2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine | 1000190-77-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine
• 英文别名: 3-benzenesulfonyl-2-methylsulfanyl-pyrido[1,2-a]pyrimidin-4-ylideneamine；3-(benzenesulfonyl)-2-methylsulfanylpyrido[1,2-a]pyrimidin-4-imine
• CAS: 1000190-77-1；614732-18-2
• 化学式: C₁₅H₁₃N₃O₂S₂
• 分子量: 331.419
• InChiKey: PUHRPYOPXGWCTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3-benzenesulfonyl-2-methanesulfinyl-pyrido[1,2-a]pyrimidin-4-ylideneamine
  参考文献：
  名称：

  Pyridopyrimidine derivatives as 5-HT6 antagonists

  摘要：

  新型吡啶吡嘧啶衍生物具有与人类5-HT6受体结合亲和力，因此可用于治疗对5-HT6受体拮抗作用敏感的疾病，如精神病、精神分裂症、躁郁症、抑郁症、神经障碍、记忆障碍、帕金森病、肌萎缩侧索硬化、阿尔茨海默病和亨廷顿舞蹈症。

  公开号：

  US20040019064A1
• 作为产物：
  描述：

  2-氨基吡啶 、 2-苯磺酰基-3,3-二(甲硫基)丙烯腈 以 乙醇 为溶剂， 反应 4.5h， 以24%的产率得到2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine
  参考文献：
  名称：

  Identification of a Potent and Selective 5-HT₆ Antagonist:  One-Step Synthesis of (E)-3-(Benzenesulfonyl)-2- (methylsulfanyl)pyrido[1,2-a]pyrimidin- 4-ylidenamine from 2-(Benzenesulfonyl)-3,3- bis(methylsulfanyl)acrylonitrile

  摘要：

  (E)-3-(苯zenesulfonyl)-2-（甲基硫anyl）pyrido[1,2-α]pyrimidin-4-ylidenamine（7）被发现是一个强大的且选择性的5-HT6拮抗剂。本研究描述了这一化合物的一步合成方法。

  DOI：

  10.1021/jm034142q

文献信息

• Pyridopyrimidine derivatives as 5-HT6 antagonists
  申请人：——

  公开号：US20040019064A1

  公开（公告）日：2004-01-29

  Novel pyridopyrimidine derivatives which have a binding affinity for the human 5-HT 6 receptor and, therefore, are useful in treating disorders responsive to antagonism of the 5-HT 6 receptor such as psychosis, schizophrenia, manic depression, depression, neurological disorder, memory disorder, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease and Huntington's chorea.

  新型吡啶吡嘧啶衍生物具有与人类5-HT6受体结合亲和力，因此可用于治疗对5-HT6受体拮抗作用敏感的疾病，如精神病、精神分裂症、躁郁症、抑郁症、神经障碍、记忆障碍、帕金森病、肌萎缩侧索硬化、阿尔茨海默病和亨廷顿舞蹈症。
• COMBINATION OF A CHOLINESTERASE INHIBITOR AND A COMPOUND WITH 5-HT6 RECEPTOR AFFINITY
  申请人：Codony-Soler Xavier

  公开号：US20100120747A1

  公开（公告）日：2010-05-13

  The present invention relates to an active substance combination comprising at least one compound with 5-HT6 receptor affinity, and at least one cholinesterase inhibitor, a medicament comprising said active substance combination, and the use of said active substance combination for the manufacture of a medicament.
• US6875771B2
  申请人：——

  公开号：US6875771B2

  公开（公告）日：2005-04-05
• [EN] COMBINATION OF A CHOLINESTERASE INHIBITOR AND A COMPOUND WITH 5-HT6 RECEPTOR AFFINITY<br/>[FR] COMBINAISON D'UN INHIBITEUR DE LA CHOLINESTÉRASE ET D'UN COMPOSÉ AYANT UNE AFFINITÉ ENVERS LE RÉCEPTEUR 5-HT6
  申请人：ESTEVE LABOR DR

  公开号：WO2007147883A1

  公开（公告）日：2007-12-27

  [EN] The present invention relates to an active substance combination comprising at least one compound with 5-HT6 receptor affinity, and at least one cholinesterase inhibitor, a medicament comprising said active substance combination, and the use of said active substance combination for the manufacture of a medicament.
  [FR] La présente invention concerne une combinaison de substances actives comprenant au moins un composé ayant une affinité pour le récepteur 5-HT6 et au moins un inhibiteur de la cholinestérase. L'invention concerne également un médicament comprenant ladite combinaison de substances actives et l'utilisation de ladite combinaison lors de la fabrication d'un médicament.
• Structure activity relationship studies of 3-arylsulfonyl-pyrido[1,2-a]pyrimidin-4-imines as potent 5-HT6 antagonists
  作者：Shuanghua Hu、Yazhong Huang、Yong-Jin Wu、Huan He、Katherine A. Grant-Young、Robert L. Bertekap、Valerie Whiterock、Patrick Brassil、Kimberley Lentz、Prasanna Sivaprakasam、David R. Langley、Ryan S. Westphal、Paul M. Scola

  DOI：10.1016/j.bmc.2014.01.003

  日期：2014.3

  Comprehensive structure activity relationship (SAR) studies were conducted on a focused screening hit, 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine (1, IC50: 4.0 nM), as 5-HT6 selective antagonists. Activity was improved some 2-4 fold when small, electron-donating groups were added to the central core as observed in 19, 20 and 26. Molecular docking of key compounds in a homology model of the human 5-HT6 receptor was used to rationalize our structure-activity relationship (SAR) findings. In pharmacokinetic experiments, compound 1 displayed good brain uptake in rats following intra-peritoneal administration, but limited oral bioavailability. (C) 2014 Elsevier Ltd. All rights reserved.