4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid (3-morpholin-4-yl-propyl)-amide | 868592-39-6

• 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-1-methyl-1H-pyrrole-2-carboxylic acid (3-morpholin-4-yl-propyl)-amide
• 英文别名: 4-amino-1-methyl-N-(3-morpholin-4-ylpropyl)pyrrole-2-carboxamide
• CAS: 868592-39-6
• 化学式: C₁₃H₂₂N₄O₂
• 分子量: 266.343
• InChiKey: XKJNDQXRCCXRLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  72.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid (3-morpholin-4-yl-propyl)-amide 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 55.0h， 生成 4-formamido-N-[1-isopentyl-5-[[1-methyl-5-(3-morpholinopropylcarbamoyl)pyrrol-3-yl]carbamoyl]pyrrol-3-yl]-1-methyl-pyrrole-2-carboxamide
  参考文献：
  名称：

  具有增强的亲脂性的双歧霉素类似物：合成和抗菌活性。

  摘要：

  描述了四十八个杂环氨基酸三聚体，它是二霉素的类似物，具有许多增强亲脂性的特征。它们含有比甲基大的烷基或环烷基；一些被乙酰胺或甲氧基苯甲酰胺N端基，并且被二甲氨基丙基或脂族杂环甲基氨基丙基取代基C端基。使用毛细管区带电泳已经评估了这些化合物主要结合至DNA AT束的能力。几种化合物，特别是那些含有噻唑的化合物，显示出对关键生物如MRSA和白色念珠菌的显着抗菌活性。而且，这些化合物对几种哺乳动物细胞系具有低毒性。

  DOI：

  10.1021/jm031089x
• 作为产物：
  描述：

  1-甲基-4-硝基吡咯-2-羧酸 在 氯化亚砜 、 palladium 10% on activated carbon 、 氢气 、 三甲胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 4-Amino-1-methyl-1H-pyrrole-2-carboxylic acid (3-morpholin-4-yl-propyl)-amide
  参考文献：
  名称：

  An evaluation of Minor Groove Binders as anti- Trypanosoma brucei brucei therapeutics

  摘要：

  A series of 32, structurally diverse MGBs, derived from the natural product distamycin, was evaluated for activity against Trypanosoma brucei brucei. Four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for Human and Animal African Trypanosomiases. Moreover, SAR indicates that the head group linking moiety is a significant modulator of biological activity. (C) 2016 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.orgilicensesiby/4.0/).

  DOI：

  10.1016/j.ejmech.2016.03.064

文献信息

• The Synthesis of Some Head to Head Linked DNA Minor Groove Binders
  作者：Abedawn I. Khalaf、Andrew R. Pitt、Martin Scobie、Colin J. Suckling、John Urwin、Roger D. Waigh、Robert V. Fishleigh、Steven C. Young、William A. Wylie

  DOI：10.1016/s0040-4020(00)00432-4

  日期：2000.7

  A series of head to head linked dimers of heterocyclic amino acids has been prepared for investigation of affinity and selectivity in binding to the minor groove of DNA. The selection of targets for synthesis was led by computer based design. Several novel dicarboxylic acid linkers including indoles, phenanthrenes, a fluorenone, and a bisbenzothiophene have been included. Analysis of binding to DNA

  已经制备了一系列首尾相连的杂环氨基酸二聚体，用于研究与DNA小沟结合的亲和力和选择性。合成目标的选择由基于计算机的设计主导。已经包括几种新颖的二羧酸连接基，包括吲哚，菲，芴酮和双苯并噻吩。通过印迹分析与DNA的结合表明对衍生自2,7-二氢菲二羧酸的化合物具有很高的亲和力，并且对包含至少4个AT对的AT富集区域具有主要选择性，但具有跨越两个CG碱基对的能力。
• Synthesis and antimicrobial activity of some netropsin analogues
  作者：Abedawn I. Khalaf、Abdolrasoul H. Ebrahimabadi、Allan J. Drummond、Nahoum G. Anthony、Simon P. Mackay、Colin J. Suckling、Roger D. Waigh

  DOI：10.1039/b408386p

  日期：——

  Nine novel lexitropsins were synthesized by linking two netropsin-like moieties through three different dicarboxylic acids; 9,10-dihydro-2,7-phenanthrenedicarboxylic acid; [(3-[(carboxymethyl)amino]carbonyl}benzoyl)amino]acetic acid and indole-2,5-dicarboxylic acid. The netropsin residues were modified by the use of N-isopentylpyrrole, 5-methylthiophene or 5-isopropylthiazole heterocyclic building blocks in place of the usual N-methylpyrrole. The compounds were tested against five gram-positive bacteria: Staphylococcus aureus, Streptomyces faecalis, methicillin resistant Staphylococcus aureus, Enterobacter cloacae, Mycobacterium fortuitum, three gram-negative bacteria: Klebsiella aerogenes, Proteus vulgaris, Escherichia coli and three fungi: Aspergillus niger, Candida albicans and Aspergillus nidulans. Some of the compounds showed significant inhibitory effects on the growth of the microorganisms.

  合成了九种新型lexitropsin，通过三种不同的二羧酸（9,10-二氢-2,7-菲二羧酸；[(3-[(羧甲基)氨基]羰基}苯甲酰)氨基]乙酸和吲哚-2,5-二羧酸）将两个类似netropsin的部分连接在一起。通过使用N-异戊基吡咯、5-甲基噻吩或5-异丙基噻唑异构体构建单元替代通常的N-甲基吡咯，对netropsin残基进行修饰。将这些化合物分别针对五种革兰阳性菌：金黄色葡萄球菌、肠球菌、耐甲氧西林金黄色葡萄球菌、克雷伯氏菌和偶然分枝杆菌，三种革兰阴性菌：气单胞菌、变形杆菌、大肠杆菌，以及三种真菌：黑曲霉、白念珠菌和安氏曲霉进行了测试。其中一些化合物对微生物的生长表现出显著的抑制作用。
• Structure-based drug design of DNA minor groove binders and evaluation of their antibacterial and anticancer properties
  作者：Hasan Y. Alniss、Hadeel M. Al-Jubeh、Yousef A. Msallam、Ruqaiyyah Siddiqui、Zinb Makhlouf、Anil Ravi、Rania Hamdy、Sameh S.M. Soliman、Naveed A. Khan

  DOI：10.1016/j.ejmech.2024.116440

  日期：2024.5

  Yet, research for novel antimicrobial and anticancer agents remains lagging behind. With their reported medical applications, DNA minor groove binders (MGBs) are worthy of exploration. In this study, the approach of structure-based drug design was implemented to generate 11 MGB compounds including a novel class of bioactive alkyne-linked MGBs. The NCI screening protocol was utilized to evaluate the antitumor

  抗菌素和化疗耐药性正在日益成为最重要的医疗问题。然而，新型抗菌剂和抗癌剂的研究仍然落后。根据报道的医学应用，DNA 小沟结合物 (MGB) 值得探索。在这项研究中，采用基于结构的药物设计方法生成了 11 种 MGB 化合物，其中包括一类新型生物活性炔连接的 MGB。 NCI 筛选方案用于评估目标 MGB 的抗肿瘤活性。此外，使用这些 MGB 对 6 种医学相关细菌进行了各种杀菌、细胞致病性、MIC90 和细胞毒性测定： 、 、 和 。此外，利用分子对接、分子动力学模拟、DNA熔解和等温滴定量热法（ITC）分析来探索最有效的MGB和DNA双链体d（CGACTAGTCG）之间的结合模式和相互作用。 NCI 结果表明，炔连接的 MGB（26 和 28）在 NCI-60 组中表现出最显着的生长抑制作用。此外，化合物MGB3、MGB4、MGB28和MGB32显示出显着的杀菌作用，抑制和介导细胞病变性，并且表现出低细胞毒性。
• An evaluation of Minor Groove Binders as anti- Trypanosoma brucei brucei therapeutics
  作者：Fraser J. Scott、Abedawn I. Khalaf、Federica Giordani、Pui Ee Wong、Sandra Duffy、Michael Barrett、Vicky M. Avery、Colin J. Suckling

  DOI：10.1016/j.ejmech.2016.03.064

  日期：2016.6

  A series of 32, structurally diverse MGBs, derived from the natural product distamycin, was evaluated for activity against Trypanosoma brucei brucei. Four compounds have been found to possess significant activity, in the nanomolar range, and represent hits for further optimisation towards novel treatments for Human and Animal African Trypanosomiases. Moreover, SAR indicates that the head group linking moiety is a significant modulator of biological activity. (C) 2016 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.orgilicensesiby/4.0/).
• Distamycin Analogues with Enhanced Lipophilicity:  Synthesis and Antimicrobial Activity
  作者：Abedawn I. Khalaf、Roger D. Waigh、Allan J. Drummond、Breffni Pringle、Ian McGroarty、Graham G. Skellern、Colin J. Suckling

  DOI：10.1021/jm031089x

  日期：2004.4.1

  Forty-eight heterocyclic amino acid trimers, analogues of distamycin, with a number of features that enhance lipophilicity are described. They contain alkyl or cycloalkyl groups larger than methyl; some are N-terminated by acetamide or methoxybenzamide and are C-terminated by dimethylaminopropyl or aliphatic heterocylic aminopropyl substituents. The ability of these compounds to bind principally to

  描述了四十八个杂环氨基酸三聚体，它是二霉素的类似物，具有许多增强亲脂性的特征。它们含有比甲基大的烷基或环烷基；一些被乙酰胺或甲氧基苯甲酰胺N端基，并且被二甲氨基丙基或脂族杂环甲基氨基丙基取代基C端基。使用毛细管区带电泳已经评估了这些化合物主要结合至DNA AT束的能力。几种化合物，特别是那些含有噻唑的化合物，显示出对关键生物如MRSA和白色念珠菌的显着抗菌活性。而且，这些化合物对几种哺乳动物细胞系具有低毒性。