(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(p-toluenesulfonyloxy)methyl]-1,3-dioxalane | 143327-63-3

• 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: (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(p-toluenesulfonyloxy)methyl]-1,3-dioxalane
• 英文别名: (2R,4S)-toluene-4-sulfonic acid 2-[2-(4-chloro-phenyl)-ethyl]-2-imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethyl ester；(2r,4s)-2-[2-(4-Chlorophenyl)ethyl]-2-[(1h-imidazol-1-yl)methyl]-4-[(p-toluenesulfonyloxy)methyl]-1,3-dioxolane；[(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate
• CAS: 143327-63-3
• 化学式: C₂₃H₂₅ClN₂O₅S
• 分子量: 476.981
• InChiKey: WMPFDNQTDKVIHW-JTHBVZDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  88
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(p-toluenesulfonyloxy)methyl]-1,3-dioxalane 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 18.5h， 以70 mg的产率得到(2R,4S)-2-[2-(4-chlorophenyl)ethyl]-4-(fluoromethyl)-2-[(1H-imidazol-1-yl)methyl]-1,3-dioxolane
  参考文献：
  名称：

  Synthesis and evaluation of imidazole–dioxolane compounds as selective heme oxygenase inhibitors: Effect of substituents at the 4-position of the dioxolane ring

  摘要：

  Several imidazole-dioxolane compounds were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds, which include a series of substituted thiophenol and substituted phenol derivatives of (2R, 4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(phenylsulfanyl)methyl]-1,3-dioxolane hydrochloride ( 3), in addition to smaller functionalized derivatives, continue our structure-activity studies by exploration of the aminothiophenol region ('northeastern region') in our original target structure azalanstat (1). In vitro, most of the compounds in this series were found to be highly potent inhibitors of the stress-induced isozyme HO-1 and the constitutive isozyme HO-2, showing only moderate selectivity for HO-1. Nevertheless, a few of the compounds displayed higher selectivity toward HO-1. None of the compounds having a larger appendage in the northeastern region were inhibitors of CYP2E1, whereas a compound having a relatively small fluorine substituent in this region did inhibit CYP2E1; all of the compounds tested exhibited high inhibitory potency against CYP3A1/3A2. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.078
• 作为产物：
  描述：

  1-[4-(4-氯苯基)-2-羟基-正丁基]咪唑 在 草酰氯 、 对甲苯磺酸 、 二甲基亚砜 、 三乙胺 作用下， 以 甲苯 、 正丁醇 为溶剂， 反应 8.0h， 生成 (2R,4S)-2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-4-[(p-toluenesulfonyloxy)methyl]-1,3-dioxalane
  参考文献：
  名称：

  WO2008/151437

  摘要：

  公开号：

文献信息

• Compounds and Methods for Treating Cancer and Diseases of the Central Nervous System
  申请人：Gupta Ajay

  公开号：US20110319459A1

  公开（公告）日：2011-12-29

  Disclosed are compounds of the general formula (I): TC n D  (I), compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumour tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.

  本发明涉及一般式（I）的化合物：TCnD（I），包括单独使用或与其他化疗药物联合使用的有效量的该化合物的组合物，以及用于治疗或预防癌症和抑制肿瘤组织生长的有用方法。这些化合物减弱了与增加血红素氧合酶活性相关的氧化损伤，并可以减少转化细胞中的细胞增殖。此外，所述化合物和组合物可用作神经保护剂，并用于治疗或预防中枢神经系统的神经退行性疾病和其他疾病。
• Methods of treating cancer with imidazolyl compounds
  申请人：Osta Biotechnologies

  公开号：US07943650B2

  公开（公告）日：2011-05-17

  Disclosed in certain embodiments is a method of treating and/or mitigating prostate cancer, ovarian cancer, melanoma, colorectal cancer, breast cancer or lung cancer, comprising administering to an individual in need thereof a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula (I): where T is optionally substituted phenyl; n is 1 to 6: C represents optionally substituted carbon; and D is imidazolyl; or a pharmaceutically acceptable salt or ester of said compound.

  在某些实施例中，揭示了一种治疗和/或缓解前列腺癌、卵巢癌、黑色素瘤、结肠直肠癌、乳腺癌或肺癌的方法，包括向需要该方法的个体给予含有以下化合物的制药组合物：公式（I）中的化合物，其中T是可选取代的苯基；n为1到6；C表示可选取代的碳；D是咪唑基；或者其药学上可接受的盐或酯。该制药组合物还包括药学上可接受的载体。
• Substituted imidazole derivatives and methods of use thereof for treating cancer
  申请人：Gupta Ajay

  公开号：US08513294B2

  公开（公告）日：2013-08-20

  Disclosed are compounds of the general formula (I): compositions comprising an effective amount of said compounds either alone or in combination with other chemotherapeutic agents, and methods useful for treating or preventing cancer and for inhibiting tumor tissue growth. These compounds attenuate the oxidative damage associated with increased heme-oxygenase activity and can reduce cell proliferation in transformed cells. In addition, the described compounds and compositions are useful as neuroprotectants and for treating or preventing neurodegenerative disorders and other diseases of the central nervous system.

  本发明公开了一般式(I)的化合物：包含所述化合物的有效量的组合物，单独使用或与其他化疗药物联合使用，以及用于治疗或预防癌症和抑制肿瘤组织生长的方法。这些化合物可以减轻与增加血红素氧合酶活性相关的氧化损伤，并且可以减少转化细胞的细胞增殖。此外，所述化合物和组合物可用作神经保护剂，并用于治疗或预防中枢神经系统的神经退行性疾病和其他疾病。
• Anti-Plasmodium activity of imidazole–dioxolane compounds
  作者：Jason Z. Vlahakis、Robert T. Kinobe、Kanji Nakatsu、Walter A. Szarek、Ian E. Crandall

  DOI：10.1016/j.bmcl.2006.01.122

  日期：2006.5

  A series of imidazole-dioxolane compounds, which we hypothesize should bind to heme and thus interfere with heme catabolism in the parasite, were assayed for inhibitory activity in Plasmodium falciparum cultures and the results were compared to those obtained with Chinese hamster ovary (CHO) cells. The majority of the compounds displayed a similar ratio of inhibitory activity in the two culture systems; however, a number of the compounds tested showed promising anti-Plasmodium activity. The mechanism of action of these compounds remains unclear, however their inability to act synergistically with chloroquine suggests that, if they are inhibiting heme detoxification, they do so in a manner that does not complement the action of chloroquine. (C) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of azalanstat analogues as heme oxygenase inhibitors
  作者：Jason Z. Vlahakis、Robert T. Kinobe、Raymond J. Bowers、James F. Brien、Kanji Nakatsu、Walter A. Szarek

  DOI：10.1016/j.bmcl.2004.12.075

  日期：2005.3

  Several analogues based on the lead structure of azalanstat were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). A number of these compounds, which are structurally distinct from metalloporphyrin HO inhibitors, were found to be selective for the HO-1 isozyme (stress induced), and had substantially less inhibitory activity on HO-2, the constitutive isozyme. (c) 2005 Elsevier Ltd. All rights reserved.