3-Chloro-4-(4-chloro-5-hydroxymethyl-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl)-benzonitrile | 476645-21-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-Chloro-4-(4-chloro-5-hydroxymethyl-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl)-benzonitrile
• 英文别名: 3-chloro-4-[4-chloro-5-(hydroxymethyl)-2-methyl-6,7-dihydro-5H-pyrido[2,3-d]pyrimidin-8-yl]benzonitrile
• CAS: 476645-21-3
• 化学式: C₁₆H₁₄Cl₂N₄O
• 分子量: 349.219
• InChiKey: WWZVFLXJAZTTIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 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：

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

  公开号：US20040198726A1

  公开（公告）日：2004-10-07

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure of formula (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, R1, R2, R4, R5, R6, A, X, and Y are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same. 1

  本发明公开了CRF受体拮抗剂，这些拮抗剂可用于治疗多种疾病，包括治疗温血动物CRF分泌过多的疾病，如中风。本发明的 CRF 受体拮抗剂具有如下式（I）结构：包括其立体异构体、原药和药学上可接受的盐，R1、R2、R4、R5、R6、A、X 和 Y 如本文所定义。还公开了含有 CRF 受体拮抗剂与药学上可接受的载体结合的组合物，以及使用这些组合物的方法。 1
• 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.