Methyl 3-[(2-cyanoacetyl)amino]-4-methylbenzoate | 1314804-47-1

• 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: Methyl 3-[(2-cyanoacetyl)amino]-4-methylbenzoate
• 英文别名: methyl 3-[(2-cyanoacetyl)amino]-4-methylbenzoate
• CAS: 1314804-47-1
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: BZUFBIOBBYRSGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.63
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  79.19
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Methyl 3-[(2-cyanoacetyl)amino]-4-methylbenzoate 在 N-氯代丁二酰亚胺 、 sodium methylate 、 potassium carbonate 、 二硫代磷酸二乙酯 作用下， 以 1,4-二氧六环 、 水 、 异丙醇 为溶剂， 反应 24.33h， 生成
  参考文献：
  名称：

  Substituted N -aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

  摘要：

  A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (> 90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-alpha in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.006
• 作为产物：
  描述：

  3-氨基-4-甲基苯甲酸甲酯 、 氰乙酸甲酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 以42%的产率得到Methyl 3-[(2-cyanoacetyl)amino]-4-methylbenzoate
  参考文献：
  名称：

  Substituted N -aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors

  摘要：

  A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (> 90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-alpha in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.006

文献信息

• Substituted N -aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors
  作者：Balekudru Devadas、Shaun R. Selness、Li Xing、Heather M. Madsen、Laura D. Marrufo、Huey Shieh、Dean M. Messing、Jerry Z. Yang、Heidi M. Morgan、Gary D. Anderson、Elizabeth G. Webb、Jian Zhang、Rajesh V. Devraj、Joseph B. Monahan

  DOI：10.1016/j.bmcl.2011.05.006

  日期：2011.7

  A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (> 90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-alpha in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model. (C) 2011 Elsevier Ltd. All rights reserved.