7-methyl-3-(5,6,7,8-tetrahydro-naphthalene-2-carbonyl)-indolizine-1,2-dicarboxylic acid dimethyl ester | 1214884-65-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 7-methyl-3-(5,6,7,8-tetrahydro-naphthalene-2-carbonyl)-indolizine-1,2-dicarboxylic acid dimethyl ester
• 英文别名: Dimethyl 7-methyl-3-(5,6,7,8-tetrahydronaphthalene-2-carbonyl)indolizine-1,2-dicarboxylate
• CAS: 1214884-65-7
• 化学式: C₂₄H₂₃NO₅
• 分子量: 405.45
• InChiKey: RLHQYGWIERCVAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  74.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-methyl-1-[2-oxo-2-(5,6,7,8-tetrahydro-naphthalen-2-yl)-ethyl]-pyridinium bromide 、 丁炔二酸二甲酯 在 三乙胺 作用下， 以 苯 为溶剂， 反应 3.0h， 以70%的产率得到7-methyl-3-(5,6,7,8-tetrahydro-naphthalene-2-carbonyl)-indolizine-1,2-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  Modulation of carcinogen metabolizing enzymes by new fused heterocycles pendant to 5,6,7,8-tetrahydronaphthalene derivatives

  摘要：

  The treatment of 2-bromo-1-(5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone (1) with pyridine, 2-methylpyridine or 4-methylpyridine afforded their corresponding pyridinum bromides 3a-c. The latter salts reacted with activated acetylene to give the corresponding indolizine derivatives 6a-c. Imidazo[1,2-a]pyridine 9a,b, quinoxaline 15, imidazo[1,2-b][1,2,4]triazole 18 and imidazo[1,2-a]benzimidazole 21 derivatives were prepared from 1 as a starting material. The investigation of the derivative influence on the carcinogen metabolizing enzymes and in the tumor initiation process revealed that 3a-c were strong inducers of epoxide hydrolase (mEH), and that 3a was an inducer of glutathione S-transferases (GSTs) and glutathione (GSH) and a potent scavenger of ROO center dot and OH center dot and inhibited the induced DNA damage, while 3b was a scavenger of ROO center dot and a moderate inhibitor of DNA damage. Additionally, 6a-c significantly induced quinine reductase (QR) activity, whereas 6b induced GSTs, and 6c elevated GSH content, while both of 6b and 6c scavenged OH center dot and inhibited the DNA damage. On the other hand, 9a possessed a moderate scavenging activity of ROO center dot and inhibitory effect on the induced DNA damage, while 18 was a strong inducer of QR activity, scavenger of OH center dot, and inhibitor of the DNA damage and 2 was a significant inhibitor of cytochrome P-450 1A (Cyp1A) and was an inducer of GSTs, and GSH, and a moderate inhibitor of the DNA damage. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.10.027

文献信息

• Modulation of carcinogen metabolizing enzymes by new fused heterocycles pendant to 5,6,7,8-tetrahydronaphthalene derivatives
  作者：Nehal A. Hamdy、Amira M. Gamal-Eldeen、Hatem A. Abdel-Aziz、Issa M.I. Fakhr

  DOI：10.1016/j.ejmech.2009.10.027

  日期：2010.2

  The treatment of 2-bromo-1-(5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone (1) with pyridine, 2-methylpyridine or 4-methylpyridine afforded their corresponding pyridinum bromides 3a-c. The latter salts reacted with activated acetylene to give the corresponding indolizine derivatives 6a-c. Imidazo[1,2-a]pyridine 9a,b, quinoxaline 15, imidazo[1,2-b][1,2,4]triazole 18 and imidazo[1,2-a]benzimidazole 21 derivatives were prepared from 1 as a starting material. The investigation of the derivative influence on the carcinogen metabolizing enzymes and in the tumor initiation process revealed that 3a-c were strong inducers of epoxide hydrolase (mEH), and that 3a was an inducer of glutathione S-transferases (GSTs) and glutathione (GSH) and a potent scavenger of ROO center dot and OH center dot and inhibited the induced DNA damage, while 3b was a scavenger of ROO center dot and a moderate inhibitor of DNA damage. Additionally, 6a-c significantly induced quinine reductase (QR) activity, whereas 6b induced GSTs, and 6c elevated GSH content, while both of 6b and 6c scavenged OH center dot and inhibited the DNA damage. On the other hand, 9a possessed a moderate scavenging activity of ROO center dot and inhibitory effect on the induced DNA damage, while 18 was a strong inducer of QR activity, scavenger of OH center dot, and inhibitor of the DNA damage and 2 was a significant inhibitor of cytochrome P-450 1A (Cyp1A) and was an inducer of GSTs, and GSH, and a moderate inhibitor of the DNA damage. (C) 2009 Elsevier Masson SAS. All rights reserved.