tert-butyl N-[(2S)-3-(4-aminophenyl)-1-oxo-1-(pentylamino)propan-2-yl]carbamate | 221077-65-2

• 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: tert-butyl N-[(2S)-3-(4-aminophenyl)-1-oxo-1-(pentylamino)propan-2-yl]carbamate
• CAS: 221077-65-2
• 化学式: C₁₉H₃₁N₃O₃
• 分子量: 349.473
• InChiKey: HZDWQWRMQQLMMU-INIZCTEOSA-N

物化性质

• 沸点：
  572.1±50.0 °C(Predicted)
• 密度：
  1.076±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  93.45
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-3-(4-aminophenyl)-1-oxo-1-(pentylamino)propan-2-yl]carbamate 在 copper diacetate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 2-{[4-((S)-2-tert-Butoxycarbonylamino-2-pentylcarbamoyl-ethyl)-phenyl]-ethoxyoxalyl-amino}-benzoic acid
  参考文献：
  名称：

  Discovery and Structure−Activity Relationship of Oxalylarylaminobenzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B

  摘要：

  Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.

  DOI：

  10.1021/jm0205696
• 作为产物：
  描述：

  (S)-[1-Pentylcarbamoyl-2-(4-nitrophenyl)-ethyl]-carbamic acid tert-butyl ester 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、100.0 kPa 条件下， 反应 4.0h， 以95%的产率得到tert-butyl N-[(2S)-3-(4-aminophenyl)-1-oxo-1-(pentylamino)propan-2-yl]carbamate
  参考文献：
  名称：

  Inhibitors of protein tyrosine phosphatase

  摘要：

  本发明涉及小分子量、非肽类的蛋白酪氨酸磷酸酶1（PTP1）的化学式I和II的抑制剂，用于治疗和/或预防非胰岛素依赖型糖尿病（NIDDM）。

  公开号：

  US06353023B1

文献信息

• Inhibitors of protein tyrosine phosphatase
  申请人：Pharmacia & Upjohn Company

  公开号：US06353023B1

  公开（公告）日：2002-03-05

  The present invention comprises small molecular weight, non-peptidic inhibitors of formula I and II of Protein Tyrosine Phosphatase 1 (PTP1) which are useful for the treatment and/or prevention of Non-Insulin Dependent Diabetes Mellitus (NIDDM).

  本发明涉及小分子量、非肽类的蛋白酪氨酸磷酸酶1（PTP1）的化学式I和II的抑制剂，用于治疗和/或预防非胰岛素依赖型糖尿病（NIDDM）。
• Discovery and Structure−Activity Relationship of Oxalylarylaminobenzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B
  作者：Gang Liu、Bruce G. Szczepankiewicz、Zhonghua Pei、David A. Janowick、Zhili Xin、Philip J. Hajduk、Cele Abad-Zapatero、Heng Liang、Charles W. Hutchins、Stephen W. Fesik、Steve J. Ballaron、Mike A. Stashko、Tom Lubben、Amanda K. Mika、Bradley A. Zinker、James M. Trevillyan、Michael R. Jirousek

  DOI：10.1021/jm0205696

  日期：2003.5.1

  Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.