5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine | 197229-98-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine
• 英文别名: N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)-2,2-dimethylpropanamide
• CAS: 197229-98-4
• 化学式: C₁₄H₂₂N₂O₂
• 分子量: 250.341
• InChiKey: YNOHDVUYAXBTFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine 在 盐酸 、 正丁基锂 、 四甲基乙二胺 、 溶剂黄146 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 3-amino-4-[(2,3-dimethylphenyl)methyl]-5-ethyl-6-methyl-1H-pyridin-2-one
  参考文献：
  名称：

  4-Benzyl- and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones, a New Family of Potent Anti-HIV Agents:  Optimization and in Vitro Evaluation against Clinically Important HIV Mutant Strains

  摘要：

  The 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 13 and 14 are representatives of a new class of highly potent non nucleoside type inhibitors of HIV-1 reverse transcriptase. To conduct SAR studies on these two lead compounds, 102 new analogues were prepared. Thirty-three compounds displayed nanomolar range activity in vitro against wild-type HIV-1, and among these, 18 were active against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1 muM. Evaluation of this group of analogues against an additional eight single [100I, 101E, 106A, 138K, 179E, 190A, 190S, 227C] and four double HIV mutant strains [100I + 103N, 101E + 103N, 103N + 181C, and 227L + 106A], which are often present in HIV infected patients, permitted the selection of eight compounds, 17x, 18b, 18c, 18f, 18g, 27, 30, and 42, which are globally more active than the lead molecules 13/14, emivirine and the currently used NNRTI, nevirapine. Further comparison of the 3'-CN-substituted benzoylpyridinone compound 18c, and the corresponding 3'-acrylonitrile-substituted analogue 30, to efavirenz, the reference molecule in anti-HIV therapy today, revealed that the pyridinone analogues displayed a superior inhibition profile in the in vitro cellular assay system. These results form a solid basis for continued optimization of the pyridinone series.

  DOI：

  10.1021/jm0407658
• 作为产物：
  描述：

  吡啶,2-氯-5-乙基-6-甲基-3-硝基- 在 palladium on activated charcoal 氢气 、 氧气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 144.25h， 生成 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine
  参考文献：
  名称：

  吡啶-2（1 H）-one衍生物4-C-烷基化的研究

  摘要：

  为了获得4-C-烷基化的吡啶-2（1 H）-1 ，研究了两种策略：基本上失效的4-氯-3-硝基吡啶酮衍生物的亲核取代和2-甲氧基-3-新戊酰氨基吡啶的锂化预期的产品。

  DOI：

  10.1016/s0040-4020(97)00771-0

文献信息

• 3-(Amino- or aminoalkyl)pyridinone derivatives and their use for the treatment of HIV related diseases
  申请人：Centre National de la Recherche Scientifique

  公开号：US06451822B1

  公开（公告）日：2002-09-17

  The present invention is concerned with 3-(amino- or aminoalkyl)pyridinone derivatives which inhibit the reverse transcriptase of the Human Immunodeficiency Virus (HIV). It relates moreover to the use of such compounds for treating HIV-related diseases. Furthermore it relates to a process for the preparation of these compounds.

  本发明涉及3-（氨基或氨基烷基）吡啶酮衍生物，其抑制人类免疫缺陷病毒（HIV）的反转录酶。此外，本发明还涉及使用这些化合物治疗与HIV相关的疾病。此外，本发明还涉及一种用于制备这些化合物的方法。
• 3-(Amino-or aminoalkyl) pyridinone derivatives and their use for the treatment of HIV related diseases
  申请人：Centre National De La Recherche Scient.

  公开号：US20030125340A1

  公开（公告）日：2003-07-03

  3-(amino- or aminoalkyl) pyridinone derivatives having the formula (1) 1 wherein Q, X, Y, and R 3 -R 6 are as defined, which derivatives are useful for the treatment of HIV related diseases.

  具有以下式子（1）的3-（氨基或氨基烷基）吡啶酮衍生物，其中Q、X、Y和R3-R6如定义，这些衍生物对于治疗与HIV相关的疾病是有用的。
• Synthesis and Antiviral Activity of 4-Benzyl Pyridinone Derivatives as Potent and Selective Non-Nucleoside Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors
  作者：Valérie Dollé、Chi Hung Nguyen、Michel Legraverend、Anne-Marie Aubertin、André Kirn、Marie Line Andreola、Michel Ventura、Laura Tarrago-Litvak、Emile Bisagni

  DOI：10.1021/jm0009437

  日期：2000.10.1

  Several 4-benzyl analogues of 5-ethyl-6-methyl-4-(phenylthio)pyridin-2(1H)-ones were synthesized and evaluated for their anti-HIV-l activities. Key transformations include metalation at the 4-C-position of 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine (5) and its coupling with benzyl bromide or benzaldehyde derivatives. Biological studies revealed that some of the new 4-benzylpyridinones show potent HIV-1 specific reverse transcriptase inhibitory properties. Compounds 14, 19, and 27, which inhibit the replication of HIV-1 in CEM-SS cells, with IC50 values ranging from 0.2 to 6 nM are the most active compounds in this series. Biochemical studies showed that compound 27 strongly inhibited the activity of a recombinant HIV-1 RT. Moreover, the infectivity of isolated HIV-1 particles was severely decreased after exposure to compound 27. Although cross resistance is frequently observed between non-nucleoside reverse transcriptase inhibitors, compound 27 was capable of inhibiting a virus resistant to nevirapine with an IC50 Of 40 nM.
• 3-(AMINO- OR AMINOALKYL)PYRIDINONE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF HIV RELATED DISEASES
  申请人：CENTRE NATIONAL DELA RECHERCHE SCIENTIFIQUE

  公开号：EP1073637A1

  公开（公告）日：2001-02-07
• US6451822B1
  申请人：——

  公开号：US6451822B1

  公开（公告）日：2002-09-17