6-benzyloxy-5-bromo-3-pyridinecarboxylic acid | 912454-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-benzyloxy-5-bromo-3-pyridinecarboxylic acid
• 英文别名: 6-benzyloxy-5-bromo-nicotinic acid；6-benzyloxy-5-bromonicotinic acid；5-bromo-6-phenylmethoxypyridine-3-carboxylic acid
• CAS: 912454-75-2
• 化学式: C₁₃H₁₀BrNO₃
• 分子量: 308.131
• InChiKey: HBEYRMVFKRGVHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-benzyloxy-5-bromo-3-pyridinecarboxylic acid 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 、 甲苯 为溶剂， 反应 20.0h， 生成 5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(phenylmethoxy)-3-pyridine carboxamide
  参考文献：
  名称：

  6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

  摘要：

  We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.

  DOI：

  10.1021/jm4010708
• 作为产物：
  描述：

  5-溴-6-羟基烟酸 在 喹啉 、 potassium hydroxide 、 三氯氧磷 作用下， 以 二甲基亚砜 为溶剂， 反应 2.13h， 生成 6-benzyloxy-5-bromo-3-pyridinecarboxylic acid
  参考文献：
  名称：

  6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds

  摘要：

  We identified 6-alkoxy-5-aryl-3-pyridinecarboxamides as potent CB1 receptor antagonists with high selectivity over CB2 receptors. The series was optimized to reduce lipophilicity compared to rimonabant to achieve peripherally active molecules with minimal central effects. Several compounds that showed high plasma exposures in rats were evaluated in vivo to probe the contribution of central vs peripheral CB1 agonism to metabolic improvement. Both rimonabant and 14g, a potent brain penetrant CB1 receptor antagonist, significantly reduced the rate of body weight gain. However, 14h, a molecule with markedly reduced brain exposure, had no significant effect on body weight. PK studies confirmed similarly high exposure of both 14h and 14g in the periphery but 10-fold lower exposure in the brain for 14h. On the basis of these data, which are consistent with reported effects in tissue-specific CB1 receptor KO mice, we conclude that the metabolic benefits of CB1 receptor antagonists are primarily centrally mediated as originally believed.

  DOI：

  10.1021/jm4010708

文献信息

• Pyridine-3-carboxamide derivatives as CB1 inverse agonists
  申请人：Hebeisen Paul

  公开号：US20060229326A1

  公开（公告）日：2006-10-12

  The present invention relates to compounds of the formula wherein X and R 1 to R 8 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of CB1 receptors, such as obesity.

  本发明涉及以下式中的化合物，其中X和R1至R8如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与CB1受体调节相关的疾病，如肥胖症。
• SIX-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
  申请人：Corte James R.

  公开号：US20090181983A1

  公开（公告）日：2009-07-16

  The present invention provides compounds of Formula (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, B, R 3 and R 11 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors or dual inhibitors of fXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

  本发明提供了式（I）的化合物：或其立体异构体，互变异构体，药学上可接受的盐或溶剂形式，其中变量A，B，R3和R11如本文所定义。式（I）的化合物可用作凝血级联和/或接触激活系统的丝氨酸蛋白酶酶的选择性抑制剂；例如凝血酶，因子Xa，因子XIa，因子IXa，因子VIIa和/或血浆卡利肯。具体而言，本发明涉及选择性因子XIa抑制剂或fXIa和血浆卡利肯的双重抑制剂化合物。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗血栓栓塞和/或炎症性疾病的方法。
• WO2007/70818
  申请人：——

  公开号：——

  公开（公告）日：——
• PYRIDINE-3-CARBOXAMIDE DERIVATIVES AS CB1 INVERSE AGONISTS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP1868999A1

  公开（公告）日：2007-12-26
• US7229999B2
  申请人：——

  公开号：US7229999B2

  公开（公告）日：2007-06-12