695215-98-6Relevant articles and documents
Piperidine scaffold as the novel P2-ligands in cyclopropyl-containing HIV-1 protease inhibitors: Structure-based design, synthesis, biological evaluation and docking study
Cen, Shan,Dong, Biao,Ma, Ling,Wang, Juxian,Wang, Yucheng,Zhang, Guoning,Zhou, Huiyu,Zhou, Jinming,Zhu, Mei
, (2020)
A series of potent HIV-1 protease inhibitors, containing diverse piperidine analogues as the P2-ligands, 4-substituted phenylsulfonamides as the P2'-ligands and a hydrophobic cyclopropyl group as the P1'-ligand, were designed, synthesized and evaluated in this work. Among these twenty-four target compounds, many of them exhibited excellent activity against HIV-1 protease with half maximal inhibitory concentration (IC50) values below 20 nM. Particularly, compound 22a containing a (R)-piperidine-3-carboxamide as the P2-ligand and a 4-methoxylphenylsulfonamide as the P2'-ligand exhibited the most effective inhibitory activity with an IC50 value of 3.61 nM. More importantly, 22a exhibited activity with inhibition of 42% and 26% against wild-type and Darunavir (DRV)-resistant HIV-1 variants, respectively. Additionally, the molecular docking of 22a with HIV-1 protease provided insight into the ligand-binding properties, which was of great value for further study.
Design, synthesis and biological evaluation of HIV-1 protease inhibitors with morpholine derivatives as P2 ligands in combination with cyclopropyl as P1′ ligand
Dong, Biao,Dou, Yue,Wang, Ju-Xian,Wang, Yu-Cheng,Zhang, Fan,Zhang, Guo-Ning,Zhu, Mei
supporting information, (2020/02/15)
A series of novel HIV-1 protease inhibitors has been designed and synthesized, which contained morpholine derivatives as the P2 ligands and hydrophobic cyclopropyl as the P1′ ligand at the meantime in this study, with the aim of improving the interactions between the active sites of HIV-1 protease and the inhibitors. Twenty-eight compounds were synthesized and assessed, among which inhibitors m18 and m1 exhibited excellent inhibitory effect on the activity of HIV-1 protease with IC50 value of 47 nM and 53 nM, respectively. The molecular modeling of m1 revealed possible hydrogen bondings or van der Waals between the inhibitor and the protease, worthy of in-depth study.
Bioactive prenylated phenyl derivatives derived from marine natural products: Novel scaffolds for the design of BACE inhibitors
López-Ogalla, Javier,García-Palomero, Esther,Sánchez-Quesada, Jorge,Rubio, Laura,Delgado, Elena,García, Pablo,Medina, Miguel,Castro, Ana,Mu?oz, Pilar
, p. 474 - 488 (2014/04/17)
Abnormal accumulation of neurotoxic beta-amyloid peptides (Aβ) is a key factor in the development of Alzheimer's disease (AD) and strategies to reduce Aβ production constitute an active field of research for the development of novel therapeutic agents for the treatment of AD. In particular, β-secretase-1 (BACE-1) has been a prime target for modulating Aβ production although obtaining drug-like BACE-1 inhibitors has proven to be highly challenging. Here we report the isolation and biochemical characterization of a marine natural product, the prenylated hydroxybenzoic acid 1, with BACE-1 inhibitory activity and ability to decrease Aβ production in cell-based assays. Synthesis and biological activity of a number of new synthetic analogues are also reported, as well as initial structure-activity relationship (SAR) analysis on this chemical family. Hence, these compounds constitute novel scaffolds from which more potent and selective BACE-1 inhibitors could be designed as potential therapeutic agents for the treatment of Alzheimer's disease.
