3-ethyl-4-methyl-2,2'-bipyrrolyl-5-carboxaldehyde | 1450982-09-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-ethyl-4-methyl-2,2'-bipyrrolyl-5-carboxaldehyde
• 英文别名: 3-ethyl-4-methyl-1H,1′H-[2,2′-bipyrrole]-5-carbaldehyde；4-ethyl-3-methyl-5-(1H-pyrrol-2-yl)-1H-pyrrole-2-carbaldehyde
• CAS: 1450982-09-8
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: IYTYKSMTXXMHTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  48.6
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-ethyl-4-methyl-2,2'-bipyrrolyl-5-carboxaldehyde 、 环丙胺 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 生成 N-((3'-ethyl-4'-methyl-[2,2'-bipyrrol]-5'-ylidene)methyl)cyclopropanamine
  参考文献：
  名称：

  tambjamines和B环功能化的prodiginines作为有效的抗疟药的合成及其构效关系。

  摘要：

  描述了94种新型联吡咯他布明胺（TAs）的合成和抗疟活性以及针对一系列恶性疟原虫菌株的B环功能化三联吡咯酮（PGs）库。活性和结构-活性之间的关系表明，PGs的C环可以被烷基胺取代，从而为TAs提供保留/增强的效力。此外，PG / TA的B环可以在4位（取代OMe）或3位和4位上被短烷基取代而不影响效能。已评估了八个代表性TA和两个PG对耐多药疟原虫的抗疟活性口服给药的小鼠剂量范围为5-100 mg / kg×4天。KAR425 TA的功效比以前任何PG所观察到的都要大，在25天和50 mg / kg×4天的剂量下，直到28天之前，对感染疟疾的小鼠提供100％的保护，并且在该模型中也可以单次口服治疗（80毫克/公斤）。这项研究提出了tambjamines中抗疟活性的第一个解释。

  DOI：

  10.1021/acs.jmedchem.5b00560
• 作为产物：
  描述：

  在 甲醇 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以714 mg的产率得到3-ethyl-4-methyl-2,2'-bipyrrolyl-5-carboxaldehyde
  参考文献：
  名称：

  2,2′-联吡咯-5-甲醛的合成及其在 B 环官能化 prodiginines 和 tambjamines 合成中的应用

  摘要：

  已经开发出用于制备一系列新型 3-烷基-、4-烷基-、3,4-二烷基-和 3-卤代-4-烷基-2,2′-联吡咯-5-甲醛的简单、多功能和具有成本效益的合成路线。这些 2,2′-联吡咯-5-甲醛作为制造生物活性天然和非天然产物的构建块具有有趣的潜力，正如 B 环官能化 prodiginines （PG） 和 tambjamines 的合成所证明的那样。

  DOI：

  10.1016/j.tet.2013.07.067

文献信息

• Small molecule anion transporters display <i>in vitro</i> antimicrobial activity against clinically relevant bacterial strains
  作者：Israel Carreira-Barral、Carlos Rumbo、Marcin Mielczarek、Daniel Alonso-Carrillo、Enara Herran、Marta Pastor、Angel Del Pozo、María García-Valverde、Roberto Quesada

  DOI：10.1039/c9cc04304g

  日期：——

  Highly active transmembrane anion transporters have demonstrated their activity against antibiotic-resistant and clinically relevant bacterial strains.

  高活性的跨膜阴离子转运蛋白已经证明对抗抗生素耐药和临床相关的细菌菌株具有活性。
• Small molecule‐facilitated anion transporters in cells for a novel therapeutic approach to cystic fibrosis
  作者：Michele Fiore、Claudia Cossu、Valeria Capurro、Cristiana Picco、Alessandra Ludovico、Marcin Mielczarek、Israel Carreira‐Barral、Emanuela Caci、Debora Baroni、Roberto Quesada、Oscar Moran

  DOI：10.1111/bph.14649

  日期：2019.6

  Background and PurposeCystic fibrosis (CF) is a lethal autosomal recessive genetic disease that originates from the defective function of the CF transmembrane conductance regulator (CFTR) protein, a cAMP‐dependent anion channel involved in fluid transport across epithelium. Because small synthetic transmembrane anion transporters (anionophores) can replace the biological anion transport mechanisms, independent of genetic mutations in the CFTR, such anionophores are candidates as new potential treatments for CF.Experimental ApproachIn order to assess their effects on cell physiology, we have analysed the transport properties of five anionophore compounds, three prodigiosines and two tambjamines. Chloride efflux was measured in large uni‐lamellar vesicles and in HEK293 cells with chloride‐sensitive electrodes. Iodide influx was evaluated in FRT cells transfected with iodide‐sensitive YFP. Transport of bicarbonate was assessed by changes of pH after a NH4+ pre‐pulse using the BCECF fluorescent probe. Assays were also carried out in FRT cells permanently transfected with wild type and mutant human CFTR.Key ResultsAll studied compounds are capable of transporting halides and bicarbonate across the cell membrane, with a higher transport capacity at acidic pH. Interestingly, the presence of these anionophores did not interfere with the activation of CFTR and did not modify the action of lumacaftor (a CFTR corrector) or ivacaftor (a CFTR potentiator).Conclusion and ImplicationsThese anionophores, at low concentrations, transported chloride and bicarbonate across cell membranes, without affecting CFTR function. They therefore provide promising starting points for the development of novel treatments for CF.