N-(benzoyl)-N'-(3-carboxy-5-pyridinyl)thiourea | 247102-02-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: N-(benzoyl)-N'-(3-carboxy-5-pyridinyl)thiourea
• 英文别名: N-benzoyl-N'-(3-carboxy-5-pyridyl)thiourea；5-(benzoylcarbamothioylamino)pyridine-3-carboxylic acid
• CAS: 247102-02-9
• 化学式: C₁₄H₁₁N₃O₃S
• 分子量: 301.326
• InChiKey: JIGQWYLTPLRKKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(benzoyl)-N'-(3-carboxy-5-pyridinyl)thiourea 在 N-甲基吗啉 、 sodium methylate 、 氯甲酸异丁酯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.25h， 生成 ethyl (3R)-3-(3-bromo-5-chloro-2-hydroxyphenyl)-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoate
  参考文献：
  名称：

  R-Isomers of Arg-Gly-Asp (RGD) mimics as potent αvβ3 inhibitors

  摘要：

  The integrin alpha(v)beta(3), vitronectin receptor, is expressed in a number of cell types and has been shown to mediate adhesion of osteoclasts to bone matrix, vascular smooth muscle cell migration, and angiogenesis. We recently disclosed the discovery of a tripeptide Arg-Gly-Asp (RGD) mimic, which has been shown to be a potent inhibitor of the integrin alpha(v)beta(3) and has excellent anti-angiogenic properties including its suppression of tumor growth in animal models. In other investigations involving RGD mimics, only compounds containing the S-isomers of the beta-amino acids have been shown to be potent. We were surprised to find the potencies of analogs containing enantiomerically pure S-isomers of beta-amino acids which were only marginally better than the corresponding racemic mixtures. We therefore synthesized RGD mimics containing R-isomers of beta-amino acids and found them to be relatively potent inhibitors of alpha(v)beta(3). One of the compounds was examined in tumor models in mice and has been shown to significantly reduce the rate of growth and the size of tumors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.034
• 作为产物：
  描述：

  5-氨基烟酸 、 苯甲酰基异硫氰酸酯 在 4-二甲氨基吡啶 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以98%的产率得到N-(benzoyl)-N'-(3-carboxy-5-pyridinyl)thiourea
  参考文献：
  名称：

  [EN] THE R-ISOMER OF BETA AMINO ACID COMPOUNDS AS INTEGRIN RECEPTOR ANTAGONISTS DERIVATIVES
  [FR] ISOMERE R DE COMPOSES D'ACIDES AMINES BETA EN TANT QUE DERIVES ANTAGONISTES DU RECEPTEUR DES INTEGRINES

  摘要：

  本发明涉及一类由公式(I)表示的化合物或其药用可接受的盐，包含公式(I)化合物的药物组合物，以及在不显著抑制αVβ6整合素的情况下选择性抑制或拮抗αVβ3和/或αVβ5整合素的方法。

  公开号：

  WO2004060376A1

文献信息

• [EN] BETA AMINO ACID DERIVATIVES AS INTEGRIN ANTAGONISTS<br/>[FR] DÉRIVÉS D'ACIDES BÊTA AMINÉS EN TANT QU'ANTAGONISTES D'INTÉGRINE
  申请人：UNIV SAINT LOUIS

  公开号：WO2014015054A1

  公开（公告）日：2014-01-23

  Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods and intermediates useful for making the pharmaceutical agents and methods of using the pharmaceutical agents are also provided.

  本发明公开了新型的药物制剂，这些药物制剂作为整合素受体的拮抗剂，能够介导血管生成和纤维化的病理过程，因此可用于药物组合物中，以及在通过抑制或拮抗这些整合素来治疗由这些整合素介导的疾病的方法中。这些新型的药物制剂包括以下公式的那些：其中变量定义如下。还提供了包含此类药物制剂的药物组合物、试剂盒和制造品。此外，还提供了用于制造药物制剂的方法和中间体，以及使用药物制剂的方法。
• [EN] META-AZACYCLIC AMINO BENZOIC ACID DERIVATIVES AS PAN INTEGRIN ANTAGONISTS<br/>[FR] DÉRIVÉS D'ACIDE AMINOBENZOÏQUE MÉTA-AZACYCLIQUE À TITRE D'ANTAGONISTES DE PAN-INTÉGRINE
  申请人：UNIV SAINT LOUIS

  公开号：WO2017117538A1

  公开（公告）日：2017-07-06

  The present disclosure provides pharmaceutical agents of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods of using the pharmaceutical agents for the treatment of a variety of diseases and disorders are also provided.

  本公开提供了以下公式的药物代理：其中变量在此处定义。还提供了包含这种药物代理的药物组合物、工具包和制造品。还提供了使用这种药物代理治疗各种疾病和疾病的方法。
• R-isomer of beta amino acid compounds as integrin receptor antagonists derivatives
  申请人：Rogers Thomas

  公开号：US20050020505A1

  公开（公告）日：2005-01-27

  The present invention relates to a class of compounds represented by the Formula I or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of the Formula I, and methods of selectively inhibiting or antagonizing the α v β 3 and/or the α v β 5 integrin without significantly inhibiting the α v β 6 integrin.

  本发明涉及一类由公式I表示的化合物或其药学上可接受的盐，包括公式I化合物的制药组合物，以及选择性抑制或拮抗αvβ3和/或αvβ5整合素而不显著抑制αvβ6整合素的方法。
• META-AZACYCLIC AMINO BENZOIC ACID DERIVATIVES AS PAN INTEGRIN ANTAGONISTS WITH IMPROVED PHARMACOKINETIC PROPERTIES AND METHODS FOR THEIR MANUFACTURE
  申请人：Saint Louis University

  公开号：EP3738953A1

  公开（公告）日：2020-11-18

  The present disclosure provides pharmaceutical agents of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods of using the pharmaceutical agents for the treatment of a variety of diseases and disorders are also provided.

  本公开提供了式中的药剂： 其中的变量在此定义。还提供了包含此类药剂的药物组合物、试剂盒和制造品。还提供了使用这些药剂治疗各种疾病和失调的方法。
• Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
  申请人：Saint Louis University

  公开号：US10035778B2

  公开（公告）日：2018-07-31

  The present disclosure provides pharmaceutical agents of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods of using the pharmaceutical agents for the treatment of a variety of diseases and disorders are also provided.

  本公开提供了式中的药剂： 其中的变量在此定义。此外，还提供了包含此类药剂的药物组合物、试剂盒和制成品。还提供了使用这些药剂治疗各种疾病和失调的方法。