6-tributylstannanyl-6-(3-fluoro-5-trifluoromethylphenyl)hex-5-enoic acid methyl ester | 864755-94-2

• 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: 6-tributylstannanyl-6-(3-fluoro-5-trifluoromethylphenyl)hex-5-enoic acid methyl ester
• 英文别名: methyl (Z)-6-[3-fluoro-5-(trifluoromethyl)phenyl]-6-tributylstannylhex-5-enoate
• CAS: 864755-94-2
• 化学式: C₂₆H₄₀F₄O₂Sn
• 分子量: 579.306
• InChiKey: KXSZFCBSLNHHIZ-UHFFFAOYSA-N

物化性质

• 沸点：
  519.7±60.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.96
• 重原子数：
  33
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-tributylstannanyl-6-(3-fluoro-5-trifluoromethylphenyl)hex-5-enoic acid methyl ester 、 5-碘-2-甲氧基-3-甲基苯甲酸甲酯 在 二(三叔丁基膦)钯 、 cesium fluoride 作用下， 以 甲苯 为溶剂， 反应 31.0h， 以58%的产率得到(Z)-5-[1-(3-fluoro-5-trifluoromethylphenyl)-5-methoxycarbonyl-pent-1-enyl]-2-methoxy-3-methylbenzoic 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
• 作为产物：
  描述：

  6-(3-fluoro-5-trifluoromethylphenyl)hex-5-ynoic acid methyl ester 、 三正丁基氢锡 在 四(三苯基膦)钯 氩 、 silica gel 作用下， 以 四氢呋喃 为溶剂， 反应 5.33h， 以to afford the vinylstannane 43 (2.651 g) as an oil in 90% yield的产率得到6-tributylstannanyl-6-(3-fluoro-5-trifluoromethylphenyl)hex-5-enoic acid methyl ester
  参考文献：
  名称：

  Alkenyldiarylmethanes, Fused Analogs And Syntheses Thereof

  摘要：

  本文介绍了一种非核苷类的HIV-1反转录酶抑制剂。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。所述化合物具有抗病毒效力。此外，所述化合物具有代谢稳定性。本文还描述了制备非核苷类HIV-1反转录酶抑制剂的过程。

  公开号：

  US20080300288A1

文献信息

• Synthesis and anti-HIV activity of new alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors (NNRTIs) incorporating benzoxazolone and benzisoxazole rings
  作者：Bo-Liang Deng、Matthew D. Cullen、Zhigang Zhou、Tracy L. Hartman、Robert W. Buckheit、Christophe Pannecouque、Erik De Clercq、Phillip E. Fanwick、Mark Cushman

  DOI：10.1016/j.bmc.2005.11.014

  日期：2006.4

  The HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) constitute a large and structurally diverse set of compounds, several of which are currently used in the treatment of AIDS. A series of novel alkenyldiarylmethanes (ADAMs) were designed and synthesized as part of an ongoing investigation to replace the metabolically labile methyl ester moieties found in the ADAM pharmacophore with stable modifications that retain the potent anti-HIV activity of the parent compounds. Unsurprisingly, the rat plasma half-lives of the new ADAMs were not improved when compared to the parent compounds, but all of the synthesized ADAMs inhibited the cytopathic effect of HIV-1 in cell culture. The most potent compound identified was (E)-5-[1-(3,7-dimethyl-2oxo-2,3-dihydro-benzoxazol-5-yl)-5-methoxycarbonyl-pent-1-enyl]-2-methoxy-3-methylbenzoic acid methyl ester (7), which inhibited the cytopathic effects of both HIV-1(RF) and HIV-1(IIIB) strains in cell cultures with EC50 values of 30 and 90 nM, respectively, and inhibited HIV-1 reverse transcriptase with an IC50 of 20 nM. (c) 2005 Elsevier Ltd. All rights reserved.
• 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。
• 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.