6-(3,4-Dichlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile | 131364-37-9

• 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: 6-(3,4-Dichlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile
• 英文别名: 4-(3,4-dichlorophenyl)-2-methylsulfanyl-6-oxo-1,6-dihydropyrimidine-5-carbonitrile；5-cyano-4-(3,4-dichlorophenyl)-2-methylsulfanyl-pyrimidin-6-one；6-(3,4-Dichlorophenyl)-4-hydroxy-2-methylthiopyrimidine-5-carbonitrile；4-(3,4-dichlorophenyl)-2-methylsulfanyl-6-oxo-1H-pyrimidine-5-carbonitrile
• CAS: 131364-37-9
• 化学式: C₁₂H₇Cl₂N₃OS
• 分子量: 312.179
• InChiKey: OIZQIJOKTOFDME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(3,4-Dichlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile 在 三氯氧磷 作用下， 以65%的产率得到4-Chloro-6-(3,4-dichlorophenyl)-2-methylthiopyrimidine-5-carbonitrile
  参考文献：
  名称：

  化学治疗剂，XVIII：合成作为利什曼原虫杀灭剂的 π 缺陷嘧啶和融合嘧啶

  摘要：

  6-芳基-5-氰基-2-硫尿嘧啶1a-d的合成已经描述了从芳香醛、硫脲和氰基乙酸乙酯的缩合-环化。1a-d 在不同反应条件下与单卤代烷烃和二卤代烷烃烷基化产生 2、3 和 6。1 与 POCl3 的相互作用提供卤代嘧啶 8a、b。用芳香胺对 8 和 3 进行亲核取代分别得到 9a-d 和 7a-d。6 - 氯 - 5 - 硝基 - 3 - 甲基尿嘧啶 (11) 通过硝化 10 与胺进行亲核取代，提供 12。一些被筛选为利什曼原虫的化合物没有表现出任何显着的活性。

  DOI：

  10.1002/ardp.19903231103
• 作为产物：
  描述：

  3,4-二氯苯甲醛 在 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 6-(3,4-Dichlorophenyl)-3,4-dihydro-2-methylthio-4-oxopyrimidine-5-carbonitrile
  参考文献：
  名称：

  化学治疗剂，XVIII：合成作为利什曼原虫杀灭剂的 π 缺陷嘧啶和融合嘧啶

  摘要：

  6-芳基-5-氰基-2-硫尿嘧啶1a-d的合成已经描述了从芳香醛、硫脲和氰基乙酸乙酯的缩合-环化。1a-d 在不同反应条件下与单卤代烷烃和二卤代烷烃烷基化产生 2、3 和 6。1 与 POCl3 的相互作用提供卤代嘧啶 8a、b。用芳香胺对 8 和 3 进行亲核取代分别得到 9a-d 和 7a-d。6 - 氯 - 5 - 硝基 - 3 - 甲基尿嘧啶 (11) 通过硝化 10 与胺进行亲核取代，提供 12。一些被筛选为利什曼原虫的化合物没有表现出任何显着的活性。

  DOI：

  10.1002/ardp.19903231103

文献信息

• Inhibitors of TNFalpha, PDE4 and B-RAF, compositions thereof and methods of use therewith
  申请人：McKenna M. Jeffrey

  公开号：US20080004271A1

  公开（公告）日：2008-01-03

  Provided herein are compounds having TNFα and/or PDE4 and/or B-RAF inhibitory activity, and compositions thereof. In particular, provided herein are compounds of the formula I: and pharmaceutically acceptable salts, solvates, hydrates, clathrates, stereoisomers, polymorphs and prodrugs thereof, wherein Ar, R 1 , R 2 , R 3 , R 4 , n and Z are as described herein. Further provided herein are methods for treating or preventing various diseases and disorders by administering to a patient one or more TNFα and/or PDE4 and/or B-RAF inhibitors. In particular, provided herein are methods for preventing or treating cancer, inflammatory disorders, cognition and memory disorders and autoimmune disorders, or one or more symptoms thereof by administering to a patient one or more TNFα and/or PDE4 and/or B-RAF inhibitors.

  本文提供具有TNFα和/或PDE4和/或B-RAF抑制活性的化合物及其组合物。特别地，本文提供了式I的化合物：以及其药学上可接受的盐、溶剂化合物、水合物、包合物、立体异构体、多晶形和前药，其中Ar、R1、R2、R3、R4、n和Z如本文所述。此外，本文提供了通过向患者给予一种或多种TNFα和/或PDE4和/或B-RAF抑制剂来治疗或预防各种疾病和疾病的方法。特别地，本文提供了通过向患者给予一种或多种TNFα和/或PDE4和/或B-RAF抑制剂来预防或治疗癌症、炎症性疾病、认知和记忆障碍和自身免疫性疾病或其一种或多种症状的方法。
• [EN] INHIBITORS OF TNFa, PDE4 AND B-RAF, COMPOSITIONS THEREOF AND METHODS OF USE THEREWITH<br/>[FR] INHIBITEURS DE TNFa, DE PDE4 ET DE B-RAF, COMPOSITIONS COMPRENANT CES INHIBITEURS ET MÉTHODES D'UTILISATION ASSOCIÉES
  申请人：SIGNAL PHARM LLC

  公开号：WO2007084560A3

  公开（公告）日：2007-09-20
• Vasoactive Thiomethyl-Pyrimidines: Promising Drug Candidates with Vascular Activity
  作者：Audrey de Andrade、Alice Araújo、Hugo Barbosa、Almir Wanderley、Oscar Malta、Janaína dos Anjos

  DOI：10.21577/0103-5053.20160289

  日期：——

  Pyrimidines and their derivatives are present in various biologically active molecules. Most of the synthetic methods employed to achieve the pyrimidinone ring consist of two stages: the synthesis of a Michael intermediate from an aldehyde and an "active methylene" containing compound; and the condensation of this intermediate with a molecule containing an uranium moiety. This may take one to two days of laboratory work. In this paper we describe a new methodology in which these derivatives are obtained via multicomponent synthesis mediated by ultrasound in only 2 hours. In order to obtain water-soluble pyrimidinone derivatives, our previous compounds were further converted into their sodium salts. In pharmacologic studies, these salts inhibited phenylephr-ineinduced contraction in isolated rat aorta, suggesting that they may act as alpha-1 antagonists and, therefore, are candidates for anti-hypertensive drugs.
• INHIBITORS OF TNF ALPHA , PDE4 AND B-RAF, COMPOSITIONS THEREOF AND METHODS OF USE THEREWITH
  申请人：Signal Pharmaceuticals LLC

  公开号：EP1984377A2

  公开（公告）日：2008-10-29
• Discovery and optimization of thieno[2,3-d]pyrimidines as B-Raf inhibitors
  作者：Garrick K. Packard、Patrick Papa、Jennifer R. Riggs、Paul Erdman、Lida Tehrani、Dale Robinson、Roy Harris、Graziella Shevlin、Sophie Perrin-Ninkovic、Robert Hilgraf、Margaret A. McCarrick、Tam Tran、Yuedi Fleming、April Bai、Samantha Richardson、Jason Katz、Yang Tang、Jim Leisten、Mehran Moghaddam、Brian Cathers、Dan Zhu、Steven Sakata

  DOI：10.1016/j.bmcl.2011.03.006

  日期：2012.1

  The serine/threonine specific protein kinase B-Raf is part of the MAPK pathway and is an interesting oncology target. We have identified thieno[2,3-d]pyrimidines as a core scaffold of small molecule B-Raf inhibitors. The SAR of analogs in this series will be described. (C) 2011 Published by Elsevier Ltd.