5-(thiophen-2-yl)-2,4-dihydro-3H-pyrazol-3-one | 385381-91-9

• 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: 5-(thiophen-2-yl)-2,4-dihydro-3H-pyrazol-3-one
• 英文别名: 3-(Thiophen-2-yl)-1H-pyrazol-5(4H)-one；3-thiophen-2-yl-1,4-dihydropyrazol-5-one
• CAS: 385381-91-9
• 化学式: C₇H₆N₂OS
• mdl: MFCD03035683
• 分子量: 166.203
• InChiKey: GFBRBQIACOYUGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(thiophen-2-yl)-2,4-dihydro-3H-pyrazol-3-one 在 sodium tetrahydroborate 、 乙醇 、 溶剂黄146 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 3.67h， 生成 4-(3-bromo-4-methoxyphenyl)-6-(methylamino)-3-(thiophen-2-yl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile
  参考文献：
  名称：

  [EN] 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES AND METHODS OF USE
  [FR] 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES ET PROCÉDÉS D'UTILISATION

  摘要：

  本发明通常涉及6-氨基-2,4-二氢吡喃并[2,3-c]吡唑醇作为一种泛素特异性蛋白酶7（USP7）抑制剂，用于治疗由USP7功能失调介导的疾病，如炎症、癌症和免疫性疾病。本文所述的发明还涉及使用本文披露的化合物在哺乳动物中治疗由USP7功能失调介导的疾病的药物组合物和方法。

  公开号：

  WO2018183587A1
• 作为产物：
  描述：

  2-噻吩甲酰乙酸乙酯 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以43%的产率得到5-(thiophen-2-yl)-2,4-dihydro-3H-pyrazol-3-one
  参考文献：
  名称：

  [EN] 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES AND METHODS OF USE
  [FR] 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES ET PROCÉDÉS D'UTILISATION

  摘要：

  本发明通常涉及6-氨基-2,4-二氢吡喃并[2,3-c]吡唑醇作为一种泛素特异性蛋白酶7（USP7）抑制剂，用于治疗由USP7功能失调介导的疾病，如炎症、癌症和免疫性疾病。本文所述的发明还涉及使用本文披露的化合物在哺乳动物中治疗由USP7功能失调介导的疾病的药物组合物和方法。

  公开号：

  WO2018183587A1

文献信息

• 6-amino-2,4-dihydropyrano [2,3-c] pyrazoles and methods of use
  申请人：Purdue Research Foundation

  公开号：US10980781B2

  公开（公告）日：2021-04-20

  The present invention generally relates to 6-amino-2,4-dihydropyrano [2,3-c] pyrazoles as a ubiquitin specific protease 7(USP7) inhibitor useful for the treatment of diseases mediated by malfunction of USP7, such as inflammation, cancer, and immunological disorders. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases mediated by malfunction of USP7, in mammals using compounds disclosed herein.

  本发明一般涉及作为泛素特异性蛋白酶7（USP7）抑制剂的6-氨基-2,4-二氢吡喃并[2,3-c]吡唑，可用于治疗由USP7功能失调介导的疾病，如炎症、癌症和免疫紊乱。本文所述的发明还涉及使用本文公开的化合物治疗哺乳动物中由 USP7 功能失常介导的疾病的药物组合物和方法。
• 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.
• 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES AND METHODS OF USE
  申请人：Purdue Research Foundation

  公开号：US20200078336A1

  公开（公告）日：2020-03-12

  The present invention generally relates to 6-amino-2,4-dihydropyrano [2,3-c] pyrazoles as a ubiquitin specific protease 7 (USP7) inhibitor useful for the treatment of diseases mediated by malfunction of USP7, such as inflammation, cancer, and immunological disorders. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases mediated by malfunction of USP7, in mammals using compounds disclosed herein.
• [EN] 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES AND METHODS OF USE<br/>[FR] 6-AMINO-2,4-DIHYDROPYRANO [2,3-C] PYRAZOLES ET PROCÉDÉS D'UTILISATION
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2018183587A1

  公开（公告）日：2018-10-04

  The present invention generally relates to 6-amino-2,4-dihydropyrano [2,3-c] pyrazoles as a ubiquitin specific protease 7 (USP7) inhibitor useful for the treatment of diseases mediated by malfunction of USP7, such as inflammation, cancer, and immunological disorders. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases mediated by malfunction of USP7, in mammals using compounds disclosed herein.

  本发明通常涉及6-氨基-2,4-二氢吡喃并[2,3-c]吡唑醇作为一种泛素特异性蛋白酶7（USP7）抑制剂，用于治疗由USP7功能失调介导的疾病，如炎症、癌症和免疫性疾病。本文所述的发明还涉及使用本文披露的化合物在哺乳动物中治疗由USP7功能失调介导的疾病的药物组合物和方法。