methyl 3-chloro-5-iodo-2-methoxybenzoate | 350236-32-7

• 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: methyl 3-chloro-5-iodo-2-methoxybenzoate
• CAS: 350236-32-7
• 化学式: C₉H₈ClIO₃
• 分子量: 326.518
• InChiKey: UNAPKPXGKINNPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 3-chloro-5-iodo-2-methoxybenzoate 在 sodium hydroxide 、 水 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以95%的产率得到3-chloro-5-iodo-2-methoxybenzoic acid
  参考文献：
  名称：

  Solid-Phase Synthesis of the Alkenyldiarylmethane (ADAM) Series of Non-Nucleoside HIV-1 Reverse Transcriptase Inhibitors

  摘要：

  The Sonogashira and Stille cross-coupling reactions have been employed in the synthesis of several non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the alkenyldiarylmethane (ADAM) series. The synthesis has been carried out both in solution and on a solid support. In contrast to previous syntheses of NNRTIs in the ADAM series, the present strategy allows the incorporation of differently substituted aromatic rings in a stereochemically defined fashion. The most potent of the new ADAMs inhibited the cytopathic effect of HIV-1(RF) in CEM-SS cell culture with an EC50 value of 20 nM.

  DOI：

  10.1021/jo0100291
• 作为产物：
  描述：

  蛋白银染试剂盒 在 磺酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 以96%的产率得到methyl 3-chloro-5-iodo-2-methoxybenzoate
  参考文献：
  名称：

  基于水杨酸的20α-羟基类固醇脱氢酶（AKR1C1）的基于结构的优化和生物学评估

  摘要：

  已确定与抑制剂3,5-二氯水杨酸（DCL）配合使用的人20α-羟基类固醇脱氢酶（AKR1C1）的Leu308Val突变体的三级结构。野生型和突变型酶的结构和动力学性质表明Leu308是抑制剂结合的选择性决定因素。Leu308Val突变导致DCL和3-溴-5-苯基水杨酸（BPSA）的抑制力分别降低13倍和3倍。用丙氨酸替代Leu308可使DCL和BPSA的效力分别降低473倍和27倍。为了优化抑制剂的效力和选择性，我们合成了5个取代的3-氯水杨酸衍生物，其中最有效的化合物3-氯-5-苯基水杨酸（K i = 0.86 nM），相对于结构相似的3α-羟基类固醇脱氢酶（AKR1C2），对AKR1C1的选择性高24倍。此外，该化合物在AKR1C1过表达的细胞中抑制孕激素的代谢，其IC 50值等于100 nM。

  DOI：

  10.1016/j.ejmech.2010.08.052

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。
• 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。
• 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.
• 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.
• [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.