2-溴-N-(4-氟-2-甲基苯基)乙酰胺 | 630119-74-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-溴-N-(4-氟-2-甲基苯基)乙酰胺
• 英文名称: 2-bromo-N-(2-methyl-4-fluorophenyl)acetamide
• 英文别名: 2-bromo-N-(4-fluoro-2-methylphenyl)acetamide
• CAS: 630119-74-3
• 化学式: C₉H₉BrFNO
• mdl: MFCD18839933
• 分子量: 246.079
• InChiKey: YKEYVYAJKGROJU-UHFFFAOYSA-N

物化性质

• 沸点：
  336.9±37.0 °C(Predicted)
• 密度：
  1.575±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1',2',3',4',5',6'-hexahydro-2'H-[2,4'-bipyridine] N-oxide 、 2-溴-N-(4-氟-2-甲基苯基)乙酰胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 2-(1-{2-[(4-fluoro-2-methylphenyl)amino]-2-oxoethyl}-4-piperidinyl)pyridinium N-oxide
  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
• 作为产物：
  描述：

  4-氟-2-甲基苯胺 生成 2-溴-N-(4-氟-2-甲基苯基)乙酰胺
  参考文献：
  名称：

  Acetamides and benzamides that are useful in treating sexual dysfunction

  摘要：

  本发明涉及使用式(I)的化合物治疗性功能障碍，以及含有式(I)化合物的组合物用于治疗性功能障碍。

  公开号：

  US20040029887A1

文献信息

• ACETAMIDES AND BENZAMIDES THAT ARE USEFUL IN TREATING SEXUAL DYSFUNCTION
  申请人：Abbott Laboratories

  公开号：EP1509213A2

  公开（公告）日：2005-03-02
• US7528134B2
  申请人：——

  公开号：US7528134B2

  公开（公告）日：2009-05-05
• [EN] ACETAMIDES AND BENZAMIDES THAT ARE USEFUL IN TREATING SEXUAL DYSFUNCTION<br/>[FR] ACETAMIDES ET BENZAMIDES UTILISES DANS LE TRAITEMENT D'UNE DYSFONCTION SEXUELLE
  申请人：ABBOTT LAB

  公开号：WO2003099266A2

  公开（公告）日：2003-12-04

  The present invention relates to the use of compounds of formula (I), for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
• Acetamides and benzamides that are useful in treating sexual dysfunction
  申请人：——

  公开号：US20040029887A1

  公开（公告）日：2004-02-12

  The present invention relates to the use of compounds of formula (I) 1 for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.

  本发明涉及使用式(I)的化合物治疗性功能障碍，以及含有式(I)化合物的组合物用于治疗性功能障碍。
• 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.