(2S,3S)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]-butanoic acid | 1360599-74-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3S)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]-butanoic acid
• 英文别名: (2S,3S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-phenylphenyl)butanoic acid
• CAS: 1360599-74-1
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: CUMYHZFFHWSCCL-KSSFIOAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]-butanoic acid 、 5,6-dichloro-2-(pyrrolidin-2-yl)-1H-benzimidazole hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以50%的产率得到tert-butyl {(2S,3S)-3-(biphenyl-4-yl)-1-[(2S)-2-(5,6-dichloro-1H-benzimidazol-2-yl)pyrrolidin-1-yl]-1-oxobutan-2-yl}carbamate
  参考文献：
  名称：

  Design and Synthesis of Prolylcarboxypeptidase (PrCP) Inhibitors To Validate PrCP As A Potential Target for Obesity

  摘要：

  Prolycarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 mu M) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a reduction in PrCP KO mice.

  DOI：

  10.1021/jm101013m
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 在 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以21.6 g的产率得到(2S,3S)-3-(biphenyl-4-yl)-2-[(tert-butoxycarbonyl)amino]-butanoic acid
  参考文献：
  名称：

  Design and Synthesis of Prolylcarboxypeptidase (PrCP) Inhibitors To Validate PrCP As A Potential Target for Obesity

  摘要：

  Prolycarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 mu M) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a reduction in PrCP KO mice.

  DOI：

  10.1021/jm101013m

文献信息

• Discovery of a new class of potent prolylcarboxypeptidase inhibitors derived from alanine
  作者：Zhicai Wu、Cangming Yang、Yusheng Xiong、Zhe Feng、Matthew Lombardo、Andreas Verras、Renee M. Chabin、Suoyu Xu、Xinchun Tong、Dan Xie、Mike E. Lassman、Urmi R. Bhatt、Margarita M. Garcia-Calvo、Wayne Geissler、Zhu Shen、Qing Chen、Ranabir Sinharoy、Jeffrey J. Hale、James R. Tata、Shirly Pinto、Dong-Ming Shen、Steven L. Colletti

  DOI：10.1016/j.bmcl.2011.12.064

  日期：2012.2

  Efforts to modify the central proline portion of lead compound 4 lead to the discovery of novel prolylcarboxypeptidase (PrCP) inhibitors. Especially, replacement with alanine afforded compound 19 displaying more potent human and mouse PrCP inhibitory activity than 4 and an overall comparable profile. (C) 2011 Published by Elsevier Ltd.
• Design and Synthesis of Prolylcarboxypeptidase (PrCP) Inhibitors To Validate PrCP As A Potential Target for Obesity
  作者：Changyou Zhou、Margareta Garcia-Calvo、Shirly Pinto、Matthew Lombardo、Zhe Feng、Kate Bender、KellyAnn D. Pryor、Urmi R. Bhatt、Renee M. Chabin、Wayne M. Geissler、Zhu Shen、Xinchun Tong、Zhoupeng Zhang、Kenny K. Wong、Ranabir Sinha Roy、Kevin T. Chapman、Lihu Yang、Yusheng Xiong

  DOI：10.1021/jm101013m

  日期：2010.10.14

  Prolycarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 mu M) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a reduction in PrCP KO mice.