({4-chloro-2-[(3-chloro-5-cyanophenyl)carbonyl]phenyl}oxy)acetic acid | 329946-46-5

• 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-cyanophenyl)carbonyl]phenyl}oxy)acetic acid
• 英文别名: 2-[4-Chloro-2-(3-chloro-5-cyanobenzoyl)phenoxy]acetic acid
• CAS: 329946-46-5
• 化学式: C₁₆H₉Cl₂NO₄
• 分子量: 350.158
• InChiKey: DJNBLFDEGGEOPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 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：
  87.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ({4-chloro-2-[(3-chloro-5-cyanophenyl)carbonyl]phenyl}oxy)acetic acid 在 N,N-二甲基甲酰胺 草酰氯 、 碳酸氢钠 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 97.0h， 生成 2-({4-chloro-2-[(3-chloro-5-cyanophenyl)carbonyl]phenyl}oxy)-N-(4-{[2,3-dihydroxy-3-methylbutyl]oxy}-2-methylphenyl)acetamide
  参考文献：
  名称：

  WO2007/121415

  摘要：

  公开号：
• 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 48.83h， 生成 ({4-chloro-2-[(3-chloro-5-cyanophenyl)carbonyl]phenyl}oxy)acetic acid
  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

• [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.
• WO2007/121415
  申请人：——

  公开号：——

  公开（公告）日：——