trans-2-{4-[(R)-2-tert-butoxycarbonylamino-3-(3,4-dichlorophenyl)propionyl]piperazin-1-yl}cyclohexanecarboxylic acid ethyl eter | 866944-99-2

• 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: trans-2-{4-[(R)-2-tert-butoxycarbonylamino-3-(3,4-dichlorophenyl)propionyl]piperazin-1-yl}cyclohexanecarboxylic acid ethyl eter
• 英文别名: trans-2-{4-[2R-(N-boc-amino)-3-(2,4-dichlorophenyl)propionyl]piperazin-1-yl}-cyclohexanecarboxylic acid ethyl ester
• CAS: 866944-99-2
• 化学式: C₂₇H₃₉Cl₂N₃O₅
• 分子量: 556.53
• InChiKey: NSIUTXFXDSJGQT-GTMAMOSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  88.18
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  trans-2-{4-[(R)-2-tert-butoxycarbonylamino-3-(3,4-dichlorophenyl)propionyl]piperazin-1-yl}cyclohexanecarboxylic acid ethyl eter 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-{4-[(R)-2-((S)-2-Amino-propionylamino)-3-(2,4-dichloro-phenyl)-propionyl]-piperazin-1-yl}-cyclohexanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Potent and orally active non-peptide antagonists of the human melanocortin-4 receptor based on a series of trans-2-disubstituted cyclohexylpiperazines

  摘要：

  The melanocortin-4 receptor (MC4R) plays an important role in the regulation of energy homeostasis. Recent studies have shown that blockade of the MC4R reverses tumor-induced weight loss in mice. Herein, we describe the synthesis and identification of potent and selective non-peptide antagonists of the human MC4R from a series of 2-ethoxycarbonylcyclohexyl-piperazines. Compound 12i was found to possess low nanomolar affinity for the MC4R, and exhibit oral bioavailability in rats. More importantly, when administered orally to mice (10 mg/kg), it led to statistically significant increases in food intake over a 24-h period. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.071
• 作为产物：
  描述：

  trans-4-(2-ethoxycarbonylcyclohexyl)piperazine-1-carboxylic acid tert-butyl ester 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 trans-2-{4-[(R)-2-tert-butoxycarbonylamino-3-(3,4-dichlorophenyl)propionyl]piperazin-1-yl}cyclohexanecarboxylic acid ethyl eter
  参考文献：
  名称：

  Potent and orally active non-peptide antagonists of the human melanocortin-4 receptor based on a series of trans-2-disubstituted cyclohexylpiperazines

  摘要：

  The melanocortin-4 receptor (MC4R) plays an important role in the regulation of energy homeostasis. Recent studies have shown that blockade of the MC4R reverses tumor-induced weight loss in mice. Herein, we describe the synthesis and identification of potent and selective non-peptide antagonists of the human MC4R from a series of 2-ethoxycarbonylcyclohexyl-piperazines. Compound 12i was found to possess low nanomolar affinity for the MC4R, and exhibit oral bioavailability in rats. More importantly, when administered orally to mice (10 mg/kg), it led to statistically significant increases in food intake over a 24-h period. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.071

文献信息

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

  公开号：WO2004058735A3

  公开（公告）日：2007-12-27