4-amino-N-[5-[2-(dimethylamino)ethylcarbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide | 162934-64-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-amino-N-[5-[2-(dimethylamino)ethylcarbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide
• CAS: 162934-64-7
• 化学式: C₁₆H₂₄N₆O₂
• 分子量: 332.406
• InChiKey: DKTPBCCBYCNQQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  97.3
• 氢给体数：
  3
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-[2-(dimethylamino)ethyl]-1-methyl-4-{[(1-methyl-4-nitro-1H-pyrrol-2-yl)carbonyl]amino}-1H-pyrrole-2-carboxamide	155791-67-6	C16H22N6O4	362.388
  ——	N-[2-(dimethylamino)ethyl]-1-methyl-4-aminopyrrolo-2-carboxamide	155791-66-5	C10H18N4O	210.279
  ——	N-<2-(dimethylamino)ethyl>-1-methyl-4-nitropyrrole-2-carboxamide	99180-54-8	C10H16N4O3	240.262

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N-[2-(dimethylamino)ethyl]-1-methyl-4-[[1-methyl-4-[(1-methylpyrrol-2-yl)diazenyl]pyrrole-2-carbonyl]amino]pyrrole-2-carboxamide	1357256-96-2	C21H28N8O2	424.506
  ——	N-[2-(dimethylamino)ethyl]-1-methyl-4-(1-methyl-4-{[5-(8-psoralenyloxy)pentanoyl]amino}pyrrole-2-carboxamido)pyrrole-2-carboxamide	——	C32H36N6O7	616.674
  ——	3-(5-{5-[2-(dimethylamino)ethylcarbamoyl]-1-methyl-pyrrol-3-ylcarbamoyl}-1-methylpyrrol-3-yl)-3,4-dihydro-3-methyl-4-oxoimdazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide	——	C22H27N11O4	509.528

反应信息

• 作为反应物：
  描述：

  1-甲基-1H-咪唑-2-羧酸 、 4-amino-N-[5-[2-(dimethylamino)ethylcarbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以70 mg的产率得到N-(N',N'-dimethylaminoethyl)-1-methyl-4-[1-methyl-4-[1-methylimidazole-2-carboxamido]pyrrole-2-carboxamido]pyrrole-2-carboxamide
  参考文献：
  名称：

  末端甲酰胺基团对聚酰胺对 DNA 序列识别的影响

  摘要：

  含有吡咯 (Py)-咪唑 (Im) 的聚酰胺结合在 DNA 的小沟中，可以通过堆叠的反平行二聚体识别特定序列。已经提出有两种不同的低能量方式来形成堆叠的二聚体，并且它们对末端甲酰氨基的存在很敏感：（i）完全重叠的堆叠模式，其中二聚体的 N 端杂环堆叠在 C 端两个杂环之间的酰胺基团上和 (ii) 交错堆叠模式，其中 N 端杂环在 C 端方向上移动大约一个单位（结构 1997, 5, 1033-1046） . 两种不同的 DNA 序列将被以这两种不同模式堆叠的相同聚酰胺识别。尽管聚酰胺作为序列特异性 DNA 识别剂的重要性，尚未系统地探索这些堆叠的可能性。作为开发可识别 DNA 中错配碱基对的试剂的计划的一部分，合成了一组具有和不具有末端甲酰胺基团的四个聚酰胺三聚体，并评估了它们与两种不同堆叠模式下预测的 DNA 识别序列的相互作用。通过使用表面等离子体共振 (SPR) 检测与固定化 DNA

  DOI：

  10.1021/ja016154b
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-羧酸 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 20.08h， 生成 4-amino-N-[5-[2-(dimethylamino)ethylcarbamoyl]-1-methylpyrrol-3-yl]-1-methylpyrrole-2-carboxamide
  参考文献：
  名称：

  Lee; Roldan; Haskell, Journal of Medicinal Chemistry, 1994, vol. 37, # 8, p. 1208 - 1213

  摘要：

  DOI：

文献信息

• Synthesis of directly linked diazine isosteres of pyrrole-polyamide that photochemically cleave DNA
  作者：Chi Wi Ong、Ya-Ting Yang、Meng-Chi Liu、Keith R. Fox、Ping Hao Liu、Hung-Wei Tung

  DOI：10.1039/c1ob06803b

  日期：——

  photo-induced DNA damage upon iradiation with UV light (365 nm). Spectrophotometric and mass spectrometric identification suggest that the azo-linkage in I did not dissociate during irradiation. Moreover, compound I produced DNase I footprints with the HexB DNA fragment at AT sites, as well as some other mixed sequences (5′-ATGTCG-3′), indicative of the additional role of the diazine-linkage for interaction at

  一种 双霉素设计并合成了包含等排的二嗪连接的吡咯的模型。合成的关键步骤涉及成功的重氮化反应。4-氨基吡咯 衍生给 重氮 盐，它们与 N-甲基吡咯得到直接连接的二嗪化合物。酰胺是等位的二嗪吡咯 在紫外线（365 nm）照射下，我证明了光诱导的DNA损伤。分光光度法和质谱法鉴定表明I中的偶氮键在辐照期间未解离。此外，化合物I在AT位点的HexB DNA片段以及其他一些混合序列产生了DNase I足迹。5′-ATGTCG-3'），表明二嗪键对双链DNA相互作用的额外作用。
• Antitumor AHMA Linked to DNA Minor Groove Binding Agents:  Synthesis and Biological Evaluation
  作者：Kamesh Rastogi、Jang-Yang Chang、Wen-Yu Pan、Ching-Huang Chen、Ting-Chao Chou、Li-Tzong Chen、Tsann-Long Su

  DOI：10.1021/jm0200714

  日期：2002.9.1

  DNA minor groove binder hybrid molecules, netropsin derivatives such as N-[2-(dimethylamino)ethyl]-1-methyl-4-aminopyrrolo-2-carboxamide (MePy) or its derivatives containing two units of N-methylpyrrolecarboxamide (diMePy) and bisbenzimidazole (Ho33258), were linked to the NH2 function of AHMA or to the CH2OH group of AHMA-ethylcarbamate to form AHMA-N-netropsins (13-16) and AHMA-ethylcarbamate-O-netropsins (19-22), and AHMA-bis-benzimidazole (AHMA-Ho33258, 25), respectively. These conjugates' in vitro antitumor activity, inhibition of a variety of human tumor cell growth, revealed that AHMA-ethylcarbamate-O-netropsin derivatives were more cytotoxic than AHMA-N-netropsin compounds. In the same studies, all compounds bearing MePy were more potent than those compounds linked with diMePy. Moreover, AHMA-netropsin derivatives bearing a succinyl chain as the linking spacer were more potent than those compounds having a glutaryl bridge. Among these hybrid molecules, AHMA-ethylcarbamate-O-succinyl-MePy (19) was 2- to 6-fold more cytotoxic than the parent compound AHMA (5) in various cell lines, whereas compound 25 had very poor solubility and was inactive. Studies on the inhibitory effect against topoisomerase II (Topo II) and DNA interaction of these conjugates showed no correlation between the potency of DNA binding and inhibitory activity against Topo II.
• Antitumor Imidazotetrazines. 41. Conjugation of the Antitumor Agents Mitozolomide and Temozolomide to Peptides and Lexitropsins Bearing DNA Major and Minor Groove-Binding Structural Motifs
  作者：Jill Arrowsmith、Sharon A. Jennings、Alan S. Clark、Malcolm F. G. Stevens

  DOI：10.1021/jm020936d

  日期：2002.12.1

  Carboxylic acids derived from the amido groups of the antitumor agents mitozolomide and temozolomide have been conjugated to simple amino acids and peptides by carbodiimide coupling. Solid-state peptide synthesis has been applied to link the acids to DNA major groove-binding peptidic motifs known to adopt alpha-helical conformations. Attachment of the acids to pyrrole and imidazole polyamidic lexitropsins gave a series of potential DNA minor groove- binding ligands. In vitro biological evaluation of a limited number of these novel conjugates failed to demonstrate any enhanced growth-inhibitory activity compared to the unconjugated drugs; sites of alkylation at tracts of multiple guanines were also unaffected. Attachment of additional residues at C-8 of the imidazotetrazines did not perturb the chemistry of activation of the bicyclic nucleus, and biological sequelae can be rationalized by invoking the liberation of a common, diffusible, reactive chemical intermediate, the methanediazonium ion.
• Synthesis of a netropsin conjugate of a water-soluble epi -quinocarcin analogue: the importance of stereochemistry at nitrogen
  作者：Brad Herberich、Jack D. Scott、Robert M. Williams

  DOI：10.1016/s0968-0896(99)00314-4

  日期：2000.3

  The efficient synthesis of a water-soluble C11a-epi-analogue (6b) of quinocarcin is described. This substance, and a netropsin amide conjugate (8) lack the capacity to inflict oxidative damage on DNA due to the stereoelectronic geometry of their oxazolidine nitrogen atoms. The capacity of these substances to alkylate DNA through the generation of an iminium species has been examined. Both compounds were found to be unreactive as DNA alkylating agents. The results of this study are discussed in the context of previous proposals on the mode of action of this family of antitumor alkaloids. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Influence of a Terminal Formamido Group on the Sequence Recognition of DNA by Polyamides
  作者：Eilyn R. Lacy、N. Minh Le、Carly A. Price、Moses Lee、W. David Wilson

  DOI：10.1021/ja016154b

  日期：2002.3.1

  synthesized, and their interactions with predicted DNA recognition sequences in the two different stacking modes were evaluated. Experimental difficulties in monitoring DNA complex formation with polyamides were overcome by using surface plasmon resonance (SPR) detection of the binding to immobilized DNA hairpin duplexes. Both equilibrium and kinetic results from SPR show that a terminal formamido group

  含有吡咯 (Py)-咪唑 (Im) 的聚酰胺结合在 DNA 的小沟中，可以通过堆叠的反平行二聚体识别特定序列。已经提出有两种不同的低能量方式来形成堆叠的二聚体，并且它们对末端甲酰氨基的存在很敏感：（i）完全重叠的堆叠模式，其中二聚体的 N 端杂环堆叠在 C 端两个杂环之间的酰胺基团上和 (ii) 交错堆叠模式，其中 N 端杂环在 C 端方向上移动大约一个单位（结构 1997, 5, 1033-1046） . 两种不同的 DNA 序列将被以这两种不同模式堆叠的相同聚酰胺识别。尽管聚酰胺作为序列特异性 DNA 识别剂的重要性，尚未系统地探索这些堆叠的可能性。作为开发可识别 DNA 中错配碱基对的试剂的计划的一部分，合成了一组具有和不具有末端甲酰胺基团的四个聚酰胺三聚体，并评估了它们与两种不同堆叠模式下预测的 DNA 识别序列的相互作用。通过使用表面等离子体共振 (SPR) 检测与固定化 DNA