N,5-dimethyl-3-(phenylsulfonyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazolin-2-amine | 1173004-13-1

• 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: N,5-dimethyl-3-(phenylsulfonyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazolin-2-amine
• 英文别名: N,5-Dimethyl-3-(phenylsulfonyl)-6,7,8,9-tetrahydropyrazolo-[1,5-a]quinazolin-2-amine；3-(benzenesulfonyl)-N,5-dimethyl-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazolin-2-amine
• CAS: 1173004-13-1
• 化学式: C₁₈H₂₀N₄O₂S
• 分子量: 356.448
• InChiKey: JYBCSMXGFAKENQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  2-乙酰基环己酮 、 N(3)-methyl-4-(phenylsulfonyl)-1H-pyrazole-3,5-diamine 在 溶剂黄146 作用下， 反应 13.0h， 生成 N,5-dimethyl-3-(phenylsulfonyl)-6,7,8,9-tetrahydropyrazolo[1,5-a]quinazolin-2-amine 、 N,9-dimethyl-3-(phenylsulfonyl)-5,6,7,8-tetrahydropyrazolo-[5,1-b]quinazolin-2-amine
  参考文献：
  名称：

  (3-Phenylsulfonylcycloalkano[e and d]pyrazolo[1,5-a]pyrimidin-2-yl)amines: Potent and Selective Antagonists of the Serotonin 5-HT₆ Receptor

  摘要：

  5-HT6 receptors are exclusively localized in the CNS and have high affinity with many psychotropic agents. Though the role of this receptor in many CNS diseases is widely anticipated, lack of definite progress in the development of 5-HT6 receptor-oriented drugs indicates a need for further discoveries of novel chemotypes with high potency and high selectivity to the receptor. Here we present preparations and biological evaluation of a series of (3-phenylsulfonylcycloalkano[e and d]pyrazolo[1,5-a]pyrimidin-2-yl)amines. Phenylsulfonylcyclopentapyrazolopyrimidine 7 was found to be a highly selective 5-HT6 receptor antagonist with high affinity (low picomolar range) and potency. 7 and a few of its analogues were further tested for biological effect on 5-HT2B receptors and hERG potassium channels, potential liability targets. Such liability appears to be minimal, based on the in vitro data.

  DOI：

  10.1021/jm100350r

文献信息

• 2-ALKYLAMINO-3-ARYLSULFONYL-CYCLOALCANO [e OR ] 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：EP2248816A2

  公开（公告）日：2010-11-10

  The invention relates to substituted 2-alkylamino-3-(arylsulfonyl)cycloalkyl[e or d]pyrazolo[1,5-a]pyrimidines, to serotonin 5-HT6 receptor antagonists, to novel drug substances and pharmaceutical compositions comprising the said compounds as active ingredients, and to novel medicaments and method for treatment and prophylaxis of various CNS diseases. 2-Alkylamino-3-arylsulfonylcycloalkyl[e]pyrazolo[1,5-a]pyrimidines of general formula 1 and 2-alkylamino-3-arylsulfonylcycloalkyl[d]pyrazolo[1,5-a]pyrimidines of general formula 2, wherein: R1 is hydrogen or C1-C3 alkyl; R2 is C1-C3 alkyl; R3 is hydrogen, one or more optionally identical halogen atoms, C1-C3 alkyl or hydroxyl group optionally substituted with C1-C3 alkyl; n is the whole numbers 1, 2 or 3.

  本发明涉及取代的2-烷基氨基-3-(芳基磺酰基)环烷基[e或d]吡唑并[1,5-a]嘧啶、5-羟色胺5-HT6受体拮抗剂、以上述化合物为活性成分的新型药物物质和药物组合物，以及治疗和预防各种中枢神经系统疾病的新型药物和方法。 通式 1 的 2-烷基氨基-3-芳基磺酰基环烷基[e]吡唑并[1,5-a]嘧啶和通式 2 的 2-烷基氨基-3-芳基磺酰基环烷基[d]吡唑并[1,5-a]嘧啶、 其中R1 是氢或 C1-C3 烷基；R2 是 C1-C3 烷基；R3 是氢、一个或多个任选相同的卤素原子、C1-C3 烷基或任选被 C1-C3 烷基取代的羟基；n 是整数 1、2 或 3。
• 2-ALKYLAMINO-3-ARYLSULFONYL-CYCLOALCANO [e OR d] PYRAZOLO[1,5-A]PYRIMIDINES AS ANTAGONISTS OF SEROTONIN 5-HT6 RECEPTORS, METHODS FOR THE PRODUCTION AND THE USE THEREOF
  申请人：Alla Chem, LLC.

  公开号：EP2248816B1

  公开（公告）日：2014-10-22
• (EN) 2-ALKYLAMINO-3-ARYLSULFONYL-CYCLOALCANO [e OR d] PYRAZOLO [1,5-A]PYRIMIDINES / ANTAGONISTS OF SEROTONIN 5-HT6 RECEPTORS, METHODS FOR THE PRODUCTION AND THE USE THEREOF
  申请人：IVASHCHENKO Andrey Alexandrovich

  公开号：US20100292256A1

  公开（公告）日：2010-11-18

  The invention relates to substituted 2-alkylamino-3-(arylsulfonyl)cycloalkyl[e or d]pyrazolo[1,5-a]pyrimidines, to serotonin 5-HT 6 receptor antagonists, to novel drug substances and pharmaceutical compositions comprising the said compounds as active ingredients, and to novel medicaments and method for treatment and prophylaxis of various CNS diseases. 2-Alkylamino-3-arylsulfonylcycloalkyl[e]pyrazolo[1,5-a]pyrimidines of general formula 1 and 2-alkylamino-3-arylsulfonylcycloalkyl[d]pyrazolo[1,5-a]pyrimidines of general formula 2, wherein: R 1 is hydrogen or C 1 -C 3 alkyl; R 2 is C 1 -C 3 alkyl; R 3 is hydrogen, one or more optionally identical halogen atoms, C 1 -C 3 alkyl or hydroxyl group optionally substituted with C 1 -C 3 alkyl; n is the whole numbers 1, 2 or 3.
• US8471009B2
  申请人：——

  公开号：US8471009B2

  公开（公告）日：2013-06-25
• [EN] 2-ALKYLAMINO-3-ARYLSULFONYL-CYCLOALCANO [e OR d] PYRAZOLO [1,5-A]PYRIMIDINES / ANTAGONISTS OF SEROTONIN 5-HT6 RECEPTORS, METHODS FOR THE PRODUCTION AND THE USE THEREOF<br/>[FR] 2-ALKYLAMINO-3-ARYLSULFONYL-CYCLO-ALCANO [E OU D] PYRAZOLO [1,5-A]PYRIMIDINES SUBSTITUÉES FONCTIONNANT COMME DES ANTAGONISTES DES RÉCEPTEURS 5-HT6 DE SÉROTONINE, PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：ALLA CHEM LLC

  公开号：WO2009093209A2

  公开（公告）日：2009-07-30

  Изобретение относится к антагонистам серотониновых 5-HT6 рецепторов - замещенным 2-aлкилaминo-3-apилcyльфoнил-циклoaлкaнo[e или d]пиpaзoлo[1,5- a]пиpимидинaм, лекарственным началам и фармацевтическим композициям, содержащим лекарственные начала в виде указанных соединений, а также к новым лекарственным средствам и способу лечения и предупреждения развития различных заболеваний ЦНС. Предложены 2-aлкилaминo-3-apилcyльфoнилциклoaлкaнo[e]пиpaзoлo[1,5-a]пиpимидины общей формулы 1 и 2-aлкилaминo-З-apилcyльфoнилциклo- aлкaнo[d]пиpaзoлo[1,5-a]пиpимидины общей формулы 2, где: R1 представляет собой атом водорода или C1-C3 алкил; R2 представляет собой C1-C3 алкил; R3 представляет собой атом водорода, один или два необязательно одинаковых атома галогена, C1-C3 алкил или необязательно замещенный C1-C3 алкилом гидроксил; n представляет собой целое число 1, 2 или 3.