[4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetyl chloride | 874889-42-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetyl chloride
• 英文别名: ({4-chloro-2-[(3-chloro-5-cyanophenyl)carbonyl]phenyl}oxy)acetyl chloride；2-[4-Chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetyl chloride；2-[4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetyl chloride
• CAS: 874889-42-6
• 化学式: C₁₆H₈Cl₃NO₃
• 分子量: 368.603
• InChiKey: ZONLEFCYJWLUOA-UHFFFAOYSA-N

物化性质

• 沸点：
  549.8±50.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetyl chloride 在 草酰氯 、 铁粉 、 氯化铵 、 N,N-二甲基甲酰胺 作用下， 以 水 为溶剂， 反应 13.0h， 生成
  参考文献：
  名称：

  二苯甲酮衍生物作为潜在的HIV-1抑制剂的合成和生物学评估

  摘要：

  背景：尽管许多药物可以在获得性免疫缺陷综合症（AIDS）患者中实现高应答，但是对于越来越多的感染抗性HIV病毒株的患者，仍需要更安全，更有效的HIV抑制剂。GW678248是最有效的二苯甲酮衍生物之一，在1 nmol / L的浓度下，对一组HIV-1病毒（野生型，K103N突变体，Y181C等）具有很高的效力。但是，与皮疹和肝脏代谢酶有关的安全性问题最终导致停止了其进一步的发展。作为对本模板结构修改的延续，在本手稿中，一系列新的二苯甲酮被描述为潜在的HIV抑制剂。 方法：按照方案1和方案2的路线合成所有标题分子，并采用MTT法检测其抗HIV-1活性。在分子模拟中，使用了与默认参数并行的AutoDock 4.0.1对接程序。 结果：鉴定了一系列具有纳摩尔抗HIV-1活性的新型二苯甲酮衍生物（BPs）。在这些抑制剂中，活性最高的类似物10i（EC50 = 2.9 nmol / L）在抑制野生型

  DOI：

  10.2174/1573406413666161111151814
• 作为产物：
  描述：

  5-氯-2-甲氧基苯甲酸 在 lithium hydroxide 、 copper(l) iodide 、 四(三苯基膦)钯 、 正丁基锂 、 草酰氯 、 三溴化硼 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 、 氯仿 、 丙酮 、 乙腈 为溶剂， 反应 51.08h， 生成 [4-chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetyl chloride
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor

  摘要：

  Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.

  DOI：

  10.1021/jm050670l

文献信息

• WO2007/121415
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] CHEMCIAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2007121415A2

  公开（公告）日：2007-10-25

  [EN] The present invention relates to a compound that is a non-nucleoside reverse transcriptase inhibitor, and to processes for the preparation and use of the same. Specifically, the present invention includes methods of using such compound in the treatment of human immunodeficiency virus infection.
  [FR] L'invention concerne un composé étant un inhibiteur de transcriptase inverse non nucléosidique, et des procédés de préparation et d'utilisation de ce composé. L'invention concerne plus précisément des procédés d'utilisation d'un tel composé dans le traitement d'infections virales d'immunodéficience humaines.
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2007121416A2

  公开（公告）日：2007-10-25

  [EN] The present invention relates to a compound that is a non-nucleoside reverse transcriptase inhibitor, and to processes for the preparation and use of the same. Specifically, the present invention includes methods of using such compound in the treatment of human immunodeficiency virus infection.
  [FR] L'invention concerne un composé étant un inhibiteur de transcriptase inverse non nucléosidique, et des procédés de préparation et d'utilisation de ce composé. L'invention concerne plus précisément des procédés d'utilisation d'un tel composé dans le traitement d'infections virales d'immunodéficience humaines.
• Structure−Activity Relationship Studies of Novel Benzophenones Leading to the Discovery of a Potent, Next Generation HIV Nonnucleoside Reverse Transcriptase Inhibitor
  作者：Karen R. Romines、George A. Freeman、Lee T. Schaller、Jill R. Cowan、Steve S. Gonzales、Jeffrey H. Tidwell、Clarence W. Andrews、David K. Stammers、Richard J. Hazen、Robert G. Ferris、Steven A. Short、Joseph H. Chan、Lawrence R. Boone

  DOI：10.1021/jm050670l

  日期：2006.1.1

  Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.
• Synthesis and Biological Evaluation of Benzophenone Derivatives as Potential HIV-1 Inhibitors
  作者：Zhendong Song、Ping Wang、Shanshan Huang、Changyuan Wang、Rui-Rui Wang、Liu-Meng Yang、Yuhong Zhen、Kexin Liu、Yong-Tang Zheng、Xiaodong Ma

  DOI：10.2174/1573406413666161111151814

  日期：2017.5.5

  Results: A series of novel benzophenone derivatives (BPs) with nanomolar anti-HIV-1 activity were identified. Of these inhibitors, analogue 10i (EC50 = 2.9 nmol/L), the most active inhibitor, was comparable to the lead compound GW678248 in inhibiting the wild-type HIV-1 virus. Additionally, analogue 13b, which not only exhibited strong inhibitory activity against the HIV-1 virus (EC50 = 4.2 nmol/L), but also

  背景：尽管许多药物可以在获得性免疫缺陷综合症（AIDS）患者中实现高应答，但是对于越来越多的感染抗性HIV病毒株的患者，仍需要更安全，更有效的HIV抑制剂。GW678248是最有效的二苯甲酮衍生物之一，在1 nmol / L的浓度下，对一组HIV-1病毒（野生型，K103N突变体，Y181C等）具有很高的效力。但是，与皮疹和肝脏代谢酶有关的安全性问题最终导致停止了其进一步的发展。作为对本模板结构修改的延续，在本手稿中，一系列新的二苯甲酮被描述为潜在的HIV抑制剂。 方法：按照方案1和方案2的路线合成所有标题分子，并采用MTT法检测其抗HIV-1活性。在分子模拟中，使用了与默认参数并行的AutoDock 4.0.1对接程序。 结果：鉴定了一系列具有纳摩尔抗HIV-1活性的新型二苯甲酮衍生物（BPs）。在这些抑制剂中，活性最高的类似物10i（EC50 = 2.9 nmol / L）在抑制野生型