2-hydroxymethyl-2-methyl-2,3-dihydro-1,4-benzodioxin | 16163-83-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 2-hydroxymethyl-2-methyl-2,3-dihydro-1,4-benzodioxin
• 英文别名: 2,3-dihydro-2-methyl-1,4-benzodioxin-2-methanol；2-hydroxymethyl-2-methyl-1,4-benzodioxan；(2-Methyl-2,3-dihydro-1,4-benzodioxin-2-yl)methanol；(3-methyl-2H-1,4-benzodioxin-3-yl)methanol
• CAS: 16163-83-0
• 化学式: C₁₀H₁₂O₃
• mdl: MFCD00957234
• 分子量: 180.203
• InChiKey: AUTFPLSMEDVRPW-UHFFFAOYSA-N

物化性质

• 熔点：
  64-66 °C(Solv: ligroine (8032-32-4))
• 沸点：
  278.7±19.0 °C(Predicted)
• 密度：
  1.160±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxymethyl-2-methyl-2,3-dihydro-1,4-benzodioxin 在 chromium(VI) oxide 、 硫酸 作用下， 以 丙酮 为溶剂， 反应 18.0h， 生成 2-methyl-1,4-benzodioxan-2-carboxylic acid
  参考文献：
  名称：

  2,4-Diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-Benzodioxan-2-ylcarbonyl)piperazin-1-yl] derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents

  摘要：

  A series of 4-amino-2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1 -yl]-6, 7-dimethoxyquinazoline derivatives was synthesized for evaluation as alpha-antagonists and antihypertensive agents. Most compounds displayed high (nM) binding affinity for alpha 1-adrenoceptors with no significant activity at alpha 2-sites. Selective antagonism of the alpha 1-mediated vasoconstrictor effects of norepinephrine is also characteristic of the series. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented, and structural similarity between the 2,4-diamino-6,7-dimethoxyquinazoline nucleus and norepinephrine is established. An alpha 1-receptor model is presented in which charge-reinforced hydrogen bonding is important for binding of both antagonist and agonist molecules. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and several compounds displayed similar efficacy to prazosin when assessed after 6 h. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compound 1 (doxazosin) was selected for further evaluation and is currently progressing through phase III clinical trials.

  DOI：

  10.1021/jm00384a009
• 作为产物：
  描述：

  2-hydroxy-2-methyl-1,4-benzodioxan 在 氢氧化钾 、 lithium aluminium tetrahydride 、 三氟化硼乙醚 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 2-hydroxymethyl-2-methyl-2,3-dihydro-1,4-benzodioxin
  参考文献：
  名称：

  Convenient synthesis of 2,2-disubstituted-2,3-dihydro-1,4-benzodioxins from 2-substituted-2-hydroxy-2,3-dihydro-1,4-benzodioxins

  摘要：

  Convenient syntheses of relatively rare 2,2-disubstituted-2,3-dihydro-1,4-benzodioxins from 2-substituted-2-hydroxy 2,3-dihydro-1,4-benzodioxins, as key synthetic intermediates, are reported. These new synthetic approaches require Lewis acid BF3-Et(2)O mediated nucleophilic substitution reaction or cyclization of suitable hydroxyphenols. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(96)01140-4

文献信息

• (2-Alkyl-1,4-benzodioxan-2-yl)carboxylic acids as potential hypolipidemic agents
  作者：Aldo Salimbeni、Elso Manghisi

  DOI：10.1002/jhet.5570170313

  日期：1980.5

  4-benzodioxane, V, and 1,5-benzodioxepine, VII, alcohols. From potassium permanganate oxidation of benzodioxane compounds V the corresponding (2-alkyl-1,4-benzodioxan-2-yl)carboxylic acids II were obtained. In a preliminary pharmacological evaluation benzodioxane acids II did not show any effect on plasma cholesterol, while producing a moderate lowering of triglycerides.

  1，2-二酚与2-烷基-3-氯-1，2-环氧丙烷反应，得到1，4-苯并二恶烷V和1，5-苯并二氧杂庚烷VII的醇的混合物。由高锰酸钾氧化苯并二恶烷化合物V，得到相应的（2-烷基-1，4-苯并二恶烷-2-基）羧酸II。在初步的药理学评估中，苯并二恶烷酸II对血浆胆固醇没有显示任何影响，同时会导致甘油三酸酯的适度降低。
• Benzodioxanyl imidazoline compounds, compositions and use
  申请人：Reckitt & Colman Products Limited

  公开号：US04397860A1

  公开（公告）日：1983-08-09

  Imidazoline derivatives of the formula ##STR1## wherein R.sup.1 is alkyl C.sub.1-7, alkenyl C.sub.2-4, cycloalkenyl C.sub.4-7, cycloalkyl C.sub.4-7 or phenyl; and their non-toxic salts. Processes for the preparation and pharmaceutical compositions thereof. The compounds exhibit presynaptic .alpha..sub.2 -adrenoreceptor antagonism.

  Imidazoline衍生物的化学式为##STR1##，其中R.sup.1为烷基C.sub.1-7，烯基C.sub.2-4，环烯基C.sub.4-7，环烷基C.sub.4-7或苯基；以及它们的无毒盐。其制备方法和药物组合物。这些化合物表现出前突触α2-肾上腺素受体拮抗作用。
• Antihypertensive 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)
  申请人：Pfizer Inc.

  公开号：US04188390A1

  公开（公告）日：1980-02-12

  Compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R represents 6,7-di(lower alkoxy) or 6,7,8-tri(lower alkoxy); m is 1 or 2, X is --CHR.sup.1 -- or --CH.sub.2 CH.sub.2 --; each R.sup.1 and R.sup.0 may be the same or different and is hydrogen or lower alkyl; each of R.sup.2 and R.sup.3 is hydrogen, lower alkoxy, lower alkyl, halogen, lower alkanoyl, lower alkoxycarbonyl, --CONR.sup.4 R.sup.5 or --SO.sub.2 NR.sup.4 R.sup.5 wherein each of R.sup.4 and R.sup.5 is hydrogen or lower alkyl; processes for their preparation; and their use as regulators of the cardiovascular system, and particularly in the treatment of hypertension.

  具有以下式子##STR1##和其药学上可接受的盐，其中R代表6,7-二(低烷氧基)或6,7,8-三(低烷氧基)；m为1或2，X为--CHR.sup.1 --或--CH.sub.2 CH.sub.2 --；每个R.sup.1和R.sup.0可以相同或不同，且为氢或低烷基；R.sup.2和R.sup.3中的每一个都为氢、低烷氧基、低烷基、卤素、低烷酰基、低烷氧羰基、--CONR.sup.4 R.sup.5或--SO.sub.2 NR.sup.4 R.sup.5，其中每个R.sup.4和R.sup.5为氢或低烷基；它们的制备过程；以及它们作为心血管系统调节剂的用途，特别是用于治疗高血压。
• <i>N</i>-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents
  作者：Alan M. Birch、Paul A. Bradley、Julie C. Gill、Frank Kerrigan、Pat L. Needham

  DOI：10.1021/jm9910122

  日期：1999.8.1

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.
• Salimbeni, Aldo; Manghisi, Elso; Arnone, Alberto, Journal of Heterocyclic Chemistry, 1988, vol. 25, p. 943 - 947
  作者：Salimbeni, Aldo、Manghisi, Elso、Arnone, Alberto

  DOI：——

  日期：——