2,5-二甲基-1-[2-(三氟甲基)苯基]-1H-吡咯-3-甲醛 | 932226-24-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 2,5-二甲基-1-[2-(三氟甲基)苯基]-1H-吡咯-3-甲醛
• 英文名称: 2,5-dimethyl-1-(2-(trifluoromethyl)phenyl)-1H-pyrrole-3-carbaldehyde
• 英文别名: 2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrole-3-carbaldehyde
• CAS: 932226-24-9
• 化学式: C₁₄H₁₂F₃NO
• mdl: MFCD09034595
• 分子量: 267.251
• InChiKey: BPGJTHYIJWQASI-UHFFFAOYSA-N

物化性质

• 沸点：
  354.6±42.0 °C(Predicted)
• 密度：
  1.20

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.214
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,5-二甲基-1-[2-(三氟甲基)苯基]-1H-吡咯-3-甲醛 在 盐酸 、 potassium hydrogensulfate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 6.5h， 生成 (5E)-5-[[2,5-dimethyl-1-[2-(trifluoromethyl)phenyl]pyrrol-3-yl]methylidene]-N,2-dimethyl-4-oxo-1H-pyrrole-3-carboxamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials

  摘要：

  In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 similar to 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.

  DOI：

  10.1021/jm400009c
• 作为产物：
  描述：

  邻氨基三氟甲苯 在 三氯氧磷 作用下， 以 neat (no solvent) 为溶剂， 反应 20.33h， 生成 2,5-二甲基-1-[2-(三氟甲基)苯基]-1H-吡咯-3-甲醛
  参考文献：
  名称：

  Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives

  摘要：

  为了确定具有抗原虫活性的蒲公英素衍生物，合成了一系列相对未被探索的基于芳基吡咯烯的蒲公英素衍生物，产率在中等到良好之间。所得化合物在体外评估其对培养的布鲁氏锥虫427株的潜在活性。几种化合物显示出主要是适度的体外抗锥虫活性，其中化合物10e和10h 显示出活性，IC50值分别为4.09和5.11微摩尔。更重要的是，对它们在人宫颈腺癌（HeLa）细胞系中的活性进行同时评估表明这些化合物无毒。

  DOI：

  10.3390/molecules25071668

文献信息

• Structure–Activity Relationship Studies of Pyrrolone Antimalarial Agents
  作者：Dinakaran Murugesan、Marcel Kaiser、Karen L. White、Suzanne Norval、Jennifer Riley、Paul G. Wyatt、Susan A. Charman、Kevin D. Read、Clive Yeates、Ian H. Gilbert

  DOI：10.1002/cmdc.201300177

  日期：2013.9

  Previously reported pyrrolones, such as TDR32570, exhibited potential as antimalarial agents; however, while these compounds have potent antimalarial activity, they suffer from poor aqueous solubility and metabolic instability. Here, further structure–activity relationship studies are described that aimed to solve the developability issues associated with this series of compounds. In particular, further

  先前报道的吡咯酮，如 TDR32570，显示出作为抗疟药的潜力；然而，虽然这些化合物具有有效的抗疟活性，但它们的水溶性较差且代谢不稳定。在这里，描述了进一步的构效关系研究，旨在解决与这一系列化合物相关的可开发性问题。特别是，对吡咯酮铅的进一步修饰，包括用哌啶取代苯环并通过支架啤酒花去除潜在代谢不稳定的酯，产生了对恶性疟原虫具有改善的体外抗疟活性的衍生物K1 是一种耐氯喹和乙胺嘧啶的寄生虫菌株，其某些衍生物对寄生虫的选择性优于哺乳动物 (L6) 细胞。选择了三种代表性化合物在疟疾感染的啮齿动物模型中进行评估，最好的化合物显示出减少寄生虫血症的能力有所提高，存活率略有增加。
• Discovery and optimisation studies of antimalarial phenotypic hits
  作者：Alka Mital、Dinakaran Murugesan、Marcel Kaiser、Clive Yeates、Ian H. Gilbert

  DOI：10.1016/j.ejmech.2015.08.044

  日期：2015.10

  There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09-29 mu M, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds. (C) 2015 The Authors. Published by Elsevier Masson SAS.
• Improving the Potency of <i>N</i>-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
  作者：Meir Touitou、Fabrizio Manetti、Camila Maringolo Ribeiro、Fernando Rogerio Pavan、Nicolò Scalacci、Katarina Zrebna、Neelu Begum、Dorothy Semenya、Antima Gupta、Sanjib Bhakta、Timothy D. McHugh、Hanoch Senderowitz、Melina Kyriazi、Daniele Castagnolo

  DOI：10.1021/acsmedchemlett.9b00515

  日期：2020.5.14

  A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.
• Discovery and Structure–Activity Relationships of Pyrrolone Antimalarials
  作者：Dinakaran Murugesan、Alka Mital、Marcel Kaiser、David M. Shackleford、Julia Morizzi、Kasiram Katneni、Michael Campbell、Alan Hudson、Susan A. Charman、Clive Yeates、Ian H. Gilbert

  DOI：10.1021/jm400009c

  日期：2013.4.11

  In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 similar to 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
• Synthesis, Structure and In Vitro Anti-Trypanosomal Activity of Non-Toxic Arylpyrrole-Based Chalcone Derivatives
  作者：Ayanda I. Zulu、Ogunyemi O. Oderinlo、Cuan Kruger、Michelle Isaacs、Heinrich C. Hoppe、Vincent J. Smith、Clinton G. L. Veale、Setshaba D. Khanye

  DOI：10.3390/molecules25071668

  日期：——

  With an intention of identifying chalcone derivatives exhibiting anti-protozoal activity, a cohort of relatively unexplored arylpyrrole-based chalcone derivatives were synthesized in moderate to good yields. The resultant compounds were evaluated in vitro for their potential activity against a cultured Trypanosoma brucei brucei 427 strain. Several compounds displayed mostly modest in vitro anti-trypanosomal activity with compounds 10e and 10h emerging as active candidates with IC50 values of 4.09 and 5.11 µM, respectively. More importantly, a concomitant assessment of their activity against a human cervix adenocarcinoma (HeLa) cell line revealed that these compounds are non-toxic.

  为了确定具有抗原虫活性的蒲公英素衍生物，合成了一系列相对未被探索的基于芳基吡咯烯的蒲公英素衍生物，产率在中等到良好之间。所得化合物在体外评估其对培养的布鲁氏锥虫427株的潜在活性。几种化合物显示出主要是适度的体外抗锥虫活性，其中化合物10e和10h 显示出活性，IC50值分别为4.09和5.11微摩尔。更重要的是，对它们在人宫颈腺癌（HeLa）细胞系中的活性进行同时评估表明这些化合物无毒。