7-(4-(4-(3-chloro-2-(trifluoromethyl)phenyl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one | 1309857-71-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 7-(4-(4-(3-chloro-2-(trifluoromethyl)phenyl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one
• 英文别名: 7-[4-[4-[3-chloro-2-(trifluoromethyl)phenyl]piperazin-1-yl]butoxy]-3,4-dihydro-1H-1,8-naphthyridin-2-one
• CAS: 1309857-71-3
• 化学式: C₂₃H₂₆ClF₃N₄O₂
• 分子量: 482.933
• InChiKey: YFIBOKLKHXZNEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-氟-1,8-萘啶-2-醇 在 palladium on carbon 、 potassium tert-butylate 、 四丁基溴化铵 、 氢气 、 三乙酰氧基硼氢化钠 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 生成 7-(4-(4-(3-chloro-2-(trifluoromethyl)phenyl)piperazin-1-yl)butoxy)-3,4-dihydro-1,8-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of PF-00217830: Aryl piperazine napthyridinones as D2 partial agonists for schizophrenia and bipolar disorder

  摘要：

  The synthesis and structure-activity relationship (SAR) of a novel series of aryl piperazine napthyridinone D-2 partial agonists is described. Our goal was to optimize the affinities for the D-2, 5-HT2A and 5-HT1A receptors, such that the D-2/5-HT2A ratio was greater than 5 to ensure maximal occupancy of these receptors when the D-2 occupancy reached efficacious levels. This strategy led to identification of PF-00217830 (2) with robust inhibition of sLMA (MED = 0.3 mg/kg) and DOI-induced head twitches in rats (31% and 78% at 0.3 and 1 mg/kg) with no catalepsy observed at the highest dose tested (10 mg/kg). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.059

文献信息

• Discovery of PF-00217830: Aryl piperazine napthyridinones as D2 partial agonists for schizophrenia and bipolar disorder
  作者：Douglas S. Johnson、Chung Choi、Lorraine K. Fay、David A. Favor、Joseph T. Repine、Andrew D. White、Hyacinth C. Akunne、Lawrence Fitzgerald、Kim Nicholls、Bradley J. Snyder、Steven Z. Whetzel、Liming Zhang、Kevin A. Serpa

  DOI：10.1016/j.bmcl.2011.01.059

  日期：2011.5

  The synthesis and structure-activity relationship (SAR) of a novel series of aryl piperazine napthyridinone D-2 partial agonists is described. Our goal was to optimize the affinities for the D-2, 5-HT2A and 5-HT1A receptors, such that the D-2/5-HT2A ratio was greater than 5 to ensure maximal occupancy of these receptors when the D-2 occupancy reached efficacious levels. This strategy led to identification of PF-00217830 (2) with robust inhibition of sLMA (MED = 0.3 mg/kg) and DOI-induced head twitches in rats (31% and 78% at 0.3 and 1 mg/kg) with no catalepsy observed at the highest dose tested (10 mg/kg). (C) 2011 Elsevier Ltd. All rights reserved.