Benzoic acid, 2-[(carboxycarbonyl)(2,3-dimethylphenyl)amino]- | 1618-52-6

• 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: Benzoic acid, 2-[(carboxycarbonyl)(2,3-dimethylphenyl)amino]-
• 英文别名: 2-(2,3-dimethyl-N-oxaloanilino)benzoic acid
• CAS: 1618-52-6
• 化学式: C₁₇H₁₅NO₅
• 分子量: 313.31
• InChiKey: LTLAECLFZXWEMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  94.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-二甲基苯胺 在 sodium hydroxide 、 copper diacetate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 为溶剂， 反应 41.0h， 生成 Benzoic acid, 2-[(carboxycarbonyl)(2,3-dimethylphenyl)amino]-
  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

文献信息

• Amino (oxo) acetic acid protein tyrosine phosphatase inhibitors
  申请人：——

  公开号：US20020035137A1

  公开（公告）日：2002-03-21

  Compounds of formula (I) 1 or therapeutically acceptable salts thereof, are protein tyrosine kinase PTP 1 B inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.

  式（I）的化合物或其治疗上可接受的盐是蛋白酪氨酸激酶PTP1B的抑制剂。公开了该化合物的制备、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。
• Discovery of a Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy
  作者：Bruce G. Szczepankiewicz、Gang Liu、Philip J. Hajduk、Cele Abad-Zapatero、Zhonghua Pei、Zhili Xin、Thomas H. Lubben、James M. Trevillyan、Michael A. Stashko、Stephen J. Ballaron、Heng Liang、Flora Huang、Charles W. Hutchins、Stephen W. Fesik、Michael R. Jirousek

  DOI：10.1021/ja0296733

  日期：2003.4.1

  Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.
• AMINO(OXO)ACETIC ACID PROTEIN TYROSINE PHOSPHATASE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP1313696A2

  公开（公告）日：2003-05-28
• [EN] AMINO(OXO)ACETIC ACID PROTEIN TYROSINE PHOSPHATASE INHIBITORS<br/>[FR] ACIDES AMINO(OXO)ACETIQUES INHIBITEURS DE LA PROTEINE TYROSINE PHOSPHATASE
  申请人：ABBOTT LAB

  公开号：WO2002018323A2

  公开（公告）日：2002-03-07

  Compound of formula (I) or therapeutically acceptable salts thereof, are protein tyrosine kinase PTP1B inhibitors. Preparation of the compounds, compositions containing the compounds, and treatment of diseases using the compounds are disclosed.
• 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.