3-amino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one | 248246-95-9

• 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: 3-amino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one
• 英文别名: 3-amino-4-[(3,5-dimethylphenyl)methyl]-5-ethyl-6-methyl-1H-pyridin-2-one
• CAS: 248246-95-9
• 化学式: C₁₇H₂₂N₂O
• 分子量: 270.374
• InChiKey: PVZMRETVOJGNDW-UHFFFAOYSA-N

物化性质

• 熔点：
  204-205 °C
• 沸点：
  474.1±45.0 °C(Predicted)
• 密度：
  1.066±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-amino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one 在 聚合甲醛 、 sodium cyanoborohydride 作用下， 以 溶剂黄146 、 乙腈 为溶剂， 以91%的产率得到3-dimethylamino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2-(1H)-one
  参考文献：
  名称：

  3-(Amino- or aminoalkyl)pyridinone derivatives and their use for the treatment of HIV related diseases

  摘要：

  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。

  公开号：

  US06451822B1
• 作为产物：
  描述：

  3,5-二甲基溴苄 在 盐酸 、 正丁基锂 、 四甲基乙二胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 17.0h， 生成 3-amino-4-(3,5-dimethylbenzyl)-5-ethyl-6-methylpyridin-2(1H)-one
  参考文献：
  名称：

  Synthesis and Antiviral Activity of 4-Benzyl Pyridinone Derivatives as Potent and Selective Non-Nucleoside Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm0009437

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 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。
• 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：US06683079B2

  公开（公告）日：2004-01-27

  3-(amino- or aminoalkyl) pyridinone derivatives having the formula (1) wherein Q, X, Y, and R3-R6 are as defined, which derivatives are useful for the treatment of HIV related diseases.

  具有以下公式（1）的3-（氨基或氨基烷基）吡啶酮衍生物，其中Q，X，Y和R3-R6如定义所述，这些衍生物对于治疗与HIV相关的疾病是有用的。
• 4-Benzyl and 4-Benzoyl-3-dimethylaminopyridin-2(1<i>H</i>)-ones:  In Vitro Evaluation of New C-3-Amino-Substituted and C-5,6-Alkyl-Substituted Analogues against Clinically Important HIV Mutant Strains
  作者：Abdellah Benjahad、Martine Croisy、Claude Monneret、Emile Bisagni、Dominique Mabire、Sophie Coupa、Alain Poncelet、Imre Csoka、Jérôme Guillemont、Christophe Meyer、Koen Andries、Rudi Pauwels、Marie-Pierre de Béthune、Daniel M. Himmel、Kalyan Das、Eddy Arnold、Chi Hung Nguyen、David S. Grierson

  DOI：10.1021/jm0408621

  日期：2005.3.1

  In a program to optimize the anti-HIV activity of the 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 9 and 10, lead compounds in a new class of highly potent non-nucleoside type inhibitors of HIV-1 reverse transcriptase, modification of the alkyl substitutents at the C-5 and C-6 positions on the pyridinone ring and of the substitutents on the C-3 amino group has been studied. Of the 17 new 5/6-modified analogues prepared, compounds 31b and 32b substituted at C-5 by an extended nonpolar chain containing an ether function and a C-6 methyl group and compound 35 bearing a C-5 ethyl/C-6 hydroxymethyl substituent pattern were selected on the basis of their in vitro activity against wild-type HIV and the three principle mutant strains, K103N, Y181C, and Y188L. When tested further, it was shown that these molecules, and in particular compound 35, are globally more active than 9, 10, and efavirenz against an additional eight single [L100I, K101E, V106A, E138K, V179E, G190A/S, and F227C] and four double HIV mutant strains [L1001 + K103N, K101E + K103N, K103N + Y181C, and F227L + V106A] which are clinically relevant. Concerning modulation of the N-3 substituent, 36 new analogues were prepared. Of these, the N-methyl-N-(2-methoxyethyl)-substituted compounds 40, 42, and 62, as well as the doubly modified compounds 77a and 77b, were selected from the initial screen and were subsequently shown to be active at sub-micromolar concentrations (IC50'S) against all the other mutant strains except K103N + Y181C and F227L + V106A. Two possible, but distinct, modes of binding of these analogues in RT were suggested from molecular modeling studies. The preferred mode of binding for compound 62, corresponding to the predicted "orientation 1", was revealed in the X-ray crystal structure of the compound 62-RT complex.
• Synthesis and Evaluation of “AZT-HEPT”, “AZT-Pyridinone”, and “ddC-HEPT” Conjugates as Inhibitors of HIV Reverse Transcriptase
  作者：Renée Pontikis、Valérie Dollé、Jean Guillaumel、Elsa Dechaux、Reine Note、Chi Hung Nguyen、Michel Legraverend、Emile Bisagni、Anne-Marie Aubertin、David S. Grierson、Claude Monneret

  DOI：10.1021/jm991125l

  日期：2000.5.1

  To test the concept that HIV reverse transcriptase could be effectively inhibited by "mixed site inhibitors", a series of seven conjugates containing both a nucleoside analogue component(AZT 1, ddC 2) and a nonnucleoside type inhibitor (HEPT analogue 12, pyridinone 27) were synthesized and evaluated for their ability to block HIV replication. The (N-3 and C-5)AZT-HEPT conjugates 15, 22, and 23 displayed 2-5 mu M anti-HIV activity, but they had no effect on the replication of HIV-2 or the HIV-1 strain with the Y181C mutation. The (C-5)AZT-pyridinone conjugates 34-37 were found to be inactive. In marked contrast, the ddC-HEPT molecule 26 displayed the same potency (EC50 = 0.45 mu M) against HTV-1 (wild type and the Y181C nevirapine-resistant strain) and HIV-2 in cell culture. No synergistic effect was-observed for these bis-substrate inhibitors, suggesting that the two individual inhibitor components in these molecules do not bind simultaneously in their respective sites. Interestingly, however, the results indicate that the AZT-HEPT conjugates and the ddC-HEPT derivative 26 inhibit reverse transcriptase (RT) in an opposite manner. One explanation for this difference is that the former compounds interact preferentially with the hydrophobic pocket in RT, whereas 26 (after supposed triphosphorylation) inhibits RT through binding in the catalytic site.
• 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