3-chloro-5-((2-oxo-1-((5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile | 1338226-05-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-chloro-5-((2-oxo-1-((5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile
• 英文别名: Doravirine metabolite M8；3-chloro-5-[2-oxo-1-[(5-oxo-1,4-dihydro-1,2,4-triazol-3-yl)methyl]-4-(trifluoromethyl)pyridin-3-yl]oxybenzonitrile
• CAS: 1338226-05-3
• 化学式: C₁₆H₉ClF₃N₅O₃
• 分子量: 411.727
• InChiKey: UFVUNOWUDOJABB-UHFFFAOYSA-N

物化性质

• 密度：
  1?+-.0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-chloro-5-((2-oxo-1-((5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile 生成 多拉韦林
  参考文献：
  名称：

  [EN] NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
  [FR] INHIBITEURS DE TRANSCRIPTASE INVERSE NON NUCLÉOSIDIQUES

  摘要：

  公式I的杂环芳香化合物：（I）是HIV反转录酶抑制剂，其中R1，R2，R3; R4和R5在此处定义。公式I的化合物及其药学上可接受的盐在抑制HIV反转录酶，预防和治疗HIV感染以及预防，延迟发病或进展和治疗艾滋病方面是有用的。这些化合物及其盐可以与其他抗病毒药物，免疫调节剂，抗生素或疫苗组合使用作为制药组合物的成分。

  公开号：

  WO2011120133A1
• 作为产物：
  描述：

  2-chloro-3-(3-chloro-5-iodophenoxy)-4-(trifluoromethyl)pyridine 在 potassium carbonate 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 20.0h， 生成 3-chloro-5-((2-oxo-1-((5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl)-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl)oxy)benzonitrile
  参考文献：
  名称：

  NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

  摘要：

  公式I的杂环芳化合物是HIV反转录酶抑制剂，其中R1、R2、R3、R4和R5在此定义。公式I的化合物及其药学上可接受的盐在抑制HIV反转录酶、预防和治疗HIV感染以及预防、延缓AIDS的发病或进展方面是有用的。这些化合物及其盐可以作为药物组合中的成分使用，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用。

  公开号：

  US20110245296A1

文献信息

• PHARMACEUTICAL COMPOSITION COMPRISING A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR
  申请人：Merck Canada Inc.

  公开号：EP2924034A1

  公开（公告）日：2015-09-30

  The invention relates to a pharmaceutical composition comprising an effective amount of the compound: or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier and further comprising an effective amount of an anti-HIV agent. The invention further relates to use of said pharmaceutical composition for the prophylaxis or treatment of infection by HIV or for the prophylaxis, treatment, or delay in the onset of AIDS in a subject in need thereof.

  本发明涉及一种药物组合物，其中包含有效量的化合物： 或其药学上可接受的盐和药学上可接受的载体，并进一步包含有效量的抗 HIV 剂。本发明进一步涉及所述药物组合物用于预防或治疗艾滋病病毒感染，或用于预防、治疗或延缓有需要的受试者的艾滋病发病。
• PROCESS FOR MAKING REVERSE TRANSCRIPTASE INHIBITORS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：EP3617193A1

  公开（公告）日：2020-03-04

  The present invention is directed to a novel process for synthesizing 3-(substituted phenoxy)-1-[(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl])-pyridin-2(1H)-one derivatives. The compounds synthesized by the processes of the invention are HIV reverse transcriptase inhibitors useful for inhibiting reverse transcriptase and HIV replication, and the treatment of human immunodeficiency virus infection in humans.

  本发明涉及一种合成 3-(取代苯氧基)-1-[(5-氧代-4,5-二氢-1H-1,2,4-三唑-3-基)甲基])-吡啶-2(1H)-酮衍生物的新工艺。本发明工艺合成的化合物是 HIV 逆转录酶抑制剂，可用于抑制逆转录酶和 HIV 复制，以及治疗人类免疫缺陷病毒感染。
• Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses
  作者：Bernard Côté、Jason D. Burch、Ernest Asante-Appiah、Chris Bayly、Leanne Bédard、Marc Blouin、Louis-Charles Campeau、Elizabeth Cauchon、Manuel Chan、Amandine Chefson、Nathalie Coulombe、Wanda Cromlish、Smita Debnath、Denis Deschênes、Kristina Dupont-Gaudet、Jean-Pierre Falgueyret、Robert Forget、Sébastien Gagné、Danny Gauvreau、Melina Girardin、Sébastien Guiral、Eric Langlois、Chun Sing Li、Natalie Nguyen、Rob Papp、Serge Plamondon、Amélie Roy、Stéphanie Roy、Ria Seliniotakis、Miguel St-Onge、Stéphane Ouellet、Paul Tawa、Jean-François Truchon、Joe Vacca、Marc Wrona、Youwei Yan、Yves Ducharme

  DOI：10.1016/j.bmcl.2013.12.070

  日期：2014.2

  The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical pharmacokinetic profile of 36 led to the prediction of a once daily low dose regimen in human. NNRTI 36, now known as MK-1439, is currently in clinical development for the treatment of HIV infection.
• A Robust Kilo-Scale Synthesis of Doravirine
  作者：Louis-Charles Campeau、Qinghao Chen、Danny Gauvreau、Mélina Girardin、Kevin Belyk、Peter Maligres、Guoyue Zhou、Chaozhan Gu、Wei Zhang、Lushi Tan、Paul D. O’Shea

  DOI：10.1021/acs.oprd.6b00163

  日期：2016.8.19

  Doravirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) currently in phase III clinical trials for the treatment of HIV infection. Herein we describe a robust kilo-scale synthesis for its manufacture. The structure and origin of major impurities were determined and their downstream fate-and-purge studied. This resulted in a redesign of the route to introduce the key nitrile functionality via a copper mediated cyanation which allowed all impurities to be controlled to an acceptable level. The improved synthesis was scaled to prepare similar to 100 kg batches of doravirine to supply all preclinical and clinical studies up to phase III. The synthesis affords high-quality material in a longest linear sequence of six steps and 37% overall yield.
• US8486975B2
  申请人：——

  公开号：US8486975B2

  公开（公告）日：2013-07-16