cis-N-ethyl-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-3-hydroxycyclobutanecarboxamide | 1393090-79-3

• 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: cis-N-ethyl-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-3-hydroxycyclobutanecarboxamide
• CAS: 1393090-79-3
• 化学式: C₁₈H₂₅FN₂O₂
• 分子量: 320.407
• InChiKey: XTDYJHUJRDWQKU-UJKQEGAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  52.57
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  cis-N-ethyl-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-3-hydroxycyclobutanecarboxamide 、 对甲苯磺酸 在 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 19.33h， 以5.59 g的产率得到N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide,4-methylbenzenesulfonic acid
  参考文献：
  名称：

  Discovery of Two Clinical Histamine H₃ Receptor Antagonists: trans-N-Ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-Fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764)

  摘要：

  The discovery of two histamine H-3 antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-03654746) and 7 (PF-03654764) required five hypothesis driven design cycles. The key to success in identifying these clinical candidates was the development of a compound design strategy that leveraged medicinal chemistry knowledge and traditional assays in conjunction with computational and in vitro safety tools. Overall, clinical compounds 6 and 7 exceeded conservative safety margins and possessed optimal pharmacological and pharmacokinetic profiles, thus achieving our initial goal of identifying compounds with fully aligned oral drug attributes, "best-in-class" molecules.

  DOI：

  10.1021/jm200939b
• 作为产物：
  描述：

  1-(4-溴-2-氟苯甲基)吡咯烷 在 正丁基锂 、 1-丙基磷酸酐 作用下， 以 四氢呋喃 、 正己烷 、 乙酸乙酯 为溶剂， 反应 18.42h， 生成 cis-N-ethyl-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-3-hydroxycyclobutanecarboxamide
  参考文献：
  名称：

  Discovery of Two Clinical Histamine H₃ Receptor Antagonists: trans-N-Ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-Fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764)

  摘要：

  The discovery of two histamine H-3 antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-03654746) and 7 (PF-03654764) required five hypothesis driven design cycles. The key to success in identifying these clinical candidates was the development of a compound design strategy that leveraged medicinal chemistry knowledge and traditional assays in conjunction with computational and in vitro safety tools. Overall, clinical compounds 6 and 7 exceeded conservative safety margins and possessed optimal pharmacological and pharmacokinetic profiles, thus achieving our initial goal of identifying compounds with fully aligned oral drug attributes, "best-in-class" molecules.

  DOI：

  10.1021/jm200939b