N-[2-(2-methylindol-1-yl)ethyl]-4-(2H-tetrazol-5-yl)benzamide | 1616960-94-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[2-(2-methylindol-1-yl)ethyl]-4-(2H-tetrazol-5-yl)benzamide
• CAS: 1616960-94-1
• 化学式: C₁₉H₁₈N₆O
• 分子量: 346.392
• InChiKey: NSBLUZNHTPDUIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  [2-(2-甲基-1H-吲哚-1-基)乙基]胺 、 5-(4-甲酸苯基)-1H-四唑 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 N-[2-(2-methylindol-1-yl)ethyl]-4-(2H-tetrazol-5-yl)benzamide
  参考文献：
  名称：

  Development of second generation EP2 antagonists with high selectivity

  摘要：

  EP2 receptor has emerged as an important biological target for therapeutic intervention. In particular, it has been shown to exacerbate disease progression of a variety of CNS and peripheral diseases. Deletion of the EP2 receptor in mouse models recapitulates several features of the COX-2 inhibition, thus presenting a new avenue for anti-inflammatory therapy which could bypass some of the adverse side effects observed by the COX-2 inhibition therapy. We have recently reported a cinnamic amide class of EP2 antagonists with high potency, but these compounds exhibited a moderate selectivity against prostanoid receptor DP1. Moreover they possess acrylamide moiety in the structure, which may result in liver toxicity over longer period of use in a chronic disease model. Thus, we now developed a second generation compounds that devoid of the acrylamide functionality and possess high potency and improved (>1000-fold) selectivity to EP2 over other prostanoid receptors. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.076

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。
• Peripherally Restricted, Highly Potent, Selective, Aqueous-Soluble EP2 Antagonist with Anti-Inflammatory Properties
  作者：Thota Ganesh、Avijit Banik、Ray Dingledine、Wenyi Wang、Radhika Amaradhi

  DOI：10.1021/acs.molpharmaceut.8b00764

  日期：2018.12.3

  receptor with small molecules could be a therapeutic strategy for treating inflammatory diseases and cancer. We recently reported a novel class of competitive antagonists of the EP2 receptor. However, earlier leads displayed low selectivity against the DP1 prostanoid receptor, moderate plasma half-life, and low aqueous solubility, which renders them suboptimal for testing in animal models of disease

  前列腺素 E 2受体 EP2 在生理学和各种病理状况中发挥重要作用。研究表明，EP2 在慢性外周和中枢神经系统疾病和癌症模型中具有促炎作用。因此，用小分子靶向 EP2 受体可能是治疗炎症性疾病和癌症的一种治疗策略。我们最近报道了一类新型的 EP2 受体竞争性拮抗剂。然而，较早的先导物对 DP1 前列腺素受体的选择性低，血浆半衰期中等，水溶性低，这使得它们不适合在疾病动物模型中进行测试。我们现在报告了一种新型化合物 TG8-69，它具有合适的类药物特性。我们提供合成、先导优化研究、药理表征、
• Prostaglandin receptor EP2 antagonists, derivatives, compositions, and uses related thereto
  申请人：Emory University

  公开号：US11077120B2

  公开（公告）日：2021-08-03

  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, 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.

  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。
• PROSTAGLANDIN RECEPTOR EP2 ANTAGONISTS, DERIVATIVES, COMPOSITIONS, AND USES RELATED THERETO
  申请人：Emory University

  公开号：EP3137074A1

  公开（公告）日：2017-03-08
• 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.