4-(4-Chloro-5-hydroxymethyl-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl)-3-methyl-benzonitrile | 476645-17-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-(4-Chloro-5-hydroxymethyl-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl)-3-methyl-benzonitrile
• 英文别名: 4-[4-chloro-5-(hydroxymethyl)-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl]-3-methylbenzonitrile
• CAS: 476645-17-7
• 化学式: C₁₇H₁₇ClN₄O
• 分子量: 328.801
• InChiKey: RBJHVVIIIZHUHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  73
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-Chloro-5-hydroxymethyl-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl)-3-methyl-benzonitrile 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 4-[1-(1-Ethyl-propyl)-7-methyl-2,2a,3,4-tetrahydro-1H-1,5,6,8-tetraaza-acenaphthylen-5-yl]-3-methyl-benzonitrile
  参考文献：
  名称：

  Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

  摘要：

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.040
• 作为产物：
  描述：

  1,1,2-乙烷三羧酸三乙酯 在 咪唑 、 甲醇 、 4-二甲氨基吡啶 、 sodium 、 sodium hydride 、 二异丁基氢化铝 、 臭氧 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 、 三氯氧磷 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 172.83h， 生成 4-(4-Chloro-5-hydroxymethyl-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl)-3-methyl-benzonitrile
  参考文献：
  名称：

  Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

  摘要：

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.040

文献信息

• TRI- AND TETRAAZA-ACENAPHTHYLEN DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
  申请人：NEUROCRINE BIOSCIENCES, INC.

  公开号：EP1392689B1

  公开（公告）日：2006-10-25
• US7446108B2
  申请人：——

  公开号：US7446108B2

  公开（公告）日：2008-11-04
• Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety
  作者：Y. St-Denis、R. Di Fabio、G. Bernasconi、E. Castiglioni、S. Contini、D. Donati、E. Fazzolari、G. Gentile、D. Ghirlanda、C. Marchionni、F. Messina、F. Micheli、F. Pavone、A. Pasquarello、F.M. Sabbatini、M.G. Zampori、R. Arban、G. Vitulli

  DOI：10.1016/j.bmcl.2005.05.040

  日期：2005.8

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.