N-((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide
• 英文别名: N-[(1R)-2-(1H-indol-3-yl)-1-[5-[2-(1H-indol-3-yl)ethyl]-4-[(4-methoxyphenyl)methyl]-1,2,4-triazol-3-yl]ethyl]-2-pyridin-4-ylacetamide
• 化学式: C₃₇H₃₅N₇O₂
• 分子量: 609.731
• InChiKey: FSFNTCWXZWJZBW-UUWRZZSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(2,4-dimethoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethanamine 、 吡啶-4-乙酸 在 N-甲基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-((R)-1-(5-(2-(1H-indol-3-yl)ethyl)-4-(4-methoxybenzyl)-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-(pyridin-4-yl)acetamide
  参考文献：
  名称：

  New Trisubstituted 1,2,4-Triazole Derivatives as Potent Ghrelin Receptor Antagonists. 3. Synthesis and Pharmacological in Vitro and in Vivo Evaluations

  摘要：

  Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the alpha-aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.

  DOI：

  10.1021/jm701292s

文献信息

• Novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors
  申请人：Perrissoud Daniel

  公开号：US20070037857A1

  公开（公告）日：2007-02-15

  The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

  本发明提供了一种新型的三唑衍生物，作为生长激素分泌素受体的胃泌素类似物配体，其符合以下公式（I），可用于治疗或预防哺乳动物，尤其是人类，通过GHS受体介导的生理和/或病理条件。本发明还提供了可用于调节这些受体并用于治疗上述疾病的GHS受体拮抗剂和激动剂，特别是生长迟缓、虚弱、短期、中期和/或长期能量平衡的调节；短期、中期和/或长期食物摄入的调节（刺激和/或抑制）；脂肪生成、脂肪堆积和/或肥胖；体重增加和/或减少；糖尿病、糖尿病I型、糖尿病II型、肿瘤细胞增殖；炎症、炎症效应、胃术后肠梗阻、术后肠梗阻和/或胃切除（胃泌素替代疗法）。
• TREAMENT FOR CHEMICAL SUBSTANCE ADDICTION
  申请人：Dickson Suzanne L.

  公开号：US20100093638A1

  公开（公告）日：2010-04-15

  The present invention provides a method for the treatment of chemical substance abuse by selectively inhibiting ghrelin activity in humans comprising administering to a human in need thereof a therapeutically-effective amount of a ghrelin receptor ligand (GHS-RL). The ghrelin receptor ligand (GHS-RL) can be selected from the group consisting of a ghrelin receptor antagonist (GHS-RA), a ghrelin receptor inverse agonist (GHS-RIA), and a ghrelin receptor partial agonist (GHS-RPA). More specifically, the invention provides a method for treating alcohol related disorders in humans comprising administering to a human in need thereof a therapeutically-effective amount of a compound which is a ghrelin receptor ligand (GHS-RL), such as a ghrelin receptor antagonist (GHS-RA), a ghrelin receptor inverse agonist (GHS-RIA) and a ghrelin receptor partial agonist (GHS-RPA).

  本发明提供了一种治疗人类化学物质滥用的方法，该方法通过选择性抑制人体中的胃饥饿素活性，包括向需要治疗的人类中投与治疗有效量的胃饥饿素受体配体（GHS-RL）。胃饥饿素受体配体（GHS-RL）可以从以下组中选择，包括胃饥饿素受体拮抗剂（GHS-RA）、胃饥饿素受体逆激动剂（GHS-RIA）和胃饥饿素受体部分激动剂（GHS-RPA）。更具体地，本发明提供了一种治疗人类酒精相关障碍的方法，包括向需要治疗的人类中投与治疗有效量的化合物，该化合物是胃饥饿素受体配体（GHS-RL），例如胃饥饿素受体拮抗剂（GHS-RA）、胃饥饿素受体逆激动剂（GHS-RIA）和胃饥饿素受体部分激动剂（GHS-RPA）。
• Novel triazole derivatives as ligands of G-protein coupled receptors
  申请人：AEterna Zentaris GmbH

  公开号：EP1958631A1

  公开（公告）日：2008-08-20

  The present invention provides novel triazole derivatives according to formula (I) as ligands of G-protein coupled receptors (GPCR), which are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, which are mediated by GPCR. The present invention further provides GPCR antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular adipogenesis, adiposity, cachexia, diabetes, diabetes type I, diabetes type II, energy balance, energy homeostasis, food intake, hyperlipidemia, hyperphagia, obesity, short-, medium- and/or long-term regulation of energy balance, short-, medium- and/or long-term regulation (stimulation and/or inhibition) of food intake.

  本发明提供了新型的三唑衍生物，其符合公式（I）作为G蛋白偶联受体（GPCR）的配体，可用于治疗或预防哺乳动物，尤其是人类中GPCR介导的生理和/或病理生理条件。本发明还提供了可用于调节这些受体的GPCR拮抗剂和激动剂，可用于治疗上述条件，特别是脂肪生成、肥胖、消瘦、糖尿病、1型糖尿病、2型糖尿病、能量平衡、能量稳态、食物摄入、高脂血症、过度进食、肥胖症、短期、中期和/或长期调节能量平衡、短期、中期和/或长期调节（刺激和/或抑制）食物摄入的方法。
• TRIAZOLE DERIVATIVES AS LIGANDS OF G-PROTEIN COUPLED RECEPTORS
  申请人：Perrissoud Daniel

  公开号：US20090042905A1

  公开（公告）日：2009-02-12

  The present invention provides triazole derivatives according to formula (I) as ligands of G-protein coupled receptors (GPCR), which are useful for the study of and/or the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, which are mediated by GPCR.

  本发明提供了公式（I）的三唑衍生物作为G蛋白偶联受体（GPCR）的配体，可用于研究和/或治疗或预防哺乳动物，尤其是人类的GPCR介导的生理和/或病理生理状况。
• NOVEL TRIAZOLE DERIVATIVES AS GHRELIN ANALOGUE LIGANDS OF GROWTH HORMONE SECRETAGOGUE RECEPTORS
  申请人：PERRISSOUD Daniel

  公开号：US20070208061A2

  公开（公告）日：2007-09-06

  The present invention provides novel triazole derivatives as ghrelin analogue ligands of growth hormone secretagogue receptors according to formula (I) that are useful in the treatment or prophylaxis of physiological and/or pathophysiological conditions in mammals, preferably humans, that are mediated by GHS receptors. The present invention further provides GHS receptor antagonists and agonists that can be used for modulation of these receptors and are useful for treating above conditions, in particular growth retardation, cachexia, short-, medium- and/or long term regulation of energy balance; short-, medium- and/or long term regulation (stimulation and/or inhibition) of food intake; adipogenesis, adiposity and/or obesity; body weight gain and/or reduction; diabetes, diabetes type I, diabetes type II, tumor cell proliferation; inflammation, inflammatory effects, gastric postoperative ileus, postoperative ileus and/or gastrectomy (ghrelin replacement therapy).

  本发明提供了一种新型的三唑衍生物，作为ghrelin类生长激素分泌素受体的类似物配体，其化学式为(I)，可用于治疗或预防哺乳动物，尤其是人类的生理和/或病理生理条件，这些条件是由GHS受体介导的。本发明还提供了GHS受体拮抗剂和激动剂，可用于调节这些受体，并且对于治疗上述条件，特别是生长迟缓、消瘦、短期、中期和/或长期的能量平衡调节；短期、中期和/或长期的食物摄入调节（刺激和/或抑制）；脂肪生成、脂肪积聚和/或肥胖；体重增加和/或减少；糖尿病、1型糖尿病、2型糖尿病、肿瘤细胞增殖；炎症、炎症作用、胃术后肠麻痹、术后肠麻痹和/或胃切除（ghrelin替代疗法）具有用处。