7-[1-oxo-1-(3-pyridyl)but-4-yl]guanine | 502507-75-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 7-[1-oxo-1-(3-pyridyl)but-4-yl]guanine
• 英文别名: 7-[4-oxo-4-(3-pyridyl)but-1-yl]guanine；2-Amino-7-(4-oxo-4-(pyridin-3-yl)butyl)-1H-purin-6(7H)-one；2-amino-7-(4-oxo-4-pyridin-3-ylbutyl)-1H-purin-6-one
• CAS: 502507-75-7
• 化学式: C₁₄H₁₄N₆O₂
• 分子量: 298.304
• InChiKey: SBSHXBWJUGSYTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-[1-oxo-1-(3-pyridyl)but-4-yl]guanine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]guanine
  参考文献：
  名称：

  Identification of Adducts Produced by the Reaction of 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol with Deoxyguanosine and DNA

  摘要：

  4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNAL is present in the blood and urine of people exposed to tobacco products and has carcinogenic activity in rodents similar to that of NNK. DNA adducts specific to NNAL have not been previously identified. Metabolic activation of NNAL by a-methyl hydroxylation, a pathway known to occur in rodent and human microsomes, would produce pyridylhydroxybutylating agents that could react with DNA. We investigated this possibility in the present study by allowing 4-(acetoxymethylnitrosamino)1-(3-pyridyl)-1-butanone (NNALCH(2)OAc) to react with dGuo and DNA. Products were identified by HPLC with UV detection, liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) and LC/ESI-tandem mass spectrometry (LC/ESI-MS/MS). In the dGuo reactions, selected ion monitoring for m/z 417, corresponding to pyridylhydroxybutylated dGuo, showed several peaks. One adduct was identified as 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (21) by neutral thermal hydrolysis, which converted it to 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]Gua (22) and 4-hydroxy-1-(3-pyridyl)-1-butanol (16). Adduct 22 was identified by comparison of its LC/ESI-MS and LC/ESI-MS/MS properties to those of standard 22. Two other adducts, O-6-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (17) and N-2-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (19), were identified by comparison of their LC/ESI-MS and LC/ESI-MS/MS properties to those of standard 17 and 19. Further evidence for the identity of 17 and 19 was obtained by mild acid hydrolysis, which converted them to the corresponding Gua bases 18 and 20, identified by comparison to synthetic standards. Neutral thermal hydrolysis of DNA that had been reacted with NNALCH2OAc produced 22, identified by comparison to a standard. Adducts 17 and 19 were identified in enzyme hydrolysates of this DNA by comparison to standards. Thus, DNA that had been allowed to react with NNALCH(2)OAc contained adducts 17, 19, and 21. The results of this study provide markers for investigating the role of specific NNAL-DNA adducts in carcinogenesis by NNAL and NNK.

  DOI：

  10.1021/tx0256376
• 作为产物：
  描述：

  2',3',5'-三乙酰鸟苷 、 4-oxo-4-(3-pyridyl)but-1-yl p-toluenesulfonate 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以1%的产率得到7-[1-oxo-1-(3-pyridyl)but-4-yl]guanine
  参考文献：
  名称：

  Identification of Adducts Produced by the Reaction of 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol with Deoxyguanosine and DNA

  摘要：

  4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNAL is present in the blood and urine of people exposed to tobacco products and has carcinogenic activity in rodents similar to that of NNK. DNA adducts specific to NNAL have not been previously identified. Metabolic activation of NNAL by a-methyl hydroxylation, a pathway known to occur in rodent and human microsomes, would produce pyridylhydroxybutylating agents that could react with DNA. We investigated this possibility in the present study by allowing 4-(acetoxymethylnitrosamino)1-(3-pyridyl)-1-butanone (NNALCH(2)OAc) to react with dGuo and DNA. Products were identified by HPLC with UV detection, liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) and LC/ESI-tandem mass spectrometry (LC/ESI-MS/MS). In the dGuo reactions, selected ion monitoring for m/z 417, corresponding to pyridylhydroxybutylated dGuo, showed several peaks. One adduct was identified as 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (21) by neutral thermal hydrolysis, which converted it to 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]Gua (22) and 4-hydroxy-1-(3-pyridyl)-1-butanol (16). Adduct 22 was identified by comparison of its LC/ESI-MS and LC/ESI-MS/MS properties to those of standard 22. Two other adducts, O-6-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (17) and N-2-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (19), were identified by comparison of their LC/ESI-MS and LC/ESI-MS/MS properties to those of standard 17 and 19. Further evidence for the identity of 17 and 19 was obtained by mild acid hydrolysis, which converted them to the corresponding Gua bases 18 and 20, identified by comparison to synthetic standards. Neutral thermal hydrolysis of DNA that had been reacted with NNALCH2OAc produced 22, identified by comparison to a standard. Adducts 17 and 19 were identified in enzyme hydrolysates of this DNA by comparison to standards. Thus, DNA that had been allowed to react with NNALCH(2)OAc contained adducts 17, 19, and 21. The results of this study provide markers for investigating the role of specific NNAL-DNA adducts in carcinogenesis by NNAL and NNK.

  DOI：

  10.1021/tx0256376

文献信息

• Therapeutic compounds and methods of use thereof
  申请人：KUALITY HERBCEUTICS LLC

  公开号：US10584108B2

  公开（公告）日：2020-03-10

  The invention provides compounds that are useful for treating or preventing cancer.

  本发明提供了可用于治疗或预防癌症的化合物。
• Kava derived therapeutic compounds and methods of use thereof
  申请人：KUALITY HERBCEUTICS LLC

  公开号：US10624943B2

  公开（公告）日：2020-04-21

  Certain embodiments of the invention provide a composition comprising at least two compounds selected from the group consisting of dihydromethysticin, methysticin, dihydrokavain, kavain, desmethoxyyangonin and 11-methoxyyangonin, wherein the composition is substantially free of flavokawain B. Certain embodiments of the invention also provide a method for treating or preventing cancer in a mammal (e.g., a human) in need of such treatment comprising, administering to the mammal a carrier and a compound selected from the group consisting of dihydromethysticin, methysticin, dihydrokavain, kavain, desmethoxyyangonin and 11-methoxyyangonin, wherein the compound is substantially free of other kava extract components.

  本发明的某些实施方案提供了一种组合物，该组合物包含至少两种选自由二氢麦角苷、甲基麦角苷、二氢卡瓦胡椒素、卡瓦胡椒素、去甲氧基麦角苷和11-甲氧基麦角苷组成的组的化合物，其中该组合物基本上不含黄卡瓦胡椒素B、向哺乳动物施用载体和选自由二氢甲基芪烷素、甲基芪烷素、二氢卡瓦胡椒素、卡瓦胡椒素、去甲氧基卡瓦胡椒素和 11-甲氧基卡瓦胡椒素组成的组的化合物，其中该化合物基本上不含其他卡瓦提取物成分。
• KAVA DERIVED THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Kuality Herbceutics LLC

  公开号：EP3068416A1

  公开（公告）日：2016-09-21
• THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF
  申请人：KUALITY HERBCEUTICS LLC

  公开号：US20180134679A1

  公开（公告）日：2018-05-17

  The invention provides compounds that are useful for treating or preventing cancer.
• [EN] KAVA DERIVED THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF<br/>[FR] COMPOSÉS THÉRAPEUTIQUES ISSUS DU KAVA ET LEURS PROCÉDÉS D'UTILISATION
  申请人：KUALITY HERBCEUTICS LLC

  公开号：WO2015070226A1

  公开（公告）日：2015-05-14

  Certain embodiments of the invention provide a composition comprising at least two compounds selected from the group consisting of dihydromethysticin, methysticin, dihydrokavain, kavain, desmethoxyyangonin and 11-methoxyyangonin, wherein the composition is substantially free of flavokawain B. Certain embodiments of the invention also provide a method for treating or preventing cancer in a mammal (e.g., a human) in need of such treatment comprising, administering to the mammal a carrier and a compound selected from the group consisting of dihydromethysticin, methysticin, dihydrokavain, kavain, desmethoxyyangonin and 11-methoxyyangonin, wherein the compound is substantially free of other kava extract components.