1-[(2R)-2-amino-3-(4-fluorophenyl)-1-oxopropyl]-4-cyclohexyl-N-(1,1-dimethylethyl)-4-piperidine carboxamide | 363191-04-2

• 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: 1-[(2R)-2-amino-3-(4-fluorophenyl)-1-oxopropyl]-4-cyclohexyl-N-(1,1-dimethylethyl)-4-piperidine carboxamide
• 英文别名: 4-F-D-Phe-4-cyclohexyl-piperidine-4-carboxylic acid tert-butyl amide；(R)-1-(2-amino-3-(4-fluorophenyl)propanoyl)-N-tert-butyl-4-cyclohexylpiperidine-4-carboxamide；1-[(2R)-2-amino-3-(4-fluorophenyl)propanoyl]-N-tert-butyl-4-cyclohexylpiperidine-4-carboxamide
• CAS: 363191-04-2
• 化学式: C₂₅H₃₈FN₃O₂
• 分子量: 431.594
• InChiKey: VPOSUBDVYKXMGF-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(2R)-2-amino-3-(4-fluorophenyl)-1-oxopropyl]-4-cyclohexyl-N-(1,1-dimethylethyl)-4-piperidine carboxamide 在 palladium on activated charcoal 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 (R)-2-[(R)-2-(4-tert-Butylcarbamoyl-4-cyclohexyl-piperidin-1-yl)-1-(4-fluoro-benzyl)-2-oxo-ethylcarbamoyl]-piperazine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist

  摘要：

  We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.020
• 作为产物：
  描述：

  保护的4-苯基哌啶-4-羧酸 在 Rh/Al₂O₃ 草酰氯 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 70.0 ℃ 、482.63 kPa 条件下， 生成 1-[(2R)-2-amino-3-(4-fluorophenyl)-1-oxopropyl]-4-cyclohexyl-N-(1,1-dimethylethyl)-4-piperidine carboxamide
  参考文献：
  名称：

  Discovery of (2S)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-4-methyl-2-piperazinecarboxamide (MB243), a potent and selective melanocortin subtype-4 receptor agonist

  摘要：

  We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. Further in vivo development of lead agonist, MB243, is disclosed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.10.020

文献信息

• SUBSTITUTED PIPERIDINES AS MELANOCORTIN RECEPTOR AGONISTS
  申请人：——

  公开号：US20030236262A1

  公开（公告）日：2003-12-25

  Certain novel 4-substituted piperidine compounds are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

  某些新型的4-取代哌啶化合物是人类黑色素皮质素受体的激动剂，特别是人类黑色素皮质素-4受体（MC-4R）的选择性激动剂。因此，它们对于治疗、控制或预防对MC-4R激活敏感的疾病和疾病具有用处，如肥胖症、糖尿病、性功能障碍，包括勃起功能障碍和女性性功能障碍。
• [EN] PIPERAZINE UREA DERIVATIVES AS MELANOCORTIN-4 RECEPTOR AGONISTS<br/>[FR] DERIVES D'UREE DE PIPERAZINE UTILISES COMME AGONISTES DES RECEPTEURS DE MELANOCORTINE-4
  申请人：MERCK & CO INC

  公开号：WO2004024720A1

  公开（公告）日：2004-03-25

  Certain novel piperazine urea derivatives are agonists of the human melanocortin-4 receptor (MC-4R) and, in particular, are receptor-subtype selective agonists of MC-4R. They are useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity and diabetes.

  某些新型哌嗪脲衍生物是人类黑色素皮质素-4受体（MC-4R）的激动剂，特别是MC-4R的受体亚型选择性激动剂。它们对于治疗、控制或预防对MC-4R激活敏感的疾病和疾病是有用的，例如肥胖症和糖尿病。
• 2-Piperazinecarboxamides as potent and selective melanocortin subtype-4 receptor agonists
  作者：Brenda L. Palucki、Min K. Park、Ravi P. Nargund、Rui Tang、Tanya MacNeil、David H. Weinberg、Aurawan Vongs、Charles I. Rosenblum、George A. Doss、Randall R. Miller、Ralph A. Stearns、Qianping Peng、Constantin Tamvakopoulos、Lex H.T. Van der Ploeg、Arthur A. Patchett

  DOI：10.1016/j.bmcl.2005.02.068

  日期：2005.4

  We report the discovery and optimization of substituted 2-piperazinecarboxamides as potent and selective agonists of the melanocortin subtype-4 receptor. The 5- and 6-alkylated piperazine compounds exhibit low bioactivation potential as measured by covalent binding in microsome preparations. (c) 2005 Elsevier Ltd. All rights reserved.
• Melanocortin subtype 4 receptor agonists: Structure–activity relationships about the 4-alkyl piperidine core
  作者：Iyassu K. Sebhat、Yingjie Lai、Khaled Barakat、Zhixiong Ye、Rui Tang、Rubana N. Kalyani、Aurawan Vongs、Tanya MacNeil、David H. Weinberg、M. Angeles Cabello、Marta Maroto、Ana Teran、Tung M. Fong、Lex H.T. Van der Ploeg、Arthur A. Patchett、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2006.11.084

  日期：2007.10

  SAR about the piperidine core in a series of MC4R agonists is described. A number of alkyl substituents that furnish compounds with good affinity and functional potency are reported. (c) 2006 Elsevier Ltd. All rights reserved.
• Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist
  作者：Zhixiong Ye、Liangqin Guo、Khaled J. Barakat、Patrick G. Pollard、Brenda L. Palucki、Iyassu K. Sebhat、Raman K. Bakshi、Rui Tang、Rubana N. Kalyani、Aurawan Vongs、Airu S. Chen、Howard Y. Chen、Charles I. Rosenblum、Tanya MacNeil、David H. Weinberg、Qianping Peng、Constantin Tamvakopoulos、Randy R. Miller、Ralph A. Stearns、Doreen E. Cashen、William J. Martin、Joseph M. Metzger、Alison M. Strack、D. Euan MacIntyre、Lex H.T. Van der Ploeg、Arthur A. Patchett、Matthew J. Wyvratt、Ravi P. Nargund

  DOI：10.1016/j.bmcl.2005.05.109

  日期：2005.8

  A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist, 3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents. (c) 2005 Elsevier Ltd. All rights reserved.