N-({trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutyl}methyl)-N-methylacetamide | 1337536-66-9

• 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: N-({trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutyl}methyl)-N-methylacetamide
• CAS: 1337536-66-9
• 化学式: C₁₉H₂₇ClN₂O
• 分子量: 334.889
• InChiKey: LQOGSAVOXSCLHL-RZDIXWSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.91
• 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：
  0.63
• 拓扑面积：
  23.55
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  N-({trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutyl}methyl)-N-methylacetamide 在 盐酸 作用下， 以 乙醚 、 乙酸乙酯 为溶剂， 以99%的产率得到N-({trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutyl}methyl)-N-methylacetamide hydrochloroic 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：

  4-溴-2-氯苯甲酸 在 Wilkinson's catalyst 、 正丁基锂 、 硼烷四氢呋喃络合物 、 氢气 、 1-丙基磷酸酐 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， -78.0~75.0 ℃ 、310.27 kPa 条件下， 反应 76.92h， 生成 N-({trans-3-[3-chloro-4-(pyrrolidin-1-ylmethyl)phenyl]-cyclobutyl}methyl)-N-methylacetamide
  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

文献信息

• Discovery of Two Clinical Histamine H₃ Receptor Antagonists: <i>trans</i>-<i>N</i>-Ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and <i>trans</i>-3-Fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-<i>N</i>-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764)
  作者：Travis T. Wager、Betty A. Pettersen、Anne W. Schmidt、Douglas K. Spracklin、Scot Mente、Todd W. Butler、Harry Howard、Daniel J. Lettiere、David M. Rubitski、Diane F. Wong、Frank M. Nedza、Frederick R. Nelson、Hans Rollema、Jeffrey W. Raggon、Jiri Aubrecht、Jody K. Freeman、John M. Marcek、Julie Cianfrogna、Karen W. Cook、Larry C. James、Linda A. Chatman、Philip A. Iredale、Michael J. Banker、Michael L. Homiski、Jennifer B. Munzner、Rama Y. Chandrasekaran

  DOI：10.1021/jm200939b

  日期：2011.11.10

  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.