双氢麦角汀 | 17479-19-5

• 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: 双氢麦角汀
• 英文名称: dihydroergocristine
• 英文别名: 9,10-dihydroergocristine；Dihydroergocristin；hydergine；DHEC；5'α-benzyl-12'-hydroxy-2'-isopropyl-(10α)-9,10-dihydro-ergotamane-18,3',6'-trione；(6aR,9R,10aR)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-5,8-dioxo-4-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: 17479-19-5
• 化学式: C₃₅H₄₁N₅O₅
• 分子量: 611.741
• InChiKey: DEQITUUQPICUMR-HJPBWRTMSA-N

物化性质

• 熔点：
  199℃ (decomposition)
• 沸点：
  899.3±65.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)
• 溶解度：
  10 mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  45
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

二氢麦角克辛的主要代谢物是8'-羟基二氢麦角克辛，这种代谢物是在肝脏中产生的。二氢麦角克辛在体内的修饰非常广泛，已经观察到几乎完全不存在未改变的药物。要了解更多关于二氢麦角克辛作为麦角硫胺混合物的一部分的信息，请访问[DB01049]。

The major metabolite of dihydroergocristine is 8'-hydroxy-dihydroergocristine is produced in the liver. The modification of dihydroergocristine in the body is very extensive and it has been observed as an almost complete absence of the unchanged drug. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit [DB01049].

来源:DrugBank

毒理性

• 蛋白质结合

二氢麦角克辛可以以结合状态存在于血浆蛋白中，占给药剂量的甚至68%。要了解更多关于二氢麦角克辛作为麦角胺甲磺酸盐混合物的一部分的信息，请访问[DB01049]。

Dihydroergocristine can be found in a bound state to plasma proteins in a proportion of even 68% of the administered dose. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 吸收

二氢麦角克辛在消化道的吸收率约为给药剂量的25%。当二氢麦角克辛在人体口服给药后，血浆峰浓度达到0.28微克/升，所需时间为0.46小时。在同一份报告中，报告了曲线下面积（AUC）为0.39微克/升·小时。要了解更多关于二氢麦角克辛作为麦角甲磺酸混合物的一部分的信息，请访问[DB01049]。

Dihydroergocristine presents an absorption in the digestive tract of about 25% of the administered dose. When dihydroergocristine was orally administered in humans and the peak plasma concentration of 0.28 mcg/l was achieved after 0.46 hours. In the same report, the AUC was reported to be 0.39 mcg/l.h. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 消除途径

二氢麦角克辛的主要排泄途径是通过胆汁，这占了超过85%的排泄剂量。尿液排泄只占给药剂量的5%。要了解更多关于二氢麦角克辛作为麦角酸甲酯混合物的一部分的信息，请访问[DB01049]。

The most important elimination route of dihydroergocristine is in via the bile and it accounts for over 85% of the eliminated dose. Urine elimination accounts only for 5% of the administered dose. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 分布容积

二氢麦角克辛呈现较大的分布体积，为52升/千克。要了解更多关于二氢麦角克辛作为麦角酸甲酯混合物的一部分的信息，请访问[DB01049]。

Dihydroergocristine presents a large volume of distribution of 52 l/kg. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit [DB01049].

来源:DrugBank

吸收、分配和排泄

• 清除

二氢麦角隐亭呈现较高的系统清除率，为2.65升/小时.克。要了解更多关于二氢麦角隐亭作为麦角隐亭甲磺酸盐混合物的一部分，请访问[DB01049]。

Dihydroergocristine presents a high systemic clearance rate of 2.65 l/h.hg. To know more about dihydroergocristine as part of the ergoloid mesylate mixture, please visit [DB01049].

来源:DrugBank

反应信息

• 作为反应物：
  描述：

  双氢麦角汀 在 镍 氢气 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 水 为溶剂， 25.0~40.0 ℃ 、101.33 kPa 条件下， 反应 38.0h， 生成 6-demethyl-6-propyl-9,10-dihydroergocristine
  参考文献：
  名称：

  Beran, Milos; Cerny, Antonin; Kuchar, Miroslav, Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 3, p. 819 - 832

  摘要：

  DOI：
• 作为产物：
  描述：

  麦角生物碱 在 镍 甲醇 作用下， 以 1,4-二氧六环 为溶剂， 以86%的产率得到双氢麦角汀
  参考文献：
  名称：

  Mayer; Eich, Pharmazie, 1984, vol. 39, # 8, p. 537 - 538

  摘要：

  DOI：

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] PYRAZOLO [4, 3-D] PYRIMIDINES USEFUL AS KINASE INHIBITORS<br/>[FR] PYRAZOLO[4,3-D]PYRIMIDINES UTILES EN TANT QU'INHIBITEURS DE KINASES
  申请人：ORIGENIS GMBH

  公开号：WO2012143144A1

  公开（公告）日：2012-10-26

  The present invention relates to novel compounds of formula (I) that are capable of inhibiting one or more kinases, especially SYK (Spleen Tyrosine Kinase), LRRK2 (Leucine-rich repeat kinase 2) and/or MYLK (Myosin light chain kinase) or mutants thereof. The compounds find applications in the treatment of a variety of diseases. These diseases include autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies, asthma, alzheimer's disease, parkinson's disease, skin disorders, eye diseases, infectious diseases and hormone-related diseases.

  本发明涉及一种能够抑制一个或多个激酶，特别是SYK（脾酪氨酸激酶）、LRRK2（富含亮氨酸重复的激酶2）和/或MYLK（肌球蛋白轻链激酶）或其突变体的化合物的新颖化合物（I）的公式。这些化合物在治疗各种疾病中发挥作用。这些疾病包括自身免疫疾病、炎症性疾病、骨疾病、代谢性疾病、神经和神经退行性疾病、癌症、心血管疾病、过敏、哮喘、阿尔茨海默病、帕金森病、皮肤疾病、眼部疾病、传染病和与激素相关的疾病。
• ANTI-AMNESIC COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
  申请人：Verleye Marc

  公开号：US20090298817A1

  公开（公告）日：2009-12-03

  The present invention relates to the use of at least one compound of formula (I) as follows: or of at least one pharmaceutically acceptable salt thereof for the preparation of a drug for the prevention or treatment of memory disorders.

  本发明涉及至少一个如下公式（I）的化合物： 或至少一种药用可接受的盐 用于制备预防或治疗记忆障碍的药物。