N-[N-(3-methoxypropyl)4-fluoropiperidin-4-ylmethyl]-3-isopropyl-imidazo[1,5-a]pyridine-1-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: N-[N-(3-methoxypropyl)4-fluoropiperidin-4-ylmethyl]-3-isopropyl-imidazo[1,5-a]pyridine-1-carboxamide
• 英文别名: N-[[4-fluoro-1-(3-methoxypropyl)piperidin-4-yl]methyl]-3-propan-2-ylimidazo[1,5-a]pyridine-1-carboxamide
• 化学式: C₂₁H₃₁FN₄O₂
• 分子量: 390.501
• InChiKey: BHTFGLVKTBURRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  58.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-噁-6-氮杂螺[2.5]辛烷-6-羧酸-1,1-二甲基乙酯 在 盐酸 、 二乙胺基三氟化硫 、 氨 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 反应 32.08h， 生成 N-[N-(3-methoxypropyl)4-fluoropiperidin-4-ylmethyl]-3-isopropyl-imidazo[1,5-a]pyridine-1-carboxamide
  参考文献：
  名称：

  Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease

  摘要：

  Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine(4) receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo [1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.051

文献信息

• Synthesis and SAR of Imidazo[1,5-a]pyridine derivatives as 5-HT4 receptor partial agonists for the treatment of cognitive disorders associated with Alzheimer's disease
  作者：Ramakrishna Nirogi、Abdul Rasheed Mohammed、Anil K. Shinde、Narsimha Bogaraju、Shankar Reddy Gagginapalli、Srinivasa Rao Ravella、Laxman Kota、Gopinadh Bhyrapuneni、Nageswara Rao Muddana、Vijay Benade、Raghava Chowdary Palacharla、Pradeep Jayarajan、Ramkumar Subramanian、Vinod Kumar Goyal

  DOI：10.1016/j.ejmech.2015.08.051

  日期：2015.10

  Alzheimer's disease (AD) is a neurodegenerative disease which has a higher prevalence and incidence in older people. The need for improved AD therapies is unmet. The 5-hydroxytryptamine(4) receptor (5-HT4R) partial agonists may be of benefit for both the symptomatic and disease-modifying treatment of cognitive disorders associated with AD. Herein, we report the design, synthesis and SAR of imidazo [1,5-a] pyridine derivatives as 5-HT4R partial agonists. The focused SAR, optimization of ADME properties resulted the discovery of compound 5a as potent, selective, brain penetrant 5-HT4 partial agonist as a lead compound with good ADME properties and efficacy in both symptomatic and disease modifying animal models of cognition. (C) 2015 Elsevier Masson SAS. All rights reserved.