N-((8-bromo-5-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)methyl)-N-(3-chlorophenyl)-4-methylthiazole-5-carboxamide | 953066-96-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-((8-bromo-5-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)methyl)-N-(3-chlorophenyl)-4-methylthiazole-5-carboxamide
• 英文别名: N-[(8-bromo-5-fluoro-2-oxo-1H-quinolin-4-yl)methyl]-N-(3-chlorophenyl)-4-methyl-1,3-thiazole-5-carboxamide
• CAS: 953066-96-1
• 化学式: C₂₁H₁₄BrClFN₃O₂S
• 分子量: 506.782
• InChiKey: XBXTXLJHFSAVEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  90.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-((8-bromo-5-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)methyl)-N-(3-chlorophenyl)-4-methylthiazole-5-carboxamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以3%的产率得到N-(3-chlorophenyl)-N-((5-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)methyl)-4-methylthiazole-5-carboxamide
  参考文献：
  名称：

  QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS

  摘要：

  本发明涉及抑制诱导型NOS合酶的新奎诺酮化合物（化学式I），以及合成和使用这些化合物的方法，包括通过向患者施用这些化合物来治疗疾病的抑制或调节一氧化氮合成和/或降低一氧化氮水平的方法。

  公开号：

  US20080139558A1
• 作为产物：
  描述：

  N-(2-bromo-5-fluorophenyl)-3-oxobutanamide 在 硫酸 、 溴 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 51.5h， 生成 N-((8-bromo-5-fluoro-2-oxo-1,2-dihydroquinolin-4-yl)methyl)-N-(3-chlorophenyl)-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

文献信息

• [EN] QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS<br/>[FR] QUINOLONES UTILES EN TANT QU'INHIBITEURS DE L'OXYDE NITRIQUE SYNTHASE INDUCTIBLE
  申请人：KALYPSYS INC

  公开号：WO2007117778A9

  公开（公告）日：2009-05-22