3-Amino-N-[(R)-1-(4-chloro-benzyl)-2-oxo-2-(4-{2-[(2-thiophen-2-yl-ethylamino)-methyl]-phenyl}-piperazin-1-yl)-ethyl]-propionamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 3-Amino-N-[(R)-1-(4-chloro-benzyl)-2-oxo-2-(4-{2-[(2-thiophen-2-yl-ethylamino)-methyl]-phenyl}-piperazin-1-yl)-ethyl]-propionamide
• 英文别名: 3-amino-N-[(2R)-3-(4-chlorophenyl)-1-oxo-1-[4-[2-[(2-thiophen-2-ylethylamino)methyl]phenyl]piperazin-1-yl]propan-2-yl]propanamide
• 化学式: C₂₉H₃₆ClN₅O₂S
• 分子量: 554.156
• InChiKey: GRAFEEBFOIOLGS-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  38
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  噻吩乙胺 在 palladium on activated charcoal 氢气 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 二乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 3-Amino-N-[(R)-1-(4-chloro-benzyl)-2-oxo-2-(4-{2-[(2-thiophen-2-yl-ethylamino)-methyl]-phenyl}-piperazin-1-yl)-ethyl]-propionamide
  参考文献：
  名称：

  Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor

  摘要：

  SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had K-i values of 21, 14, and 15 nM, respectively, possessed low efficacy in cAMP stimulation (similar to15% of alpha-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of alpha-MSH-stimulated cAMP release in a dose-dependent manner (11l, IC50 = 36 nM). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.055

文献信息

• Ligands of melanocortin receptors and compositions and methods related thereto
  申请人：Neurocrine Biosciences, Inc.

  公开号：US20040053933A1

  公开（公告）日：2004-03-18

  Compounds which function as melanocortin receptor ligands and having utility in the treatment of melanocortin receptor-based disorders. The compounds have the following structure (I): 1 including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein Ar, R 1 , R 2 , R 3a , R 3b , R 4a , R 4b , R 5 , R 7a , R 7b , q, r, X, Y 1 , Y 2 , Y 3 and Y 4 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

  具有在治疗基于黑色素细胞素受体的疾病中有用的功能的化合物。这些化合物具有以下结构（I）：包括立体异构体，前药和其药用可接受的盐，其中Ar，R1，R2，R3a，R3b，R4a，R4b，R5，R7a，R7b，q，r，X，Y1，Y2，Y3和Y4如本文所定义。还公开了含有结构（I）化合物的药物组合物，以及与其使用相关的方法。
• Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor
  作者：Joseph Pontillo、Joseph A. Tran、Beth A. Fleck、Dragan Marinkovic、Melissa Arellano、Fabio C. Tucci、Marion Lanier、Jodie Nelson、Jessica Parker、John Saunders、Brian Murphy、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2004.08.055

  日期：2004.11

  SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had K-i values of 21, 14, and 15 nM, respectively, possessed low efficacy in cAMP stimulation (similar to15% of alpha-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of alpha-MSH-stimulated cAMP release in a dose-dependent manner (11l, IC50 = 36 nM). (C) 2004 Elsevier Ltd. All rights reserved.