4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile | 859173-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile
• 英文别名: 4-[[7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-pyridin-4-yl-[1,2,4]triazolo[4,3-b]pyridazin-5-yl]methyl]benzonitrile
• CAS: 859173-03-8
• 化学式: C₂₅H₁₇ClN₆O₂
• 分子量: 468.902
• InChiKey: LLYIGDJSRYWVSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  92.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7-(4-chlorophenyl)-2-methyl-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3,6(2H,5H)-dione 、 对氰基溴化苄 、 potassium carbonate 在 水 、 Sodium sulfate-III 、 crude product 、 4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile 、 mono trifluoro acetate 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 0.33h， 以to give the title compound, 4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile (6.5 mg, 40%) as the mono trifluoro acetate salt as a yellow solid的产率得到4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile
  参考文献：
  名称：

  Azabicyclic heterocycles as cannabinoid receptor modulators

  摘要：

  本申请描述了符合公式I的化合物，包括所有的前药、药学上可接受的盐和立体异构体，以及包含至少一种符合公式I的化合物和可选的一种或多种其他治疗剂的制药组合物，以及使用符合公式I的化合物进行治疗的方法，包括单独使用和与一种或多种其他治疗剂的组合使用。公式I的化合物包括R1、R2、R3、R4、R5、m和n。

  公开号：

  US20050171110A1
• 作为试剂：
  描述：

  7-(4-chlorophenyl)-2-methyl-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3,6(2H,5H)-dione 、 对氰基溴化苄 、 potassium carbonate 在 水 、 Sodium sulfate-III 、 crude product 、 4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile 、 mono trifluoro acetate 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 0.33h， 以to give the title compound, 4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile (6.5 mg, 40%) as the mono trifluoro acetate salt as a yellow solid的产率得到4-((7-(4-chlorophenyl)-2-methyl-3,6-dioxo-8-(pyridin-4-yl)-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-5(6H)-yl)methyl)benzonitrile
  参考文献：
  名称：

  Azabicyclic heterocycles as cannabinoid receptor modulators

  摘要：

  本申请描述了符合I式的化合物，其中包括所有的前药、药学上可接受的盐和立体异构体，以及至少包含一种符合I式的化合物和可选的一种或多种其他治疗剂的制药组合物，以及使用符合I式的化合物进行单独治疗或与一种或多种其他治疗剂联合治疗的方法。符合I式的化合物包括R1、R2、R3、R4、R5、m和n。

  公开号：

  US07816357B2

文献信息

• Reductions in log P Improved Protein Binding and Clearance Predictions Enabling the Prospective Design of Cannabinoid Receptor (CB1) Antagonists with Desired Pharmacokinetic Properties
  作者：Bruce A. Ellsworth、Philip M. Sher、Ximao Wu、Gang Wu、Richard B. Sulsky、Zhengxiang Gu、Natesan Murugesan、Yeheng Zhu、Guixue Yu、Doree F. Sitkoff、Kenneth E. Carlson、Liya Kang、Yifan Yang、Ning Lee、Rose A. Baska、William J. Keim、Mary Jane Cullen、Anthony V. Azzara、Eva Zuvich、Michael A. Thomas、Kenneth W. Rohrbach、James J. Devenny、Helen E. Godonis、Susan J. Harvey、Brian J. Murphy、Gerry G. Everlof、Paul I. Stetsko、Olafur Gudmundsson、Susan Johnghar、Asoka Ranasinghe、Kamelia Behnia、Mary Ann Pelleymounter、William R. Ewing

  DOI：10.1021/jm4010835

  日期：2013.12.12

  Several strategies have been employed to reduce the long in vivo half-life of our lead CB1 antagonist, triazolopyridazinone 3, to differentiate the pharmacokinetic profile versus the lead clinical compounds. An in vitro and in vivo clearance data set revealed a lack of correlation; however, when compounds with <5% free fraction were excluded, a more predictable correlation was observed. Compounds with log P between 3 and 4 were likely to have significant free fraction, so we designed compounds in this range to give more predictable clearance values. This strategy produced compounds with desirable in vivo half-lives, ultimately leading to the discovery of compound 46. The progression of compound 46 was halted due to the contemporaneous marketing and clinical withdrawal of other centrally acting CB1 antagonists; however, the design strategy successfully delivered a potent CB1 antagonist with the desired pharmacokinetic properties and a clean off-target profile.
• AZABICYCLIC HETEROCYCLES AS CANNABINOID RECEPTOR MODULATORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1697371A1

  公开（公告）日：2006-09-06
• US7816357B2
  申请人：——

  公开号：US7816357B2

  公开（公告）日：2010-10-19
• [EN] AZABICYCLIC HETEROCYCLES AS CANNABINOID RECEPTOR MODULATORS<br/>[FR] HETEROCYCLES AZABICYCLIQUES EN TANT QUE MODULATEURS DE RECEPTEUR CANABINOIDES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2005063762A1

  公开（公告）日：2005-07-14

  The present application describes compounds according to Formula I, pharmaceutical compositions comprising at least one compound according to Formula I and optionally one or more additional therapeutic agents and methods of treatment using the compounds according to Formula I both alone and in combination with one or more additional therapeutic agents. The compounds have the general Formula I. including all prodrugs, pharmaceutically acceptable salts and stereoisomers, R1, R2, R3, R4, R5, m and n are described herein.