(+/-)-1,10a-dihydropyrrolo<1,2-b>isoquinoline-3,10(2H,5H)dione | 103201-08-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (+/-)-1,10a-dihydropyrrolo<1,2-b>isoquinoline-3,10(2H,5H)dione
• 英文别名: 1,2,3,5,10,10a-hexahydrobenzindolizine-3,10-dione；1,2-dihydropyrrolo[1,2-b]isoquinoline-3,10(5H,10aH)-dione；1,2,3,5,10,10a-hexahydropyrrolo[1,2-b]isoquinolin-3,10dione；1,10a-Dihydropyrrolo[1,2-b]isoquinoline-3,10[2H,5H]-dione；1,2,5,10a-tetrahydropyrrolo[1,2-b]isoquinoline-3,10-dione
• CAS: 103201-08-7
• 化学式: C₁₂H₁₁NO₂
• 分子量: 201.225
• InChiKey: LBXRLFJWQZJFGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-1,10a-dihydropyrrolo<1,2-b>isoquinoline-3,10(2H,5H)dione 在 盐酸羟胺 、 sodium acetate trihydrate 作用下， 以 乙醇 、 水 为溶剂， 生成 1,10a-dihydropyrrolo[1,2-b]isoquinoline-3,10[2H,5H]-dione oxime
  参考文献：
  名称：

  Benzoc[c]-1,5-naphthyridines and related compounds as memory enhancing

  摘要：

  公开了一种新颖的化合物，其化学式为##STR1##其中m为1或2；每个X独立地为H、卤素、较低烷基、较低烷氧基、--CF.sub.3或--OH；R为H、较低烷基、氯代较低烷基、溴代较低烷基、碘代较低烷基、氨基较低烷基、较低烷基氨基较低烷基、二较低烷基氨基较低烷基、芳基较低烷基、二芳基较低烷基、噻吩基较低烷基、呋喃基较低烷基、较低烷酰基、氯代较低烷酰基、溴代较低烷酰基、碘代较低烷酰基、氨基较低烷酰基、较低烷基氨基较低烷酰基、二较低烷基氨基较低烷酰基、芳酰基、芳基较低烷酰基或二芳基较低烷酰基、噻吩基较低烷酰基、呋喃基较低烷酰基；而R.sub.1为.dbd.O、##STR2##或--NR.sub.2 R.sub.3，其中R.sub.2和R.sub.3独立地为H或较低烷基，或与它们连接的氮原子一起构成##STR3##R.sub.4又为H、较低烷基、羟基较低烷基、芳基、芳基较低烷基或二芳基较低烷基，但有一个限制条件，即当R.sub.1为--NR.sub.2 R.sub.3时，R不存在，当R.sub.1为.dbd.O时，R不是酰基，当R.sub.1为##STR4##时，R不是氯代较低烷基、溴代较低烷基或碘代较低烷基；或其药学上可接受的酸盐，用于增强记忆。

  公开号：

  US04742061A1
• 作为产物：
  描述：

  5-氧代吡咯烷-2-羧酸乙酯 在 aluminum (III) chloride 、 氯化亚砜 、 sodium hydride 、 sodium hydroxide 作用下， 以 水 、 苯 为溶剂， 反应 32.0h， 生成 (+/-)-1,10a-dihydropyrrolo<1,2-b>isoquinoline-3,10(2H,5H)dione
  参考文献：
  名称：

  Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands

  摘要：

  A series of 17-cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3 '-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1 '- and/or 4 '-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6 '- and/or 7 '-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6 '-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.02.055

文献信息

• Benzo(c)-1,5-naphthyridines useful for treating a patient having drug
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US04652567A1

  公开（公告）日：1987-03-24

  There are disclosed novel compounds of the formula ##STR1## where X is H, halogen, loweralkyl, loweralkoxy, --CF.sub.3, or --OH; R is H, loweralkyl, arylloweralkyl, diarylloweralkyl, loweralkanoyl, arylloweralkanoyl or diarylloweralkanoyl; and R.sub.1 is H.sub.2, O or --NR.sub.2 R.sub.3, R.sub.2 and R.sub.3 being independently H or loweralkyl, or taken together with the nitrogen atom to which they are attached constitute ##STR2## R.sub.4 in turn being H, loweralkyl, hydroxyloweralkyl, aryl, arylloweralkyl or diarylloweralkyl or pharmaceutically acceptable acid addition salts thereof, which are useful for enhancing memory.

  揭示了一种新颖的化合物，其化学式为##STR1##其中X为H、卤素、较低的烷基、较低的烷氧基、--CF.sub.3或--OH；R为H、较低的烷基、芳基较低的烷基、二芳基较低的烷基、较低的烷酰基、芳基较低的烷酰基或二芳基较低的烷酰基；R.sub.1为H.sub.2、O或--NR.sub.2 R.sub.3，其中R.sub.2和R.sub.3独立地为H或较低的烷基，或者与它们连接的氮原子一起构成##STR2##R.sub.4又为H、较低的烷基、羟基较低的烷基、芳基、芳基较低的烷基或二芳基较低的烷基，或其药用可接受的酸盐，用于增强记忆。
• Schmidt rearrangement of 1,2,3,5,10,10a-hexahydropyrrolo[1,2-<i>b</i>]-isoquinoline-3,10-diones
  作者：Jean-Yves Mérour、FranÇOise Cossais、Simone Piroëlle、Daniel Mazéas

  DOI：10.1002/jhet.5570310116

  日期：1994.1

  The Schmidt rearrangement of 1,2,3,5,10,10a-hexahydropyrrolo[1,2-b]isoquinoline-3,10-diones has been studied. The structure of the lactams obtained has been determined by chemical reactivity and characterized by means of ir, 1H and 13C nmr spectroscopy.

  研究了1,2,3,5,10,10a-六氢吡咯并[1,2- b ]异喹啉-3,10-二酮的施密特重排。所获得的内酰胺的结构已经通过化学反应性确定并且通过ir，1 H和13 C nmr光谱法表征。
• Studies on pyrrolidinones. synthesis of fused 1,5-naphthyridines
  作者：Rufine Akué-Gédu、Daniel Couturier、Jean-Pierre Hénichart、Benoît Rigo、Gerard Sanz、Luc Van Hijfte、Anne Bourry

  DOI：10.1016/j.tet.2012.04.056

  日期：2012.7

  The synthesis of new condensed indolizinediones derived from pyroglutamic acid is described. The Semmler–Wolff transposition of the oxime of these ketones leads to fused dihydro-1,5-naphthyridinones. Easy introduction of side amino chains indicates that potential DNA-intercalating heterocyclic systems fused on 1,5-naphthyridine nucleus could be obtained in these series.

  描述了衍生自焦谷氨酸的新的缩合吲哚并二酮的合成。这些酮肟的Semmler-Wolff换位导致二氢-1,5-萘并吡啶二酮稠合。容易引入侧氨基链表明，在这些系列中可以获得潜在的DNA嵌入杂环体系，它们融合在1,5-萘啶核上。
• Synthesis of novel 1,2,3,4-tetrahydrobenzo[<i>c</i>]-1,5-naphthyridines from pyrrolo[1,2-<i>b</i>]isoquinolines
  作者：Lawrence L. Martin、Susan J. Scott、Linda L. Setescak、Donna Van Engen

  DOI：10.1002/jhet.5570240609

  日期：1987.11

  (5a) was prepared by a novel synthetic route involving the rearrangement of (±)-(Z)-1,10a-dihydropyrrolo[1,2-b]isoquinoline-3,10(2H,5H)-dione oxime to afford 1,4-dihydrobenzo[c]-1,5-naphthyridin-2(3H)-one, which was reduced to 5a. The cholinomimetic activity observed with 5a prompted the synthesis and biological evaluation of additional analogues.

  1,2,3,4-四氢苯并[ c ] -1,5-萘啶（5a）是通过涉及（±）-（Z）-1,10a-二氢吡咯并[1,2- b ]异喹啉-3,10（2 H，5 H）-二酮肟制得1,4-二氢苯并[ c ] -1,5-萘啶-2（3 H）-一，还原为5a。用5a观察到的拟胆碱活性促使其他类似物的合成和生物学评估。
• Studies on pyrrolidinones: a reaction of methylene dichloride under Friedel–Crafts conditions. Synthesis of an α-hydroxymethyl ketone in the hexahydrobenzo[f]indolizine series
  作者：Anne Bourry、Rufine Akué-Gédu、Jean-Pierre Hénichart、Gérard Sanz、Benoı̂t Rigo

  DOI：10.1016/j.tetlet.2004.01.057

  日期：2004.3

  When carried out in methylene dichloride, the Friedel–Crafts cyclization of N-arylmethyl pyroglutamates can lead to addition of a CH2OH group in the position α to the newly formed ketone function.

  当在二氯甲烷中进行时，N-芳基甲基焦谷氨酸的Friedel-Crafts环化反应可导致在α位上的CH 2 OH基团新形成的酮官能团加成。

表征谱图