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::: Tenofovir disoproxil fumarate 泰诺福韦:::

FDA近日批准泰诺福韦(Tenofovir)上市。已批准的适应证为与其它抗逆转录病毒药物联合应用治疗HIV-1感染。泰诺福韦(Tenofovir)是第一个被批准用于治疗HIV-1感染的核苷酸类似物。核苷酸类似物与核苷类似物阻断HIV复制的作用机制相似。许多抗病毒药物单独和联合使用可以明显减少HIV复制，提高病人生存率。但由于HIV变异迅速，易产生耐药性，需要不断开发新的药物来抑制耐药病毒株。FDA批准泰诺福韦(Tenofovir)是根据两项临床试验结果，这两项研究纳入病人数超过700例。这些病人先前一直用抗逆转录病毒药物进行治疗，但抑制HIV复制作用不明显，而用该药治疗24-48周可降低血浆病毒负荷量。

一项试验共纳入病毒负荷量400-100000拷贝/ml、已用4种药物进行抗逆转录病毒治疗8周以上的189例HIV感染者。病人随机分4组，原有的抗逆转录病毒药物治疗不变，分别加用75mg/d,150mg/d,300mg/d泰诺福韦(Tenofovir)或安慰剂治疗24周。治疗24周后，全部病人(包括安慰剂组)改用泰诺福韦(Tenofovir)300mg每天1次。另一项试验纳入病毒负荷量为400-10000拷贝/ml、接受抗逆转录病毒治疗8周以上的552例病人。病人随机分2组，分别用泰诺福韦(Tenofovir)(300mg)或安慰剂，每天1次，原来的药物治疗方案不变。

结果显示，与安慰剂组相比，治疗组病人血中HIVRNA数量显著降低，不良反应和实验室检查异常的发生率与安慰剂组无显著差异，耐药的发生率也非常低，约为3%。由于批准泰诺福韦(Tenofovir)是根据对以往接受过抗逆转录病毒治疗病人的试验结果，对初治病人的疗效还不确定，因此，初治病人和儿童是否适用还有待更多的临床研究。此外，目前也没有该药长期临床疗效评价的资料。泰诺福韦(Tenofovir)常见的不良反应是轻度到中度的胃肠反应，包括腹泻、恶心、呕吐、胃胀、乳酸酸中毒、肝肿大伴脂肪肝等，这些不良反应在单独或联合使用核苷类似物时也常出现。

Tenofovir (Trade name Viread) is an anti-HIV drug approved by the FDA (In October of 2001) to be used in combination with other HIV fighting medications. Viread belongs to a new class of drugs called Nucleotide Reverse Transcriptase Inhibitors (NtRTI). These are related to Nucleoside Reverse Transcriptase Inhibitors (NRTI) like zidovudine (AZT, Retrovir). The body converts Viread into a chemical that prevent HIV from reproducing in uninfected cells, but it does not help cells that have already been infected with the virus. As people with HIV lose CD4 cells - one of the immune system's main defenses - they become more likely to get infections and illnesses.

Currently available anti-HIV drugs like AZT need three separate chemical steps before they are active. Viread needs only two chemical reactions (phosphorylation) to occur before it can start working. Partly due to this unique chemical feature, Viread also carries a "negative charge", allowing it to stay in the cells where it is active for a longer period. As a result, Viread only needs to be taken once a day.

Tenofovir disoproxil fumarate (TDF)
Cas Number: 202138-50-9
Chemical name: 9-[(R)-2-[[bis[[(isopropoxycarbonyl) oxy] methoxy] phosphinyl] methoxy] propyl] adenine fumarate

Intermediates for Tenofovir disoproxil fumarate (TDF)
1. Tenofovir disoproxil (TD)
Cas Number: 201341-05-1
Chemical name: 5-[[(1R)-2-(6-Amino-9H-purin-9-yl)-1-methylethoxy]methyl]-2,4,6,8-tetraoxa-5-phosphanononanedioic acid bis(1-methylethyl) ester 5-oxide

2. Tenofovir; PMPA; R-PMPA
Cas Number: 147127-20-6
Chemical name: (R)-9-(2-phosphonomethoxypropyl)adenine

Specifications

White or off-white crystalline powder
Metling point: 276.0 ~ 280.0 degrees C
Assay: not less than 98.0%
Specific rotation [a] 20/D: -20 ~ -22 degrees, c=1, 0.1M HCL
Water: not more than 0.5%
Heavy metal: not more than 20ppm

3. R-PMPA diethyl ester

5. Diethyl p-toluenesulfonyloxy methylphosphonate
CAS Number: 31618-90-3

4. R–9-(2-hydroxypropyl)adenine