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| 1 | S-DAPYs类似物的分子设计、合成及抑制HIV-1的活性研究显示文摘我们以已上市的etravirine和正在临床研究的VRX-480773两个逆转录酶抑制剂为模板,通过杂交这两个化合物的药效团,获得含酰胺片段的S—DAPYs类似物,该类似物对野生型HIV-1病毒株具有中等强度抑制活性.而Maurizio所发现的另一类无酰胺片段的S.DAPYs类似物却表现出优异的抑制活性.为了考察酰胺片段对S-DAPYs类似物抑制HIV-1活性的影响,本文合成了一系列无酰胺片段的S—DAPYs类似物.生物活性结果表明,3个化合物(6g、6m和6s)对野生型HIV-1具有中等强度抑制活性(EC50在6.5~15.4μmol/L范围内),弱于相应的具有酰胺片段的类似物.此外,分子模拟还揭示了酰胺片段可与K103形成至关重要的氢键作用,这为新型非核苷类逆转录酶抑制剂的设计奠定了理论基础. | 万正勇 陈芬儿 Erik De Clercq Dirk Daelemans Christophe Pannecouque | 2015 | 中国科学:化学2015，45，9： | 2 |
| 2 | 非核苷类逆转录酶抑制剂的研究XVⅢ:4-烯丙基和4-叠氮基取代的三嗪类化合物的合成及抗HIV活性(英文)显示文摘在已有工作基础上,基于分子对接设计合成了8个新的4-烯丙基取代和4-叠氮基取代的二芳基三嗪类衍生物。抗HIV-1活性的测试结果表明所有新化合物均具有抗HIV-1活性。其中化合物7c不仅抑制HIV-1野生株的复制(IC50=0.034μmol·L-1,SI=6475),且对Y181C和K103C双突变酶显示出较强的抑制活性,其IC50值为9.39μmol·L-1,高于奈韦拉平。 | 熊远珍 胡海荣 陈芬儿 Jan Balzarini Christophe Pannecouque Erik De Clercq | 2009 | 药学学报2009，44，2： | 2 |
| 3 | Development of fluorine-substituted NH_(2)-biphenyl-diarylpyrimidines as highly potent non-nucleoside reverse transcriptase inhibitors:Boosting the safety and metabolic stability显示文摘Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1(EC_(50)=1.0 nmol/L),but the poor metabolic stability in human liver microsomes(t_(1/2)=14.6 min)and insufficient selectivity(SI=2059)with high cytotoxicity(CC_(50)=2.08μmol/L)remained major issues associated with JK-4b.The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b,leading to the discovery of a novel series of fluorine-substituted NH_(2)-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain(EC_(50)=1.8–349 nmol/L).The best compound 5t in this collection(EC_(50)=1.8 nmol/L,CC_(50)=117μmol/L)was 32-fold in selectivity(SI=66,443)compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains,such as L100I,K103N,E138K,and Y181C.The metabolic stability of 5t was also significantly improved(t_(1/2)=74.52 min),approximately 5-fold higher than JK-4b in human liver microsomes(t_(1/2)=14.6 min).Also,5t possessed good stability in both human and monkey plasma.No significant in vitro inhibition effect toward CYP enzyme and hERG was observed.The single-dose acute toxicity test did not induce mice death or obvious pathological damage.These findings pave the way for further development of 5t as a drug candidate. | Xin Jin Shuai Wang Limin Zhao Wenjuan Huang Yinxiang Zhang Christophe Pannecouque Erik De Clercq Ge Meng Huri Piao Fener Chen | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 1 |
| 4 | A novel in vivo model for the study of HIV-1 transcription inhibitors: Evaluation of new 6-Desfluoro-quinolone derivatives (6-DFQs)显示文摘 | Stevens M Pollicita M Pannecouque C | 2007 | Antimicrob Agents Chemother2007，51，4： | 1 |
| 5 | Substituted 2-aminothiazoles are exceptional inhibitors of neuronal degeneration in tau-driven models of Alzheimer's disease显示文摘 | Lagoja I Pannecouque C Griffioen G | | 0，，05： | 1 |
| 6 | Anti-HIV Activity of a Series of Cosalane Amino Acid Conjugates显示文摘 | Santhosh KC Clercq ED Pannecouque C | 2000 | Bioorg Med Chem Lett2000，10，22： | 1 |
| 7 | Antiretroviral activity of semisynthetic derivatives of glycooeotide antibiotics 显示文摘 | Balzarini J Pannecouque C De Clercq E | 2003 | JMed Chem2003，46，13： | 1 |
| 8 | Potent anti-HIV (Type 1 and Type 2) activity of polyoxometalates: structure-activity relationship and mechanism of action显示文摘 | WITVROUW M WEIGOLD H PANNECOUQUE C | 2004 | J Med Chem2004，43，5： | 1 |
| 9 | Anti-HIV activity of thiosemicarbazone and semicarbazone dervatives of (±)-3-menthone显示文摘 | Mishra V Pandeya S N Pannecouque C | 2002 | Arch Pharm Pharm Med Chem2002，5，： | 1 |
| 10 | Syn- thesis and anti-HIV activity of a bile acid analog of co- salane显示文摘 | Kannan A Clercq E D Pannecouque C | 2001 | Tetrahedron2001，57，46： | 1 |
| 11 | Synthesisand studies of new 2-(coumarin-4-yloxy)-4,6-(substituted)-S-triazine derivatives as potential anti-HIV agents显示文摘 | Mahajan D H Pannecouque C De-Clercq E | 2009 | ArchPharm(Weinheim)2009，342，5： | 1 |
| 12 | Pyridine N-oxide derivatives inhibit viral transactivation by interfering with NF-kappaB binding显示文摘 | Stevens M Pannecouque C De Clercq E | | 0，，08： | 1 |
| 13 | Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability显示文摘Considering the undesirable metabolic stability of our recently identified NNRTI 5(t1/2=96 min)in human liver microsomes,we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine.This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity.The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes(t1/2=2754 min),which was about 29-fold longer than that of 5(t1/2=96 min).This compound conferred picomolar inhibition of WT HIV-1(EC50=0.9 nmol/L)and low nanomolar activity against five clinically drug-resistant mutant strains.It maintained particularly low cytotoxicity(CC50=264μmol/L)and good selectivity(SI=256,438).Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138.Also,compound 9g was characterized by good safety profiles.It displayed no apparent inhibition of CYP enzymes and h ERG.The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg.These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs. | Ya-Li Sang Christophe Pannecouque Erik De Clercq Shuai Wang Fen-Er Chen | 2023 | Acta Pharmaceutica Sinica B2023，13，7： | 1 |
| 14 | Synthesis of new covalently bound K-Carrageenan-AZT conjugates with improved Anti-HIV activities显示文摘 | Vlieghe P Clerc T Pannecouque C | 2002 | J Med Chem2002，45，6： | 1 |
| 15 | Design, synthesis, anti-HIV activity and cytotoxicity of novel schiff' s base of indeoquinoxalin-ll-one derivatives显示文摘 | SELVAM P CLERCP E D PANNECOUQUE C | 2013 | Int J Drug Des Discov2013，4，： | 1 |
| 16 | Novel in vivo model for the study of human immunodeficiency virus type 1 transcription inhibitors: evaluation of new 6-desfluoroquinolone derivatives 显示文摘 | Stevens M Pollicita M Pannecouque C | 2007 | Antimierob Agents Chemother2007，51，4： | 1 |
| 17 | Synthesis and anti-HIV activity of 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole structurally-related 1,2-substituted benzimidazoles显示文摘 | Angela Rao Alba Chimirri Erik De Clercq Anna Maria Monforte Pietro Monforte Christophe Pannecouque Maria Zappalà | 2002 | Il Farmaco2002，，10： | 1 |
| 18 | Synthesis of new covalently bound kappa-carrageenan-AZT conjugates with- improved anti-HIV activities 显示文摘 | VLIEGHE P CLERC1 T PANNECOUQUE C | 2002 | J Med Chem2002，45，6： | 1 |
| 19 | Viral entry as the primary target for the anti-HIV activity of chicoric acid and its tetraacetyl esters 显示文摘 | Pluymers W Neamati N Pannecouque C | 2000 | Mol Pharmacol2000，58，3： | 1 |
| 20 | 查看详情显示文摘 | El-Sabbagh O.I Baraka M.M Ibrahim S.M Pannecouque P Andrei G Snoeck R Balzarini J Rashad A.A | | 0，，： | 1 |
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