2-{4-[3-(2,4-dichlorophenyl)propionyl]-1-piperazinyl}-1-[1S-amino-3-methbutyl]-5-trifluoromethylbenzene | 626212-09-7

• 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: 2-{4-[3-(2,4-dichlorophenyl)propionyl]-1-piperazinyl}-1-[1S-amino-3-methbutyl]-5-trifluoromethylbenzene
• 英文别名: (1S)-[2-{4-[3-(2,4-dichlorophenyl)propionyl]-1-piperazinyl}-5-(trifluoromethyl)phenyl]-3-methylbutylamine；1-[4-[2-[(1S)-1-amino-3-methylbutyl]-4-(trifluoromethyl)phenyl]piperazin-1-yl]-3-(2,4-dichlorophenyl)propan-1-one
• CAS: 626212-09-7
• 化学式: C₂₅H₃₀Cl₂F₃N₃O
• 分子量: 516.434
• InChiKey: DCXQILJCXFVJDJ-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  49.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-{4-[3-(2,4-dichlorophenyl)propionyl]-1-piperazinyl}-1-[1S-amino-3-methbutyl]-5-trifluoromethylbenzene 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-{4-[3-(2,4-dichlorophenyl)propionyl]-1-piperazinyl}-1-[1S-(3-aminopropionylamido)-3-methylbutyl]-5-trifluoromethylbenzene
  参考文献：
  名称：

  Arylpropionylpiperazines as antagonists of the human melanocortin-4 receptor

  摘要：

  A series of 3-arylpropionylpiperazines were synthesized as antagonists of the melanocortin-4 receptor. Their potency was found to be increased by replacing the alpha-methyl substituent of the initial lead 11 with a larger s-Bu or i-Bu group. Further potency enhancement was observed when a glycine or beta-alanine was incorporated onto the benzylamine. Some compounds demonstrated good potency, moderate selectivity, and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.088
• 作为产物：
  描述：

  2-氟-5-(三氟甲基)苯甲醛 在 盐酸 、 titanium(IV) tetraethanolate 、 三甲基铝 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-{4-[3-(2,4-dichlorophenyl)propionyl]-1-piperazinyl}-1-[1S-amino-3-methbutyl]-5-trifluoromethylbenzene
  参考文献：
  名称：

  Arylpropionylpiperazines as antagonists of the human melanocortin-4 receptor

  摘要：

  A series of 3-arylpropionylpiperazines were synthesized as antagonists of the melanocortin-4 receptor. Their potency was found to be increased by replacing the alpha-methyl substituent of the initial lead 11 with a larger s-Bu or i-Bu group. Further potency enhancement was observed when a glycine or beta-alanine was incorporated onto the benzylamine. Some compounds demonstrated good potency, moderate selectivity, and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.088

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。
• Design, Synthesis, In Vitro, and In Vivo Characterization of Phenylpiperazines and Pyridinylpiperazines as Potent and Selective Antagonists of the Melanocortin-4 Receptor
  作者：Joe A. Tran、Wanlong Jiang、Fabio C. Tucci、Beth A. Fleck、Jenny Wen、Yang Sai、Ajay Madan、Ta Kung Chen、Stacy Markison、Alan C. Foster、Sam R. Hoare、Daniel Marks、John Harman、Caroline W. Chen、Melissa Arellano、Dragan Marinkovic、Haig Bozigian、John Saunders、Chen Chen

  DOI：10.1021/jm701137s

  日期：2007.12.13

  Benzylamine and pyridinemethylamine derivatives were synthesized and characterized as potent and selective antagonists of the melanocortin-4 receptor (MC4R). These compounds were also profiled in rodents for their pharmacokinetic properties. Two compounds with diversified profiles in chemical structure, pharmacological activities, and pharmacokinetics, 10 and 12b, showed efficacy in an established murine cachexia model. For example, 12b had a K-i value of 3.4 nM at MC4R, was more than 200-fold selective over MC3R, and had a good pharmacokinetic profile in mice, including high brain penetration. Moreover, 12b was able to stimulate food intake in the tumor-bearing mice and reverse their lean body mass loss. Our results provided further evidence that a potent and selective MC4R antagonist with appropriate pharmacokinetic properties might potentially be useful for the treatment of cancer cachexia.
• [EN] LIGANDS OF MELANOCORTIN RECEPTORS AND COMPOSITIONS AND METHODS RELATED THERETO<br/>[FR] LIGANDS DE RECEPTEURS DE LA MELANOCORTINE, COMPOSITIONS ET PROCEDES ASSOCIES
  申请人：NEUROCRINE BIOSCIENCES INC

  公开号：WO2005042516A3

  公开（公告）日：2005-12-01
• Arylpropionylpiperazines as antagonists of the human melanocortin-4 receptor
  作者：Wanlong Jiang、Fabio C. Tucci、Caroline W. Chen、Melissa Arellano、Joe A. Tran、Nicole S. White、Dragan Marinkovic、Joseph Pontillo、Beth A. Fleck、Jenny Wen、John Saunders、Ajay Madan、Alan C. Foster、Chen Chen

  DOI：10.1016/j.bmcl.2006.05.088

  日期：2006.9

  A series of 3-arylpropionylpiperazines were synthesized as antagonists of the melanocortin-4 receptor. Their potency was found to be increased by replacing the alpha-methyl substituent of the initial lead 11 with a larger s-Bu or i-Bu group. Further potency enhancement was observed when a glycine or beta-alanine was incorporated onto the benzylamine. Some compounds demonstrated good potency, moderate selectivity, and oral bioavailability. (c) 2006 Elsevier Ltd. All rights reserved.