159005-71-7Relevant articles and documents
Preliminary SAR and biological evaluation of potent HIV-1 protease inhibitors with pyrimidine bases as novel P2 ligands to enhance activity against DRV-resistant HIV-1 variants
Zhu, Mei,Ma, Ling,Zhou, Huiyu,Dong, Biao,Wang, Yujia,Wang, Zhen,Zhou, Jinming,Zhang, Guoning,Wang, Juxian,Liang, Chen,Cen, Shan,Wang, Yucheng
, (2020)
Introducing pyrimidine bases, the basic components of nucleic acid, to P2 ligands might enhance the potency of Human Immunodeficiency Virus-1 (HIV-1) protease inhibitors because of the carbonyl and amino groups promoting the formation of extensive hydrogen bonding interactions. In this work, we provide evidence that inhibitor 10e, with N-2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide as the P2 ligand and a 4-methoxylphenylsulfonamide as the P2′ ligand, displayed remarkable enzyme inhibitory and antiviral activity, with the IC50 2.53 nM in vitro and a promising inhibition ratio with 68% against wild-type HIV-1 in vivo, with low cytotoxicity. This inhibitor also exhibited appreciable antiviral activity against DRV-resistant HIV-1 variants, which was of great value for further study.
Rational design and Structure?Activity relationship of coumarin derivatives effective on HIV-1 protease and partially on HIV-1 reverse transcriptase
Zhu, Mei,Ma, Ling,Wen, Jiajia,Dong, Biao,Wang, Yujia,Wang, Zhen,Zhou, Jinming,Zhang, Guoning,Wang, Juxian,Guo, Ying,Liang, Chen,Cen, Shan,Wang, Yucheng
, (2020)
Since dual inhibitors may yield lower toxicity and reduce the likelihood of drug resistance, as well as inhibitors of HIV-1 PR and RT constitute the core of chemotherapy for AIDS treatment, we herein designed and synthesized new coumarin derivatives characterized by various linkers that exhibited excellent potency against PR and a weak inhibition of RT. Among which, compounds 6f and 7c inhibited PR with IC50 values of 15.5 and 62.1 nM, respectively, and weakly affected also RT with IC50 values of 241.8 and 188.7 μM, respectively, showing the possibility in the future of developing dual HIV-1 PR/RT inhibitors. Creative stimulation for further research of more potent dual HIV-1 inhibitors was got according to the molecular docking studies.
(Hydroxyethyl) sulfonamide HIV-1 protease inhibitors: Identification of the 2-methylbenzoyl moiety at P-2
Freskos,Bertenshaw,Getman,Heintz,Mischke,Blystone,Bryant,Funckes-Shippy,Houseman,Kishore,Kocan,Mehta
, p. 445 - 450 (1996)
We have discovered a potent low molecular weight series of HIV-1 protease inhibitors incorporating the (R)-(hydroxyethyl) sulfonamide isostere.
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.
Nitrogen-containing heterocyclic amino derivative, preparation method thereof and anti-HIV-1 medicine
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, (2021/08/21)
The invention provides a nitrogen-containing heterocyclic ring amino derivative, a preparation method thereof and an anti-HIV-1 medicine, and belongs to the technical field of medicine application. The nitrogen-containing heterocyclic ring amino derivative provided by the invention can interfere with the process of hydrolyzing Gap and Gap-Pol precursor polyprotein by HIV-1 protease, and has high HIV-1 protease inhibitory activity; meanwhile, the nitrogen-containing heterocyclic ring amino derivative provided by the invention has remarkable inhibitory activity on wild type anti-HIV-1 medicine strains and high anti-DRV-medicine strains, has low cytotoxicity, and has a good application prospect as an anti-AIDS medicine.
