4-amino-3-benzoyl-6-ethyl-2-methylpyridine | 144291-69-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-amino-3-benzoyl-6-ethyl-2-methylpyridine
• 英文别名: (4-amino-6-ethyl-2-methylpyridin-3-yl)-phenylmethanone
• CAS: 144291-69-0
• 化学式: C₁₅H₁₆N₂O
• 分子量: 240.305
• InChiKey: IYMZNJFPHPAHCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  56
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-amino-3-benzoyl-6-ethyl-2-methylpyridine 、 氰乙酸 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 乙酸乙酯 为溶剂， 反应 0.17h， 生成 7-ethyl-5-methyl-2-oxo-4-phenyl-1,2-dihydro-1,6-naphthyridine-3-carbonitrile
  参考文献：
  名称：

  Structure Guided Lead Generation for M. tuberculosis Thymidylate Kinase (Mtb TMK): Discovery of 3-Cyanopyridone and 1,6-Naphthyridin-2-one as Potent Inhibitors

  摘要：

  M. tuberculosis thymidylate kinase (Mtb TMK) has been shown in vitro to be an essential enzyme in DNA synthesis. In order to identify novel leads for Mtb TMK, we performed a high throughput biochemical screen and an NMR based fragment screen through which we discovered two novel classes of inhibitors, 3-cyanopyridones and 1,6-naphthyridin-2-ones, respectively. We describe three cyanopyridone subseries that arose during our hit to lead campaign, along with cocrystal structures of representatives with Mtb TMK. Structure aided optimization of the cyanopyridones led to single digit nanomolar inhibitors of Mtb TMK. Fragment based lead generation, augmented by crystal structures and the SAR from the cyanopyridones, enabled us to drive the potency of our 1,6-naphthyridin-2-one fragment hit from 500 mu M to 200 nM while simultaneously improving the ligand efficiency. Cyanopyridone derivatives containing sulfoxides and sulfones showed cellular activity against M. tuberculosis. To the best of our knowledge, these compounds are the first reports of non-thymidine-like inhibitors of Mtb TMK.

  DOI：

  10.1021/jm5012947
• 作为产物：
  描述：

  3-benzoyl-6-ethyl-2-methyl-4-[(4-methylphenylsulphonyl)amino]pyridine 、 乙氧甲酰基亚甲基三苯基膦 在 钠 、 甲醇 、 水 、 盐酸 、 乙醚 、 乙酸乙酯 、 氯化钠 、 magnesium sulfate 、 丙酮 作用下， 以 邻二甲苯 为溶剂， 反应 8.0h， 以to give 5,7-diethyl-4-methyl-1,6-naphthyridin-2(1H)-one (D) (0.31 g) as a solid, m.p. 220°-223° C.的产率得到4-amino-3-benzoyl-6-ethyl-2-methylpyridine
  参考文献：
  名称：

  1,6-naphthyridone derivatives having angiotensin II antagonist activity

  摘要：

  本发明涉及公式I的药用化合物，其中R.sup.1，R.sup.2，R.sup.3，R.sup.4，Ra，Rb，A，X和Z具有本文中定义的各种含义，以及它们的非毒性盐和含有它们的制药组合物。这些新型化合物在治疗高血压和充血性心力衰竭等疾病方面具有价值。本发明还涉及制造新型化合物的工艺以及在医疗治疗中使用这些化合物的方法。

  公开号：

  US05217976A1

文献信息

• Pyridinyl compounds which are useful as angiotensin II antagonists
  申请人：Imperial Chemical Industries PLC

  公开号：US05236937A1

  公开（公告）日：1993-08-17

  The invention concerns pharmaceutically useful compounds of the formula I, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, Rz, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment. ##STR1##

  该发明涉及公式I的药物有用化合物，其中R.sup.1，R.sup.2，R.sup.3，R.sup.4，R.sup.5，R.sup.6，R.sup.7，Rz，X和Z具有此处定义的各种含义，以及它们的非毒性盐和含有它们的药物组合物。这些新型化合物对于治疗高血压和充血性心力衰竭等病症具有价值。该发明还涉及制造这些新型化合物的过程以及在医疗治疗中使用这些化合物。
• 1,6-naphthyridinone derivatives having angiotension II antagonist
  申请人：Imperial Chemical Industries PLC

  公开号：US05294620A1

  公开（公告）日：1994-03-15

  The invention concerns pharmaceutically useful compounds of the formula I, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, Ra, Rb, A, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.

  本发明涉及公式I的具有药用价值的化合物，其中R.sup.1、R.sup.2、R.sup.3、R.sup.4、Ra、Rb、A、X和Z具有本文中定义的各种含义，以及它们的非毒性盐和含有它们的制药组合物。这些新型化合物在治疗高血压和充血性心力衰竭等疾病方面具有价值。本发明还涉及制造这些新化合物的过程以及在医疗治疗中使用这些化合物的方法。
• Pyridine and quinoline derivatives, processes for their manufacture and their use as angiotensin II antagonists
  申请人：ZENECA LIMITED

  公开号：EP0499415A1

  公开（公告）日：1992-08-19

  The invention concerns pharmaceutically useful compounds of the formula I, in which R¹, R², R³, R⁴, R⁵, R⁶, R⁷, Rz, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.

  本发明涉及式 I 的药用化合物，其中 R¹、R²、R³、R⁴、R⁵、R⁶、R⁷、Rz、X 和 Z 具有本文定义的各种含义，以及它们的无毒盐和含有它们的药物组合物。这些新型化合物具有治疗高血压和充血性心力衰竭等疾病的价值。本发明还涉及新型化合物的生产工艺以及这些化合物在医疗中的应用。
• Naphthyridine derivatives as angiotensin II inhibitors
  申请人：AstraZeneca AB

  公开号：EP0516392B1

  公开（公告）日：2001-08-29
• US5236937A
  申请人：——

  公开号：US5236937A

  公开（公告）日：1993-08-17