3-(4-fluoro-phenylsulfonyl)-5,7-dimethyl-2-methylthio-pyrazolo[1,5-a]pyrimidine | 1173103-86-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 3-(4-fluoro-phenylsulfonyl)-5,7-dimethyl-2-methylthio-pyrazolo[1,5-a]pyrimidine
• 英文别名: 3-(4-Fluorophenyl)sulfonyl-5,7-dimethyl-2-methylsulfanylpyrazolo[1,5-a]pyrimidine
• CAS: 1173103-86-0
• 化学式: C₁₅H₁₄FN₃O₂S₂
• 分子量: 351.425
• InChiKey: ZKKWRCSTEPFZDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  98
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-(4-fluorophenylsulfonyl)-5-(methylthio)-2H-pyrazol-3-ylamine 、 乙酰丙酮 在 溶剂黄146 作用下， 生成 3-(4-fluoro-phenylsulfonyl)-5,7-dimethyl-2-methylthio-pyrazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Synthesis and SAR of 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines as potent serotonin 5-HT6 receptor antagonists

  摘要：

  Syntheses of a series of novel 3-sulfonyl-pyrazolo[1,5-a]pyrimidines and their 5-HT6 receptor antagonistic structure-activity relationship are disclosed. The nature and position of substituents, which affect their receptor antagonistic activity, are analyzed. Among all synthesized derivatives, {3-(3-chlorophenylsulfonyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-yl}-methyl-amine 33 (K-i = 190 pM), (3-phenylsulfonyl-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 44 (K-i = 240 pM), (3-phenylsulfonyl-5-metoxymethyl-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 50 (K-i = 270 pM), and (3-phenylsulfonyl-5-methyl-7-metoxymethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 52 (K-i = 280 pM) are the most potent antagonists of the 5-HT6 receptors. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.055

文献信息

• (EN) 3-SULFONYL-PYRAZOLO[1,5-A] PYRIMIDINES / ANTAGONISTS OF SEROTONIN 5-HT6 RECEPTORS, METHODS FOR THE PRODUCTION AND THE USE THEREOF
  申请人：Ivashcenko Andrey Alexandrovich

  公开号：US20100331347A1

  公开（公告）日：2010-12-30

  The present invention relates to novel substituted 3-(arylsulfonyl)pyrazolo[1,5-a]pyrimidines of general formula 1 pharmaceutically acceptable salts and/or hydrates, to novel serotonin 5-HT 6 receptor antagonists, to novel drug substances, pharmaceutical compositions, medicaments and methods for their preparation and use for treatment and prophylaxis of pathological states and diseases of CNS, pathogenesis of which is associated with disturbance of serotonin 5-HT 6 receptor activation. In compounds of general formula 1 Ar represents optionally substituted aryl or heterocyclyl; R 1 , R 2 and R 3 independently of each other represent hydrogen, C 1 -C 3 alkyl or phenyl; R 4 represents hydrogen, optionally substituted C 1 -C 5 alkyl, substituted hydroxyl group or substituted sulfanyl group.

  本发明涉及新型的取代的3-(芳基磺酰基)吡唑并[1,5-a]嘧啶通式1的药学上可接受的盐和/或水合物，新型的血清素5-HT6受体拮抗剂，新型的药物物质、制药组合物、药物和其制备和使用的方法，用于治疗和预防与血清素5-HT6受体激活紊乱相关的中枢神经系统的病理状态和疾病的发病机制。在通式1中，Ar代表可选取代的芳基或杂环基；R1、R2和R3分别代表氢、C1-C3烷基或苯基；R4代表氢、可选取代的C1-C5烷基、取代的羟基基团或取代的磺酰基基团。
• 3-SULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES / ANTAGONISTS OF SEROTONIN 5-HT6 RECEPTORS, METHODS FOR THE PRODUCTION AND THE USE THEREOF
  申请人：Alla Chem, LLC.

  公开号：EP2248815A2

  公开（公告）日：2010-11-10

  The present invention relates to novel substituted 3-(arylsulfonyl)pyrazolo[1,5-a]pyrimidines of general formula 1 pharmaceutically acceptable salts and/or hydrates, to novel serotonin 5-HT6 receptor antagonists, to novel drug substances, pharmaceutical compositions, medicaments and methods for their preparation and use for treatment and prophylaxis of pathological states and diseases of CNS, pathogenesis of which is associated with disturbance of serotonin 5-HT6 receptor activation. In compounds of general formula 1 Ar represents optionally substituted aryl or heterocyclyl; R1, R2 and R3 independently of each other represent hydrogen, C1-C3 alkyl or phenyl; R4 represents hydrogen, optionally substituted C1-C5 alkyl, substituted hydroxyl group or substituted sulfanyl group.

  本发明涉及通式 1 的新型取代 3-(芳基磺酰基)吡唑并[1,5-a]嘧啶的药学上可接受的盐和/或水合物，涉及新型血清素 5-HT6 受体拮抗剂，涉及新型药物物质、药物组合物、药物及其制备和使用方法，用于治疗和预防中枢神经系统的病理状态和疾病，其发病机制与血清素 5-HT6 受体激活紊乱有关。 在通式 1 的化合物中 Ar 代表任选取代的芳基或杂环基；R1、R2 和 R3 相互独立地代表氢、C1-C3 烷基或苯基；R4 代表氢、任选取代的 C1-C5 烷基、取代的羟基或取代的硫基。
• US8552005B2
  申请人：——

  公开号：US8552005B2

  公开（公告）日：2013-10-08
• Synthesis and SAR of 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines as potent serotonin 5-HT6 receptor antagonists
  作者：Alexandre V. Ivachtchenko、Elena S. Golovina、Madina G. Kadieva、Volodymyr M. Kysil、Oleg D. Mitkin、Sergey E. Tkachenko、Ilya Okun

  DOI：10.1016/j.bmc.2010.12.055

  日期：2011.2

  Syntheses of a series of novel 3-sulfonyl-pyrazolo[1,5-a]pyrimidines and their 5-HT6 receptor antagonistic structure-activity relationship are disclosed. The nature and position of substituents, which affect their receptor antagonistic activity, are analyzed. Among all synthesized derivatives, 3-(3-chlorophenylsulfonyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-2-yl}-methyl-amine 33 (K-i = 190 pM), (3-phenylsulfonyl-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 44 (K-i = 240 pM), (3-phenylsulfonyl-5-metoxymethyl-7-methyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 50 (K-i = 270 pM), and (3-phenylsulfonyl-5-methyl-7-metoxymethyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 52 (K-i = 280 pM) are the most potent antagonists of the 5-HT6 receptors. (C) 2010 Elsevier Ltd. All rights reserved.