5-allyl-1-methyl-5-pyrimidine-2,4,6-trione | 1000993-88-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-allyl-1-methyl-5-pyrimidine-2,4,6-trione
• 英文别名: 5-allyl-1-methylpyrimidine-2,4,6-trione；5-allylbarbiturate；1-Methyl-5-prop-2-enyl-1,3-diazinane-2,4,6-trione
• CAS: 1000993-88-3
• 化学式: C₈H₁₀N₂O₃
• 分子量: 182.179
• InChiKey: PBSLBBVJAMDTMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-allyl-1-methyl-5-pyrimidine-2,4,6-trione 、 (4-methoxyphenyl)-[3-(3-trifluoromethyl-3H-diazirin-3-yl)phenyl]iodonium trifluoroacetate 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 48.0h， 以60%的产率得到5-allyl-1-methyl-5-(m-trifluoromethyldiazirinylphenyl)barbituric acid
  参考文献：
  名称：

  烯丙基间三氟甲基二氮丙啶甲氧巴比妥：一种异常有效的对映选择性和光反应性巴比妥酸盐全身麻醉剂

  摘要：

  我们合成了 5-allyl-1-methyl-5-( m -trifluoromethyl-diazirynylphenyl)barbituric acid ( 14 )，一种含有三氟甲基二氮丙啶的通用麻醉剂甲氧巴比妥衍生物，通过手性色谱法将外消旋混合物分离成对映体，并确定了构型通过 X 射线晶体学将 (+)-对映异构体作为S。此外，我们还获得了具有高特异性放射性的3 H 标记配体。R -(-)- 14比临床使用的最有效的巴比妥类药物硫喷妥钠强一个数量级，其全身麻醉剂 EC 50接近丙泊酚和依托咪酯，而S -(+)- 14效力低 10 倍。此外，在接近其麻醉效力的浓度下，R -(-)- 14既能增强 GABA 诱导的电流，又能增加对人 α1β2/3γ2L GABA A受体中激动剂 muscimol的亲和力。最后，发现R -(-)- 14是一种非常有效的光标记试剂，可并入人 α1β3 GABA

  DOI：

  10.1021/jm300631e
• 作为产物：
  描述：

  烯丙基丙二酸二甲酯 、 N-甲基脲 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以69%的产率得到5-allyl-1-methyl-5-pyrimidine-2,4,6-trione
  参考文献：
  名称：

  烯丙基间三氟甲基二氮丙啶甲氧巴比妥：一种异常有效的对映选择性和光反应性巴比妥酸盐全身麻醉剂

  摘要：

  我们合成了 5-allyl-1-methyl-5-( m -trifluoromethyl-diazirynylphenyl)barbituric acid ( 14 )，一种含有三氟甲基二氮丙啶的通用麻醉剂甲氧巴比妥衍生物，通过手性色谱法将外消旋混合物分离成对映体，并确定了构型通过 X 射线晶体学将 (+)-对映异构体作为S。此外，我们还获得了具有高特异性放射性的3 H 标记配体。R -(-)- 14比临床使用的最有效的巴比妥类药物硫喷妥钠强一个数量级，其全身麻醉剂 EC 50接近丙泊酚和依托咪酯，而S -(+)- 14效力低 10 倍。此外，在接近其麻醉效力的浓度下，R -(-)- 14既能增强 GABA 诱导的电流，又能增加对人 α1β2/3γ2L GABA A受体中激动剂 muscimol的亲和力。最后，发现R -(-)- 14是一种非常有效的光标记试剂，可并入人 α1β3 GABA

  DOI：

  10.1021/jm300631e

文献信息

• Binding site location on GABA _A receptors determines whether mixtures of intravenous general anaesthetics interact synergistically or additively in vivo
  作者：Daniel E. Kent、Pavel Y. Savechenkov、Karol S. Bruzik、Keith W. Miller

  DOI：10.1111/bph.14843

  日期：2019.12

  Background and PurposeGeneral anaesthetics can act on synaptic GABAA receptors by binding to one of three classes of general anaesthetic sites. Canonical drugs that bind selectively to only one class of site are etomidate, alphaxalone, and the mephobarbital derivative, R‐mTFD‐MPAB. We tested the hypothesis that the general anaesthetic potencies of mixtures of such site‐selective agents binding to the same or to different sites would combine additively or synergistically respectively.Experimental ApproachThe potency of general anaesthetics individually or in combinations to cause loss of righting reflexes in tadpoles was determined, and the results were analysed using isobolographic methods.Key ResultsThe potencies of combinations of two or three site‐selective anaesthetics that all acted on a single class of site were strictly additive, regardless of which single site was involved. Combinations of two or three site‐selective anaesthetics that all bound selectively to different sites always interacted synergistically. The strength of the synergy increased with the number of separate sites involved such that the percentage of each agent's EC50 required to cause anaesthesia was just 35% and 14% for two or three sites respectively. Propofol, which binds non‐selectively to the etomidate and R‐mTFD‐MPAB sites, interacted synergistically with each of these agents.Conclusions and ImplicationsThe established pharmacology of the three anaesthetic binding sites on synaptic GABAA receptors was sufficient to predict whether a mixture of anaesthetics interacted additively or synergistically to cause loss of righting reflexes in vivo. The principles established here have implications for clinical practice.