Xu, Shujing published the artcileDesign, synthesis, and mechanistic investigations of phenylalanine derivatives containing a benzothiazole moiety as HIV-1 capsid inhibitors with improved metabolic stability, Product Details of C9H8O4, the publication is European Journal of Medicinal Chemistry (2022), 113903, database is CAplus and MEDLINE.
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.
European Journal of Medicinal Chemistry published new progress about 1877-71-0. 1877-71-0 belongs to esters-buliding-blocks, auxiliary class Carboxylic acid,Benzene,Ester, name is 3-(Methoxycarbonyl)benzoic acid, and the molecular formula is C20H28B2O4S2, Product Details of C9H8O4.
Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics