蝇蕈醇溴酸盐 | 18174-72-6

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 蝇蕈醇溴酸盐
• 中文别名: 毒蝇蕈醇氢溴酸盐；5-氨基甲基-3-羟基异恶唑氢溴酸
• 英文名称: muscimol hydrobromide
• 英文别名: 5-(aminomethyl)-1,2-oxazol-3-one;hydron;bromide
• CAS: 18174-72-6
• 化学式: BrH*C₄H₆N₂O₂
• 分子量: 195.016
• InChiKey: OPZOJWHOZRKYQX-UHFFFAOYSA-N

物化性质

• 熔点：
  172 °C
• 溶解度：
  乙醇：1 mg/mL
• 稳定性/保质期：
  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  0.0
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  64.4
• 氢给体数：
  3
• 氢受体数：
  3

ADMET

毒理性

• 毒性总结

毒蝇鹅膏素是一种强效的GABAA激动剂，激活大脑主要抑制性神经递质GABA的受体。毒蝇鹅膏素实际上与GABAA受体复合物上的同一结合位点结合，与GABA本身一样，而不是像其他GABAergic药物（如巴比妥类药物和苯二氮卓类药物）那样结合到单独的调节位点。GABAA受体在大脑中广泛分布，因此当毒蝇鹅膏素被给药时，它会改变多个区域的神级元活动，包括大脑皮层、海马和脑干。然而，尽管毒蝇鹅膏素传统上被认为是一种选择性的GABAA激动剂，它也是GABAC受体的强效部分激动剂，因此其效果概况是同时对这两个目标的作用结果。（L1142）

Muscimol is a potent GABAA agonist, activating the receptor for the brain's major inhibitory neurotransmitter, GABA. Muscimol actually binds to the same binding site on the GABAA receptor complex as GABA itself, as opposed to other GABAergic drugs such as barbiturates and benzodiazepines which bind to separate regulatory sites. GABAA receptors are widely distributed in the brain, and so when muscimol is administered, it alters neuronal activity in multiple regions including the cerebral cortex, hippocampus, and cerebellum. However while muscimol is conventionally thought of as a selective GABAA agonist, it is also a potent partial agonist at the GABAC receptor, and so its effects profile results from a combined action at both targets. (L1142)

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

Muscimol是一种神经毒素，能产生幻觉。

Muscimol is neurotoxic and produces hallucinations. (L1142)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服、皮肤、吸入和 parenteral（被污染的药物）。 (A3101)

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

莫西摩拉是致幻的。

Muscimol is hallucinogenic. (L1142)

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险品标志：
  T
• 安全说明：
  S22,S36/37/39,S45
• 危险类别码：
  R25
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  6-((2-chloro-6-ethylbenzyl)oxy)-3,4-dihydronaphthalen-2(1H)-one 、 蝇蕈醇溴酸盐 在 溶剂黄146 、 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 5-(((6-((2-chloro-6-ethylbenzyl)oxy)-1,2,3,4-tetrahydronaphthalen-2-yl)amino)methyl)-2H-isoxazol-3-one
  参考文献：
  名称：

  FUSED (HETERO)CYCLIC COMPOUNDS AS S1P MODULATORS

  摘要：

  这项发明涉及(S1P)调节剂的(杂)环化合物，包括这种化合物的药物组合物，以及在通过S1P受体介导的疾病或紊乱的治疗、缓解或预防中的用途。

  公开号：

  US20170174672A1
• 作为产物：
  描述：

  3-(Phenylmethoxy)-5-isoxazolemethanamine 在 氢溴酸 作用下， 以 溶剂黄146 为溶剂， 反应 24.0h， 以179 mg的产率得到蝇蕈醇溴酸盐
  参考文献：
  名称：

  4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors

  摘要：

  The insect GABA receptor (GABAR), which-is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol, analogues; were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas Synthesized analogues did, not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement Of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in Compounds that exhibited significantly enhanced antagonism with IC50 value in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 mu M analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed Competitive antagonism, with IC50 values of 30, 34, 1:07, and 96 mu M in the ac, bc, ad, and bd variants, respectively, and exhibited Moderate insecticidal activity against houseflies, with an LD50, value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs.

  DOI：

  10.1021/acs.jafc.5b01843

文献信息

• FUSED (HETERO)CYCLIC COMPOUNDS AS S1P MODULATORS
  申请人：AbbVie Deutschland GmbH & Co. KG

  公开号：US20170174672A1

  公开（公告）日：2017-06-22

  The invention relates to (hetero)cyclic compounds as S1P modulators, pharmaceutical compositions comprising such compounds, and uses thereof in the treatment, alleviation or prevention of diseases or disorders mediated by an S1P receptor.

  这项发明涉及(S1P)调节剂的(杂)环化合物，包括这种化合物的药物组合物，以及在通过S1P受体介导的疾病或紊乱的治疗、缓解或预防中的用途。
• 4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors
  作者：Genyan Liu、Fumiyo Ozoe、Kenjiro Furuta、Yoshihisa Ozoe

  DOI：10.1021/acs.jafc.5b01843

  日期：2015.7.22

  The insect GABA receptor (GABAR), which-is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol, analogues; were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas Synthesized analogues did, not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement Of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in Compounds that exhibited significantly enhanced antagonism with IC50 value in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 mu M analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed Competitive antagonism, with IC50 values of 30, 34, 1:07, and 96 mu M in the ac, bc, ad, and bd variants, respectively, and exhibited Moderate insecticidal activity against houseflies, with an LD50, value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs.