5-bromo-6-(1-methylethoxy)-3-pyridinecarboxylic acid | 1311275-95-2

• 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: 5-bromo-6-(1-methylethoxy)-3-pyridinecarboxylic acid
• 英文别名: 5-Bromo-6-isopropoxynicotinic acid；5-bromo-6-propan-2-yloxypyridine-3-carboxylic acid
• CAS: 1311275-95-2
• 化学式: C₉H₁₀BrNO₃
• 分子量: 260.087
• InChiKey: ONPIWLDXHFEDIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  5-bromo-6-(1-methylethoxy)-3-pyridinecarboxylic acid 、 (1R,2R)-2-氨基环己醇盐酸盐 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以73%的产率得到5-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(1-methylethoxy)-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-bromo-6-isopropoxynicotinic acid methyl ester 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 5-bromo-6-(1-methylethoxy)-3-pyridinecarboxylic acid
  参考文献：
  名称：

  US2023/124301

  摘要：

  公开号：

文献信息

• [EN] NOVEL OXADIAZOLE COMPOUNDS<br/>[FR] COMPOSÉS INÉDITS D'OXADIAZOLE
  申请人：ABBOTT LAB

  公开号：WO2011071570A1

  公开（公告）日：2011-06-16

  Novel oxadiazole compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions as agonists or antagonists of the S1P family of G protein-coupled receptors for treating diseases associated with modulation of S1P family receptor activity, in particular by affording a beneficial immunosuppressive effect are disclosed.

  新型噁二唑化合物，含有这种化合物的药物组合物以及将这些化合物或组合物用作治疗与调节S1P家族G蛋白偶联受体活性相关的疾病的激动剂或拮抗剂的用途被披露，特别是通过提供有益的免疫抑制作用。
• Novel Oxadiazole Compounds
  申请人：Cusack Kevin P.

  公开号：US20110207704A1

  公开（公告）日：2011-08-25

  Novel oxadiazole compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions as agonists or antagonists of the S1P family of G protein-coupled receptors for treating diseases associated with modulation of S1P family receptor activity, in particular by affording a beneficial immunosuppressive effect are disclosed.

  本发明涉及新型噁二唑类化合物、含有该类化合物的制药组合物，以及将这些化合物或组合物作为S1P家族G蛋白偶联受体的激动剂或拮抗剂，用于治疗与S1P家族受体活性调节相关的疾病，特别是通过提供有益的免疫抑制作用。
• NOVEL OXADIAZOLE COMPOUNDS
  申请人：Abbott Laboratories

  公开号：EP2509424A1

  公开（公告）日：2012-10-17
• 6-Alkoxy-5-aryl-3-pyridinecarboxamides, a New Series of Bioavailable Cannabinoid Receptor Type 1 (CB1) Antagonists Including Peripherally Selective Compounds
  作者：Stephan Röver、Mirjana Andjelkovic、Agnès Bénardeau、Evelyne Chaput、Wolfgang Guba、Paul Hebeisen、Susanne Mohr、Matthias Nettekoven、Ulrike Obst、Wolfgang F. Richter、Christoph Ullmer、Pius Waldmeier、Matthew B. Wright

  DOI：10.1021/jm4010708

  日期：2013.12.27

  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.
• US2023/124301
  申请人：——

  公开号：——

  公开（公告）日：——