(Z)-6-(2,3-dihydro-2,7-dimethyl-3-oxo-benzo[d]isoxazol-5-yl)-6-(3-fluoro-5-trifluoromethylphenyl)-hex-5-enoic acid methyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: (Z)-6-(2,3-dihydro-2,7-dimethyl-3-oxo-benzo[d]isoxazol-5-yl)-6-(3-fluoro-5-trifluoromethylphenyl)-hex-5-enoic acid methyl ester
• 英文别名: methyl (Z)-6-(2,7-dimethyl-3-oxo-1,2-benzoxazol-5-yl)-6-[3-fluoro-5-(trifluoromethyl)phenyl]hex-5-enoate
• 化学式: C₂₃H₂₁F₄NO₄
• 分子量: 451.418
• InChiKey: AOVCRSVOCRZBMP-FXBPXSCXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-甲基水杨酸 在 氢氧化钾 、 sodium hydroxide 、 sodium hypochlorite 、 二(三叔丁基膦)钯 、 盐酸羟胺 、 四丁基溴化铵 、 potassium carbonate 、 cesium fluoride 、 N,N'-羰基二咪唑 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 111.5h， 生成 (Z)-6-(2,3-dihydro-2,7-dimethyl-3-oxo-benzo[d]isoxazol-5-yl)-6-(3-fluoro-5-trifluoromethylphenyl)-hex-5-enoic acid methyl ester
  参考文献：
  名称：

  Synthesis, Anti-HIV Activity, and Metabolic Stability of New Alkenyldiarylmethane HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

  摘要：

  Non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are part of the combination therapy currently used to treat HIV infection. Based on analogy with known HIV-1 NNRT inhibitors, 18 novel alkenyldiarylmethanes (ADAMs) containing 5-chloro-2-methoxyphenyl, 3-eyanophenyl, or 3-fluoro-5-trifluoromethylphenyl groups were synthesized and evaluated as HIV inhibitors. Their stabilities in rat plasma have also been investigated. Although introducing 5-chloro-2-methoxyphenyl or 3-fluoro-5-trifluoromethylphenyl groups into alkenyldiarylmethanes does not maintain the antiviral potency, the structural modification of alkenyldiarylmethanes with a 3-cyanophenyl substituent can be made without a large decrease in activity. The oxazolidinonyl group was introduced into the alkenyldiarylmethane framework and found to confer enhanced metabolic stability in rat plasma.

  DOI：

  10.1021/jm050452s

文献信息

• Alkenyldiarylmethanes, Fused Analogs And Syntheses Thereof
  申请人：Cushman Mark S.

  公开号：US20080300288A1

  公开（公告）日：2008-12-04

  Non-nucleoside inhibitors of HIV-1 reverse transcriptase are described. Such inhibitors may be used as part of a combination therapy to treat HIV infection. Compounds described herein exhibit antiviral potency. In addition, compounds described herein exhibit metabolic stability. Also described herein are processes for preparing Non-nucleoside inhibitors of HIV-1 reverse transcriptase.

  HIV-1反转录酶的非核苷类抑制剂被描述。这些抑制剂可以作为治疗HIV感染的联合疗法的一部分使用。本文描述的化合物具有抗病毒效力。此外，本文描述的化合物具有代谢稳定性。本文还描述了制备HIV-1反转录酶非核苷类抑制剂的过程。
• [EN] ALKENYLDIARYLMETHANES, FUSED ANALOGS AND SYNTHESES THEREOF<br/>[FR] ALCENYLDIARYLMETHANES, ANALOGUES FONDUS ET SYNTHESE
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2007005531A2

  公开（公告）日：2007-01-11

  [EN] Non-nucleoside inhibitors of HIV-I reverse transcriptase are described. Such inhibitors may be used as part of a combination therapy to treat HIV infection. Compounds described herein exhibit antiviral potency. In addition, compounds described herein exhibit metabolic stability. Also described herein are processes for preparing Non-nucleoside inhibitors of HIV-I reverse transcriptase.
  [FR] L'invention concerne des inhibiteurs non nucléosidiques de la transcriptase inverse du VIH-I. Ces inhibiteurs peuvent être partiellement impliqués dans une polythérapie visant à traiter l'infection à VIH. Les composés de l'invention possèdent en outre un effet antiviral puissant, et se caractérisent par une stabilité métabolique. Par ailleurs, l'invention concerne des procédés de préparation de ces inhibiteurs non nucléosidiques de la transcriptase inverse du VIH-I.
• Synthesis, Anti-HIV Activity, and Metabolic Stability of New Alkenyldiarylmethane HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors
  作者：Bo-Liang Deng、Tracy L. Hartman、Robert W. Buckheit,、Christophe Pannecouque、Erik De Clercq、Phillip E. Fanwick、Mark Cushman

  DOI：10.1021/jm050452s

  日期：2005.9.1

  Non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are part of the combination therapy currently used to treat HIV infection. Based on analogy with known HIV-1 NNRT inhibitors, 18 novel alkenyldiarylmethanes (ADAMs) containing 5-chloro-2-methoxyphenyl, 3-eyanophenyl, or 3-fluoro-5-trifluoromethylphenyl groups were synthesized and evaluated as HIV inhibitors. Their stabilities in rat plasma have also been investigated. Although introducing 5-chloro-2-methoxyphenyl or 3-fluoro-5-trifluoromethylphenyl groups into alkenyldiarylmethanes does not maintain the antiviral potency, the structural modification of alkenyldiarylmethanes with a 3-cyanophenyl substituent can be made without a large decrease in activity. The oxazolidinonyl group was introduced into the alkenyldiarylmethane framework and found to confer enhanced metabolic stability in rat plasma.