4-(3-氯苯基)-3-氧丁酸乙酯 | 221122-22-1

• 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-(3-氯苯基)-3-氧丁酸乙酯
• 中文别名: 3-氯-B-氧代苯丁酸乙基酯
• 英文名称: 4-(3-chlorophenyl)-3-oxobutyric acid ethyl ester
• 英文别名: ethyl 4-(3-chlorophenyl)-3-oxobutanoate
• CAS: 221122-22-1
• 化学式: C₁₂H₁₃ClO₃
• 分子量: 240.686
• InChiKey: FWNXDGGKZYXZFO-UHFFFAOYSA-N

物化性质

• 沸点：
  320.6±22.0 °C(Predicted)
• 密度：
  1.198±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3-氯苯基)-3-氧丁酸乙酯 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以86%的产率得到ethyl (2Z)-3-amino-4-(3-chlorophenyl)but-2-enoate
  参考文献：
  名称：

  Structural Optimization and Biological Evaluation of 2-Substituted 5-Hydroxyindole-3-carboxylates as Potent Inhibitors of Human 5-Lipoxygenase

  摘要：

  Pharmacological suppression of leukotriene biosynthesis by inhibitors of 5-lipoxygenase (5-LO) is a strategy to intervene with inflammatory and allergic disorders. We recently presented 2-amino-5-hydroxy-1H-indoles as efficient 5-LO inhibitors in cell-based and cell-free assays. Structural optimization led to novel benzo[g]indole-3-carboxylates exemplified by ethyl 2-(3-chlorobenzyl)-5-hydroxy-1H-benzo[g]indole-3-carboxylate (compound 11a), which inhibits 5-LO activity in human neutrophils and recombinant human 5-LO with IC50 values of 0.23 and 0.086 mu M, respectively. Notably, 11a efficiently blocks 5-LO product formation in human whole blood assays (IC50 = 0.83-1.6 mu M) and significantly prevented leukotriene B-4 production in pleural exudates of carrageenan-treated rats, associated with reduced severity of pleurisy. Together, on the basis of their high potency against 5-LO and the marked efficacy in biological systems, these novel and straightforward benzo[g]indole-3-carboxylates may have potential as anti-inflammatory therapeutics.

  DOI：

  10.1021/jm900212y
• 作为产物：
  描述：

  (3-氯苯基)乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 4-(3-氯苯基)-3-氧丁酸乙酯
  参考文献：
  名称：

  Bioisosteric replacement of an acylureido moiety attached to an indolin-2-one scaffold with a malonamido or a 2/4-pyridinoylamido moiety produces a selectively potent Aurora-B inhibitor

  摘要：

  Bioisosteric replacement of acylureido moiety in 6-acylureido-3-pyrrolylmethylidene-2-oxoindoline derivatives resulted in a series of malonamido derivatives with indolin-2-one scaffold (11-14). Further conformational restrictions of the malonamido moiety led to 2-oxo-1,2-dihydropyridine (21-25) or a 4-oxo-1,4-dihydropyridine derivatives (31-36). 4-Oxo-1,4-dihydropyridine derivatives were more potent Aurora B inhibitors than their 2-oxo-1,2-dihydropyridine counterparts and demonstrated cytotoxicities against A549 and HepG2 cells in the submicromolar range. In A549 cells, 31h decreased phosphorylation of histone H3, triggered polyploidy, induced expression of pro-apoptotic Fas and FasL with subsequent activation of caspase 8, resulting into apoptosis. In a Huh7-xenograft mouse model, 31h demonstrated potent in vivo efficacy with a daily dose of 5 mg/kg.

  DOI：

  10.1016/j.ejmech.2014.07.033

文献信息

• [EN] HISTONE DEMETHYLASE INHIBITORS<br/>[FR] INHIBITEURS DE L'HISTONE DÉMÉTHYLASE
  申请人：QUANTICEL PHARMACEUTICALS INC

  公开号：WO2014089364A1

  公开（公告）日：2014-06-12

  Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

  本文提供了替代嘧啶基吡唑啉、嘧啶基吡唑啉和嘧啶基吡咪啉衍生物化合物以及包含这些化合物的药物组合物。这些化合物和组合物对于抑制组蛋白去甲基化酶具有用途。此外，这些化合物和组合物对于治疗癌症，如前列腺癌、乳腺癌、膀胱癌、肺癌和/或黑色素瘤等癌症有用。
• [EN] MACROCYCLIC FUSED PYRRAZOLES AS MCL-1 INHIBITORS<br/>[FR] PYRRAZOLES FUSIONNÉS MACROCYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE MCL-1
  申请人：ASCENTAGE PHARMA SUZHOU CO LTD

  公开号：WO2020151738A1

  公开（公告）日：2020-07-30

  Provided are compounds represented by Formula IA: (IA), and the pharmaceutically acceptable salts and solvates thereof, wherein R, R 1a, R 1b, L 1, L 2, L 3, X, A, B and C are as defined as set forth in the specification. Also provided compounds of Formula IA for use to treat a condition or disorder responsive to Mcl-1 inhibition such as cancer.

  提供由化学式IA表示的化合物，以及其在药学上可接受的盐和溶剂化合物，其中R、R 1a、R 1b、L 1、L 2、L 3、X、A、B和C的定义如规范中所述。还提供了化学式IA的化合物，用于治疗对Mcl-1抑制敏感的疾病或紊乱，如癌症。
• [DE] VERWENDUNG VON INDOL-3-CARBONSÄUREESTERN ZUR HEMMUNG DER MIKROSOMALEN PROSTAGLANDIN E2 SYNTHASE<br/>[EN] USE OF INDOLE-3-CARBOXYLIC ESTERS FOR INHIBITING MICROSOMAL PROSTAGLANDIN E2 SYNTHASE<br/>[FR] UTILISATION D'ESTERS DE L'ACIDE INDOL-3-CARBOXYLIQUE POUR L'INHIBITION DE LA PROSTAGLANDINE E2 SYNTHASE MICROSOMALE
  申请人：UNIV TUEBINGEN

  公开号：WO2009146696A1

  公开（公告）日：2009-12-10

  Die vorliegende Erfindung betrifft die Verwendung von lndol-3-carbonsäureestern und seiner Derivate zur Hemmung der induzierbaren mikrosomalen Prostaglandin E2 Synthase-1 und/oder zur Hemmung der 5-Lipoxygenase. Insbesondere betrifft die Erfindung die Verwendung von Derivaten des 3-Carboxy-aryl[g]indols, vor allem von 2-Aryl- und 2-Arylalkyl-Aryl[g]indol-3-carbonsäureestern sowie deren strukturellen Abkömmlingen zur Hemmung der induzierbaren mikrosomalen Prostaglandin E2 Synthase-1 und / oder zur Hemmung der 5-Lipoxygenase. Ferner betrifft die Erfindung die Verwendung von lndol-3-carbonsäureestern zur Herstellung eines Arzneimittels zur Behandlung von PGE2- und / oder 5-LO-vermittelter Erkrankungen und krankhafter Zustände, insbesondere von entzündlichen chronischen Entzündungen wie rheumatoide Arthritis, Osteoarthritis, Erkrankungen des kardiovaskulären Systems, Asthma, allergische Rhinitis, Multiple Sklerose, entzündliche Hauterkrankungen, Osteoporose und Krebs, Schmerz und Fieber, bei denen PGE2 und / oder 5-LO Produkte eine Rolle spielen.

  本发明涉及使用indol-3-羧酸酯及其衍生物来抑制可诱导的微粒体前列腺素E2合成酶-1和/或抑制5-脂氧合酶。具体涉及使用3-羧基芳基[g]吲哚的衍生物，特别是2-芳基和2-芳基烷基芳基[g]吲哚-3-羧酸酯及其结构衍生物来抑制可诱导的微粒体前列腺素E2合成酶-1和/或抑制5-脂氧合酶。此外，本发明涉及使用indol-3-羧酸酯来制备药物，用于治疗PGE2和/或5-LO介导的疾病和病态，特别是慢性炎症性疾病，如类风湿性关节炎，骨关节炎，心血管系统疾病，哮喘，过敏性鼻炎，多发性硬化症，炎性皮肤病，骨质疏松症和癌症，以及疼痛和发热，在其中PGE2和/或5-LO产物发挥作用。
• HISTONE DEMETHYLASE INHIBITORS
  申请人：Quanticel Pharmaceuticals, Inc.

  公开号：US20140194469A1

  公开（公告）日：2014-07-10

  Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

  本文提供了代替的吡唑基吡啶、吡唑基吡嗪和吡唑基嘧啶衍生物化合物及包含该化合物的药物组合物。该化合物和组合物可用于抑制组蛋白去甲基化酶。此外，该化合物和组合物可用于治疗癌症，如前列腺癌、乳腺癌、膀胱癌、肺癌和/或黑色素瘤等。
• Histone demethylase inhibitors
  申请人：Quanticel Pharmaceuticals, Inc.

  公开号：US08987461B2

  公开（公告）日：2015-03-24

  Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

  本文提供了取代的吡唑基吡啶、吡唑基吡嗪和吡唑基嘧啶衍生物化合物以及包含该化合物的药物组合物。该化合物和组合物对于抑制组蛋白去甲基化酶具有用途。此外，该化合物和组合物对于治疗癌症，例如前列腺癌、乳腺癌、膀胱癌、肺癌和/或黑色素瘤等具有用途。