3-chloro-N-((2-chloropyridin-4-yl)methyl)aniline | 1155195-15-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-chloro-N-((2-chloropyridin-4-yl)methyl)aniline
• 英文别名: 3-chloro-N-[(2-chloropyridin-4-yl)methyl]aniline
• CAS: 1155195-15-5
• 化学式: C₁₂H₁₀Cl₂N₂
• 分子量: 253.131
• InChiKey: YMEIFARWJIGHEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-甲基-1,3-噻唑-5-羰酰氯 、 3-chloro-N-((2-chloropyridin-4-yl)methyl)aniline 以 N,N-二甲基甲酰胺 为溶剂， 以46%的产率得到N-(3-chlorophenyl)-N-((2-chloropyridin-4-yl)methyl)-4-methylthiazole-5-carboxamide
  参考文献：
  名称：

  Discovery of Inducible Nitric Oxide Synthase (iNOS) Inhibitor Development Candidate KD7332, Part 1: Identification of a Novel, Potent, and Selective Series of Quinolinone iNOS Dimerization Inhibitors that are Orally Active in Rodent Pain Models

  摘要：

  There are three isoforms of dimeric nitric oxide synthases (NOS) that convert arginine to citrulline and nitric oxide. Inducible NOS is implicated in numerous inflammatory diseases and, mote recently, in neuropathic pain states. The majority of existing NOS inhibitors are either based on the structure of arginine or are substrate competitive. We describe the identification from an ultra high-throughput screen of a novel series of quinolinone small molecule, nonarginine iNOS dimerization inhibitors. SAR studies on the screening hit, coupled with an in vivo lipopolysaccharide (LPS) challenge assay measuring plasma nitrates and drug levels, rapidly led to the identification of compounds 12 and 42-potent inhibitors of the human and mouse iNOS enzyme that were highly selective over endothelial NOS (eNOS). Following oral dosing, compounds 12 and 42 gave a statistical reduction in pain behaviors in the mouse formalin model, while 12 also statistically reduced neuropathic pain behaviors in the chronic constriction injury (Bennett) model.

  DOI：

  10.1021/jm900173b
• 作为产物：
  描述：

  4-溴甲基-2-氯吡啶 、 3-氯苯胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以67%的产率得到3-chloro-N-((2-chloropyridin-4-yl)methyl)aniline
  参考文献：
  名称：

  Discovery of Inducible Nitric Oxide Synthase (iNOS) Inhibitor Development Candidate KD7332, Part 1: Identification of a Novel, Potent, and Selective Series of Quinolinone iNOS Dimerization Inhibitors that are Orally Active in Rodent Pain Models

  摘要：

  There are three isoforms of dimeric nitric oxide synthases (NOS) that convert arginine to citrulline and nitric oxide. Inducible NOS is implicated in numerous inflammatory diseases and, mote recently, in neuropathic pain states. The majority of existing NOS inhibitors are either based on the structure of arginine or are substrate competitive. We describe the identification from an ultra high-throughput screen of a novel series of quinolinone small molecule, nonarginine iNOS dimerization inhibitors. SAR studies on the screening hit, coupled with an in vivo lipopolysaccharide (LPS) challenge assay measuring plasma nitrates and drug levels, rapidly led to the identification of compounds 12 and 42-potent inhibitors of the human and mouse iNOS enzyme that were highly selective over endothelial NOS (eNOS). Following oral dosing, compounds 12 and 42 gave a statistical reduction in pain behaviors in the mouse formalin model, while 12 also statistically reduced neuropathic pain behaviors in the chronic constriction injury (Bennett) model.

  DOI：

  10.1021/jm900173b