3'-氧代海索比妥 | 427-30-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 3'-氧代海索比妥
• 中文别名: 环丙胺,N-[2-(2,4,6-三甲基苯氧基)乙基]-
• 英文名称: 3'-Ketohexobarbital
• 英文别名: 1,5-dimethyl-5-(3-oxo-cyclohex-1-enyl)-pyrimidine-2,4,6-trione；1,5-dimethyl-5-(3-oxo-cyclohex-1-enyl)-barbituric acid；1,5-Dimethyl-5-(3-oxo-cyclohex-1-enyl)-barbitursaeure；3,5-Dimethyl-5-<3-oxo-cyclohexen-(1)-yl>-barbitursaeure；5-<3-Oxo-cyclohexen-(1)-yl>-3,5-dimethyl-barbitursaeure；3,5-Dimethyl-5-<3-oxo-cyclohexenyl-(1)>-barbitursaeure；3'-Oxohexobarbital；1,5-dimethyl-5-(3-oxocyclohexen-1-yl)-1,3-diazinane-2,4,6-trione
• CAS: 427-30-5
• 化学式: C₁₂H₁₄N₂O₄
• 分子量: 250.254
• InChiKey: JLDHHLBFGIBRGN-UHFFFAOYSA-N

物化性质

• 保留指数：
  2055

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  83.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

3p-羟基己巴比妥已知的人类代谢物包括(2S)-2-氨基-5-[[(2R)-1-(羧甲基氨基)-3-[1-(1,5-二甲基-2,4,6-三氧代-1,3-二氮杂环戊烷-5-基)-3-氧环己基]硫基-1-氧代丙烷-2-基]氨基]-5-氧代戊酸。

3p-Oxohexobarbital has known human metabolites that include (2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-3-[1-(1,5-dimethyl-2,4,6-trioxo-1,3-diazinan-5-yl)-3-oxocyclohexyl]sulfanyl-1-oxopropan-2-yl]amino]-5-oxopentanoic acid.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2933540000

反应信息

• 作为反应物：
  描述：

  3'-氧代海索比妥 在 palladium on activated charcoal 作用下， 生成 5-(3-hydroxy-phenyl)-1,5-dimethyl-barbituric acid
  参考文献：
  名称：

  Tsukamoto et al., Pharmaceutical Bulletin, 1956, vol. 4, p. 371,374

  摘要：

  DOI：
• 作为产物：
  描述：

  Norhexobarbital 在 chromium(VI) oxide 、 sodium hydroxide 、 乙酸酐 作用下， 生成 3'-氧代海索比妥
  参考文献：
  名称：

  Tsukamoto et al., Pharmaceutical Bulletin, 1956, vol. 4, p. 371,374

  摘要：

  DOI：

文献信息

• Characterization of hamster NAD⁺-dependent 3(17)β-hydroxysteroid dehydrogenase belonging to the aldo-keto reductase 1C subfamily
  作者：Satoshi Endo、Misato Noda、Akira Ikari、Kenjiro Tatematsu、Ossama El-Kabbani、Akira Hara、Yukio Kitade、Toshiyuki Matsunaga

  DOI：10.1093/jb/mvv057

  日期：2015.11

  The cDNAs for morphine 6-dehydrogenase (AKR1C34) and its homologous aldo-keto reductase (AKR1C35) were cloned from golden hamster liver, and their enzymatic properties and tissue distribution were compared. AKR1C34 and AKR1C35 similarly oxidized various xenobiotic alicyclic alcohols using NAD+, but differed in their substrate specificity for hydroxysteroids and inhibitor sensitivity. While AKR1C34 showed 3α/17β/20α-hydroxysteroid dehydrogenase activities, AKR1C35 efficiently oxidized various 3β- and 17β-hydroxysteroids, including biologically active 3β-hydroxy-5α/β-dihydro-C19/C21-steroids, dehydroepiandrosterone and 17β-estradiol. AKR1C35 also differed from AKR1C34 in its high sensitivity to flavonoids, which inhibited competitively with respect to 17β-estradiol (Ki 0.11–0.69 μM). The mRNA for AKR1C35 was expressed liver-specific in male hamsters and ubiquitously in female hamsters, whereas the expression of the mRNA for AKR1C34 displayed opposite sexual dimorphism. Because AKR1C35 is the first 3(17)β-hydroxysteroid dehydrogenase in the AKR superfamily, we also investigated the molecular determinants for the 3β-hydroxysteroid dehydrogenase activity by replacement of Val54 and Cys310 in AKR1C35 with the corresponding residues in AKR1C34, Ala and Phe, respectively. The mutation of Val54Ala, but not Cys310Phe, significantly impaired this activity, suggesting that Val54 plays a critical role in recognition of the steroidal substrate.

  从金黄地鼠肝脏中克隆了羟基脱氢酶（AKR1C34）及其同源醛酮还原酶（AKR1C35）的 cDNA，并比较了它们的酶学性质和组织分布。AKR1C34 和 AKR1C35 均能利用 NAD+ 氧化各种外源性的脂环醇，但在羟基类固醇的底物特异性和抑制剂敏感性方面有所不同。AKR1C34 显示出 3α/17β/20α-羟基类固醇脱氢酶活性，而 AKR1C35 能有效氧化多种 3β-和 17β-羟基类固醇，包括具有生物活性的 3β-羟基-5α/β-二氢C19/C21-类固醇、脱氢表雄酮和 17β-雌二醇。AKR1C35 在黄酮类化合物的高敏感性方面也与 AKR1C34 不同，黄酮类化合物以竞争方式抑制 17β-雌二醇（Ki 0.11–0.69 μM）。AKR1C35 的 mRNA 在雄性地鼠中肝脏特异性表达，而在雌性地鼠中普遍表达，AKR1C34 的 mRNA 表达则显示出相反的性二态性。由于 AKR1C35 是 AKR 超家族中第一个 3(17)β-羟基类固醇脱氢酶，我们还通过将 AKR1C35 中的 Val54 和 Cys310 替换为 AKR1C34 中的相应残基 Ala 和 Phe，研究了 3β-羟基类固醇脱氢酶活性的分子决定因素。Val54Ala 突变显著损害了这一活性，而 Cys310Phe 突变则没有，这表明 Val54 在识别甾体底物中起着关键作用。
• Metabolism of Drugs. XVI. The Metabolic Fate of Methylhexabital (5-Cyclohexenyl-3, 5-dimethylbarbituric Acid). (6). Studies on the Reduction of 3-Keto-MHB (5-(3-Oxo-1-cyclohexenyl)-3, 5-dimethylbarbituric Acid) and on Pharmacological Activity of the Biotransformation Products of Methylhexabital from the Urine of Rabbits.
  作者：Hidetoshi Yoshimura

  DOI：10.1248/cpb.6.13

  日期：——

  Two isomeric hydroxyl compounds, m.p. 213∼215°(decomp.) and m.p. 143∼143.5°, were obtained by reduction of 3-keto-MHB (5-(3-oxo-1-cyclohexenyl)-3, 5-dimethylbarbituric acid) and those were identical in all respects with the amjor urinary metabolites, the diastereoisomeric (+)-α-and (+)-β-3-OH-MHB (5-(3-hydroxy-1-cyclohexenyl)-3, 5-dimethylbarbituric acid), respectively, except the optical property. Pharmacological activity of four main metabolites of MHB obtained previously were also examined but none showed any hypnotic action.

  通过还原 3-酮基-MHB（5-(3-氧代-1-环己烯基)-3, 5-二甲基巴比妥酸），得到了两种异构羟基化合物，其熔点分别为 213∼215°（分解）和 143∼143。除了光学性质外，它们与尿液中的主要代谢物非对映异构体 (+)-α 和 (+)-β-3-OH-MHB (5-(3-hydroxy-1-cyclohexenyl)-3, 5-dimethylbarbituric acid) 在所有方面都相同。此外，还对之前获得的四种 MHB 主要代谢物的药理活性进行了研究，但没有发现任何催眠作用。
• Yoshimura, Pharmaceutical Bulletin, 1957, vol. 5, p. 561,562
  作者：Yoshimura

  DOI：——

  日期：——
• Tsukamoto et al., Pharmaceutical Bulletin, 1956, vol. 4, p. 371,374
  作者：Tsukamoto et al.

  DOI：——

  日期：——

表征谱图