Benzoic acid, 2-fluoro-4,5-dimethoxy-, hydrazide | 1260855-26-2

• 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: Benzoic acid, 2-fluoro-4,5-dimethoxy-, hydrazide
• 英文别名: 2-fluoro-4,5-dimethoxybenzohydrazide
• CAS: 1260855-26-2
• 化学式: C₉H₁₁FN₂O₃
• 分子量: 214.196
• InChiKey: BXRSZUVAKVRVEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.45
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  73.58
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Benzoic acid, 2-fluoro-4,5-dimethoxy-, hydrazide 、 在 1-丙基磷酸酐 、 三乙胺 作用下， 反应 1.0h， 生成 2-(2-Fluoro-4,5-dimethoxyphenyl)-5-[2-(1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl]-1,3,4-oxadiazole
  参考文献：
  名称：

  Surveying heterocycles as amide bioisosteres within a series of mGlu7 NAMs: Discovery of VU6019278

  摘要：

  This letter describes a diversity-oriented library approach to rapidly assess diverse heterocycles as bioisosteric replacements for a metabolically labile amide moiety within a series of mGlu(7) negative allosteric modulators (NAMs). SAR rapidly honed in on either a 1,2,4- or 1,3,4-oxadizaole ring system as an effective bioisostere for the amide. Further optimization of the southern region of the mGlu(7) NAM chemotype led to the discovery of VU6019278, a potent mGlu(7) NAM (IC50=501 nM, 6.3% L-AP4 Min) with favorable plasma protein binding (rat f(u)=0.10), low predicted hepatic clearance (rat CLhep=27.7 mL/min/kg) and high CNS penetration (rat K-p=4.9, K-p,K-uu=0.65).

  DOI：

  10.1016/j.bmcl.2019.03.016
• 作为产物：
  描述：

  2-fluoro-4,5-dimethoxybenzoic acid methyl ester 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 Benzoic acid, 2-fluoro-4,5-dimethoxy-, hydrazide
  参考文献：
  名称：

  Surveying heterocycles as amide bioisosteres within a series of mGlu7 NAMs: Discovery of VU6019278

  摘要：

  This letter describes a diversity-oriented library approach to rapidly assess diverse heterocycles as bioisosteric replacements for a metabolically labile amide moiety within a series of mGlu(7) negative allosteric modulators (NAMs). SAR rapidly honed in on either a 1,2,4- or 1,3,4-oxadizaole ring system as an effective bioisostere for the amide. Further optimization of the southern region of the mGlu(7) NAM chemotype led to the discovery of VU6019278, a potent mGlu(7) NAM (IC50=501 nM, 6.3% L-AP4 Min) with favorable plasma protein binding (rat f(u)=0.10), low predicted hepatic clearance (rat CLhep=27.7 mL/min/kg) and high CNS penetration (rat K-p=4.9, K-p,K-uu=0.65).

  DOI：

  10.1016/j.bmcl.2019.03.016