[2-[(Benzodioxol-5-yl)oxy]ethyl]amine | 72955-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: [2-[(Benzodioxol-5-yl)oxy]ethyl]amine
• 英文别名: 2-benzo[1,3]dioxol-5-yloxy-ethylamine；2-(3,4-methylenedioxyphenoxy)-ethylamine；5-(2-aminoethoxy)-2H-1,3-benzodioxole；2-(1,3-benzodioxol-5-yloxy)ethanamine
• CAS: 72955-85-2
• 化学式: C₉H₁₁NO₃
• mdl: MFCD09906751
• 分子量: 181.191
• InChiKey: ZMEQUDXFAHZUPR-UHFFFAOYSA-N

物化性质

• 沸点：
  296.4±28.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  53.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  [2-[(Benzodioxol-5-yl)oxy]ethyl]amine 在 吡啶 、 三氯氧磷 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 6.0h， 生成 9-Phenyl-6,7-dihydro-1,3,5-trioxa-8-aza-cyclohepta[f]indene
  参考文献：
  名称：

  Bremner, John B.; Browne, Elaine J.; Gunawardana, Indrani W. K., Australian Journal of Chemistry, 1984, vol. 37, # 1, p. 129 - 141

  摘要：

  DOI：
• 作为产物：
  描述：

  (1,3-苯并二氧戊环-5-基氧基)乙腈 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.0h， 以87%的产率得到[2-[(Benzodioxol-5-yl)oxy]ethyl]amine
  参考文献：
  名称：

  Bremner, John B.; Browne, Elaine J.; Gunawardana, Indrani W. K., Australian Journal of Chemistry, 1984, vol. 37, # 1, p. 129 - 141

  摘要：

  DOI：

文献信息

• Carbazolyl-(4)-oxypropanolamine compounds and therapeutic compositions
  申请人：Boehringer Mannheim GmbH

  公开号：US04503067A1

  公开（公告）日：1985-03-05

  Carbazolyl-(4)-oxypropanolamine compounds of the formula ##STR1## wherein R.sub.1 is hydrogen, lower alkanoyl or aroyl; R.sub.2 is hydrogen, lower alkyl or arylalkyl; R.sub.3 is hydrogen or lower alkyl; R.sub.4 is hydrogen or lower alkyl, or when X is oxygen, R.sub.4 together with R.sub.5 can represent --CH.sub.2 --O--; X is a valency bond, --CH.sub.2 --, oxygen or sulfur; Ar is mono- or bicyclic aryl or pyridyl; R.sub.5 and R.sub.6 are individually selected from hydrogen, halogen, hydroxyl, lower alkyl, aminocarbonyl, lower alkoxy, aralkyloxy, lower alkylthio, lower alkylsulphinyl or lower alkylsulphonyl; R.sub.5 and R.sub.6 together can represent methylenedioxy; and the salts thereof with physiologically acceptable acids are outstandingly effective in the treatment and prophylaxis of circulatory and cardiac diseases, e.g., hypertension and angina pectoris.

  Carbazolyl-(4)-oxypropanolamine化合物的化学式为##STR1##其中R.sub.1是氢，较低的烷酰基或芳酰基；R.sub.2是氢，较低的烷基或芳基烷基；R.sub.3是氢或较低的烷基；R.sub.4是氢或较低的烷基，或者当X是氧时，R.sub.4与R.sub.5一起可以代表--CH.sub.2--O--；X是一个价键，--CH.sub.2--，氧或硫；Ar是单环或双环芳基或吡啶基；R.sub.5和R.sub.6分别选自氢，卤素，羟基，较低的烷基，氨基甲酰基，较低的烷氧基，芳基烷氧基，较低的烷基硫基，较低的烷基磺基；R.sub.5和R.sub.6一起可以代表亚甲二氧基；以及它们与生理上可接受的酸盐在治疗和预防循环和心脏疾病，例如高血压和心绞痛方面具有卓越的疗效。
• Change of Mechanical Activity to Contraction from the Relaxation Induced by the Intracellular Ca2+ Antagonist KT-362; Effects of Alkylation of Side Chain, and Substitution of 2,3,4,5-Tetrahydro-1,5-Benzothiazepine Derivatives.
  作者：Naoto UEYAMA、Shyuichi WAKABAYASHI、Tsuyoshi TOMIYAMA

  DOI：10.1248/cpb.45.1761

  日期：——

  KT-362 (5-[3-[2-(3, 4-Dimethoxyphenyl)ethyl]aminopropionyl]-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine fumarate) is an intracellular Ca2+ antagonist. The compound obtained by introducing methyl groups onto the nitrogen (R2) of the side chain of KT-362 showed vasoconstrictive activity. Therefore we synthesized various derivatives, and examined their activities. Substitution at position R2 of the side chain resulted in potent contractile activity, and the optimal alkyl length was to or three carbons. The potency was further increased by the introduction of a chloro group at the R1 position of 2, 3, 4, 5-tetrahydro-1, 5-benzothiazepines. One of the synthesized compounds, 8-chloro-5-N-ethyl-N-[2-(3, 4-dimethyoxyphenyl)ethyl]aminopropionyl}-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine fumarate (9b), showed an EC50 value of 3.47×10-8 M for contraction of rabbit iliac artery. The action of compound 9b was antagonized competitively by an H1-histamine receptor antagonist, diphenhydramine, and the pA2 value was 7.82. The maximum constriction was inhibited by a Ca2+ entry blocker, nicardipine, but not by an α1-adrenoreceptor antagonist, prazosin. In a Ca2+-free medium, tonic constriction induced by 9b disappeared, and only a phasic constriction was oberved. Though this phasic constriction was inhibited by diphenhydramine, it was not inhibited by prazosin or nicardipine.

  KT-362 （5-[3-[2-(3, 4-二甲氧基苯基)乙基]氨基丙酰基]-2, 3, 4, 5-四氢-1, 5-苯并硫氮杂卓富马酸盐）是一种细胞内 Ca2+ 拮抗剂。在 KT-362 侧链的氮（R2）上引入甲基后得到的化合物具有收缩血管的活性。因此，我们合成了多种衍生物，并研究了它们的活性。侧链 R2 位置的取代可产生强效收缩活性，最佳烷基长度为一到三个碳原子。在 2, 3, 4, 5-四氢-1, 5-苯并硫氮杂卓的 R1 位引入一个氯基，可进一步提高药效。合成的化合物之一，8-氯-5-N-乙基-N-[2-（3，4-二甲氧基苯基）乙基]氨基丙酰基}-2，3，4，5-四氢-1，5-苯并硫氮杂卓富马酸盐（9b）对兔髂动脉收缩的 EC50 值为 3.47×10-8 M。化合物 9b 的作用被 H1-组胺受体拮抗剂苯海拉明竞争性拮抗，pA2 值为 7.82。Ca2+ 进入阻断剂尼卡地平能抑制最大收缩，但α1-肾上腺素受体拮抗剂哌唑嗪不能抑制收缩。在不含 Ca2+ 的介质中，9b 诱导的强直性收缩消失了，只有阶段性收缩。虽然苯海拉明能抑制这种阶段性收缩，但哌唑嗪或尼卡地平却不能抑制这种收缩。
• Multitarget 1,4-Dioxane Compounds Combining Favorable D₂-like and 5-HT_1A Receptor Interactions with Potential for the Treatment of Parkinson’s Disease or Schizophrenia
  作者：Fabio Del Bello、Dario Ambrosini、Alessandro Bonifazi、Amy H. Newman、Thomas M. Keck、Mario Giannella、Gianfabio Giorgioni、Alessandro Piergentili、Loredana Cappellacci、Antonio Cilia、Silvia Franchini、Wilma Quaglia

  DOI：10.1021/acschemneuro.8b00677

  日期：2019.5.15

  2-methoxy derivative 3 showed a multitarget combination of 5-HT1A/D4 agonism and D2/D3/5-HT2A antagonism, which may be a favorable profile for the treatment of schizophrenia. Interestingly, the 3-hydroxy derivative 8 behaved as a partial agonist at D2 and as a potent full agonist at D3 and D4 subtypes. In addition to its potent 5-HT1A receptor agonism, such a dopaminergic profile makes 8 a potential multitarget

  N-((6,6-diphenyl-1,4-dioxan-2-yl)methyl)-2-phenoxyethan-1-amine 骨架苯氧基部分不同位置的甲氧基和羟基取代对亲和力的影响评估了 D2 样、5-HT1A 和 α1-肾上腺素能受体亚型的活性。发现了具有多巴胺能和血清素能谱的合适组合的多目标化合物。特别是，2-甲氧基衍生物 3 表现出 5-HT1A/D4 激动和 D2/D3/5-HT2A 拮抗的多靶点组合，这可能是治疗精神分裂症的有利特征。有趣的是，3-羟基衍生物 8 在 D2 中充当部分激动剂，在 D3 和 D4 亚型中充当有效的完全激动剂。除了其有效的 5-HT1A 受体激动作用外，这种多巴胺能谱使 8 成为治疗帕金森症的潜在多靶点化合物 s 疾病 (PD)。事实上，5-HT1A 受体的激活可能有助于减少与多巴胺能刺激相关的运动障碍副作用。
• Synthesis and calcium ion antagonistic activity of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzothiazines
  作者：Masanobu Fujita、Susumu Ito、Atsutoshi Ota、Nobuharu Kato、Koji Yamamoto、Yoichi Kawashima、Hideyasu Yamauchi、Junichi Iwao

  DOI：10.1021/jm00169a011

  日期：1990.7

  As an extension of the previous investigation (J. Med. Chem. 1988, 31, 919), we synthesized a series of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H- 1,4-benzothiazines (3) and evaluated their Ca2+ antagonistic activities. Ca2+ antagonistic activity was measured with isolated depolarized guinea pig taenia cecum. On the basis of their potent Ca2+ antagonistic activity, six benzothiazines were selected and further evaluated for their vasocardioselectivity. Among these six compounds, the key compound 15 [3,4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[3,4- (methylenedioxy)phenoxy]ethyl]amino]propoxy]phenyl]-4-methyl-3-oxo- 2H-1,4-benzothiazine hydrogen fumarate] was recognized as having the lowest cardioselectivity. Following optical resolution, the absolute configuration of the compound's optically active enantiomer was determined by means of X-ray crystallography of a synthetic precursor (+)-4a. The Ca2+ antagonistic activity of 15 was found to reside primarily in (+)-15 (which was about 7 times more potent than (-)-15). The in vitro study showed that (+)-15 had a low cardioselectivity compared to verapamil and diltiazem. This result suggests that (+)-15 would exhibit less adverse effects due to cardiac inhibition than diltiazem and verapamil in therapeutic use.
• Novel Calcium Antagonists with Both Calcium Overload Inhibition and Antioxidant Activity. 2. Structure−Activity Relationships of Thiazolidinone Derivatives
  作者：Tatsuya Kato、Tomokazu Ozaki、Kazuhiko Tamura、Yoshiyuki Suzuki、Michitaka Akima、Nobuhiro Ohi

  DOI：10.1021/jm9900927

  日期：1999.8.1

  CP-060 (1), 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-[3-[N-methyl-N-[2-[3,4-(methylenedioxy)phenoxy]ethyl]amino]propyl]-1,3-thiazolidin-4-one, is a novel type of Ca2+ antagonist possessing both Ca2+ overload inhibition and antioxidant activity. The structure-activity relationships for this series of compounds were studied by synthesizing the analogues and evaluating these three kinds of activity. Ca2+ antagonistic activity was largely determined by the lipophilicity of the phenyl group at the 2-position and the length of the alkyl chains. As for-the antioxidant activity, it was demonstrated that the phenolic hydroxyl group is an essential structural element. Compounds with potent activity were! evaluated for their effect on the coronary blood flow in vivo. Among these compounds, compound 1 was shown to be the most potent. Furthermore, the enantiomers of 1 were resolved by high-performance liquid chromatography with a chiral column. Compound (-)-1 showed about 10 times higher Ca2+ antagonistic activity than (+)-1, though both enarrtiomers had similar potency in Ca2+ overload inhibition and antioxidant activity. An X-ray crystal structure determination of (-)-1 hydrogen fumarate identified (-)-1 as having S configuration at the 2-position.