost is low. The method solves the problems of high catalyst price, high separation difficulty, high metal residue, more reaction three wastes and the like in the original process, greatly reduces the cost, provides technical guarantee for development of an industrial production process of erlotinib, and also provides a new reference method for synthesis of other anti-tumor drugs with quinazoline structures.
Visible-light induced copper(i)-catalyzed oxidative cyclization of: O -aminobenzamides with methanol and ethanol via HAT
Bhargava Reddy, Mandapati,Prasanth, Kesavan,Anandhan, Ramasamy
supporting information, p. 9601 - 9605 (2020/12/28)
The use of the in situ generated ligand-copper superoxo complex absorbing light energy to activate the alpha C(sp3)-H of MeOH and EtOH via the hydrogen atom transfer (HAT) process for the synthesis of quinazolinones by oxidative cyclization of alcohols with o-aminobenzamide has been investigated. The synthetic utility of this protocol offers an efficient synthesis of a quinazolinone intermediate for erlotinb (anti-cancer agent) and 30 examples were reported.
