6-fluoro-8-(1,3,5-trimethyl-1H-pyrazol-4-yl)chroman-2-carboxylic acid | 1206912-72-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 6-fluoro-8-(1,3,5-trimethyl-1H-pyrazol-4-yl)chroman-2-carboxylic acid
• 英文别名: 6-fluoro-8-(1,3,5-trimethylpyrazol-4-yl)-3,4-dihydro-2H-chromene-2-carboxylic acid
• CAS: 1206912-72-2
• 化学式: C₁₆H₁₇FN₂O₃
• 分子量: 304.321
• InChiKey: LEPUWIILSCNQHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(4-methoxytetrahydro-2H-pyran-4-yl)pyridin-3-amine 、 6-fluoro-8-(1,3,5-trimethyl-1H-pyrazol-4-yl)chroman-2-carboxylic acid 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 2.0h， 以65.3%的产率得到6-fluoro-N-(6-(4-methoxytetrahydro-2H-pyran-4-yl)pyridin-3-yl)-8-(1,3,5-trimethyl-1H-pyrazol-4-yl)chroman-2-carboxamide
  参考文献：
  名称：

  De Novo Design of a Picomolar Nonbasic 5-HT_1B Receptor Antagonist

  摘要：

  We describe herein the discovery of novel, de novo designed, 5-HT1B receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT1B antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT1B receptor.

  DOI：

  10.1021/jm901200t
• 作为产物：
  描述：

  6-fluoro-4-hydroxy-8-(1,3,5-trimethyl-1H-pyrazol-4-yl)chroman-2-carboxylic acid 在 三乙基硅烷 、 三氟乙酸 作用下， 反应 3.0h， 以55%的产率得到6-fluoro-8-(1,3,5-trimethyl-1H-pyrazol-4-yl)chroman-2-carboxylic acid
  参考文献：
  名称：

  De Novo Design of a Picomolar Nonbasic 5-HT_1B Receptor Antagonist

  摘要：

  We describe herein the discovery of novel, de novo designed, 5-HT1B receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT1B antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT1B receptor.

  DOI：

  10.1021/jm901200t

文献信息

• De Novo Design of a Picomolar Nonbasic 5-HT_1B Receptor Antagonist
  作者：David A. Nugiel、Jennifer R. Krumrine、Daniel C. Hill、James R. Damewood、Peter R. Bernstein、Cynthia D. Sobotka-Briner、JianWei Liu、Anna Zacco、M. Edward Pierson

  DOI：10.1021/jm901200t

  日期：2010.2.25

  We describe herein the discovery of novel, de novo designed, 5-HT1B receptor antagonists that lack a basic moiety and that provide improved hERG and in vitro phospholipidosis profiles. We used a known 5-HT1B antagonist template as our starting point and focused on replacing the piperazine moiety. Pyrazole-based ideas were designed and synthesized among a small library of piperazine replacements. To our knowledge, these are the first potent, nonbasic, functionally active antagonists of the 5-HT1B receptor.