3-chloro-N-((8-fluoroisoquinolin-4-yl)methyl)benzenamine | 1050203-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-chloro-N-((8-fluoroisoquinolin-4-yl)methyl)benzenamine
• 英文别名: 3-chloro-N-[(8-fluoroisoquinolin-4-yl)methyl]aniline
• CAS: 1050203-57-0
• 化学式: C₁₆H₁₂ClFN₂
• 分子量: 286.736
• InChiKey: GUUPWGOTFFPLIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲基噻唑-5-甲酸 、 3-chloro-N-((8-fluoroisoquinolin-4-yl)methyl)benzenamine 在 氯化亚砜 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以42%的产率得到N-(3-chlorophenyl)-N-((8-fluoroisoquinolin-4-yl)methyl)-4-methylthiazole-5-carboxamide
  参考文献：
  名称：

  WO2008/103615

  摘要：

  公开号：
• 作为产物：
  描述：

  8-fluoro-4-methylisoquinolin-1(2H)-one 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 、 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 3-chloro-N-((8-fluoroisoquinolin-4-yl)methyl)benzenamine
  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

文献信息

• [EN] ISOQUINOLINES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS<br/>[FR] ISOQUINOLINES UTILISÉES COMME INHIBITEURS D'OXYDE NITRIQUE SYNTHASE INDUCTIBLE
  申请人：KALYPSYS INC

  公开号：WO2008103615A1

  公开（公告）日：2008-08-28

  [EN] Disclosed herein are new isoquinoline compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibition of nitric oxide synthase activity in a human or animal subject are also provided for the treatment disease.
  [FR] La présente invention concerne de nouveaux composés d'isoquinoline, des compositions, ainsi que leur application en tant que produits pharmaceutiques pour traiter des maladies. Elle concerne également des procédés permettant d'inhiber l'activité d'oxyde nitrique synthase chez un sujet humain ou animal afin de traiter des maladies.