methyl 2-[4-({N-[(allyloxy)carbonyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-L-phenylalanyl}amino)butoxy]-6-hydroxybenzoate

• 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: methyl 2-[4-({N-[(allyloxy)carbonyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-L-phenylalanyl}amino)butoxy]-6-hydroxybenzoate
• 英文别名: 2-{4-[2-(S)-Allyloxycarbonylamino-3-{4-[(2-carboxy-phenyl)-oxalyl-amino]-phenyl}-propionylamino]-butoxy}-6-hydroxy-benzoic acid methyl ester；2-[4-[(2S)-3-[4-(3-hydroxy-2-methoxycarbonylphenoxy)butylamino]-3-oxo-2-(prop-2-enoxycarbonylamino)propyl]-N-oxaloanilino]benzoic acid
• 化学式: C₃₄H₃₅N₃O₁₂
• 分子量: 677.665
• InChiKey: JTJBRKLISQICDU-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  49
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  218
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,6-二羟基苯甲酸甲酯 在 盐酸 、 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 间苯二酚 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 methyl 2-[4-({N-[(allyloxy)carbonyl]-4-[(carboxycarbonyl)(2-carboxyphenyl)amino]-L-phenylalanyl}amino)butoxy]-6-hydroxybenzoate
  参考文献：
  名称：

  Selective Protein Tyrosine Phosphatase 1B Inhibitors:  Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands

  摘要：

  Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling cascades. We identified several salicylic acid-based ligands for the second phosphotyrosine binding site of PTP1B using a NMR-based screening. Structure-based linking with a catalytic site-directed oxalylarylaminobenzoic acid-based pharmacophore led to the identification of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity over the highly homologous T-cell PTPase (TCPTP) and high selectivity over other phosphatases.

  DOI：

  10.1021/jm034088d

文献信息

• Selective protein tyrosine phosphatatase inhibitors
  申请人：Liu Gang

  公开号：US06972340B2

  公开（公告）日：2005-12-06

  Compounds of formula (I) or therapeutically acceptable salts thereof, are selective protein tyrosine kinase-B (PTP1B) inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of disorders using the compounds are disclosed.

  化合物的分子式(I)或其治疗上可接受的盐是选择性蛋白酪氨酸激酶-B(PTP1B)抑制剂。该文披露了该类化合物的制备、含有该类化合物的组合物以及使用该类化合物治疗疾病的方法。
• [EN] SELECTIVE PROTEIN TYROSINE PHOSPHATASE INHIBITORS<br/>[FR] INHIBITEURS SELECTIFS DE PROTEINE TYROSINE PHOSPHATASE
  申请人：ABBOTT LAB

  公开号：WO2003020688A1

  公开（公告）日：2003-03-13

  Compounds of formula (I) or therapeutically acceptable salts thereof, are selective protein tyrosine kinase-B (PTP1B) inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of disorders using the compounds are disclosed.

  式(I)的化合物或其治疗上可接受的盐是选择性的蛋白酪氨酸激酶-B (PTP1B) 抑制剂。本文披露了该化合物的制备、含有该化合物的组合物以及使用该化合物治疗疾病的方法。
• US6972340B2
  申请人：——

  公开号：US6972340B2

  公开（公告）日：2005-12-06
• [EN] SELECTIVE PROTEIN TYROSINE PHOSPHATATASE INHIBITORS<br/>[FR] INHITIBTEURS SELECTIFS DE LA PROTEINE TYROSINE PHOSPHATATASE
  申请人：ABBOTT LAB

  公开号：WO2003072537A2

  公开（公告）日：2003-09-04

  Compounds of formula (I), or therapeutically acceptable salts thereof, are selective protein tyrosine kinase-B (PTP1B) inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of disorders using the compounds are disclosed.
• Selective Protein Tyrosine Phosphatase 1B Inhibitors:  Targeting the Second Phosphotyrosine Binding Site with Non-Carboxylic Acid-Containing Ligands
  作者：Gang Liu、Zhili Xin、Heng Liang、Cele Abad-Zapatero、Philip J. Hajduk、David A. Janowick、Bruce G. Szczepankiewicz、Zhonghua Pei、Charles W. Hutchins、Stephen J. Ballaron、Michael A. Stashko、Thomas H. Lubben、Cathy E. Berg、Cristina M. Rondinone、James M. Trevillyan、Michael R. Jirousek

  DOI：10.1021/jm034088d

  日期：2003.7.1

  Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling cascades. We identified several salicylic acid-based ligands for the second phosphotyrosine binding site of PTP1B using a NMR-based screening. Structure-based linking with a catalytic site-directed oxalylarylaminobenzoic acid-based pharmacophore led to the identification of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity over the highly homologous T-cell PTPase (TCPTP) and high selectivity over other phosphatases.