2-[(2,3-二甲基苯氧基)甲基]环氧乙烷 | 41457-31-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 2-[(2,3-二甲基苯氧基)甲基]环氧乙烷
• 英文名称: 1,2-epoxy-3-[2,3-dimethylphenoxy]propane
• 英文别名: 1-(2',3'-dimethylphenoxy)-2,3-epoxypropane；1,2-epoxy-3-(2,3-dimethylphenoxy)propane；2,3-dimethyl-1-(2,3-epoxypropoxy)benzene；2-(2,3-dimethyl-phenoxymethyl)-oxirane；1-xylenoxypropane-2,3-oxide；1-(2,3-dimethyl)-phenoxy-2,3-epoxypropane；2-[(2,3-Dimethylphenoxy)methyl]oxirane
• CAS: 41457-31-2
• 化学式: C₁₁H₁₄O₂
• 分子量: 178.231
• InChiKey: RWBSWKZPQXYNNO-UHFFFAOYSA-N

物化性质

• 沸点：
  110-112 °C(Press: 1 Torr)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[(2,3-二甲基苯氧基)甲基]环氧乙烷 在 potassium thioacyanate 作用下， 以 水 为溶剂， 反应 24.0h， 以52%的产率得到2-((2,3-dimethylphenoxy)methyl)thiirane
  参考文献：
  名称：

  NBS / DMSO介导的由芳氧基甲基噻喃合成（2,3-二氢苯并[ b ] [1,4]草酰-3-基）甲醇†

  摘要：

  通过芳氧基甲基硫烷和N-溴琥珀酰亚胺（NBS）在DMSO下微波辐射反应合成了（2,3-二氢苯并[ b ] [1,4]氧杂嘧啶-3-基）甲醇。该反应机理被认为是由芳氧基甲基噻喃和NBS生成的1-溴-2-（芳氧基甲基）噻喃-1-鎓的分子内芳族亲电取代，以及随后的噻吩-1-鎓的DMSO亲核开环反应，随后是排水量。当前的方法提供了一种直接和简单的策略，可以从容易获得的芳氧基甲基噻喃有效地制备（2,3-二氢苯并[ b ] [1,4]氧杂蒽-3-基）甲醇。

  DOI：

  10.1039/c8nj01117f
• 作为产物：
  描述：

  1-Chloro-3-(2,3-dimethylphenoxy)propan-2-ol 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 生成 2-[(2,3-二甲基苯氧基)甲基]环氧乙烷
  参考文献：
  名称：

  Antihypertensive indole derivatives of phenoxypropanolamines with .beta.-adrenergic receptor antagonist and vasodilating activity

  摘要：

  A series of 25 aryloxypropanolamines containing the 3-indolyl-tert-butyl [i.e., 1,1-dimethyl-2-(1H-indol-3-yl)ethyl] or substituted 3-indolyl-tert-butyl moiety as the N substituent is reported. These compounds have been tested for antihypertensive activity in spontaneously hypertensive rats (SHR), beta-adrenergic receptor antagonist action in conscious normotensive rats, vasodilating activity in ganglion-blocked rats with blood pressure maintained by angiotensin II infusion, and for intrinsic sympathomimetic action (ISA) in reserpinized rats. Some of the compounds exhibit antihypertensive activity in combination with beta adrenergic receptor antagonist and vasodilating action. The structure--activity relationships in these tests are discussed.

  DOI：

  10.1021/jm00177a015

文献信息

• Design and synthesis of a series of combined vasodilator-.beta.-adrenoceptor antagonists based on 6-arylpyridazinones
  作者：R. A. Slater、W. Howson、G. T. G. Swayne、E. M. Taylor、D. R. Reavill

  DOI：10.1021/jm00397a013

  日期：1988.2

  synthesized and evaluated as combined vasodilator/beta-adrenoceptor antagonists and potential antihypertensive agents. Many of the early compounds displayed an unacceptably high level of intrinsic sympathomimetic activity (ISA) and a relatively short duration of action. Disubstitution in the 2,3-positions or in the 4-position of the aryloxy ring gave compounds with low ISA levels and, in some instances,

  已经合成了一系列新的6- [4-[[（（芳氧基）酰基]氨基]苯基] -4,5-二氢吡啶并酮，并被评估为血管扩张剂/β-肾上腺素能受体拮抗剂和潜在的降压药。许多早期化合物显示出高水平的固有拟交感神经活性（ISA）和相对较短的作用时间。在芳氧基环的2，3-位或4-位二取代得到的化合物具有较低的ISA水平，并且在某些情况下改善了作用时间。所有这些化合物都是血管扩张药，但5-甲基哒嗪酮衍生物的抗高血压活性始终高于其5-H较低的同系物。
• Studies on Agents with Vasodilator and ,B-Blocking Activities. IV.
  作者：Toshimi SEKI、Tomio NAKAO、Takeshi MASUDA、Kohichi HASUMI、Kotaro GOTANDA、Tsutomu ISHIMORI、Seijiro HONMA、Nobuyoshi MINAMI、Kenyu SHIBATA、Kikuo YASUDA

  DOI：10.1248/cpb.44.2061

  日期：——

  A series of novel pyridazinone derivatives (II) having a phenoxypropanolamine moiety was synthesized. Their hypotensive and β-blocking activities were evaluated after intravenous administration of the compounds to anesthetized rats. Among them, the 5-chloro-2-cyanophenoxy derivative (29) showed the promising dual activities and was selected for further studies.

  合成了一系列具有苯氧基丙醇胺结构的新型哒嗪酮衍生物（II）。在静脉注射给麻醉大鼠后，评估了它们的降压和β-阻断活性。其中，5-氯-2-氰基苯氧基衍生物（29）显示出有前途的双重活性，并被选中进行进一步研究。
• Studies on Agents with Vasodilator and .BETA.-Blocking Activities. II.
  作者：Toshimi SEKI、Takayuki TAKEZAKI、Rikio OHUCHI、Hiroshi OHUYABU、Yoshitaka TANIMOTO、Takashi YAMAGUCHI、Norinobu SAITOH、Tsutomu ISHIMORI、Kikuo YASUDA

  DOI：10.1248/cpb.43.247

  日期：——

  A series of phenoxypropanolamines having a hydrazinopyridazinyl moiety was synthesized. Their hypotensive and β-blocking activities were evaluated after intravenous administration of the compounds to anethetized rats.Some of them exhibited both activities. In particular, compound 20k is a candidate for clinical use due to its hypotensive activity, equal to that of hydralazine, and its β-blocking activity, 2.7-fold more potent than that of propranolol.

  一系列含有哒嗪基肼结构的苯氧丙醇胺类化合物被合成，并通过静脉注射给麻醉大鼠后评估了它们的降压和β阻断活性。其中一些化合物显示了这两种活性。特别是化合物20k，由于其降压活性与肼达嗪相当，且β阻断活性比普萘洛尔强2.7倍，因此被认为是临床应用的候选药物。
• Substituted 3-phenoxy-1-alkoxycarbonylalkylamino-propanol-2-s having
  申请人：E. I. du Pont de Nemours & Co.

  公开号：US05051446A1

  公开（公告）日：1991-09-24

  The present invention relates to new compounds of the formula I ##STR1## as well as their preparation, pharmaceutical preparations containing same, and method of treating acute myocardial infarction. The compounds which possess beta-adrenoceptor blocking activity are very shortacting and are preferably intended for treatment of acute myocardial infarction by administration by means of injection.

  本发明涉及公式I的新化合物，以及它们的制备、含有这些化合物的药物制剂，以及治疗急性心肌梗死的方法。具有β-肾上腺素受体阻滞活性的这些化合物作用时间很短，最好用注射的方式进行急性心肌梗死的治疗。
• Stereoselectivity in the metabolism of the .BETA.-adrenergic blocking agent, (.+-.)-1-tert-butylamino-3-(2,3-dimethylphenoxy)-2-propanol hydrochloride (xibenolol hydrochloride, D-32), in man.
  作者：SEIJIRO HONMA、TOMIHARU ITO、AKIRA KAMBEGAWA

  DOI：10.1248/cpb.33.760

  日期：——

  After oral administration of deuterium-labeled pseudoracemic D-32 to human subjects, the enantiomeric metabolites in plasma and urine were analyzed by gas chromatography-mass spectrometry. D-32 was biotransformed to 3 major metabolites, 4-hydroxy D-32, 3-hydroxymethyl D-32 and 3-carboxy D-32. Twenty-five percent of the racemic dose was excreted into the urine as 4-hydroxy D-32, and 80% of 4-hydroxy D-32 in the urine was derived from (-)-D-32. Sixty percent of 3-carboxy D-32 in the urine was derived from (+)-D-32. About 1% of the racemic dose was excreted into the urine as unchanged material, but of this, in which (+)-D-32 amounted to 3-5 times more than (-)-D-32. The area under the plasma concentration-time curve of (-)-4-hydroxy D-32 was 2.6 times larger than that of (+)-4-hydroxy D-32. The half-lives of (-)-4-hydroxy D-32, (+)-4-hydroxy D-32 and both enantiomers of D-32 were 3.8, 2.4 and 3h, respectively. Thus, a marked difference in the metabolism between (-)-D-32 and (+)-D-32 was found. As 4-hydroxy D-32 and 3-hydroxymethyl D-32 are the active metabolites, the pharmacological effectiveness of D-32 after oral administration is represented by the total amount of (-)-4-hydroxy D-32 and (-)-3-hydroxymethyl D-32.

  口服给药氘标记的伪外消旋D-32后，分析了人类受试者血浆和尿液中的对映体代谢物，采用气相色谱-质谱法。D-32转化为三种主要代谢物，分别是4-羟基D-32、3-羟甲基D-32和3-羧基D-32。25%的外消旋剂量以4-羟基D-32的形式排泄到尿液中，尿液中80%的4-羟基D-32来源于(-)-D-32。尿液中60%的3-羧基D-32来源于(+)-D-32。约1%的外消旋剂量以未改变的物质形式排泄到尿液中，其中(+)-D-32的量是(-)-D-32的3-5倍。(-)-4-羟基D-32的血浆浓度-时间曲线下面积是(+)-4-羟基D-32的2.6倍。(-)-4-羟基D-32、(+)-4-羟基D-32以及两种D-32对映体的半衰期分别为3.8小时、2.4小时和3小时。因此，发现(-)-D-32和(+)-D-32在代谢上存在显著差异。由于4-羟基D-32和3-羟甲基D-32是活性代谢物，因此口服给药后D-32的药效由(-)-4-羟基D-32和(-)-3-羟甲基D-32的总量决定。