6-methyl-5-propyl-2-pyridone | 80675-95-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-methyl-5-propyl-2-pyridone
• 英文别名: 6-methyl-5-propyl-1H-pyridin-2-one；2-Oxo-6-methyl-5-propyl-1,2-dihydro-pyridin；6-Methyl-5-propyl-<2>pyridon；6-Methyl-5-propyl-2-pyridon；6-Methyl-5-propyl-pyridon-2；6-methyl-5-propyl-1H-pyridin-2-one
• CAS: 80675-95-2
• 化学式: C₉H₁₃NO
• 分子量: 151.208
• InChiKey: QYRHCPANHPUSTN-UHFFFAOYSA-N

物化性质

• 熔点：
  129-130 °C
• 沸点：
  318.6±15.0 °C(Predicted)
• 密度：
  0.971±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  6-methyl-5-propyl-2-pyridone 在 镍 盐酸 、 正丁基锂 、 四甲基乙二胺 、 硫酸 、 苄基三乙基氯化铵 、 氢气 、 硝酸 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 80.0 ℃ 、202.65 kPa 条件下， 反应 23.0h， 生成 3-amino-4-[(3,5-dimethylphenyl)methyl]-6-methyl-5-propyl-1H-pyridin-2-one
  参考文献：
  名称：

  4-Benzyl and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones:  In Vitro Evaluation of New C-3-Amino-Substituted and C-5,6-Alkyl-Substituted Analogues against Clinically Important HIV Mutant Strains

  摘要：

  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.

  DOI：

  10.1021/jm0408621
• 作为产物：
  描述：

  2-己酮 在 盐酸 、 sodium methylate 、 哌啶乙酸盐 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 反应 75.5h， 生成 6-methyl-5-propyl-2-pyridone
  参考文献：
  名称：

  2-吡啶酮衍生物作为HIV-1特异性逆转录酶抑制剂的合成和评估。1.邻苯二甲酰亚胺基烷基和-烷基氨基类似物。

  摘要：

  一种有效的（IC50 = 30 nM）特异性非核苷HIV-1逆转录酶（RT）抑制剂3- [N-（邻苯二甲酰亚胺甲基）氨基] -5-乙基-6-甲基吡啶-2（1H）-一（1）是通过体外筛选程序发现的。该化合物不会抑制（IC50> 300微米）其他DNA和RNA聚合酶，包括HIV-2 RT和SIV-RT。不幸的是，这种（氨基甲基）邻苯二甲酰亚胺的水解不稳定性不能用作抗病毒剂。在本系列的第一篇论文中，描述了初步开发工作，该工作生产了乙基邻苯二甲酰亚胺20，该水解稳定的化合物具有降低的HIV-1 RT抑制活性（100倍）和在H9细胞中的抗病毒活性弱（CIC95 = 40 microM）。结构活性研究表明了5-乙基的重要性，吡啶酮环上的6-甲基取代基图案以及在吡啶酮和邻苯二甲酰亚胺杂环之间需要一个灵活的两个原子的连接基。这些引线1和20为进一步开发这种抑制剂结构类型提供了基础，从中选择了几种化合物（随附报告的主题）进行临床评估。

  DOI：

  10.1021/jm00099a006

文献信息

• [EN] NITROGEN CONTAINING 2,3-DIHYDROQUINAZOLINONE COMPOUNDS AS NAV1.8 INHIBITORS<br/>[FR] COMPOSÉS 2,3-DIHYDROQUINAZOLINE CONTENANT DE L'AZOTE SERVANT D'INHIBITEURS DE NAV1.8
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2022129281A1

  公开（公告）日：2022-06-23

  Compounds of formula (I) are described, wherein each of the variable groups is as defined in the specification. Also described are pharmaceutical compositions containing a compound of formula (I), and uses of the compounds and pharmaceutical compositions for inhibiting Nav1.8 voltage-gated sodium channels and treating Nav1.8 mediated diseases, disorders, and conditions, such as pain and pain-associated diseases, disorders, and conditions and cardiovascular diseases, disorders, and conditions, such as atrial fibrillation.

  本文描述了公式(I)的化合物，其中每个变量组的定义如规范中所述。还描述了含有公式(I)化合物的制药组合物，以及使用这些化合物和制药组合物来抑制Nav1.8电压门控钠通道并治疗Nav1.8介导的疾病、障碍和病症，如疼痛和与疼痛相关的疾病、障碍和病症以及心血管疾病、障碍和病症，如心房颤动。
• Pilipenko, V. S.; Shusherina, N. P., Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, p. 1891 - 1893
  作者：Pilipenko, V. S.、Shusherina, N. P.

  DOI：——

  日期：——
• SHUSHERINA N. P.; PILIPENKO V. S.; BENTANELI L. V., ZH. ORGAN. XIMII, 1979, 15, HO 6, 1277-1281
  作者：SHUSHERINA N. P.、 PILIPENKO V. S.、 BENTANELI L. V.

  DOI：——

  日期：——
• PILIPENKO V. S.; ALIMIRZOEV F. A.; STEPANYANTS A. U., ZH. ORGAN. XIMII, 1979, 15, HO 12, 2586-2590
  作者：PILIPENKO V. S.、 ALIMIRZOEV F. A.、 STEPANYANTS A. U.

  DOI：——

  日期：——
• PILIPENKO, V. S.;SHUSHERINA, N. P., ZH. ORGAN. XIMII, 1981, 17, N 10, 2122-2125
  作者：PILIPENKO, V. S.、SHUSHERINA, N. P.

  DOI：——

  日期：——