ethyl 3-chloro-4-nitrobenzoate | 90537-39-6

• 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: ethyl 3-chloro-4-nitrobenzoate
• 英文别名: 3-Chlor-4-nitro-benzoesaeureaethylester
• CAS: 90537-39-6
• 化学式: C₉H₈ClNO₄
• 分子量: 229.62
• InChiKey: PKKLIUDCVJOQJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 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：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-chloro-4-nitrobenzoate 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 3-morpholino-4-nitrobenzoic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of novel oxindole-based RTK inhibitors as anti-cancer agents

  摘要：

  Given that receptor tyrosine kinases (RTKs) have emerged as key regulators of all aspects of cancer development, including proliferation, invasion, angiogenesis and metastasis, the RTK family represents an important therapeutic target for anti-cancer drug development. Oxindole structure has been used in RTK inhibitors such as SU4984 and intedanib. In this study, two series of new heterocyclic compounds containing oxindole scaffold have been designed and synthesized, and their inhibitory activity against the proliferation of nine cancer cell lines has been evaluated. Among them, compounds 9a and 9b displayed the strongest anti-proliferative activity with the IC(50)s below 10 mu M. Flow cytometric analysis showed that the compounds 9a and 9b dose-dependently arrested the cell cycle at G0/G1 phase. Although the leading compounds SU4984 and intedanib targets FGFR1, the kinase activity test revealed that these compounds only showed slight inhibitory activity on FGFR1 kinase. Further enzymatic test aided by molecular docking simulation in the ATP-binding site demonstrated that 9a and 9b are potent inhibitors of c-Kit kinase. These compounds are worthy of further evaluation as anticancer agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.017
• 作为产物：
  描述：

  乙醇 、 3-氯-4-硝基苯甲酸 在 硫酸 作用下， 生成 ethyl 3-chloro-4-nitrobenzoate
  参考文献：
  名称：

  Synthesis and biological evaluation of novel oxindole-based RTK inhibitors as anti-cancer agents

  摘要：

  Given that receptor tyrosine kinases (RTKs) have emerged as key regulators of all aspects of cancer development, including proliferation, invasion, angiogenesis and metastasis, the RTK family represents an important therapeutic target for anti-cancer drug development. Oxindole structure has been used in RTK inhibitors such as SU4984 and intedanib. In this study, two series of new heterocyclic compounds containing oxindole scaffold have been designed and synthesized, and their inhibitory activity against the proliferation of nine cancer cell lines has been evaluated. Among them, compounds 9a and 9b displayed the strongest anti-proliferative activity with the IC(50)s below 10 mu M. Flow cytometric analysis showed that the compounds 9a and 9b dose-dependently arrested the cell cycle at G0/G1 phase. Although the leading compounds SU4984 and intedanib targets FGFR1, the kinase activity test revealed that these compounds only showed slight inhibitory activity on FGFR1 kinase. Further enzymatic test aided by molecular docking simulation in the ATP-binding site demonstrated that 9a and 9b are potent inhibitors of c-Kit kinase. These compounds are worthy of further evaluation as anticancer agents. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.10.017

文献信息

• [EN] MODULATORS OF THE G PROTEIN-COUPLED MAS RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR MAS COUPLÉ À LA PROTÉINE G ET TRAITEMENT DE TROUBLES APPARENTÉS
  申请人：ARENA PHARM INC

  公开号：WO2014182673A1

  公开（公告）日：2014-11-13

  The present invention relates to compounds of Formula (la) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that modulate the activity of the Mas receptor, and are useful in methods of treatment and alleviation of diseases and disorders of the heart, brain, kidney, immune system, and reproductive system resulting from ischemia, or reperfusion subsequent to ischemia, and any downstream complication(s) related thereto. These diseases and disorders include, for example, vascular disorders, such as: coronary heart disease, atherosclerosis, ischemia, reperfusion injury, angina pectoris, myocardial infarction, the no-reflow phenomenon, hypertension, transient ischemic attack, ischemic colitis, mesenteric ischemia, acute limb ischemia, and skin discoloration caused by reduced blood flow to the skin; and calcium-signaling disorders such as: arrhythmia, tachycardia, bradycardia, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, Wolff-Parkinson-White syndrome, ventricular arrhythmia, ventricular tachycardia, ventricular fibrillation, reperfusion arrhythmia, and reperfusion-induced cardiomyocyte cell death.

  本发明涉及公式（la）的化合物及其药用可接受的盐、溶剂化合物和水合物，这些化合物调节Mas受体的活性，在治疗和缓解由缺血引起的心脏、脑、肾脏、免疫系统和生殖系统的疾病和紊乱方面有用，以及由缺血后再灌注引起的任何下游并发症。这些疾病和紊乱包括，例如，血管疾病，如：冠心病、动脉粥样硬化、缺血、再灌注损伤、心绞痛、心肌梗死、无回流现象、高血压、短暂性脑缺血发作、缺血性结肠炎、肠系膜缺血、急性肢体缺血以及由于皮肤血流减少导致的皮肤变色；以及钙信号紊乱，如：心律失常、心动过速、心动过缓、心房颤动、心房扑动、阵发性室上性心动过速、沃尔夫-帕金森-怀特综合征、室性心律失常、室性心动过速、室颤、再灌注心律失常和再灌注诱导的心肌细胞死亡。
• HETEROCYCLYC SULFONAMIDES HAVING EDG-1 ANTAGONISTIC ACTIVITY
  申请人：Grewal Gurmit

  公开号：US20100029643A1

  公开（公告）日：2010-02-04

  The invention relates to chemical compounds of formula (I), (Ia) and (Ib) or pharmaceutically acceptable salts thereof, which possess Edg-1 antagonistic activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-cancer effect in a warm-blooded animal, such as man.

  该发明涉及化学式（I），（Ia）和（Ib）或其药学上可接受的盐的化合物，其具有Edg-1拮抗活性，因此在抗癌活性和人或动物体的治疗方法中有用。该发明还涉及制造上述化学化合物的过程，含有它们的制药组合物以及在制造用于在温血动物（如人）中产生抗癌效果的药物的制造中使用它们。
• [EN] HETEROCYCLYC SULFONAMIDES HAVING EDG-I ANTAGONISTIC ACTIVITY<br/>[FR] SULFONAMIDES HÉTÉROCYCLIQUES À ACTIVITÉ ANTAGONISTE DE EDG-1
  申请人：ASTRAZENECA AB

  公开号：WO2008056150A1

  公开（公告）日：2008-05-15

  [EN] The invention relates to chemical compounds of formula (I), (Ia) and (Ib) or pharmaceutically acceptable salts thereof, which possess Edg-1 antagonistic activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an anti-cancer effect in a warm-blooded animal, such as man.
  [FR] L'invention porte sur des composés chimiques de formule (I), (Ia) et (Ib) ou sur des sels pharmaceutiquement acceptables de ceux-ci, qui possèdent une activité antagoniste de Edg-1 et sont en conséquence utiles pour leur activité anti-cancer et donc dans des procédés de traitement du corps humain ou animal. L'invention porte également sur des procédés de fabrication desdits composés chimiques, sur des compositions pharmaceutiques les contenant et sur leur utilisation dans la fabrication de médicaments utilisés pour produire un effet anti-cancer chez un animal à sang chaud, tel que l'homme.