胍那决尔 | 40580-59-4

• 物质功能分类: 原料药 - 循环系统用药 - 抗高血压病药
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 胍那决尔
• 中文别名: 胍环定
• 英文名称: guanadrel
• 英文别名: 2-(1,4-dioxaspiro[4.5]decan-3-ylmethyl)guanidine
• CAS: 40580-59-4
• 化学式: C₁₀H₁₉N₃O₂
• mdl: MFCD00865923
• 分子量: 213.28
• InChiKey: HPBNRIOWIXYZFK-UHFFFAOYSA-N

物化性质

• 沸点：
  341.5±40.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL，DMSO：30mg/mL，乙醇：30mg/mL
• 物理描述：
  Solid
• 熔点：
  213.5-215

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  82.9
• 氢给体数：
  2
• 氢受体数：
  3

ADMET

代谢

主要是肝脏的

Primarily hepatic

来源:DrugBank

代谢

大约40-50%的药物在肝脏中代谢为2,3-二羟基丙基胍和几种未识别的代谢物。这些代谢物的降压活性尚不清楚。

Approximately 40-50% of the drug is metabolized in the liver to 2,3-dihydroxypropylguanidine and several unidentified metabolites. The hypotensive activity of the metabolites is not known.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

三环类抗抑郁药、吩噻嗪类药物以及间接作用的拟交感神经药（例如，麻黄碱、苯丙醇胺）可能会阻止胍那苄进入肾上腺素能神经元或逆转胍那苄的降压效果。麻黄碱已被证明可以迅速逆转胍那苄的药理作用。胍那苄可能会增强直接作用的拟交感神经药物（如去甲肾上腺素或苯肾上腺素）的药理活性。

Tricyclic antidepressants, phenothiazines, and indirect-acting sympathomimetics (eg, ephedrine, phenylpropanolamine) may block the uptake of guanadrel into adrenergic neurons or reverse the hypotensive effect of guanadrel. Ephedrine has been shown to rapidly reverse the pharmacologic effects of guanadrel. Guanadrel may potentiate the pharmacologic activity of direct-acting sympathomimetic agents such as norepinephrine or phenylephrine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

单胺氧化酶抑制剂据报道会拮抗胍乙啶的降压效果；... 胍乙啶在正在接受MAO抑制剂的患者中是禁忌的，这些药物在给予胍乙啶前至少应该停止使用1周。

Monoamine oxidase inhibitors reportedly antagonize the hypotensive effect of guanadrel; ... guanadrel is contraindicated in patients receiving MAO inhibitors and that these drugs should be discontinued for at least 1 week prior to administration of guanadrel.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

去甲肾上腺素类药物应谨慎使用，因为甘那德可能增强这些药物的升压和致心律失常反应。

Vasopressors should be administered with caution since guanadrel may enhance the pressor and arrhythmogenic responses to these drugs.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

当停止使用三环类抗抑郁药治疗接受胍那苄的患者时，应谨慎行事，尤其是如果突然停止使用抗抑郁药，因为胍那苄的增强临床效果（例如，低血压）可能会发生。由于许多非处方感冒、过敏和哮喘制剂含有拟交感神经药，接受胍那苄治疗的患者应被告知，除非先咨询他们的医生或药剂师，否则不应使用这些制剂进行自我治疗。

Caution should be exercised when tricyclic antidepressant therapy is discontinued in patients receiving guanadrel, particularly if discontinuance of the antidepressant is abrupt, since enhanced clinical effects (e.g., hypotension) of guanadrel may occur. Because many nonprescription cold, allergy, and asthma preparations contain sympathomimetic agents, patients receiving guanadrel should be warned not to use these preparations for self-medication unless first consulting with their physician or pharmacist.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

过量服用最重要的并发症是严重的低血压（通常是体位性）。低血压应通过采用特伦德伦堡体位来治疗，必要时应给予静脉输液。

The most important complication of overdose being profound hypotension (usually orthostatic). ...Hypotension should be treated by the use of Trendelenburg position, and iv fluids should be administered when necessary.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

迅速且容易从胃肠道吸收。

Rapidly and readily absorbed from the gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

硫酸胍那苄迅速且几乎完全通过口服给药被吸收。通常在口服给药后1.5-2小时达到血浆峰浓度。硫酸胍那苄的降压效果通常在0.5-2小时内开始，4-6小时达到峰值，并持续4-14小时。

Guanadrel sulfate is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations usually are achieved 1.5-2 hr after oral administration. The hypotensive effect of guanadrel sulfate usually has an onset of 0.5-2 hrs, peaks at 4-6 hr, and persists for 4-14 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约20%的冠脉素与血浆蛋白结合，浓度范围广泛。该药物广泛分布到大多数身体组织和液体中。药物很少，如果有的话，穿过血脑屏障或分布到眼睛中。目前尚不清楚冠脉素是否分布到乳汁中或穿过人类胎盘。在小鼠中，该药物已显示以小浓度穿过胎盘。

Approximately 20% of guanadrel is bound to plasma proteins over a wide concentration range. The drug is widely distributed into most body tissues and fluids. Little, if any, of the drug crosses the blood-brain barrier or distributes into the eye. It is not known whether guanadrel is distributed into milk or crosses the placenta in humans. The drug has been shown to cross the placenta in small concentrations in mice

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

冠纳德雷尔通过肾脏和非肾脏途径从体内清除。在肾功能不全的患者中，其消除功能受损；在一组平均肌酐清除率为每分钟13毫升的患者中，总体清除率降低了4到5倍。

Guanadrel is cleared from the body by both renal and nonrenal disposition. Its elimination is impaired in patients with renal insufficiency; total-body clearance was reduced by 4- to 5-fold in a group of patients with a clearance of creatinine averaging 13 ml per minute.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约40-50%的药物在肝脏中代谢……。关阿德拉及其代谢物主要通过尿液排出。大约85%的口服剂量在24小时内通过尿液排出；40-50%的剂量以原形通过尿液排出。

Approximately 40-50% of the drug is metabolized in the liver ... . Guanadrel and its metabolites are excreted principally in urine. Approximately 85% of an oral dose of the drug is excreted in urine within 24 hrs; 40-50% of the dose is excreted in urine unchanged.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  胍那决尔 、 六氟乙酰丙酮 生成 N-(1,4-dioxaspiro[4.5]decan-3-ylmethyl)-4,6-bis(trifluoromethyl)pyrimidin-2-amine
  参考文献：
  名称：

  KAISER, DAVID G.;VANGIESSEN, GARRETT J.;SHAH, JYOTI A.;WEBER, DENNIS J., J. CHROMATOGR. BIOMED. APPL., 434,(1988) N, C. 135-143

  摘要：

  DOI：
• 作为产物：
  描述：

  1,4-二噁螺[4.5]癸烷-2-甲胺 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 11.0h， 生成 胍那决尔
  参考文献：
  名称：

  Synthesis of Biologically Important Guanidine-Containing Molecules Using Triflyl-Diurethane Protected Guanidines

  摘要：

  DOI：

  10.1055/s-1999-3653

文献信息

• 1,5-Substituted indol-2-yl amide derivatives
  申请人：Nettekoven Matthias

  公开号：US20070123515A1

  公开（公告）日：2007-05-31

  The present invention relates to compounds of formula I wherein R 1 to R 4 and G are as defined in the description and claims and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及式I的化合物，其中R1至R4和G如描述和索赔中定义的，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• INDOL-2-YL-PIPERAZIN-1-YL-METHANONE DERIVATIVES
  申请人：Nettekoven Matthias

  公开号：US20080188484A1

  公开（公告）日：2008-08-07

  The present invention relates to compounds of formula I wherein A and R 1 to R 4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及公式I的化合物，其中A和R1至R4如描述和声明中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• BENZOFURAN AND BENZOTHIOPHENE-2-CARBOXYLIC ACID AMIDE DERIVATIVES
  申请人：Mohr Peter

  公开号：US20090029976A1

  公开（公告）日：2009-01-29

  The present invention relates to compounds of formula I wherein X, A and R 1 to R 4 are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及公式I的化合物，其中X，A和R1至R4如描述和索赔中所定义，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
  申请人：DeAngelis Alan

  公开号：US20060058393A1

  公开（公告）日：2006-03-16

  The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR modulators to treat or inhibit the progression of, for example, dyslipidemia.

  这项发明涉及4-((苯氧烷基)硫基)-苯氧乙酸及其类似物，含有它们的组合物，以及将它们用作PPAR调节剂来治疗或抑制例如脂质代谢异常的进展的方法。
• 1,1-Dioxo-thiomorpholinyl indolyl methanone derivatives
  申请人：Nettekoven Matthias

  公开号：US20070123526A1

  公开（公告）日：2007-05-31

  The present invention relates to compounds of formula I wherein R 1 , R 2 and G are as defined in the description and claims and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及式I的化合物，其中R1、R2和G如描述和索赔中定义的，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。