抗艾滋病药物的研究进展

为了遏止AIDS的迅猛流行 ,降低AIDS的发病和致死 ,针对HIV 1感染的各个环节 ,人们研制出一系列抗病毒药物 ,取得了一些成功的治疗经验 ,提出药物研究的重点方向是 :有多个作用靶点、能作用于感染病毒的细胞、调节机体免疫等。目前正利用丰富的中草药资源 。

A convenient synthesis of 1-alkyl-5-amino-6-phenylethyluracils as potential non-nucleoside HIV-1RT inhibitors

1-Alkyl-5-amino-6-phenylethyluracils （1a, 1b） were synthesized as potential non-nucleoside HIV-1RT inhibitors. A convenient synthetic procedure was developed for the preparation of 1-alkyl-5-amino or 5-aminosubstituted-6-phenylethyluracils, which were synthesized in three or four steps from 6-methyluracil in good yield. The development of a one-pot reaction that simultaneously removed the benzyl protection group and reduced the nitro group greatly improved the yield of the synthesis. Compounds 1a and 1b are analogs of MKC-442, which is an efficient inhibitor of HIV-1 reverse transcriptase, 1a and 1b were tested for their inhibition of HIV-1RT, and moderate activity was found for 1a.

医务人员艾滋病病毒职业暴露防护工作指导原则(试行)

根据卫生部2004年1月报告,目前全国HIV感染者已有84万人;据国内外专业人士估计,到2010年,中国感染HIV的人数将会超过1亿。2004年12月1日是第17个“世界艾滋病宣传日”,今年宣传的主题是“关注妇女,抗击艾滋”。护理人员是开展艾滋病健康教育的主力军,同时在工作中又可能会接触到艾滋病病毒,因此掌握艾滋病的相关知识和防护技能尤为重要。本刊特刊登国家卫生部于今年6月颁布的《医务人员艾滋病病毒职业暴露防护工作指导原则(试行)》和1篇对护理人员进行HIV/AIDS教育效果方面的论文,以期对大家的工作有所帮助。

Synthesis and anti-HIV-1 activity evaluation of N-1-alkyl-5-halogeno-6-alkylamino uracils as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

N-1-alkyl-5-halogeno-6-alkylamino uracils,which are novel 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio) thymine (HEPT) analogues,were synthesized as the selective and potent non-nucleoside human immunodeficiency virus(HIV)-1 reverse transcriptase inhibitors.Some of the compounds showed potent inhibitory activity against HIV-1 reverse transcriptase.For instance,compounds 1d,1m and 1n exhibited potent anti-HTV-1 activity with the IC_(50) values of 13.3,11.7 and 3.15μM,respectively, which are comparable to that of nevirapine(IC_(50) 8.38μM).

Route improvement of 3-substituted-4-(2-methylcyclohexyloxy)-6-phenethylpyridinone

trans-3-Isopropyl-4-（2-methylcyclohexyloxy）-6-phenethylpyridin-2（1H）-one, as reverse transcriptase （NNRTIs）, exhibited significant potent activity not only against wild-type HIV-1 strains but also on mutant strains. For furthering study this compound, the original synthetic route should be shorten to improve the total yield. In this report, we designed an efficient synthetic strategy to obtain the target compound with higher yield.

Synthesis and biological evaluation of novel 1-aryl-5-iodo-6-benzyluracils as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

We have synthesized the novel compounds 1a-1i,which are a series of hybrid analogues to 6-benzyl-1-（benzyloxymethyl）- 5-iodouracil,a compound showing strong activity against HIV-1.We also evaluated the activity of these compounds as the inhibitors of HIV-1 reverse transcriptase（HIV-1 RT）,and they have demonstrated moderate activity.

Synthesis and biological evaluation of novel 2-arylalkylthio-5-iodo-6-benzyl S-DABOs as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

A series of novel dihydro-alkylthio-benzyl-oxopyrimidines （S-DABOs） 7a-f have been designed and synthesized with an efficient method. Biological evaluation of their HIV-1 reverse transcriptase inhibitory activities was performed using Nevirapine （NVP） as a reference compound. Among the series, compound 7d shows the highest reverse transcriptase inhibitory activity, which is better than Nevirapine.

Design, synthesis and activity evaluation of novel pyridinone derivatives as anti-HIV-1 dual(RT/IN) inhibitors

Three series of novel anti-immunodeficiency virus 1 （HIV-1） dual （RT/1N） inhibitors were rationally designed by introducing a functioning diketo acid （DKA） into pyridin-2-one scaffold. To efficiently analyze inhibitory activity, these compounds were screened against HIV-1 RT and IN respectively via surface plasmon resonance （SPR）, and active compounds were subsequently evaluated by enzyme assay. It was noteworthy that compound A2 exhibited moderate activity against both HIV-1 RT and IN. This result provided information for further development of pyridinone analogues as potent dual HIV-1 inhibitors.

Pyridin-2(1H)-ones as HIV-1 NNRTIs:a combinatorial optimization strategy

With rapid spread of HIV(human immunodeficiency virus) on a global scale and increasingly severe drug-resistance of it,it is urgently necessary to develop novel effective anti-HIV drugs.Non-nucleoside reverse transcriptase inhibitor(NNRTIs)is one of the most significant antiretroviral drugs for fighting against HIV infection due to their various structures,unique mode of action,good efficacy and low toxicity.Pyridinone derivatives,a type of NNRTIs,have been reported to achieve remarkable development in the past few decades.In this review,we summarized current drug design and medicinal chemistry efforts toward the development of next-generation pyridinones as HIV-1 NNRTIs.