4-氯-苯甲酸1-(4-甲氧基苯基)酰肼盐酸盐 | 13815-62-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氯-苯甲酸1-(4-甲氧基苯基)酰肼盐酸盐
• 英文名称: 4-chloro-N-(4-methoxyphenyl)benzohydrazide hydrochloride
• 英文别名: 4-Chloro-benzoic Acid 1-(4-Methoxyphenyl)hydrazide Hydrochloride；4-chloro-N-(4-methoxyphenyl)benzohydrazide;hydrochloride
• CAS: 13815-62-8
• 化学式: C₁₄H₁₃ClN₂O₂*ClH
• 分子量: 313.183
• InChiKey: ANYDSWOBDUWVHE-UHFFFAOYSA-N

物化性质

• 熔点：
  179-180 °C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-氯-苯甲酸1-(4-甲氧基苯基)酰肼盐酸盐 在 溶剂黄146 、 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 25.0h， 生成 3-[1-(4-chlorobenzoyl)-5-methoxy-3-methylindol-2-yl]-N-(4-methylphenyl)sulfonylpropanamide
  参考文献：
  名称：

  Development of Potent and Selective Indomethacin Analogues for the Inhibition of AKR1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase) in Castrate-Resistant Prostate Cancer

  摘要：

  Castrate-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer. CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and/or adaptive intratumoral androgen biosynthesis. AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens. This makes AKR1C3 a target for the treatment of CRPC. AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5 alpha-dihydrotestosterone. Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2. Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity. The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1C3 cells. The AKR1C3.NADP(+).2'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode. The compounds reported are promising agents for the development of therapeutics for CRPC.

  DOI：

  10.1021/jm3017656
• 作为产物：
  描述：

  Acetaldehyd-N₁-(p-chlorbenzoyl)-p-methoxy-phenylhydrazon 在 盐酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以99%的产率得到4-氯-苯甲酸1-(4-甲氧基苯基)酰肼盐酸盐
  参考文献：
  名称：

  Development of Potent and Selective Indomethacin Analogues for the Inhibition of AKR1C3 (Type 5 17β-Hydroxysteroid Dehydrogenase/Prostaglandin F Synthase) in Castrate-Resistant Prostate Cancer

  摘要：

  Castrate-resistant prostate cancer (CRPC) is a fatal, metastatic form of prostate cancer. CRPC is characterized by reactivation of the androgen axis due to changes in androgen receptor signaling and/or adaptive intratumoral androgen biosynthesis. AKR1C3 is upregulated in CRPC where it catalyzes the formation of potent androgens. This makes AKR1C3 a target for the treatment of CRPC. AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, which inactivate 5 alpha-dihydrotestosterone. Indomethacin, used to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2. Parallel synthetic strategies were used to generate libraries of indomethacin analogues, which exhibit reduced cyclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity. The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selectivity over AKR1C1/AKR1C2, and blocked testosterone formation in LNCaP-AKR1C3 cells. The AKR1C3.NADP(+).2'-des-methyl-indomethacin crystal structure was determined, and it revealed a unique inhibitor binding mode. The compounds reported are promising agents for the development of therapeutics for CRPC.

  DOI：

  10.1021/jm3017656

文献信息

• Indoleacetic acid and indenacetic acid derivatives as therapeutic agents with reduced gastrointestinal toxicity
  申请人：Marnett J. Lawrence

  公开号：US20050250839A1

  公开（公告）日：2005-11-10

  The presently disclosed subject matter provides derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) that are characterized by substantially reduced cyclooxygenase inhibiting activity, yet retain the ability to interact with and modulate the activities of other polypeptides such as the class of peroxisome proliferators-activated receptors (PPARs) and γ-secretase. Also provided are methods of using the derivatives to treat pathological disorders.

  目前披露的主题提供了非甾体类抗炎药（NSAIDs）的衍生物，其特点是具有明显降低的环氧合酶抑制活性，但仍保留与其他多肽（如过氧化物酶体增殖物激活受体（PPARs）和γ-分泌酶）相互作用和调节活性的能力。还提供了使用这些衍生物治疗病理性疾病的方法。
• [EN] INDOMETHACIN ANALOGS FOR THE TREATMENT OF CASTRATE-RESISTANT PROSTATE CANCER<br/>[FR] ANALOGUES DE L'INDOMÉTACINE DESTINÉS AU TRAITEMENT DU CANCER DE LA PROSTATE RÉSISTANT À LA CASTRATION
  申请人：UNIV VANDERBILT

  公开号：WO2013059245A1

  公开（公告）日：2013-04-25

  Provided are compositions for inhibiting a biological activity of an aldoketo reductase family 1, member C3 (AKR1 C3) polypeptide. In some embodiments, the compositions are indomethacin derivatives that are AKR1 C3-specific inhibitors. Also provided are methods for producing disclosed indomethacin derivatives that substantially lack cyclooxygenase inhibitory activity but that have AKR1C3 inhibitory activity, methods for inhibiting AKR1C3 polypeptide biological activities, and methods for treating prostate tumors in subjects.

  提供了用于抑制醛酮还原酶家族1成员C3（AKR1 C3）多肽的生物活性的组合物。在某些实施例中，这些组合物是吲哚美酸衍生物，是AKR1 C3特异性抑制剂。还提供了生产所述吲哚美酸衍生物的方法，这些衍生物基本缺乏环氧合酶抑制活性，但具有AKR1C3抑制活性，以及抑制AKR1C3多肽生物活性的方法，以及治疗受试者前列腺肿瘤的方法。
• 9-Acyl-1,2,3,4-tetrahydrocarbazole-3 and 4-carboxylic acids
  申请人：Sterling Drug Inc.

  公开号：US03948939A1

  公开（公告）日：1976-04-06

  Novel 9-aroyl-1,2,3,4-tetrahydrocarbazoles bearing a carboxy substituent at position 3 or 4 and corresponding esters having antiinflammatory activity, the preparation thereof and novel intermediates therefor are described.

  描述了具有3或4位上的羧基取代基的新型9-芳酰基-1,2,3,4-四氢吲哚衍生物及具有抗炎活性的相应酯类化合物，以及它们的制备方法和新型中间体。
• Profiling indomethacin impurities using high-performance liquid chromatography and nuclear magnetic resonance
  作者：Sonja Hess、Uwe Teubert、Jutta Ortwein、Kurt Eger

  DOI：10.1016/s0928-0987(01)00198-1

  日期：2001.12

  and reliable for the detection of eight impurities in indomethacin. In addition to the HPLC-UV method, 1H nuclear magnetic resonance (NMR) was used to investigate indomethacin regarding impurities. For that purpose, related substances 2-9 were systematically added to indomethacin and investigated. The NMR method was found to be very useful for the identification of impurities in bulk substance without

  研究了消炎药消炎痛有关新的相关杂质。因此，通过独立合成来制备相关物质2-9并进行物理化学表征。为了测定消炎痛及其相关物质，开发并验证了一种新的HPLC-UV方法。消炎痛及其杂质在流动相由甲醇和0.2％磷酸水溶液组成的C（18）色谱柱上以1.5 ml / min的流速洗脱，并通过320 nm的UV检测进行定量。总体而言，HPLC-UV方法简便，可靠，可检测消炎痛中的八种杂质。除HPLC-UV方法外，还使用1H核磁共振（NMR）研究吲哚美辛中的杂质。为了这个目的，将相关物质2-9系统地添加到消炎痛中进行研究。已发现，无需事先分离，NMR方法对于鉴定散装物质中的杂质非常有用。HPLC-UV和NMR均用于分析38批在欧洲市场上可获得的消炎痛。结果是，尽管满足当前药典方法的规范，但仍有42％的批次不符合药典要求。一些批次包含先前未描述的杂质8，而其他批次包含来自两种不同合成途径的副产物。本文介绍的方
• [1-(P-Chlorobenzoyl)-5-methoxy-2-methyl-3-indole]acetoxyacetic acid and
  申请人：Troponwerke Dinklage & Company

  公开号：US03966956A1

  公开（公告）日：1976-06-29

  [1-(P-CHLOROBENZOYL)-5-METHOXY-2-METHYL-3-INDOLE]-ACETOXYACETIC ACID OF THE FORMULA ##SPC1## Possesses outstanding antiphlogistic activity without the side effects of certain conventional antiphlogistic pharmaceuticals.

  化学式为[1-(对氯苯甲酰)-5-甲氧基-2-甲基-3-吲哚]-乙酰氧乙酸的化合物具有优异的抗炎活性，而且没有某些传统抗炎药物的副作用。