(5-methyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine | 1220643-97-9

• 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: (5-methyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine
• 英文别名: N-Methyl-N-[5-methyl-3-(phenylsulfonyl)pyrazolo[1,5-A]pyrimidin-2-YL]amine；3-(benzenesulfonyl)-N,5-dimethylpyrazolo[1,5-a]pyrimidin-2-amine
• CAS: 1220643-97-9
• 化学式: C₁₄H₁₄N₄O₂S
• mdl: MFCD32685292
• 分子量: 302.357
• InChiKey: LLRSKWJLJFTWMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  84.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4,4-二甲氧基-2-丁酮 、 N(3)-methyl-4-(phenylsulfonyl)-1H-pyrazole-3,5-diamine 在 溶剂黄146 作用下， 生成 (5-methyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine 、 (7-methyl-3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methyl-amine
  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

• SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOF
  申请人：Ivashchenko Andrey Alexandrovich

  公开号：US20110178078A1

  公开（公告）日：2011-07-21

  The invention relates to the novel substituted 3-arylsulfonyl-pyrazolo[1,5-a]pyrimidines of the general formula 1, pharmaceutically acceptable salts and/or hydrates thereof, serotonin 5-HT 6 receptor antagonists and pharmaceutical compositions, and also to method for prophylaxis and treatment of various diseases of central nervous system at humans and warm-blooded animals pathogenesis of which is associated with serotonin 5-HT 6 receptors, in particular, Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, and other neurodegenerative diseases, cognitive disorders and obesity. In the general formula 1: wherein: X═S, SO or NH; R 1 represents hydrogen, optionally substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl or heterocyclyl; R 2 represents hydrogen, halogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, aryldiazenyl or optionally substituted amino group; R 3 represents hydrogen, optionally substituted C 1 -C 3 alkyl, substituted hydroxyl, pyridyl or optionally substituted amino group, besides, in cases when X═S or X═NH, at least one of R 1 , R 2 or R 3 represent substituted C 1 -C 3 alkyl, cycloalkyl, adamantyl, aryl, heterocyclyl, halogen, substituted hydroxyl, optionally substituted amino group, aryldiazenyl, or at least two of R 1 , R 2 or R 3 represent hydrogen; R 4 represents C 1 -C 3 alkyl; R 5 represents hydrogen, one or two halogens, C 1 -C 3 alkyl or optionally substituted hydroxyl.

  该发明涉及新的取代的3-芳基磺酰基吡唑并[1,5-a]嘧啶，其通式为1，其药学上可接受的盐和/或水合物，血清素5-HT6受体拮抗剂和制药组合物，以及用于预防和治疗与血清素5-HT6受体相关的中枢神经系统各种疾病的方法，特别是阿尔茨海默病、帕金森病、亨廷顿病、精神分裂症和其他神经退行性疾病、认知障碍和肥胖症。在通式1中：其中：X═S、SO或NH；R1代表氢、可选取代的C1-C3烷基、环烷基、金刚烷基、芳基或杂环基；R2代表氢、卤素、可选取代的C1-C3烷基、取代的羟基、芳基重氮基或可选取代的氨基基团；R3代表氢、可选取代的C1-C3烷基、取代的羟基、吡啶基或可选取代的氨基基团，此外，在X═S或X═NH的情况下，至少有R1、R2或R3中的一个代表取代的C1-C3烷基、环烷基、金刚烷基、芳基、杂环基、卤素、取代的羟基、可选取代的氨基基团、芳基重氮基，或者R1、R2或R3中的至少两个代表氢；R4代表C1-C3烷基；R5代表氢、一个或两个卤素、C1-C3烷基或可选取代的羟基。
• [EN] SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOF<br/>[FR] 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES SUBSTITUÉES, ANTAGONISTES DES RÉCEPTEURS 5-HT6 DE SÉROTONINE, PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：IVASHCHENKO ANDREY ALEXANDROVICH

  公开号：WO2010041983A1

  公开（公告）日：2010-04-15

  Данное изобретение относится к новым замещенным 3-apилcyльфoнил-пиpaзoлo[1,5-a]пиpимидинaм общей формулы 1, их фармацевтически приемлемым солям и/или гидратам, антагонистам серотониновых 5-HT6 рецепторов и фармацевтическим композициям, а также способу лечения и предупреждения развития различных заболеваний центральной нервной системы у людей и теплокровных животных, патогенез которых связан с 5-HT6 рецепторами, в частности, болезни Альцгеймера, болезни Паркинсона, болезни Гантингтона, шизофрении, других нейродегенеративных заболеваний, когнитивных расстройств и ожирения. В общей формуле 1: где: X = S, SO или NH; R1 представляет собой атом водорода, необязательно замещенный С1-С3алкил, циклоалкил, адамантил, арил или гетероциклил; R2 представляет собой атом водорода, атом галогена, необязательно замещенный С1-С3алкил, замещенный гидроксил, арилдиазенил или необязательно замещенную аминогруппу; R3 представляет собой атом водорода, необязательно замещенный С1-С3алкил, замещенный гидроксил, пиридил или необязательно замещенную аминогруппу, причем, в случаях, когда X = S или X = NH, по крайней мере, один из R1, R2 или R3 представляет собой замещенный С1-С3алкил, циклоалкил, адамантил, арил, гетероциклил, атом галогена, замещенный гидроксил, необязательно замещенную аминогруппу, арилдиазенил или, по крайней мере, два из R1, R2 или R3 представляют собой атом водорода; R4 представляет собой С1-С3алкил; R5 представляет собой атом водорода, один или два атома галогена, С1-С3алкил или необязательно замещенный гидроксил.

  This invention relates to new substituted 3-arylcylyl-pyrazolo [1,5-a] pyrimidines of general formula 1, their pharmaceutically acceptable salts and/or hydrates, antagonists of serotonin 5-HT6 receptors and pharmaceutical compositions, as well as a method of treating and preventing the development of various central nervous system diseases in humans and warm-blooded animals, the pathogenesis of which is associated with 5-HT6 receptors, in particular Alzheimer's disease, Parkinson's disease, Huntington's disease, schizophrenia, other neurodegenerative diseases, cognitive disorders, and obesity. In general formula 1: where: X = S, SO or NH; R1 represents a hydrogen atom, optionally substituted with C1-C3 alkyl, cycloalkyl, adamantyl, aryl or heterocycle; R2 represents a hydrogen atom, a halogen atom, optionally substituted with C1-C3 alkyl, substituted with hydroxyl, aryl diazenyl or optionally substituted amino group; R3 represents a hydrogen atom, optionally substituted with C1-C3 alkyl, substituted with hydroxyl, pyridyl or optionally substituted amino group, wherein in cases where X = S or X = NH, at least one of R1, R2 or R3 represents a substituted C1-C3 alkyl, cycloalkyl, adamantyl, aryl, heterocycle, halogen atom, substituted hydroxyl, optionally substituted amino group, aryl diazenyl or at least two of R1, R2 or R3 represent a hydrogen atom; R4 represents C1-C3 alkyl; R5 represents a hydrogen atom, one or two halogen atoms, C1-C3 alkyl or optionally substituted hydroxyl.
• SUBSTITUTED 3-ARYLSULFONYL-PYRAZOLO[1,5-A]PYRIMIDINES, SEROTONIN 5-HT6 RECEPTOR ANTAGONISTS AND METHODS FOR THE PRODUCTION AND USE THEREOF AND METHODS FOR THE PRODUCTION AND USE THEREOF
  申请人：Alla Chem, LLC.

  公开号：EP3020719B1

  公开（公告）日：2017-09-20
• 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.