2-(2-isopropyl-6-methoxyphenoxy)ethanoyl chloride | 659727-85-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(2-isopropyl-6-methoxyphenoxy)ethanoyl chloride
• 英文别名: 2-(2-i-propyl-6-methoxyphenoxy)ethanoyl chloride；2-(2-Methoxy-6-propan-2-ylphenoxy)acetyl chloride
• CAS: 659727-85-2
• 化学式: C₁₂H₁₅ClO₃
• 分子量: 242.702
• InChiKey: JAQXTJCVXBLQCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-哌嗪基-4-氨基-6,7-二甲氧基喹唑啉 、 2-(2-isopropyl-6-methoxyphenoxy)ethanoyl chloride 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 8.0h， 生成 Rec 15/2615
  参考文献：
  名称：

  Synthesis, Pharmacological Evaluation, and Structure−Activity Relationship and Quantitative Structure−Activity Relationship Studies on Novel Derivatives of 2,4-Diamino-6,7-dimethoxyquinazoline α₁-Adrenoceptor Antagonists

  摘要：

  A new series of novel piperazine and non-piperazine derivatives of 2,4-diamino-6,7-dimethoxyquinazoline was synthesized and evaluated for binding affinity toward alpha(1)-adrenergic and other G-protein-coupled aminergic receptors. The alpha(1)-adrenoceptor (AR) subtype selectivity was also investigated for the most interesting compounds. Only compound 16 showed moderate selectivity toward the alpha(1b)-AR subtype. Selected compounds were tested in vivo in a dog model indicating activity on blood pressure and on the lower urinary tract. Compound 10 showed in vivo potency close to that of prazosin. Powerful interpretative and predictive theoretical QSAR models have been obtained. The theoretical descriptors employed in the rationalization of the alpha(1)-adrenergic binding affinity depict the key features for receptor binding which can be summarized in an electrostatic interaction between the protonated amine function and a primary nucleophilic site of the receptor, complemented by short-range attractive (polar and dispersive) and repulsive (steric) intermolecular interactions. Moreover, on predictive grounds, the ad hoc derived size and shape QSAR model developed in a previous paper (Rastelli, G.; et al. J. Mol. Struct. 1991, 251, 307-318) proved to be successful in predicting nanomolar alpha(1)-adrenergic binding affinity for compound 28.

  DOI：

  10.1021/jm9805337
• 作为产物：
  描述：

  2-(2-isopropyl-6-methoxyphenoxy)acetic acid 生成 2-(2-isopropyl-6-methoxyphenoxy)ethanoyl chloride
  参考文献：
  名称：

  Quinazolinyl-amino derivatives having .alpha.-antagonist activity

  摘要：

  本文描述了新的喹唑啉基氨基衍生物，可用作α1-肾上腺素受体阻滞剂。这些化合物可用作治疗与α-肾上腺素能系统过度活跃相关的疾病和疾病的治疗剂，例如动脉高血压、前列腺良性增生、高眼压和高胆固醇血症。本文还描述了制备上述化合物的方法。

  公开号：

  US05798362A1

文献信息

• Chiral analogues of (+)-cyclazosin as potent α1B-adrenoceptor selective antagonist
  作者：Gianni Sagratini、Michela Buccioni、Gabriella Marucci、Elena Poggesi、Matthew Skorski、Stefano Costanzi、Dario Giardinà

  DOI：10.1016/j.bmc.2018.05.023

  日期：2018.7

  or amine groups, namely (−)-2, (+)-3, (−)-4–(−)-8, (+)-9. Moreover, we studied the activity of some their opposite enantiomers, namely (−)-1, (−)-3, (+)-6, and (−)-9, to evaluate the influence of stereochemistry on selectivity. The benzyloxycarbonyl and methyl (4aS,8aR) analogues (+)-3 and (−)-6 improved in a significant way the α1B selectivity of the progenitor compound: 4 and 14 time vs. the α1D subtype

  （+） - Cyclazosin [（+） - 1]是α的最选择性拮抗剂之一1B -肾上腺素能受体亚型（选择性比率，α 1B /α 1A  = 13，α 1B /α 1D  = 38-39）。为了提高选择性，我们合成和药理学上研究针对α的阻断活性1的几个纯手性类似物（+）的肾上腺素能受体-配cyclazosin在羰基或胺基团，即不同的取代基（ - ） - 2，（+） - 3-，（−）-4 – （−）-8，（+）-9。此外，我们研究了一些相反的对映异构体（-）的活性-1，（-）-3，（+）-6和（-）-9来评估立体化学对选择性的影响。苄氧羰基和甲基（4a S，8a R）类似物（+）-3和（-）-6以显着方式提高了前体化合物的α1B选择性：与α1D亚型和35和35相比，分别为4和14倍。分别是α1A亚型的77倍。该研究证实了疏水性的重要性CIS建立相互作用与α这些分子的-octahydroqu
• Searching for cyclazosin analogues as α1B-adrenoceptor antagonists
  作者：Dario Giardinà、O Polimanti、G Sagratini、P Angeli、U Gulini、G Marucci、C Melchiorre、E Poggesi、A Leonardi

  DOI：10.1016/s0014-827x(02)00025-3

  日期：2003.7

  A series of quinazoline derivatives, 2-20, structurally related to the racemic alpha(1)-adrenoceptor antagonist cyclazosin (1), were synthesized and evaluated for their functional antagonism at alpha(1)- and alpha(2)-adrenoceptors and for their binding affinity at human cloned alpha(1a)-, alpha(1b)- and alpha(1d)-adrenoceptor subtypes. They displayed, like 1, preferential antagonism and selectivity for alpha(1) versus alpha(2)-adrenoceptors. Compounds 10, 13, and 18 showed high potency at alpha(1)-adrenoceptors similar to that of 1 (pK(B) values 8.47-8.89 versus 8.67), whereas 13 and 15 were endowed with the highest alpha(1)-adrenoceptor selectivity, only 3- to 4-fold lower than that of 1. In binding experiments, all of the compounds displayed an affinity practically similar to that found for 1, with the exception of 19 and 20 that were definitely less potent. The s-triazine analogue 18 was the most potent of the series with pK(i) values of 10.15 (alpha(1a)), 10.22 (alpha(1b)) and 10.40 (alpha(1d)), resulting 77-fold more potent than 1 at alpha(1a)-adrenoceptors. In addition, the majority of compounds, like prototype 1, showed the same trend of preferential affinity for alpha(1d)- and alpha(1b)-adrenoceptors that alpha(1a)-subtype. In conclusion, we identified compounds 2-5, 10, 12 and 13, bearing either an aliphatic- or an arylalkyl- or aryloxyalkyl-acyl function, with an interesting subtype-selectivity profile, which makes them suitable candidates for their resolution as enantiomers structurally related to (+)-cyclazosin.
• J. Med. Chem. 1999, 42, 427-437
  作者：

  DOI：——

  日期：——