1-(tributylstannanyl)-2-methoxy-3-methyl-5-[4-(2-oxo-oxazolidin-3-yl)-but-1-enyl]benzoic acid methyl ester

• 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: 1-(tributylstannanyl)-2-methoxy-3-methyl-5-[4-(2-oxo-oxazolidin-3-yl)-but-1-enyl]benzoic acid methyl ester
• 英文别名: 1-(tributylstannanyl)-2-methoxy-3-methyl-5-[4-(2-oxooxazolidin-3-yl)-but-1-enyl]benzoic acid methyl ester；2-methoxy-3-methyl-5-[(tributylstannanyl)-4-(2-oxo-oxazolidin-3-yl)but-1-enyl]benzoic acid methyl ester；methyl 2-methoxy-3-methyl-5-[(Z)-4-(2-oxo-1,3-oxazolidin-3-yl)-1-tributylstannylbut-1-enyl]benzoate
• 化学式: C₂₉H₄₇NO₅Sn
• 分子量: 608.406
• InChiKey: MSJYUCYEKCPYTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  36
• 可旋转键数：
  17
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(tributylstannanyl)-2-methoxy-3-methyl-5-[4-(2-oxo-oxazolidin-3-yl)-but-1-enyl]benzoic acid methyl ester 在 potassium fluoride 、 碘 、 palladium diacetate 、 2-(二叔丁基膦)联苯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 23.33h， 生成 methyl 5-[(E)-1-(3,4-dimethoxyphenyl)-4-(2-oxooxazolidin-3-yl)but-1-enyl]-2-methoxy-3-methyl-benzoate
  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：

  2-methoxy-3-methyl-5-[4-(2-oxo-oxazolidin-3-yl)but-1-ynyl]benzoic acid methyl ester 、 三正丁基氢锡 在 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 以76%的产率得到1-(tributylstannanyl)-2-methoxy-3-methyl-5-[4-(2-oxo-oxazolidin-3-yl)-but-1-enyl]benzoic acid methyl ester
  参考文献：
  名称：

  Alkenyldiarylmethanes, Fused Analogs And Syntheses Thereof

  摘要：

  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。

  公开号：

  US20080300288A1

文献信息

• Synthesis of alkenyldiarylmethanes (ADAMs) containing benzo[d]isoxazole and oxazolidin-2-one rings, a new series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors
  作者：Bo-Liang Deng、Yujie Zhao、Tracy L. Hartman、Karen Watson、Robert W. Buckheit Jr.、Christophe Pannecouque、Erik De Clercq、Mark Cushman

  DOI：10.1016/j.ejmech.2008.09.013

  日期：2009.3

  stable bioisosteres, compounds bearing benzo[d]isoxazole and oxazolidine-2-one rings were designed and evaluated as a new series of potent HIV-1 non-nucleoside reverse transcriptase inhibitors with anti-HIV activity. All of the resulting ADAMs were found to inhibit HIV-1 RT with poly(rC)·oligo(dG) as the template primer. The most promising compound in this series was ADAM 3, with EC50 values of 40 nM (vs

  为了继续用稳定的生物等排体取代链烯基二芳基碳酸铅的代谢不稳定的甲基酯（ADAM），设计了带有苯并[ d ]异恶唑和恶唑烷-2-酮环的化合物，并将其评估为一系列新的有效HIV-1非-具有抗HIV活性的核苷逆转录酶抑制剂。发现所有所得的ADAM均以poly（rC）·oligo（dG）为模板引物抑制HIV-1 RT。该系列中最有前途的化合物是ADAM 3，其EC 50值为40 nM（vs HIV-1 RF）和20 nM（vs HIV-1 IIIB）。化合物3还抑制HIV-1逆转录酶，IC 50为0.91μM。ADAM 4在CEM-SS细胞中具有0.6μM的抗病毒EC 50和51.4分钟的血浆半衰期。
• Replacement of the Metabolically Labile Methyl Esters in the Alkenyldiarylmethane Series of Non-Nucleoside Reverse Transcriptase Inhibitors with Isoxazolone, Isoxazole, Oxazolone, or Cyano Substituents
  作者：Bo-Liang Deng、Tracy L. Hartman、Robert W. Buckheit,、Christophe Pannecouque、Erik De Clercq、Mark Cushman

  DOI：10.1021/jm060449o

  日期：2006.8.1

  The alkenyldiarylmethanes (ADAMs) are a unique class of non-nucleoside reverse transcriptase inhibitors that have potential value in the treatment of HIV/AIDS. However, the potential usefulness of the ADAMs is limited by the presence of metabolically labile methyl ester moieties. A series of novel ADAMs were therefore designed and synthesized in order to replace the metabolically labile methyl ester moieties of the existing ADAM lead compounds with hydrolytically stable, fused isoxazolone, isoxazole, oxazolone, or cyano substituents on the aromatic rings. The methyl ester and methoxy substituents on both of the aromatic rings in the parent compound 1 were successfully replaced with metabolically stable moieties with retention of anti-HIV activity and a general decrease in cytotoxicity.