trans-3-(chloroacetamido)-6-methoxy-3,4-dihydro-2H-1-benzopyran-4-ol | 116004-91-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: trans-3-(chloroacetamido)-6-methoxy-3,4-dihydro-2H-1-benzopyran-4-ol
• 英文别名: 2-chloro-N-(4-hydroxy-6-methoxychroman-3-yl)acetamide
• CAS: 116004-91-2
• 化学式: C₁₂H₁₄ClNO₄
• 分子量: 271.7
• InChiKey: UOMOQTSDKLVZSA-CABZTGNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.84
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  67.79
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  trans-3-(chloroacetamido)-6-methoxy-3,4-dihydro-2H-1-benzopyran-4-ol 在 sodium hydroxide 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 4.0h， 生成 trans-9-methoxy-3,4,4a,10b-tetrahydro-2H,5H-1-benzopyrano<4,3-b>-1,4-oxazine
  参考文献：
  名称：

  Synthesis and pharmacology of trans-4-n-propyl-3,4,4a,10b-tetrahydro-2H,5H-1-benzopyrano[4,3-b]1,4-oxazin-7- and -9-ols. The significance of nitrogen pka values for central dopamine receptor activation

  摘要：

  The 6-oxa analogues of potent dopamine agonists, hexahydronaphthoxazines (4a,4b), have been tested for dopamine receptor binding and stimulating activity and were found to be almost inactive. pKa value determinations indicated that these compounds are protonated to approximately 2%, while potent compounds are protonated to a much greater extent. These results strongly support the assumption that the protonated form of DA agonists is the active species at the receptor.

  DOI：

  10.1021/jm00119a020
• 作为产物：
  描述：

  3-amino-6-methoxychroman-4-one hydrochloride 在 sodium tetrahydroborate 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 2.0h， 生成 trans-3-(chloroacetamido)-6-methoxy-3,4-dihydro-2H-1-benzopyran-4-ol
  参考文献：
  名称：

  Synthesis and pharmacology of trans-4-n-propyl-3,4,4a,10b-tetrahydro-2H,5H-1-benzopyrano[4,3-b]1,4-oxazin-7- and -9-ols. The significance of nitrogen pka values for central dopamine receptor activation

  摘要：

  The 6-oxa analogues of potent dopamine agonists, hexahydronaphthoxazines (4a,4b), have been tested for dopamine receptor binding and stimulating activity and were found to be almost inactive. pKa value determinations indicated that these compounds are protonated to approximately 2%, while potent compounds are protonated to a much greater extent. These results strongly support the assumption that the protonated form of DA agonists is the active species at the receptor.

  DOI：

  10.1021/jm00119a020

文献信息

• Exception That Proves the Rule: Investigation of Privileged Stereochemistry in Designing Dopamine D₃R Bitopic Agonists
  作者：Francisco O. Battiti、Amy Hauck Newman、Alessandro Bonifazi

  DOI：10.1021/acsmedchemlett.9b00660

  日期：2020.10.8

  D3R agonist FOB02-04A (5), we investigated the chemical space around the linker portion of the molecule via insertion of a hydroxyl substituent and ring-expansion of the trans-cyclopropyl moiety into a trans-cyclohexyl scaffold. Moreover, to further elucidate the importance of the primary pharmacophore stereochemistry in the design of bitopic ligands, we investigated the chiral requirements of (+)-PD128907

  在这项研究中，从我们的选择性 D 3 R 激动剂FOB02-04A ( 5 ) 开始，我们通过插入羟基取代基和反式环丙基部分环扩展成反式，研究了分子接头部分周围的化学空间。-环己基支架。此外，为了进一步阐明主要药效团立体化学在双位配体设计中的重要性，我们通过合成和解析研究了(+)-PD128907 ( (+)-(4a R ,10b R )-2) )的手性要求所有顺式和反式中的双位类似物其-9-甲氧基-3,4,4a，10b-四氢-2-组合ħ，5 ħ -chromeno [4,3- b ] [1,4]恶嗪骨架。尽管在获得具有改进生物特征的新类似物方面缺乏成功，但与我们目前的先导相比，由于生物特征较差或根本没有改进而导致的“负面”结果对于更好地理解化学空间和用于目标识别的最佳立体化学至关重要。在此，我们确定了必要的结构信息，以了解正构和双位配体-受体结合相互作用之间的差异，区分 D 3 R 活性