3-(1,3-thiazol-2-yl)-2-pyrazolin-5-one | 338760-17-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 3-(1,3-thiazol-2-yl)-2-pyrazolin-5-one
• 英文别名: 3-(1,3-Thiazol-2-yl)-1,4-dihydropyrazol-5-one
• CAS: 338760-17-1
• 化学式: C₆H₅N₃OS
• 分子量: 167.191
• InChiKey: CWGCPKOGCVZKEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1,3-thiazol-2-yl)-2-pyrazolin-5-one 、 3,5-二甲基-2-吡咯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 4-[1-(3,5-Dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-5-thiazol-2-yl-2,4-dihydro-pyrazol-3-one
  参考文献：
  名称：

  Structure-guided identification of novel VEGFR-2 kinase inhibitors via solution phase parallel synthesis

  摘要：

  Structural analysis of the essential binding elements of the oxindole-based kinase inhibitor (1) led to the identification of a novel class of heterocyclic-substituted pyrazolones. Knoevenagel condensation of a variety of activated methylene nucleophiles with indole or pyrrole carboxaldehydes provided a focused library of molecules, each containing elements of kinase pharmacophore probe. Initial screening for VEGFR-2 kinase inhibit ion eliminated several of the probes. Identification of ail active pyrazolone motif and further optimization resulted in several highly potent VEGFR-2 inhibitors with cellular efficacy, anti-angiogenic activity ex vivo in rat aortic ring explant cultures, and oral anti-tumor efficacy in nude mice. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.063
• 作为产物：
  描述：

  2-乙酰基噻唑 在 H₄N₂*HO^(1-) 、 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 3-(1,3-thiazol-2-yl)-2-pyrazolin-5-one
  参考文献：
  名称：

  Structure-guided identification of novel VEGFR-2 kinase inhibitors via solution phase parallel synthesis

  摘要：

  Structural analysis of the essential binding elements of the oxindole-based kinase inhibitor (1) led to the identification of a novel class of heterocyclic-substituted pyrazolones. Knoevenagel condensation of a variety of activated methylene nucleophiles with indole or pyrrole carboxaldehydes provided a focused library of molecules, each containing elements of kinase pharmacophore probe. Initial screening for VEGFR-2 kinase inhibit ion eliminated several of the probes. Identification of ail active pyrazolone motif and further optimization resulted in several highly potent VEGFR-2 inhibitors with cellular efficacy, anti-angiogenic activity ex vivo in rat aortic ring explant cultures, and oral anti-tumor efficacy in nude mice. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.063

文献信息

• Heterocyclic substituted pyrazolones
  申请人：Cephalon, Inc.

  公开号：US06455525B1

  公开（公告）日：2002-09-24

  The present invention is directed to novel heterocyclic substituted pyrazolones, including pharmaceutical compositions, diagnostic kits, assay standards or reagents containing the same, and methods of using the same as therapeutics. The invention is also directed to intermediates and processes for making these novel compounds.

  本发明涉及新颖的杂环取代吡唑酮，包括含有这些化合物的药物组合物、诊断试剂盒、检测标准或试剂，以及将其用作治疗的方法。该发明还涉及制备这些新化合物的中间体和方法。
• [EN] HETEROCYCLIC SUBSTITUTED PYRAZOLONES<br/>[FR] PYRAZOLONES HETEROCYCLIQUES SUBSTITUES
  申请人：CEPHALON INC

  公开号：WO2001032653A1

  公开（公告）日：2001-05-10

  The present invention is directed to novel heterocyclic substituted pyrazolones, including pharmaceutical compositions, diagnostic kits, assay standards or reagents containing the same, and methods of using the same as therapeutics. The invention is also directed to intermediates and processes for making these novel compounds.

  本发明涉及新型杂环取代吡唑酮化合物，包括制备这些化合物的中间体和方法，以及包含这些化合物的药物组合物、诊断试剂盒、检测标准或试剂，并将其用作治疗的方法。
• Pyrazolone-based anaplastic lymphoma kinase (ALK) inhibitors: Control of selectivity by a benzyloxy group
  作者：Rabindranath Tripathy、Robert J. McHugh、Arup K. Ghose、Gregory R. Ott、Thelma S. Angeles、Mark S. Albom、Zeck Huang、Lisa D. Aimone、Mangeng Cheng、Bruce D. Dorsey

  DOI：10.1016/j.bmcl.2011.10.055

  日期：2011.12

  Anaplastic lymphoma kinase (ALK) is transmembrane receptor tyrosine kinase, with oncogenic variants that have been implicated in ALCL, NSCLC and other cancers. Screening of a VEGFR2-biased kinase library resulted in identification of 1 which showed cross-reactivity with ALK. SAR on the indole segment of 1 showed that a subtle structural modification (the ethoxy group of 1 changed to a benzyloxy to generate 5a) enhanced potency (ALK), selectivity for VEGFR2 and IR along with improvement in metabolic stability. From docking studies of ALK versus VEGFR2 kinase, we postulated that the loss of entropy of the VEGFR2 in the bound form with 5a might be the origin of the reduced activity against that protein. Modification of the heterocyclic segment showed that thiazole-bearing pyrazolones preserved enzyme potency, and enhanced inhibition of NPM-ALK autophosphorylation in ALK-positive ALCL cells (Karpas-299). SAR of the benzyloxy group resulted in compounds which demonstrated good cellular potency in Karpas-299 cells. Compound 8 showed best overall profile for the series with broad kinome selectivity and liver micorsome stability. Compound 8 showed reasonable iv PK in rat, but with little oral exposure. (C) 2011 Elsevier Ltd. All rights reserved.
• HETEROCYCLIC SUBSTITUTED PYRAZOLONES
  申请人：CEPHALON, INC.

  公开号：EP1226141A1

  公开（公告）日：2002-07-31
• US6455525B1
  申请人：——

  公开号：US6455525B1

  公开（公告）日：2002-09-24