163438-09-3Relevant articles and documents
Design and evaluation of novel piperidine HIV-1 protease inhibitors with potency against DRV-resistant variants
Zhu, Mei,Zhou, Huiyu,Ma, Ling,Dong, Biao,Zhou, Jinming,Zhang, Guoning,Wang, Minghua,Wang, Juxian,Cen, Shan,Wang, Yucheng
, (2021/06/02)
A novel class of HIV-1 protease inhibitors with flexible piperidine as the P2 ligand was designed with the aim of improving extensive interactions with the active subsites. Many inhibitors exhibited good to excellent inhibitory effect on enzymatic activity and viral infectivity. In particular, inhibitor 3a with (R)-piperidine-3-carboxamide as the P2 ligand and 4-methoxybenzenesulfonamide as the P2’ ligand showed an enzyme Ki value of 29 pM and antiviral IC50 value of 0.13 nM, more than six-fold enhancement of activity compared to DRV. Furthermore, there was no significant change in potency against DRV-resistant mutations and HIV-1NL4?3 variant for 3a. Besides, inhibitor 3a exhibited potent antiviral activity against subtype C variants with low nanomole EC50 values. In addition, the molecular modeling revealed important hydrogen bonds and other favorable van der Waals interactions with the backbone atoms of the protease and provided insight for designing and optimizing more potent HIV-1 protease inhibitors.
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
, (2020/11/03)
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.
Oxa-spiral diphosphine ligand and application thereof in alpha, beta-unsaturated carboxylic acid asymmetric hydrogenation
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Paragraph 0083-0085, (2019/04/04)
The invention provides an oxa-spiral diphosphine ligand. The oxa-spiral diphosphine ligand has a structure shown by a general formula (I) as shown in description, wherein R1, R2, R3 and R4 in the general formula (I) are same and are alkyl, alkoxy, aryl, aroxyl, or hydrogen atoms; R1, R2, R3 and R4 comprise forms of ring formation, non-ring formation, any two ring formation or multiple-ring formation between pairs; R5 and R6 are alkyl, aryl or hydrogen atoms; and R7 and R8 are alkyl or benzyl or aryl. The invention further provides application of the oxa-spiral diphosphine ligand O-SDP in the alpha, beta-unsaturated carboxylic acid asymmetric hydrogenation. A complex of the oxa-spiral diphosphine ligand O-SDP and ruthenium has excellent activity and enantioselectivity in the asymmetric hydrogenation of the alpha, beta-unsaturated carboxylic acid in multiple types, and a chiral carboxylic acid product is obtained with the enantioselectivity being up to 99%. The synthesis method can be applied to the construction of a core skeleton of chemical molecules with important activity, wherein the chemical molecules comprise Paroxetine, Femoxetine, nipecotic acid and Sacubitril.
