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百时美施贵宝新型抗艾药Fostemsavir(BMS-663068)的合成方法

(2014-09-15 19:33:28)
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bms-663068

fostemsavir

百时美施贵宝新型抗艾滋病药物HIV吸附抑制剂Fostemsavir(BMS-663068)

百时美施贵宝抗艾滋病新药Fostemsavir(BMS-663068)是一种新型的吸附抑制剂,目前处于2期临床。

全球范围内,有多达3400万HIV感染者。由于过去20年中HIV治疗管理的显著科学进步,现在患者能带病生存更长的时间,但同时一些患者已对现有方案产生抗性或不耐受。新的治疗选择,尤其是新的药物类别,无论现在或将来,对这类群体都很必要。

抗HIV药物司他夫定(Stavudine,d4T)、惠妥滋(去羟肌苷,ddI),Sustiva(EFV),以及Atazanavir(PI类药物, 商品名:Reyataz)和目前市场上已有的其他抗HIV药物一样,其机制是作用于HIV病毒进入宿主细胞后的阶段,它们可抑制病毒胞内复制的各个环节,从而有效控制提内病毒含量。近年来,研究者开始更加关注那些可以阻止HIV病毒进入宿主细胞的药物。

百时美施贵宝的Fostemsavir(BMS-663068)是Temsavir (BMS-626529)的前药, 也是首个处于临床研究的吸附抑制剂,BMS-663068在体内由碱性磷酸酶转化成具有活性的BMS-626529,作用于病毒进入靶细胞的第一步骤的,BMS-626529可以特异性地与病毒包膜gp120蛋白的某个位点相结合,而该位点正是病毒与CD4受体结合并启动进入程序的关键点。通过靶向病毒生命周期的早期阶段,Fostemsavir(BMS-663068)有望以一种不同于现有抗逆转录病毒药物的独特作用方式,破坏HIV病毒,可以为因HIV耐药而造成的治疗失败提供更好的选择。

2014年3月8日百时美施贵宝(BMS)在第21届逆转录病毒和机会性感染大会(CROI 2014)上公布了其实验性HIV药物Fostemsavir(BMS-663068)的IIb期临床数据,证实该药与增效剂ritonavir(利托那韦)增效的一种蛋白酶抑制剂Reyataz(atazanavir,阿扎那韦)具有类似的反应率(HIV-1 RNA <50 c/mL,表明病毒复制无法检测到),BMS-663068治疗组实现HIV-1 RNA<50 c/mL患者比例为69-80%,而对照组(ritonavir+Reyataz)比例为75%。该项研究彰显了BMS-663068的独特作用机制,该药是一种新颖的吸附抑制剂,能够阻止病毒最初吸附宿主CD4+T细胞并进入宿主免疫细胞。

Bristol-Myers Squibb’s Fostemsavir (BMS-663068), a prodrug of novel oral HIV-1 attachment inhibitor Temsavir (BMS-626529), is in clinical development for the treatment of HIV infection.

Chemical Structure of Fostemsavir_BMS-663068_Prodrug of Temsavir-Bristol-Myers Squibb 百时美施贵宝抗HIV新药Fostemsavir的化学结构Current HIV treatment combines medications from different antiretroviral classes that interfere with different steps of the viral life cycle. But no existing drugs target the very first step, initial attachment of the virus to a vulnerable host cell.

Chemical Structure of Temsavir (BMS-626529), Active Component of BMS-663068_Fostemsavir_HIV-1 attachment inhibitor_Bristol-Myers Squibb


 

通用名:Fostemsavir
别名:BMS-663068
英文化学名:{3-[2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl]-4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl}methyl dihydrogen phosphate
中文化学名:1-苯甲酰基-4-[2-[4-甲氧基-7-(3-甲基-1H-1,2,4-三唑-1-基)-1-[(膦酰氧基)甲基]-1H-吡咯并[2,3-c]吡啶-3-基]-1,2- 二氧代乙基]-哌嗪
CAS 登录号:864953-29-7 (BMS-663068),864953-39-9 (BMS-663068 氨基丁三醇盐)
作用机制:HIV吸附抑制剂
适应症:HIV
药物公司:百时美施贵宝

通用名:Temsavir
别名:BMS-626529
英文化学名:1-(4-benzoylpiperazin-1-yl)-2-[4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]ethane-1,2-dione
CAS 登录号:701213-36-7
作用机制:HIV吸附抑制剂
适应症: 抗HIV药
药物公司:百时美施贵宝

一般名(洋名):Fostemsavir
開発コード: BMS-663068
CAS登録番号:864953-29-7
薬効分類名:経口HIV-1アタッチメント阻害剤,BMS-626529のプロドラッグ
効能?効果:抗HIV薬
製造会社:ブリストル?マイヤーズ?スクイブ株式会社

Synthesis of Fostemsavir (BMS-663068) Tris, A Prodrug of BMS’s First-In-Class HIV-1 Attachment Inhibitor Temsavir (BMS-626529) 百时美施贵宝新型抗HIV药物Fostemsavir的合成方法

Synthesis of Fostemsavir (BMS-663068) Tris, BMS's First-In-Class HIV-1 Attachment Inhibitor 百时美施贵宝新型抗艾药Fostemsavir的合成方法


 

Sources:

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Bristol-Myers Squibb. A Phase IIb Randomized, Controlled, Partially-Blinded Trial to Investigate Safety, Efficacy and Dose-Response of BMS-663068 in Treatment-experienced HIV-1 Subjects, Followed by an Open-Label Period on the Recommended Dose. ClinicalTrials.gov Identifier:NCT01384734. Study Start Date:July 2011. Estimated Study Completion Date:July 2018. Last accessed September 14, 2014.

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US8436168 相关中国专利:制备HIV附着抑制剂前药化合物的方法及中间体.发明人:J.C.特里普 等.申请公布号:CN103339130A (从yaopha.com下载此专利). 申请公布日:2013.10.02.申请号:2012800071538.申请日:2012.01.27.申请人:百时美施贵宝公司。

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摘自:yaopha

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