Xu, Shujing; Sun, Lin; Dick, Alexej; Zalloum, Waleed A.; Huang, Tianguang; Meuser, Megan E.; Zhang, Xujie; Tao, Yucen; Cherukupalli, Srinivasulu; Ding, Dang; Ding, Xiao; Gao, Shenghua; Jiang, Xiangyi; Kang, Dongwei; De Clercq, Erik; Pannecouque, Christophe; Cocklin, Simon; Liu, Xinyong; Zhan, Peng published an article on January 5 ,2022. The article was titled 《Design, synthesis, and mechanistic investigations of phenylalanine derivatives containing a benzothiazole moiety as HIV-1 capsid inhibitors with improved metabolic stability》, and you may find the article in European Journal of Medicinal Chemistry.Recommanded Product: 3-(Methoxycarbonyl)benzoic acid The information in the text is summarized as follows:
Further clin. development of I, a lead compound targeting HIV-1 capsid, is impeded by low antiviral activity and inferior metabolic stability. By modifying the benzene (region I) and indole of I, we identified two potent compounds II [R = propargyl, 4-NH2Ph] with significantly improved metabolic stability. Compared to PF74, II [R = 4-NH2Ph] displayed greater metabolic stability in human liver microsomes (HLMs) with half-life (t1/2) 109-fold that of PF74. Moreover, mechanism of action (MOA) studies demonstrated that II [R = propargyl, 4-NH2Ph] effectively mirrored the MOA of compounds that interact within the I interprotomer pocket, showing direct and robust interactions with recombinant CA, and 7u displaying antiviral effects in both the early and late stages of HIV-1 replication. Furthermore, MD simulation corroborated that II [R = 4-NH2Ph] was bound to the I binding site, and the results of the online molinspiration software predicted that II [R = propargyl, 4-NH2Ph] had desirable physicochem. properties. Unexpectedly, this series of compounds exhibited better antiviral activity than I against HIV-2, represented by compound II [R = propargyl] whose anti-HIV-2 activity was almost 5 times increased potency over I. Therefore, we have rationally redesigned the I chemotype to inhibitors with novel structures and enhanced metabolic stability in this study. We hope that these new compounds can serve as a blueprint for developing a new generation of HIV treatment regimens. The experimental process involved the reaction of 3-(Methoxycarbonyl)benzoic acid(cas: 1877-71-0Recommanded Product: 3-(Methoxycarbonyl)benzoic acid)
3-(Methoxycarbonyl)benzoic acid(cas: 1877-71-0) belongs to esters. Esters are more polar than ethers but less polar than alcohols. Recommanded Product: 3-(Methoxycarbonyl)benzoic acid They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics