N-(3-benzenesulfonyl-2-methylsulfanyl-pyrido[1,2-a]pyrimidin-4-ylidene)-methylamine | 651310-95-1

• 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: N-(3-benzenesulfonyl-2-methylsulfanyl-pyrido[1,2-a]pyrimidin-4-ylidene)-methylamine
• 英文别名: 3-(benzenesulfonyl)-N-methyl-2-methylsulfanylpyrido[1,2-a]pyrimidin-4-imine
• CAS: 651310-95-1
• 化学式: C₁₆H₁₅N₃O₂S₂
• 分子量: 345.446
• InChiKey: GINMLVYMHLSXEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  95.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-苯磺酰基-3,3-二(甲硫基)丙烯腈 以 乙醇 、 二氯甲烷 为溶剂， 生成 N-(3-benzenesulfonyl-2-methylsulfanyl-pyrido[1,2-a]pyrimidin-4-ylidene)-methylamine
  参考文献：
  名称：

  Structure activity relationship studies of 3-arylsulfonyl-pyrido[1,2-a]pyrimidin-4-imines as potent 5-HT6 antagonists

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2014.01.003

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。
• 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.