瓦尔米 | 126-52-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 瓦尔米
• 中文别名: 凡眠特；炔己胺酯；炔己蚁胺
• 英文名称: ethinamate
• 英文别名: ZINC00001385；carbamic acid-(1-ethynyl-cyclohexyl ester)；Carbamidsaeure-(1-aethinyl-cyclohexylester)；Carbaminsaeure-<1-ethinyl-cyclohexylester>；<1-Ethinyl-cyclohexyl>-carbamat；(1-ethynylcyclohexyl) carbamate
• CAS: 126-52-3
• 化学式: C₉H₁₃NO₂
• 分子量: 167.208
• InChiKey: GXRZIMHKGDIBEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  2

ADMET

代谢

肝脏的。

Hepatic.

来源:DrugBank

代谢

乙炔雌三醇在肝脏中至少部分被灭活，通过环己基环的羟基化；产物被结合并作为葡萄糖醛酸苷排出体外。

ETHINAMATE IS INACTIVATED @ LEAST PARTLY BY LIVER, BY HYDROXYLATION OF CYCLOHEXYL RING; PRODUCT IS CONJUGATED & EXCRETED AS GLUCURONIDE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

乙炔酰胺从胃肠道迅速吸收，部分在肝脏代谢。三个主要代谢物之一是羟基乙炔酰胺（由环己基环的羟基化产生），目前尚不清楚这种代谢物是否具有任何药理效果。羟基乙炔酰胺与葡萄糖醛酸结合，形成大约与自由羟基乙炔酰胺相等量的物质。

Ethinamate is rapidly absorbed from the gastrointestinal tract and is in part metabolized by the liver. The major of three metabolites is hydroxyethinamate (yielded by hydroxylation of the cyclohexyl ring), and it is yet unclear whether this metabolite has any pharmacologic effect. Hydroxyethinamate is combined with glucuronide to form approximately equal quantities with free hydroxyethinamate.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏的。半衰期：2.5小时

Hepatic. Half Life: 2.5 hours

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

作用机制尚不清楚。然而，研究表明，乙炔酰胺抑制碳酸酐酶I和II（生物化学杂志。1992年12月15日;267(35):25044-50）。不过，乙炔酰胺的这种抑制作用不够强，因此不能将碳酸酐酶I和II牵涉到其作用机制中。

The mechanism of action is not known. However, studies have shown that ethinamate inhibits carbonic anhydrases I and II (J Biol Chem. 1992 Dec 15;267(35):25044-50). This inhibition by ethinamate is not sufficiently strong, however, to implicate carbonic anhydrases I and II in the mechanism of action.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类无致癌性（未列入国际癌症研究机构IARC清单）。

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

它们会导致说话含糊不清、迷失方向和“醉酒”行为。它们在身体和心理上都具有成瘾性。

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

口服给药后迅速吸收。

Rapidly absorbed following oral administration.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

过量症状包括呼吸急促或缓慢或困难呼吸、心跳缓慢、严重虚弱、慢性混乱、言语不清和蹒跚。

Symptoms of overdose include shortness of breath or slow or troubled breathing, slow heartbeat, severe weakness, chronic confusion, slurred speech, and staggering.

来源:Toxin and Toxin Target Database (T3DB)

吸收、分配和排泄

• 吸收

口服给药后迅速吸收。

Rapidly absorbed following oral administration.

来源:DrugBank

吸收、分配和排泄

乙炔雌三醇在肝脏中至少部分被灭活，通过环己基环的羟基化；产物被结合并作为葡萄糖醛酸苷排出体外。

ETHINAMATE IS INACTIVATED @ LEAST PARTLY BY LIVER, BY HYDROXYLATION OF CYCLOHEXYL RING; PRODUCT IS CONJUGATED & EXCRETED AS GLUCURONIDE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

它被广泛代谢，但初步经验表明，可以通过体外血液透析去除相当数量的物质。...高脂溶性...。

IT IS EXTENSIVELY METABOLIZED, BUT PRELIMINARY EXPERIENCE INDICATES APPRECIABLE QUANTITIES CAN BE REMOVED BY EXTRACORPOREAL HEMODIALYSIS. ... HIGH LIPID SOLUBILITY ... .

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

ETHINAMATE的吸收和清除在非禁食受试者单次口服治疗剂量后进行了研究。平均最大血浆浓度在1小时后观察到（血液中的半衰期为2.3小时）。

ABSORPTION & CLEARANCE OF ETHINAMATE WAS STUDIED AFTER SINGLE ORAL DOSAGES IN THERAPEUTIC RANGE TO NONFASTING SUBJECTS. MEAN MAX PLASMA LEVEL WAS OBSERVED AFTER 1 HR (T/2 IN BLOOD 2.3 HR).

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

迅速吸收。... 肾脏消除。大约36%的给药剂量在24小时内出现在尿液中。

Rapidly absorbed. ... Renal elimination. Approximately 36% of administered dose appears in urine within 24 hours.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  瓦尔米 、 2,4-二硝基苯肼 生成 1-cyclohex-1-enyl-ethanone-(2,4-dinitro-phenylhydrazone)
  参考文献：
  名称：

  乙草胺，乙炔和甲基对羟基苯丙醚的鉴定。

  摘要：

  DOI：

  10.1002/jps.2600530740
• 作为产物：
  描述：

  在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 瓦尔米
  参考文献：
  名称：

  钯（II）双恶唑啉催化羰基丙酸酯的羰基化反应：5-甲氧基-3（2H）-呋喃酮的高效合成

  摘要：

  钯和CO：羰基化1与[钯（TFA）2（±） - L1（TFA =三氟乙酸盐），得到spirofuranone 2在96％的产率与所述立体化学的反转在C17。C17- Epi - 1还提供了相同的产物2，并保留了C17的立体化学。标记研究表明，将13 CO并入呋喃酮环的C5'位置。实现了该新反应的第一个不对称形式。

  DOI：

  10.1002/anie.201303684

文献信息

• PRODRUG COMPOSITIONS, PRODRUG NANOPARTICLES, AND METHODS OF USE THEREOF
  申请人：Washington University

  公开号：US20160279060A1

  公开（公告）日：2016-09-29

  The present invention encompasses prodrug compositions, nanoparticles comprising one or more prodrugs, and methods of use thereof.

  本发明涵盖了前药组合物、包含一种或多种前药的纳米粒子，以及其使用方法。
• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• [EN] ACRYLATE-FUNCTIONAL BRANCHED ORGANOSILICON COMPOUND, METHOD OF PREPARING SAME, AND COPOLYMER FORMED THEREWITH<br/>[FR] COMPOSÉ D'ORGANOSILICIUM RAMIFIÉ À FONCTION ACRYLATE, SON PROCÉDÉ DE PRÉPARATION ET COPOLYMÈRE FORMÉ AVEC CELUI-CI
  申请人：DOW SILICONES CORP

  公开号：WO2020142474A1

  公开（公告）日：2020-07-09

  A method of preparing an acrylate-functional branched organosilicon compound ("compound") is provided, and comprises reacting (A) a branched organosilicon compound and (B) an acrylate compound in the presence of (C) a catalyst, wherein component (A) has the general formula X-Si(R1)3, where X comprises a halogen-functional moiety and each R1 is selected from R and –OSi(R4)3, with the proviso that at least one R1 is –OSi(R4)3; each R4 is selected from R, –OSi(R5)3, and –[OSiR2]mOSiR3; each R5 is selected from R, –OSi(R6)3, and –[OSiR2]mOSiR3; each R6 is selected from R and –[OSiR2]mOSiR3; each R is an independently selected hydrocarbyl group; and 0≤m≤100; with the proviso that at least one of R4, R5 and R6 is –[OSiR2]mOSiR3. The compound prepared by the method, a copolymer comprising the reaction product of the compound and a second compound, a method of forming the copolymer, and a composition comprising the copolymer are each also provided.

  提供了一种制备丙烯酸酯官能化分支有机硅化合物（“化合物”）的方法，包括在催化剂存在下，使（A）分支有机硅化合物和（B）丙烯酸酯化合物发生反应，其中组分（A）具有一般式X-Si（R1）3，其中X包括卤素官能基，每个R1从R和–OSi（R4）3中选择，但至少一个R1为–OSi（R4）3；每个R4从R、–OSi（R5）3和–[OSiR2]mOSiR3中选择；每个R5从R、–OSi（R6）3和–[OSiR2]mOSiR3中选择；每个R6从R和–[OSiR2]mOSiR3中选择；每个R是独立选择的烃基；且0≤m≤100；但至少一个R4、R5和R6为–[OSiR2]mOSiR3。还提供了通过该方法制备的化合物，包括化合物和第二化合物的反应产物的共聚物，形成共聚物的方法，以及包含共聚物的组合物。
• Improvement process for debrominative rearrangements
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0370153A1

  公开（公告）日：1990-05-30

  This invention relates to an improvement in the standard procedures involving a debrominative rearrangement reaction of a terminal dibromoolefin with activated magnesium in tetrahydrofuran.

  这项发明涉及改进标准程序，涉及将末端二溴烯与四氢呋喃中活化的镁进行去溴重排反应。

表征谱图