ethchlorvynol | 113-18-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethchlorvynol
• 英文别名: (E)-1-chloro-3-ethylpent-1-en-4-yn-3-ol
• CAS: 113-18-8
• 化学式: C₇H₉ClO
• 分子量: 144.601
• InChiKey: ZEHYJZXQEQOSON-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

大约90%的剂量在肝脏中代谢。一些乙氯乙烯醇也可能在肾脏中代谢。乙氯乙烯醇和代谢物会经历广泛的肠肝循环。

About 90% of a dose is metabolized in the liver. Some ethchlorvynol may also be metabolized in the kidneys. Ethchlorvynol and metabolites undergo extensive enterohepatic recirculation.

来源:DrugBank

代谢

大约90%的剂量在肝脏中代谢。一些乙醇也可能在肾脏中代谢。

About 90% of a dose is metabolized in the liver. Some ethchlovynol may also be metabolized in the kidneys.

来源:Hazardous Substances Data Bank (HSDB)

代谢

尽管乙氯乙烯醇的代谢命运尚未完全阐明，但有证据表明这种药物被广泛代谢，可能是在肝脏中。还有一些证据表明肾脏在药物代谢中可能发挥重要作用。

Although the metabolic fate of ethchlorvynol has not been fully elucidated, there is evidence that the drug is extensively metabolized, probably in the liver. There is also some evidence that the kidneys may play an essential role in metabolism of the drug.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏的新陈代谢最初被认为是微不足道的，但这一点后来被部分驳斥了，因为发现乙醇氯醛在肝脏中很容易被代谢。尽管代谢物尚未被识别，但似乎发生了葡萄糖苷酸结合以及化学结构中不饱和键的羟基化与还原。

Metabolism in liver originally was assumed to be negligible, but this has been somewhate disproved since it was later found that ethchlorvynol is readily metabolized in liver. Although metabolites have not yet been identified, it would appear that glucuronide conjugation occurs as well as hydroxylation with reduction of unsaturated bonds in the chemical structure.

来源:Hazardous Substances Data Bank (HSDB)

代谢

大约90%的药物将经历生物转化，很可能是在肝脏中，因为乙氯戊醇在胆汁中的浓度是在血清中的三倍。

Approximately 90% of the drug will undergo biotransformation, probably in the liver, since ethchlorvynol is concentrated in bile to three times as much as in serum.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

尽管确切的机制尚不清楚，但可以看出乙氯戊醇以类似于巴比妥类药物的方式抑制中枢神经系统。巴比妥类药物与GABA_A受体的一个与Cl^-离子通道相关的独特结合位点结合，增加了Cl^-离子通道开启的时间长度。因此，GABA在丘脑中的突触后抑制效应被延长。

Although the exact mechanism of action is unknown, ethchlorvynol appears to depress the central nervous system in a manner similar to that of barbiturates. Barbiturates bind at a distinct binding sites associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

它们会导致言语不清、定向障碍和“醉酒”行为。它们在身体和心理上都会产生依赖。

They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口腔，从胃肠道快速吸收。

Oral, rapidly absorbed from gastrointestinal tract.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

过量症状包括血小板减少。

Symptoms of overdose include thrombocytopenia.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

从胃肠道快速吸收。

Rapidly absorbed from gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

药物缓慢消失主要是由于广泛的组织分布。

... SLOW DISAPPEARANCE OF DRUG WAS SHOWN TO BE DUE LARGELY TO EXTENSIVE TISSUE DISTRIBUTION.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

经口服摄入1克乙氯戊醇后，15-30分钟内出现中枢神经系统抑制的症状。分布体积大于总体内水分的体积。在急性中毒患者中……脑脊液中的浓度达到血浆中浓度的50%。

AFTER ORAL INGESTION OF 1 G OF ETHCHLORVYNOL, SYMPTOMS OF CNS DEPRESSION OCCUR WITHIN 15-30 MIN. VOL OF DISTRIBUTION IS GREATER THAN VOL OF TOTAL BODY WATER. IN ACUTELY INTOXICATED PATIENT ... CONCN IN CSF REACHES 50% OF THAT IN PLASMA.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

药物主要由肝脏代谢，但大约10%的常规剂量通过尿液排出。

DRUG IS MAINLY /METABOLIZED BY THE/ LIVER, BUT APPROX 10% OF USUAL DOSE IS EXCRETED INT URINE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

从胃肠道快速吸收...口服200毫克、500毫克和750毫克...分别在1到2小时内产生0.9到2.5微克/毫升、4.2到6.5微克/毫升和8微克/毫升的峰浓度.../人类/

RAPIDLY ABSORBED FROM GI TRACT ... ORAL ADMIN OF 200 MG, 500 MG & 750 MG ... PRODUCED PEAK PLASMA LEVELS OF 0.9 TO 2.5 MCG/ML, 4.2 TO 6.5 MCG/ML & 8 MCG/ML, RESPECTIVELY, WITHIN 1 TO 2 HR ... /HUMAN/

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• [EN] COMPOUNDS AND THEIR USE AS BACE INHIBITORS<br/>[FR] COMPOSÉS ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BACE
  申请人：ASTRAZENECA AB

  公开号：WO2016055858A1

  公开（公告）日：2016-04-14

  The present application relates to compounds of formula (I), (la), or (lb) and their pharmaceutical compositions/preparations. This application further relates to methods of treating or preventing Αβ-related pathologies such as Down's syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia, including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease.

  本申请涉及式(I)、(Ia)或(Ib)的化合物及其药物组合物/制剂。本申请进一步涉及治疗或预防与Αβ相关的病理学，如唐氏综合症，β-淀粉样蛋白血管病，如但不限于脑淀粉样蛋白血管病或遗传性脑出血，与认知损害相关的疾病，如但不限于MCI（“轻度认知损害”），阿尔茨海默病，记忆丧失，与阿尔茨海默病相关的注意力缺陷症状，与疾病如阿尔茨海默病或痴呆症相关的神经退行性疾病，包括混合性血管性和退行性起源的痴呆，早老性痴呆，老年性痴呆和与帕金森病相关的痴呆的方法。
• [EN] METHYL OXAZOLE OREXIN RECEPTOR ANTAGONISTS<br/>[FR] MÉTHYLOXAZOLES ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE
  申请人：MERCK SHARP & DOHME

  公开号：WO2016089721A1

  公开（公告）日：2016-06-09

  The present invention is directed to methyl oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.

  本发明涉及甲基噁唑化合物，其为促进睡眠的受体拮抗剂。本发明还涉及所述化合物在潜在治疗或预防涉及促进睡眠的神经和精神疾病和疾病中的用途。本发明还涉及包含这些化合物的组合物。本发明还涉及这些组合物在潜在预防或治疗涉及促进睡眠的疾病中的用途。
• HETEROBICYCLIC COMPOUNDS
  申请人：Amgen Inc.

  公开号：US20130225552A1

  公开（公告）日：2013-08-29

  Heterobicyclic compounds of Formula (I): or a pharmaceutically-acceptable salt, tautomer, or stereoisomer thereof, as defined in the specification, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, Huntington's Disease, and the like.

  Formula (I)的杂环化合物： 或其药用可接受的盐、互变异构体或立体异构体，如规范中所定义，并含有它们的组合物，以及制备这种化合物的方法。本文还提供了通过抑制PDE10来治疗由此可治疗的疾病或疾病的方法，如肥胖症、非胰岛素依赖型糖尿病、精神分裂症、躁郁症、强迫症、亨廷顿病等。
• [EN] NAPHTHALENE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] COMPOSÉS DE NAPHTHALÈNE CARBOXAMIDE, MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1
  申请人：MERCK SHARP & DOHME

  公开号：WO2011149801A1

  公开（公告）日：2011-12-01

  The present invention is directed to naphthalene carboxamide compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimers disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的萘甲酰胺化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] COMT INHIBITING METHODS AND COMPOSITIONS<br/>[FR] PROCÉDÉS D'INHIBITION DE LA COMT ET COMPOSITIONS ASSOCIÉES
  申请人：LIEBER INST FOR BRAIN DEV

  公开号：WO2016123576A1

  公开（公告）日：2016-08-04

  The present inventions include a method of inhibiting COMT enzyme in a subject as well as compounds of formula I, or a pharmaceutically acceptable salt thereof, that are useful in the treatment of various disorders mediated by COMT, including Parkinson's disease and/or schizophrenia.

  这些发明包括一种抑制受试者中COMT酶的方法，以及式I的化合物或其药用可接受盐，这些化合物在治疗由COMT介导的各种疾病中有用，包括帕金森病和/或精神分裂症。

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