3-Methyl-N-[(4-phenylpiperidin-1-yl)methyl]benzamide | 918408-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-Methyl-N-[(4-phenylpiperidin-1-yl)methyl]benzamide
• CAS: 918408-28-3
• 化学式: C₂₀H₂₄N₂O
• 分子量: 308.423
• InChiKey: ALZFDRFMVFNHJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-甲基马尿酸 在 copper diacetate 、 三乙胺 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 18.0h， 生成 3-Methyl-N-[(4-phenylpiperidin-1-yl)methyl]benzamide
  参考文献：
  名称：

  Discovery of 3-Methyl-N-(1-oxy-3‘,4‘,5‘,6‘-tetrahydro-2‘H-[2,4‘-bipyridine]-1‘-ylmethyl)benzamide (ABT-670), an Orally Bioavailable Dopamine D₄ Agonist for the Treatment of Erectile Dysfunction

  摘要：

  The goal of this study was to identify a structurally distinct D-4-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl) piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl) piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein.

  DOI：

  10.1021/jm060662k

文献信息

• Discovery of 3-Methyl-<i>N</i>-(1-oxy-3‘,4‘,5‘,6‘-tetrahydro-2‘<i>H</i>-[2,4‘-bipyridine]-1‘-ylmethyl)benzamide (ABT-670), an Orally Bioavailable Dopamine D₄ Agonist for the Treatment of Erectile Dysfunction
  作者：Meena V. Patel、Teodozyj Kolasa、Kathleen Mortell、Mark A. Matulenko、Ahmed A. Hakeem、Jeffrey J. Rohde、Sherry L. Nelson、Marlon D. Cowart、Masaki Nakane、Loan N. Miller、Marie E. Uchic、Marc A. Terranova、Odile F. El-Kouhen、Diana L. Donnelly-Roberts、Marian T. Namovic、Peter R. Hollingsworth、Renjie Chang、Brenda R. Martino、Jill M. Wetter、Kennan C. Marsh、Ruth Martin、John F. Darbyshire、Gary Gintant、Gin C. Hsieh、Robert B. Moreland、James P. Sullivan、Jorge D. Brioni、Andrew O. Stewart

  DOI：10.1021/jm060662k

  日期：2006.12.1

  The goal of this study was to identify a structurally distinct D-4-selective agonist with superior oral bioavailability to our first-generation clinical candidate 1a (ABT-724) for the potential treatment of erectile dysfunction. Arylpiperazines such as (heteroarylmethyl) piperazine 1a, benzamide 2, and acetamides such as 3a,b exhibit poor oral bioavailability. Structure-activity relationship (SAR) studies with the arylpiperidine template provided potent partial agonists such as 4d and 5k that demonstrated no improvement in oral bioavailability. Further optimization with the (N-oxy-2-pyridinyl) piperidine template led to the discovery of compound 6b (ABT-670), which exhibited excellent oral bioavailability in rat, dog, and monkey (68%, 85%, and 91%, respectively) with comparable efficacy, safety, and tolerability to 1a. The N-oxy-2-pyridinyl moiety not only provided the structural motif required for agonist function but also reduced metabolism rates. The SAR study leading to the discovery of 6b is described herein.