2-bromo-N-(4-bromo-2-methylphenyl)acetamide

• 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: 2-bromo-N-(4-bromo-2-methylphenyl)acetamide
• 化学式: C₉H₉Br₂NO
• mdl: MFCD02974393
• 分子量: 306.985
• InChiKey: SDGIGHAMXMUCHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

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-bromo-N-(4-bromo-2-methylphenyl)acetamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以60%的产率得到2-(1-{2-[(4-bromo-2-methylphenyl)amino]-2-oxoethyl}piperidin-4-yl)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：

  溴乙酰氯 、 2-甲基-4-溴苯胺 在 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 2-bromo-N-(4-bromo-2-methylphenyl)acetamide
  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

• Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line
  作者：Naheed Akhter、Sidra Batool、Samreen Gul Khan、Nasir Rasool、Fozia Anjum、Azhar Rasul、Şevki Adem、Sadaf Mahmood、Aziz ur Rehman、Mehr un Nisa、Zainib Razzaq、Jørn B. Christensen、Mohammed A. S. Abourehab、Syed Adnan Ali Shah、Syahrul Imran

  DOI：10.3390/ph16020211

  日期：——

  the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of −176.749 kcal/mol and −170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively

  基于三唑的乙酰胺是各种药理活性药物的重要支架。在目前的工作中，通过化学修饰 2-(4-异丁基苯基)丙酸提供了 1,2,4-三唑和乙酰胺的结构杂化物 (1)。通过在不同的反应条件下将化合物 1 的三唑与不同的亲电子试剂偶联，以相当大的产率 (70-76%) 生成了目标化合物 7a-f。这些三唑偶联的乙酰胺衍生物通过理化和光谱（HRMS、FTIR、13CNMR 和 1HNMR）方法进行了验证。研究了所有衍生物对 HepG2 细胞系的抗肝癌作用。邻位有两个甲基的化合物7f在所有化合物中表现出最高的抗增殖活性，IC50值为16.782 µg/mL。 7f是最有效的抗癌分子，其毒性也非常低，为1.190.02%。分子对接表明，所有化合物，尤其是7f，对c-kit酪氨酸激酶和蛋白激酶B分别表现出优异的结合亲和力，分别为-176.749 kcal/mol和-170.066 kcal/mol。化合物7f被认为是最适合治疗肝细胞癌的药物药效团。
• 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.