3-羟基氨基-1-甲基-5H-吡啶并(4,3-b)吲哚 | 74317-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 3-羟基氨基-1-甲基-5H-吡啶并(4,3-b)吲哚
• 英文名称: 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole
• 英文别名: 3-hydroxylamino-1-methyl-5H-pyrido[4,3-b]indole；3-hydroxyamino-1-methyl-5H-pyrido<4,3-b>indole；3-Hydroxyamino-1-methyl-5H-pyrido(4,3-b)indole；N-(1-methyl-5H-pyrido[4,3-b]indol-3-yl)hydroxylamine
• CAS: 74317-45-6
• 化学式: C₁₂H₁₁N₃O
• 分子量: 213.239
• InChiKey: VWXMRYZUBOAGIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  60.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-羟基氨基-1-甲基-5H-吡啶并(4,3-b)吲哚 在 disodium hydrogenphosphate sodium dihydrogenphosphate 、 sodium azide 、 sodium perchlorate 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 49.5h， 生成 N-(1-甲基-5H-吡啶并[4,3-b]吲哚-3-基)-乙酰胺
  参考文献：
  名称：

  Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue

  摘要：

  We report the synthesis of N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide, 7, its N-pivaloyloxy analogue, 9, and improved synthesis of indole-2-acetonitrile, 3 (70% in five steps from indole-2-carboxylic acid), the carcinogenic amine Trp-P-2, 4 (40% from 3), and the nitro compound, 5 (40% from 4 by oxidation with H,02 using MO(CO)6 catalyst). In aqueous solution at neutral pH, 7 primarily undergoes C-O bond cleavage to yield the hydroxamic acid, 8, but under the same conditions the sterically hindered 9 decomposes predominately by N-O bond cleavage with a pH independent rate constant that is 7.5-fold smaller than that for 7. In the pH range 0.5-7.0 three different processes for the decomposition of 9 were detected by kinetics. Only the process that dominates at neutral pH generates a nitrenium species that can be trapped by N ((3)) over bar. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.08.005
• 作为产物：
  描述：

  3-氨基-1-甲基-5H-吡啶[4,3-b]吲哚 在 palladium on activated charcoal 、 hexacarbonyl molybdenum 双氧水 、 一水合肼 、 三氟乙酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 3-羟基氨基-1-甲基-5H-吡啶并(4,3-b)吲哚
  参考文献：
  名称：

  Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue

  摘要：

  We report the synthesis of N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide, 7, its N-pivaloyloxy analogue, 9, and improved synthesis of indole-2-acetonitrile, 3 (70% in five steps from indole-2-carboxylic acid), the carcinogenic amine Trp-P-2, 4 (40% from 3), and the nitro compound, 5 (40% from 4 by oxidation with H,02 using MO(CO)6 catalyst). In aqueous solution at neutral pH, 7 primarily undergoes C-O bond cleavage to yield the hydroxamic acid, 8, but under the same conditions the sterically hindered 9 decomposes predominately by N-O bond cleavage with a pH independent rate constant that is 7.5-fold smaller than that for 7. In the pH range 0.5-7.0 three different processes for the decomposition of 9 were detected by kinetics. Only the process that dominates at neutral pH generates a nitrenium species that can be trapped by N ((3)) over bar. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.08.005

文献信息

• Deoxyribonucleic acid modification by mutagenic 3-amino-1-methyl-5H-pyrido(4,3-b)indole: The chemical events.
  作者：YUICHI HASHIMOTO、KOICHI SHUDO、TOSHIHIKO OKAMOTO

  DOI：10.1248/cpb.32.4300

  日期：——

  3-Amino-1-methyl-5H-pyrido [4, 3-b] indole (Trp-P-2) is a mutagen/carcinogen isolated from a pyrolysate of L-tryptophan. The active metabolite of Trp-P-2, 3-hydroxyamino-1-methyl-5H-pyrido [4, 3-b] indole (N-OH-Trp-P-2), was synthesized and the chemical reactions of N-OH-Trp-P-2 with deoxyribonucleic acid were investigated. The structure of the nucleic acid base covalently bound with Trp-P-2 was elucidated as 3-(C8-guanyl) amino-1-methyl-5H-pyrido [4, 3-b] indole (Gua-Trp-P-2) by comparison with a synthetic sample. The initial chemical events in carcinogenesis caused by Trp-P-2 were established.

  3-氨基-1-甲基-5H-吡啶并[4，3-b]吲哚（Trp-P-2）是从 L-色氨酸的热解产物中分离出来的一种诱变剂/致癌物质。研究人员合成了 Trp-P-2 的活性代谢物--3-羟基氨基-1-甲基-5H-吡啶并[4，3-b]吲哚（N-OH-Trp-P-2），并研究了 N-OH-Trp-P-2 与脱氧核糖核酸的化学反应。通过与合成样品的对比，阐明了与 Trp-P-2 共价结合的核酸碱基的结构为 3-(C8-鸟嘌呤基)氨基-1-甲基-5H-吡啶并[4, 3-b] 吲哚（Gua-Trp-P-2）。确定了 Trp-P-2 致癌的最初化学事件。
• Protection against Trp-P-2 mutagenicity by purpurin: mechanism of in vitro antimutagenesis
  作者：T. Marczylo

  DOI：10.1093/mutage/15.3.223

  日期：2000.5.1

  Purpurin (1,2,4-trihydroxy-9,10-anthraquinone) is a natural pigment isolated from madder root (Rubia tinctorum) which inhibits the mutagenicity of a number of heterocyclic amines in the Ames mutagenicity test. Two effects were observed in the presence of purpurin. The rate of degradation of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole [Trp-P-2(NHOH)] at neutral pH was increased. The major product of this purpurin-dependent degradation was identified as the parent amine 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Secondly, the rate of Trp-P-2 N-hydroxylation, the major route of bioactivation, by PCB-treated rat hepatic microsomes was markedly decreased. Cytochrome P450-dependent O-dealkylation of methoxy-, ethoxy- and pentoxyresorufin by these microsomes was also significantly inhibited by purpurin. The nature of this inhibition was competitive. Spectrophotometric investigations suggest no direct interaction between Trp-P-2 and purpurin. Furthermore, no evidence for Trp-P-2 binding was observed with carminic acid, a structural analog of purpurin, when it was immobilized on ω-aminohexyl agarose. Therefore, in vitro the proposed mechanism by which purpurin protects against heterocyclic amine-induced mutagenesis involves competitive inhibition of cytochrome P450-dependent bioactivation and accelerated degradation of the N-hydroxylamine to the parent amine.

  紫嘌呤（1,2,4-三羟基-9,10-蒽醌）是从茜草根（Rubia tinctorum）中分离出来的一种天然色素，在艾姆斯致突变试验中可抑制多种杂环胺的致突变性。在紫丁香素的作用下，观察到两种效应。在中性 pH 值下，3-羟基氨基-1-甲基-5H-吡啶并[4,3-b]吲哚[Trp-P-2(NHOH)]的降解率增加。经鉴定，这种紫癜素依赖性降解的主要产物是母胺 3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-2）。其次，经多氯联苯处理的大鼠肝脏微粒体的 Trp-P-2 N- 羟基化速率（生物活化的主要途径）明显降低。这些微粒体依赖细胞色素 P450 对甲氧基、乙氧基和戊氧基resorufin 进行的 O-脱烷基化反应也受到紫嘌呤的显著抑制。这种抑制的性质是竞争性的。分光光度法研究表明，Trp-P-2 和紫嘌呤之间没有直接的相互作用。此外，将紫嘌呤的结构类似物卡明酸固定在ω-氨基己基琼脂糖上时，也没有观察到与 Trp-P-2 结合的证据。因此，在体外，紫草素防止杂环胺诱变的拟议机制包括竞争性抑制依赖细胞色素 P450 的生物活化和加速 N-羟胺降解为母胺。
• NEGISHI, KAZUO;WAKATA, AKIHIRO;HIRAMOTO, KAZUYUKI;HAYATSU, HIKOYA, 12TH SYMP. NUCL. ACIDS CHEM., KANAZAWA, OCT. 30-NOV. 1, 1984, OXFORD; WAS+
  作者：NEGISHI, KAZUO、WAKATA, AKIHIRO、HIRAMOTO, KAZUYUKI、HAYATSU, HIKOYA

  DOI：——

  日期：——
• Synthesis and characterization of the aqueous solution chemistry of the food-derived carcinogen model N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide and its N-pivaloyloxy analogue
  作者：Sridharan Rajagopal、Michael E Brooks、Thach-Mien Nguyen、Michael Novak

  DOI：10.1016/j.tet.2003.08.005

  日期：2003.9

  We report the synthesis of N-acetoxy-N-(1-methyl-5H-pyrido[4,5-b]indol-3-yl)acetamide, 7, its N-pivaloyloxy analogue, 9, and improved synthesis of indole-2-acetonitrile, 3 (70% in five steps from indole-2-carboxylic acid), the carcinogenic amine Trp-P-2, 4 (40% from 3), and the nitro compound, 5 (40% from 4 by oxidation with H,02 using MO(CO)6 catalyst). In aqueous solution at neutral pH, 7 primarily undergoes C-O bond cleavage to yield the hydroxamic acid, 8, but under the same conditions the sterically hindered 9 decomposes predominately by N-O bond cleavage with a pH independent rate constant that is 7.5-fold smaller than that for 7. In the pH range 0.5-7.0 three different processes for the decomposition of 9 were detected by kinetics. Only the process that dominates at neutral pH generates a nitrenium species that can be trapped by N ((3)) over bar. (C) 2003 Elsevier Ltd. All rights reserved.