Design, synthesis, and biological evaluation of piperidinyl-substituted [1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential anti-HIV-1 agents with reduced cytotoxicity

被引：28

作者：

Huang, Boshi ^{[1
]}

Kang, Dongwei ^{[1
]}

Tian, Ye ^{[1
]}

Daelemans, Dirk ^{[2
]}

De Clercq, Erik ^{[2
]}

Pannecouque, Christophe ^{[2
]}

Zhan, Peng ^{[1
]}

Liu, Xinyong ^{[1
]}

机构：

[1] Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China

[2] Katholieke Univ Leuven, Lab Virol & Chemotherapy, Rega Inst Med Res, Leuven, Belgium

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2021年 / 97卷 / 01期

基金：

中国国家自然科学基金;

关键词：

1; 2; 4]Triazolo[1; 5-a]pyrimidines; anti-HIV-1; potency; molecular docking; reduced cytotoxicity; reverse transcriptase; BEARING BRIDGEHEAD NITROGEN; HIV-1; NNRTIS; DISCOVERY; DIARYLPYRIMIDINES; INHIBITORS; OPTIMIZATION; POTENCY; DRUG;

D O I：

10.1111/cbdd.13760

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Taking the previously reported compound BH-7d as the lead, we designed and synthesized a series of piperidinyl-substituted [1,2,4]triazolo[1,5-a]pyrimidines, and their anti-HIV activities as well as cytotoxicities were evaluated. Several compounds exhibited moderate anti-HIV (IIIB) potency, among which2bwas the most active one (EC50 = 4.29 mu M). Structure-activity relationships derived from the antiretroviral results were analyzed. Additionally, most compounds demonstrated reduced cytotoxicity (CC50 > 200 mu M) compared with those ofBH-7dand etravirine. Molecular docking study further revealed the binding conformation of2bin the binding pocket of HIV-1 reverse transcriptase.

引用

页码：67 / 76

页数：10

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