1,2-dihydro-5-<(ethylenedioxy)-ethyl>-1-methyl-2(1H)-pyridone | 162330-26-9

• 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: 1,2-dihydro-5-<(ethylenedioxy)-ethyl>-1-methyl-2(1H)-pyridone
• 英文别名: 1-methyl-5-(2-methyl-[1,3]dioxolan-2-yl)-1H-pyridin-2-one；1-Methyl-5-(2-methyl-[1,3]dioxolan-2-yl)-1H-pyridin-2-on
• CAS: 162330-26-9
• 化学式: C₁₀H₁₃NO₃
• 分子量: 195.218
• InChiKey: LADFUWSJKUBDRK-UHFFFAOYSA-N

物化性质

• 熔点：
  89-91 °C(Solv: hexane (110-54-3))
• 沸点：
  356.3±42.0 °C(Predicted)
• 密度：
  1.209±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  40.46
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  1,2-dihydro-5-<(ethylenedioxy)-ethyl>-1-methyl-2(1H)-pyridone 在 盐酸 、 正丁基锂 作用下， 反应 6.5h， 生成 (E)-N-tert-butyl-4-<2-(1,2-dihydro-1-methyl-2-oxopyridine-5-yl)-2-methylethenyl>benzamide
  参考文献：
  名称：

  Novel 5α-reductase inhibitors. Synthesis and structure-activity studies of 5-substituted 1-methyl-2-pyridones and 1-methyl-2-piperidones

  摘要：

  In search for nonsteroidal inhibitors of 5 alpha-reductase for the treatment of benign prostatic hyperplasia (BPH) and possibly prostate cancer, substrate mimicks were synthesized comprising of a 1-methyl-2-pyridone (2, 4-16) or 1-methyl-2-piperidone (1, 3, 17-22) moiety (mimicking steroidal ring A) and a diisopropyl (1, 2, (E)-5-(E)-7, (Z)-5-(Z)-7, 11-13, 17-19) or a tert-butyl (3, 4, (E)-8-(E)-10, (Z)-8(Z)-10, 14-16, 20-22) benzamide (mimicking steroidal ring D). The bridge connecting the 5 and 4 positions of the rings consisted of amide (CONH: 1-4), ethenyl (CH=CH, CCH3=CH, CH=CH3: (E)-5-(E)-10, (Z)-5(Z)-10) or ethylene groups (CH2CH2, CHCH3CH2, CH2CHCH3: 11-22). The amides 1-4 were obtained by amidation of the carboxylic acid chlorides with the 4-amino-N-substituted benzamides. The ethenyl compounds (E)-5(E)-10 and (Z)-5-(Z)-10 were synthesized by Wittig reaction of the carbonyl compounds and the corresponding triphenylphosphonium salts and subsequent separation of the stereoisomers. Depending on the time of reaction, catalytic hydrogenation of the ethenyl isomers (E)-5-(E)-10 led to the pyridone-substituted ethylene compounds 11-16 as well as to the piperidone-substituted ethylene compounds 17-22. The 5 alpha-reductase inhibitory properties were determined using rat ventral prostate, as well as human BPH and prostate cancer as source, 1 beta,2 beta-[H-3]testosterone as substrate and a HPLC procedure for the separation of dihydrotestosterone (DHT). Tested at a concentration of 100 mu M, the inhibition values of 1-22 ranged from 0-99%. Significant differences were observed between rat and human enzyme. The most active compound was N,N-diisopropyl-4-[2-(1-methyl-2-oxo-piperidine-5-yl)ethylene]benzamide 17 (IC50: 13 mu M).

  DOI：

  10.1016/0223-5234(94)90104-x
• 作为产物：
  描述：

  3-(2-甲基-1,3-二氧戊环-2-基)吡啶 、 硫酸二甲酯 在 potassium hexacyanoferrate(III) 作用下， 生成 1,2-dihydro-5-<(ethylenedioxy)-ethyl>-1-methyl-2(1H)-pyridone
  参考文献：
  名称：

  Novel 5α-reductase inhibitors. Synthesis and structure-activity studies of 5-substituted 1-methyl-2-pyridones and 1-methyl-2-piperidones

  摘要：

  In search for nonsteroidal inhibitors of 5 alpha-reductase for the treatment of benign prostatic hyperplasia (BPH) and possibly prostate cancer, substrate mimicks were synthesized comprising of a 1-methyl-2-pyridone (2, 4-16) or 1-methyl-2-piperidone (1, 3, 17-22) moiety (mimicking steroidal ring A) and a diisopropyl (1, 2, (E)-5-(E)-7, (Z)-5-(Z)-7, 11-13, 17-19) or a tert-butyl (3, 4, (E)-8-(E)-10, (Z)-8(Z)-10, 14-16, 20-22) benzamide (mimicking steroidal ring D). The bridge connecting the 5 and 4 positions of the rings consisted of amide (CONH: 1-4), ethenyl (CH=CH, CCH3=CH, CH=CH3: (E)-5-(E)-10, (Z)-5(Z)-10) or ethylene groups (CH2CH2, CHCH3CH2, CH2CHCH3: 11-22). The amides 1-4 were obtained by amidation of the carboxylic acid chlorides with the 4-amino-N-substituted benzamides. The ethenyl compounds (E)-5(E)-10 and (Z)-5-(Z)-10 were synthesized by Wittig reaction of the carbonyl compounds and the corresponding triphenylphosphonium salts and subsequent separation of the stereoisomers. Depending on the time of reaction, catalytic hydrogenation of the ethenyl isomers (E)-5-(E)-10 led to the pyridone-substituted ethylene compounds 11-16 as well as to the piperidone-substituted ethylene compounds 17-22. The 5 alpha-reductase inhibitory properties were determined using rat ventral prostate, as well as human BPH and prostate cancer as source, 1 beta,2 beta-[H-3]testosterone as substrate and a HPLC procedure for the separation of dihydrotestosterone (DHT). Tested at a concentration of 100 mu M, the inhibition values of 1-22 ranged from 0-99%. Significant differences were observed between rat and human enzyme. The most active compound was N,N-diisopropyl-4-[2-(1-methyl-2-oxo-piperidine-5-yl)ethylene]benzamide 17 (IC50: 13 mu M).

  DOI：

  10.1016/0223-5234(94)90104-x

文献信息

• Sugasawa; Kirisawa, Pharmaceutical Bulletin, 1955, vol. 3, p. 190,192
  作者：Sugasawa、Kirisawa

  DOI：——

  日期：——