5-HEAT | 214416-49-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-HEAT
• 英文别名: N-[2-[5-(2-hydroxyethoxy)-1H-indol-3-yl]ethyl]acetamide
• CAS: 214416-49-6
• 化学式: C₁₄H₁₈N₂O₃
• 分子量: 262.309
• InChiKey: CZPLTTWZQPLXMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  74.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  乙酸酐 、 2-[3-(2-amino-ethyl)-indol-5-yloxy]-ethanol 在 TEA 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以70%的产率得到5-HEAT
  参考文献：
  名称：

  Melatonin Receptor Ligands:  Synthesis of New Melatonin Derivatives and Comprehensive Comparative Molecular Field Analysis (CoMFA) Study

  摘要：

  The CoMFA methodology was applied to melatonin receptor ligands in order to establish quantitative structure-affinity relationships. One hundred thirty-three compounds were considered: they were either collected from literature or newly synthesized in order to gain information about the less explored positions. To this end, various melatonin derivatives were prepared and their affinity for quail optic tecta melatonin receptor was tested. Compounds were aligned on the putative active conformation of melatonin proposed by our previously reported pharmacophore search, and their relative affinities were calculated from the displacement of 2-[I-125]-iodomelatonin on different tissues expressing aMT receptors. Compounds were grouped into three sets according to their topology. Subset A: melatonin-like compounds; subset B: N-acyl-2-amino-8-methoxytetralins and related compounds; subset C: N-acyl-phenylalkylamines and related compounds. CoMFA models were derived for each set, using the steric, electrostatic, and lipophilic fields as structural descriptors; the PLS analyses were characterized by good statistical parameters, taking into account the heterogeneity of the binding data, obtained with different experimental protocols. From the CoMFA model for the melatonin-like compounds, besides the well-known positive effect of 2-substitution, a low steric tolerance for substituents in 1, 6, and 7, and a negative effect of electron-rich 4-substituents were observed; the information provided by the newly synthesized compounds was essential for these results. Moreover, a comprehensive model for the 133 compounds, accounting for a common alignment and a common mode of interaction at the melatonin receptor, was derived (Q(2) = 0.769, R-2 = 0.905). This model validates our previously reported pharmacophore search and offers a clear depiction of the structure-affinity relationships for the melatonin receptor ligands.

  DOI：

  10.1021/jm9810093

文献信息

• Substituted dimeric compounds
  申请人：——

  公开号：US20020035114A1

  公开（公告）日：2002-03-21

  The invention relates to compounds of formula (I): A—G 1 —Cy—G 2 —Cy—G 3 —B  (I) wherein: A represents NR 1 C(Q)R 2 , C(Q)NR 2 R 3 or NR 1 C(Q)NR 2 R 3 , B represents NR 1 C(Q)R 2 , C(Q)NR 2 R 3 , NR 1 C(Q)NR 2 R 3 , C(Q)OR 1 , NR 1 C(Q)OR 2 or NR 2 R 3 , G 1 and G 3 represent an optionally substituted alkylene chain, Cy represents a ring structure 1 G 2 represents a chain and medicinal products containing the same which are useful in treating or in preventing melatoninergic disorders.

  本发明涉及式(I)的化合物：A-G1-Cy-G2-Cy-G3-B  (I)，其中：A代表NR1C(Q)R2，C(Q)NR2R3或NR1C(Q)NR2R3，B代表NR1C(Q)R2，C(Q)NR2R3，NR1C(Q)NR2R3，C(Q)OR1，NR1C(Q)OR2或NR2R3，G1和G3代表可选取代的烷基链，Cy代表环结构，G2代表链，以及含有这些化合物的药物，其在治疗或预防褪黑激素失调方面有用。
• INDOLE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP3095781A1

  公开（公告）日：2016-11-23

  [Problem] To provide a compound useful as a MT1 and/or MT2 receptor agonist. [Solution] The present inventors have studied on MT1 and/or MT2 receptor agonists, and have confirmed that indole compounds have the activity. As a result, the present invention is accomplished. That is, a compound represented by formula (I) or a salt thereof according to the present invention has a MT1 and/or MT2 receptor agonistic activity and has a low ability of migrating into the central nervous system. Therefore, the compound or a salt thereof can be used as a peripheral MT1 and/or MT2 receptor agonist, and therefore can be used as a therapeutic and/or prophylactic agent for urinary incontinence, particularly stress urinary incontinence and mixed urinary incontinence.

  [问题]提供一种可作为 MT1 和/或 MT2 受体激动剂的化合物。[解决方案] 本发明人对 MT1 和/或 MT2 受体激动剂进行了研究，并确认吲哚化合物具有这种活性。因此，本发明得以实现。也就是说，根据本发明，由式（I）代表的化合物或其盐具有 MT1 和/或 MT2 受体激动活性，并且迁移到中枢神经系统的能力较低。因此，该化合物或其盐可用作外周 MT1 和/或 MT2 受体激动剂，从而可用作尿失禁，特别是压力性尿失禁和混合性尿失禁的治疗和/或预防剂。
• Nouveaux dérivés dimériques substitués, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
  申请人：LES LABORATOIRES SERVIER

  公开号：EP1038863B1

  公开（公告）日：2003-06-04
• Methods and compositions for treatment of hypertension
  申请人：Czeisler A. Charles

  公开号：US20050137247A1

  公开（公告）日：2005-06-23

  Methods and compositions for treating and/or preventing hypertension are provided. The methods involve administration of melatonin, or an analog thereof, to a subject. The methods and compositions may be used to treat various forms of hypertension, including essential hypertension.
• MELATONIN-BASED TREATMENT AND DIAGNOSIS OF BILE DUCT DISEASE
  申请人：Alpini Gianfranco

  公开号：US20140079680A1

  公开（公告）日：2014-03-20

  Methods and composition for a melatonin signaling modulator-based diagnosis and therapy are described. For example, in certain aspects methods for administering an anti-tumor therapy using a melatonin signaling modulator are described. Furthermore, the invention provides compositions and methods for detecting biliary tract disease such as cholangiocarcinoma.