(2E)-N-[2-(2-甲基-1H-吲哚-1-基)乙基]-3-(3,4,5-三甲氧基苯基)-2-丙烯酰胺 | 1164462-05-8

• 物质功能分类: 生物化工 - 抑制剂
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 中文名称: (2E)-N-[2-(2-甲基-1H-吲哚-1-基)乙基]-3-(3,4,5-三甲氧基苯基)-2-丙烯酰胺
• 英文名称: (2E)-N-[2-(2-methyl-1H-indol-1-yl)ethyl]-3-(3,4,5-trimethoxyphenyl)-2-propenamide
• 英文别名: (E)-N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide；TG4-155；TG4155；N-(2-(2-methyl-1H-indol-1-yl)ethyl)-3-(3,4,5-trimethoxyphenyl)acrylamide；(E)-N-[2-(2-methylindol-1-yl)ethyl]-3-(3,4,5-trimethoxyphenyl)prop-2-enamide
• CAS: 1164462-05-8
• 化学式: C₂₃H₂₆N₂O₄
• 分子量: 394.47
• InChiKey: YBHUXHFZLMFETJ-MDZDMXLPSA-N

物化性质

• 沸点：
  641.3±55.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于 DMSO（高达 35 mg/ml）或乙醇（高达 10 mg/ml）。

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  61.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P280,P305+P351+P338,P337+P313
• 危险性描述：
  H315,H319,H335

制备方法与用途

生物活性

TG4-155是一种有效的、选择性的前列腺素受体EP2（PTGER2）拮抗剂，其Ki值为9.9 nM。

靶点

Target	Value
PTGER2 (Cell-free assay)	9.9 nM (Ki)

反应信息

• 作为产物：
  描述：

  2-(2-甲基-1H-吲哚-1-基)乙腈 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 (2E)-N-[2-(2-甲基-1H-吲哚-1-基)乙基]-3-(3,4,5-三甲氧基苯基)-2-丙烯酰胺
  参考文献：
  名称：

  Lead Optimization Studies of Cinnamic Amide EP2 Antagonists

  摘要：

  Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (similar to 10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role.

  DOI：

  10.1021/jm5000672
• 作为试剂：
  描述：

  3,4,5-三甲氧基肉桂酸 、 2-二甲氨基吡啶 、 [2-(2-甲基-1H-吲哚-1-基)乙基]胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 在 (2E)-N-[2-(2-甲基-1H-吲哚-1-基)乙基]-3-(3,4,5-三甲氧基苯基)-2-丙烯酰胺 、 乙酸乙酯 、 盐酸 、 碳酸氢钠 、 水 、 Brine 、 crude product 、 ethyl acetate n-hexane 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以to furnish pure compound product TG4-155 (300 mg, 85% yield)的产率得到(2E)-N-[2-(2-甲基-1H-吲哚-1-基)乙基]-3-(3,4,5-三甲氧基苯基)-2-丙烯酰胺
  参考文献：
  名称：

  PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO

  摘要：

  本公开涉及前列腺素受体EP2拮抗剂、衍生物、组合物及相关方法。在某些实施例中，本公开涉及通过向需要治疗或预防EP2受体激活在生理作用中的疾病和病症，例如但不限于脑损伤、炎症性疾病、癫痫后神经炎症、疼痛、子宫内膜异位症、癌症、类风湿性关节炎、皮肤炎症、血管炎症、结肠炎和神经系统疾病的受试者中，通过给予含有本文所披露的化合物的制药组合物来进行治疗的方法。

  公开号：

  US20140179750A1

文献信息

• [EN] PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO<br/>[FR] ANTAGONISTES DU RÉCEPTEUR EP2 DES PROSTAGLANDINES, DÉRIVÉS, COMPOSITIONS ET UTILISATIONS ASSOCIÉS
  申请人：UNIV EMORY

  公开号：WO2015167825A1

  公开（公告）日：2015-11-05

  The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.

  该披露涉及前列腺素受体EP2拮抗剂，衍生物，组合物以及相关方法。在某些实施例中，该披露涉及治疗或预防EP2受体激活在生理作用中起作用的疾病和疾病的方法，例如但不限于脑损伤，炎症性疾病，癫痫后的神经炎症，疼痛，子宫内膜异位症，癌症，类风湿性关节炎，皮肤炎症，血管炎症，结肠炎和神经系统疾病，通过向需要的受试者给予包含本文所披露的化合物的药物组合物进行治疗。
• [EN] PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, AND USES RELATED THERETO<br/>[FR] ANTAGONISTES DU RÉCEPTEUR EP2 DE LA PROSTAGLANDINE, DÉRIVÉS, ET UTILISATIONS ASSOCIÉS
  申请人：UNIV EMORY

  公开号：WO2020191208A1

  公开（公告）日：2020-09-24

  The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, epilepsy, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.

  该公开涉及前列腺素受体EP2拮抗剂、衍生物、组合物以及相关方法。在某些实施方式中，该公开涉及治疗或预防EP2受体激活在生理角色中发挥作用的疾病和情况的方法，例如但不限于脑损伤、炎症性疾病、癫痫、癫痫后的神经炎症、疼痛、子宫内膜异位症、癌症、类风湿性关节炎、皮肤炎症、血管炎症、结肠炎和神经系统疾病，通过向需要的受试者施用含有本文所披露的化合物的药物组合物。
• Prostaglandin receptor EP2 antagonists, derivatives, compositions, and uses related thereto
  申请人：Emory University

  公开号：US10052332B2

  公开（公告）日：2018-08-21

  The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.

  本公开涉及前列腺素受体EP2拮抗剂、衍生物、组合物及其相关方法。在某些实施方案中，本公开涉及通过向有需要的受试者施用包含本文公开的化合物的药物组合物来治疗或预防 EP2 受体激活具有生理作用的病症和疾病的方法，这些病症和疾病包括但不限于脑损伤、炎症性疾病、癫痫发作后的神经损伤、疼痛、子宫内膜异位症、癌症、类风湿性关节炎、皮肤炎症、血管炎症、结肠炎和神经系统疾病。
• Prostaglandin Receptor EP2 Antagonists, Derivatives, Compositions, and Uses Related Thereto
  申请人：Emory University

  公开号：US20170042905A1

  公开（公告）日：2017-02-16

  The disclosure relates to Prostaglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, neuroinflamation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.
• PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, AND USES RELATED THERETO
  申请人：Emory University

  公开号：US20220162186A1

  公开（公告）日：2022-05-26

  The disclosure relates to Prostnglandin receptor EP2 antagonists, derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing conditions and diseases in which EP2 receptor activation has a physiological role, such as but not limited to, brain injury, inflammatory diseases, epilepsy, neuroinflammation after a seizure, pain, endometriosis, cancer, rheumatoid arthritis, skin inflammation, vascular inflammation, colitis, and neurological disorders by administering a pharmaceutical composition comprising a compound disclosed herein to a subject in need thereof.