二氢麦角考宁 | 25447-65-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 麦角林及其衍生物
• 中文名称: 二氢麦角考宁
• 英文名称: dihydroergocornine
• 英文别名: 9,10-dihydroergocornine；12'-hydroxy-2',5'α-diisopropyl-(10α)-9,10-dihydro-ergotamane-18,3',6'-trione；12'-Hydroxy-2',5'α-diisopropyl-(10α)-9,10-dihydro-ergotaman-18,3',6'-trion；Dihydroergocornin；(6aR,9R,10aR)-N-[(1S,2S,4R,7S)-2-hydroxy-5,8-dioxo-4,7-di(propan-2-yl)-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9,10,10a-hexahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide
• CAS: 25447-65-8
• 化学式: C₃₁H₄₁N₅O₅
• 分子量: 563.697
• InChiKey: SEALOBQTUQIVGU-QNIJNHAOSA-N

物化性质

• 熔点：
  185-187 °C (decomp)
• 沸点：
  844.6±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  41
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

二氢麦角考宁的生物转化通过肽部分分子中的脯氨酸的氧化和裂解，以及酰胺键的断裂产生二氢麦角酸酰胺。一些衍生物代谢物保留了麦角生物碱的基本环状结构。要了解更多关于药物动力学的信息，请访问[DB01049]。

The biotransformation of dihydroergocornine occurs via oxidation and cleavage of the proline in the peptide portion of the molecule as well as by the splitting of the amide bond yielding dihydrolysergic acid amide. Some of the derivate metabolites retain the essential ring structure of the ergot alkaloid. To know more about the pharmacokinetics please visit [DB01049].

来源:DrugBank

毒理性

• 蛋白质结合

要了解更多关于药代动力学信息，请访问[DB01049]。

To know more about the pharmacokinetics please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 吸收

二氢麦角Cornine在人经口服给药后的吸收非常迅速，与混合物或大多数成分相比。达到最大血浆浓度0.57纳克当量/毫升的时间为1.4小时。它呈现出0.32小时的吸收半衰期。吸收百分比约为25%，这与麦角混合物中登记的吸收情况相对应。要了解更多关于药代动力学信息，请访问[DB01049]。

Dihydroergocornine absorption in man after oral administration is very rapid when compared to the mixture or most of the components. The time to reach maximum plasma concentration or 0.57 ng-eq/ml is 1.4 hours. It presents an absorption half-life of 0.32 hours. The absorption percentage is of about 25% which corresponds to the registered absorption presented in the ergoloid mixture. To know more about the pharmacokinetics please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 消除途径

当口服给药时，二氢麦角Cornine几乎完全通过粪便排出。尿液分泌仅占给药剂量的2.5%。另一方面，当静脉给药时，肾脏排泄可以占到给药剂量的约10%。要了解更多关于药代动力学信息，请访问[DB01049]。

When orally administered, dihydroergocornine is almost completely eliminated via feces. The urinary secretion accounts only for 2.5% of the administered dose. On the other hand, when administered intravenously, the renal excretion can account for approximately 10% of the administered dose. To know more about the pharmacokinetics please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 分布容积

要了解更多关于药代动力学信息，请访问[DB01049]。

To know more about the pharmacokinetics please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 清除

在目前的文献中没有发现与清除率相关的药代动力学。

No pharmacokinetic related to the clearance rate was found in current literature.

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  二氢麦角考宁 在 1,4-二氧六环 、 N-溴代丁二酰亚胺(NBS) 作用下， 生成 2-bromo-12'-hydroxy-2',5'α-diisopropyl-(10α)-9,10-dihydro-ergotamane-18,3',6'-trione
  参考文献：
  名称：

  麦角酸环系统上的取代基。三，卤化。45.关于麦角生物碱的交流

  摘要：

  描述了麦角酸和二氢麦角酸系列的2-卤素衍生物的生产和性质。

  DOI：

  10.1002/hlca.19570400716
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 1,4-二氧六环 、 钯 作用下， 60.0 ℃ 、2.94 MPa 条件下， 生成 二氢麦角考宁
  参考文献：
  名称：

  天然二氢衍生物链接到了mutterkornalkaloide。（9. MitteilungüberMutterkornalkaloide）

  摘要：

  DOI：

  10.1002/hlca.19430260633

文献信息

• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• [EN] IMIDAZOLINONE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'IMIDAZOLINONE EN TANT QU'ANTAGONISTES DE RÉCEPTEURS CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2010077752A1

  公开（公告）日：2010-07-08

  The present invention is directed to imidazolinone derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及嘧啶啉酮衍生物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• PIPERIDINONE CARBOXAMIDE AZAINDANE CGRP RECEPTOR ANTAGONISTS
  申请人：Bell Ian M.

  公开号：US20120122899A1

  公开（公告）日：2012-05-17

  The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及哌啶酮羧酰胺吖啶衍生物，它们是CGRP受体拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗CGRP参与的这类疾病中使用这些化合物和组合物。
• [EN] FUSED HETEROCYCLIC AZAINDANE CARBOXAMIDE CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES AZAINDANE CARBOXAMIDES HÉTÉROCYCLIQUES FUSIONNÉS DE RÉCEPTEURS DU CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2013066360A1

  公开（公告）日：2013-05-10

  The present invention is directed to fused heterocyclic azaindane carboxamide derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及融合的杂环氮吲哚羧酰胺衍生物，其为CGRP受体拮抗剂，在治疗或预防涉及CGRP的疾病，如偏头痛方面有用。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• Cgrp Receptor Antagonists
  申请人：Burgey S. Christopher

  公开号：US20070287696A1

  公开（公告）日：2007-12-13

  Compounds of Formula I: and Formula II: (where variables R 1 , R 2 , R 3 , R 4 , A, B, D, G, J, Q, T, W, X and Y are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, pharmaceutical compositions comprising these compounds, use of these compounds and compositions to prevent or treat diseases involving CGRP.

  化合物的化学式I：和化学式II：（其中变量R1、R2、R3、R4、A、B、D、G、J、Q、T、W、X和Y的定义如下）可作为CGRP受体拮抗剂，在涉及CGRP的疾病的治疗或预防中有用，包括这些化合物的药物组合物、使用这些化合物和组合物来预防或治疗涉及CGRP的疾病。