6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzoxazol-5-yl)hex-5-ynoic acid methyl ester | 882882-84-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: 6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzoxazol-5-yl)hex-5-ynoic acid methyl ester
• 英文别名: 6-(3,7-Dimethyl-2-oxo-2,3-dihydrobenzoxazol-5-yl)-hex-5-ynoic Acid Methyl Ester；methyl 6-(3,7-dimethyl-2-oxo-1,3-benzoxazol-5-yl)hex-5-ynoate
• CAS: 882882-84-0
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: IXCSMNPIDSLGGN-UHFFFAOYSA-N

物化性质

• 熔点：
  97-98 °C
• 沸点：
  443.7±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzoxazol-5-yl)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 6.83h， 以to afford the vinylstannane 72 (3.07 g) as oil in 90% yield的产率得到6-(tributylstannanyl)-6-(2,3-dihydro-3,7-dimethyl-2-oxobenzoxazol-5-yl)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
• 作为产物：
  描述：

  5-iodo-7-methyl-3H-benzoxazol-2-one 在 bis-triphenylphosphine-palladium(II) chloride copper(l) iodide 、 四丁基碘化铵 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 反应 47.0h， 生成 6-(3,7-dimethyl-2-oxo-2,3-dihydrobenzoxazol-5-yl)hex-5-ynoic acid methyl ester
  参考文献：
  名称：

  Synthesis and anti-HIV activity of new alkenyldiarylmethane (ADAM) non-nucleoside reverse transcriptase inhibitors (NNRTIs) incorporating benzoxazolone and benzisoxazole rings

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2005.11.014

文献信息

• Investigation of the alkenyldiarylmethane non-nucleoside reverse transcriptase inhibitors as potential cAMP phosphodiesterase-4B2 inhibitors
  作者：Matthew D. Cullen、York-Fong Cheung、Miles D. Houslay、Tracy L. Hartman、Karen M. Watson、Robert W. Buckheit、Christophe Pannecouque、Erik De Clercq、Mark Cushman

  DOI：10.1016/j.bmcl.2007.12.015

  日期：2008.2

  The alkenyldiarylmethanes ( ADAMs) are currently being investigated as non- nucleoside HIV- 1 reverse transcriptase inhibitors ( NNRTIs) of potential value in the treatment of HIV infection and AIDS. During the course of these studies, a number of ADAM analogues have been identified that protect HIV- infected cells from the cytopathic effects of the virus by an unknown, HIV- 1 RT- independent mechanism. Since the phosphodiesterase 4 family is required for HIV infection, the effect of various ADAMs on the activity of PDE4B2 was investigated in an effort to determine if the ADAMs could possibly be targeting phosphodiesterases. Six compounds representative of the ADAM class were tested for inhibition of cAMP hydrolysis by PDE4B2 enzymatic activity. Four ADAMs were found to be weak inhibitors of PDE4B2 and two of them were inactive. The experimental results are consistent with an antiviral mechanism that does not include inhibition of PDE4 isoforms. (C) 2007 Elsevier Ltd. All rights reserved.
• [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.
• 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 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.