N-[(S)-1-(2-{4-[(3R,4S)-4-(4-CHLORO-PHENYL)-1-(TETRAHYDRo-PYRAN-4-YL)-PYRROLIDINE-3-CARBONYL]-PIPERAZIN-1-YL}-5-METHYL-PHENYL)-2-METHYL-PROPYL]-3-DIMETHYLAMINO-PROPIONAMIDE | 851482-86-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[(S)-1-(2-{4-[(3R,4S)-4-(4-CHLORO-PHENYL)-1-(TETRAHYDRo-PYRAN-4-YL)-PYRROLIDINE-3-CARBONYL]-PIPERAZIN-1-YL}-5-METHYL-PHENYL)-2-METHYL-PROPYL]-3-DIMETHYLAMINO-PROPIONAMIDE
• 英文别名: N-[(1S)-1-[2-[4-[(3R,4S)-4-(4-chlorophenyl)-1-(oxan-4-yl)pyrrolidine-3-carbonyl]piperazin-1-yl]-5-methylphenyl]-2-methylpropyl]-3-(dimethylamino)propanamide
• CAS: 851482-86-5
• 化学式: C₃₆H₅₂ClN₅O₃
• 分子量: 638.294
• InChiKey: XJIWJTAALOWWFJ-RASJINCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  {4-[2-((S)-1-AMINO-2-METHYL-PROPYL)-4-METHYL-PHENYL]-PIPERAZIN-1-YL}-[(3R,4S)-4-(4-CHLORO-PHENYL)-1-(TETRAHYDRO-PYRAN-4-YL)-PYRROLIDIN-3-YL]-METHANONE 、 N,N-二甲基-Β-丙氨酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以60%的产率得到N-[(S)-1-(2-{4-[(3R,4S)-4-(4-CHLORO-PHENYL)-1-(TETRAHYDRo-PYRAN-4-YL)-PYRROLIDINE-3-CARBONYL]-PIPERAZIN-1-YL}-5-METHYL-PHENYL)-2-METHYL-PROPYL]-3-DIMETHYLAMINO-PROPIONAMIDE
  参考文献：
  名称：

  Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor

  摘要：

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a K-i of 1.0 nM and an EC50 of 3.8 nM while its 3R,4S-isomer 13b-2 exhibited a K-i of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.115

文献信息

• [EN] LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] LIGANDS DU RECEPTEUR DE LA MELANOCORTINE ET COMPOSITIONS ET METHODES ASSOCIEES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005040109A1

  公开（公告）日：2005-05-06

  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): (R4)s (R 2)n N~ X1-X2 (CR1aCRlb)q 1~ N R1-lm 1 O R3 (I) including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R1, R1a, R1b, R2, R3, R4, X1 X2 and X3 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

  化合物作为黑色素皮质激素受体配体，并在治疗基于黑色素皮质激素受体的疾病中具有用途。这些化合物具有以下结构（I）：（R4）s（R 2）n N〜X1-X2（CR1aCRlb）q 1〜N R1-lm 1 O R3（I），包括立体异构体，前药和其药用盐，其中m、n、q、s、R1、R1a、R1b、R2、R3、R4、X1、X2和X3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。
• Ligands of melanocortin receptors and compositions and methods related thereto
  申请人：Tran Anh Joe

  公开号：US20050192286A1

  公开（公告）日：2005-09-01

  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): including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein m, n, q, s, R 1 , R 1 a, R 1b , R 2 , R 3 , R 4 , X 1 , X 2 and X 3 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激素受体的疾病中有用的功能的化合物。该化合物具有以下结构（I）：包括立体异构体，前药和药物可接受的盐，其中m，n，q，s，R1，R1a，R1b，R2，R3，R4，X1，X2和X3如本文所定义。还公开了含有结构（I）的化合物的制药组合物，以及与其使用相关的方法。
• Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor
  作者：Chen Chen、Wanlong Jiang、Joe A. Tran、Fabio C. Tucci、Beth A. Fleck、Stacy Markison、Jenny Wen、Ajay Madan、Sam R. Hoare、Alan C. Foster、Dragan Marinkovic、Caroline W. Chen、Melissa Arellano、John Saunders

  DOI：10.1016/j.bmcl.2007.10.115

  日期：2008.1

  A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a K-i of 1.0 nM and an EC50 of 3.8 nM while its 3R,4S-isomer 13b-2 exhibited a K-i of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats. (C) 2007 Elsevier Ltd. All rights reserved.