1-(2,4-difluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde | 125126-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(2,4-difluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde
• 英文别名: 1-(2,4-difluorophenyl)-2,5-dimethylpyrrole-3-carbaldehyde
• CAS: 125126-73-0
• 化学式: C₁₃H₁₁F₂NO
• mdl: MFCD08444739
• 分子量: 235.233
• InChiKey: MVDLNJHLFFSBDE-UHFFFAOYSA-N

物化性质

• 沸点：
  332.7±42.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.153
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methylamino-4-thiazolinone 、 1-(2,4-difluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 5-[[1-(2,4-difluorophenyl)-2,5-dimethylpyrrol-3-yl]methylidene]-2-(methylamino)-1,3-thiazol-4-one
  参考文献：
  名称：

  Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3-alkyl-2-(alkylimino)thiazolidin-4-one chemotype

  摘要：

  High affinity and selective S1P(4) receptor (S1P(4)-R) small molecule agonists may be important proof-of-principle tools used to clarify the receptor biological function and effects to assess the therapeutic potential of the S1P4-R in diverse disease areas including treatment of viral infections and thrombocytopenia. A high-throughput screening campaign of the Molecular Libraries-Small Molecule Repository was carried out by our laboratories and identified (2Z,5Z)-5-((1-(2-fluorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)-3-methyl-2-(methylimino) thiazolidin-4-one as a promising S1P(4)-R agonist hit distinct from literature S1P(4)-R modulators. Rational chemical modifications of the hit allowed the identification of a promising lead molecule with low nanomolar S1P(4)-R agonist activity and exquisite selectivity over the other S1P(1-3,5)-Rs family members. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the effects of the S1P(4)-R signaling cascade and elucidate the molecular basis of the receptor function. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.049
• 作为产物：
  描述：

  2,4-二氟苯胺 在 silica gel 、 对甲苯磺酸 、 三氯氧磷 作用下， 以 neat (no solvent) 为溶剂， 反应 3.25h， 生成 1-(2,4-difluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carbaldehyde
  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

文献信息

• [EN] IMIDAZOLE-BASED ANTIMICROBIAL AGENTS<br/>[FR] AGENTS ANTIMICROBIENS À BASE D'IMIDAZOLE
  申请人：PROCOMCURE BIOTECH GMBH

  公开号：WO2016087618A1

  公开（公告）日：2016-06-09

  The present invention relates to novel therapeutic agents suitable for use in the treatment of mammalian disease and in particular to novel therapeutic agents suitable for use in the treatment of microbial infection in mammals. The present invention further relates to the use of pharmaceutical compositions comprising said agents in the treatment of medical conditions in mammals, in particular in the treatment of microbial infection. The agents and pharmaceutical compositions of the invention are of particular relevance in the treatment of diseases associated with antibiotic-resistant microbes.

  本发明涉及新型治疗剂，适用于治疗哺乳动物疾病，特别是适用于治疗哺乳动物微生物感染的新型治疗剂。本发明还涉及包含上述剂的药物组合物在治疗哺乳动物的医疗状况中的使用，特别是在治疗微生物感染中的使用。本发明的剂和药物组合物在治疗与抗生素耐药微生物相关的疾病方面具有特殊意义。
• Imidazole-based antimicrobial agents
  申请人：Procomcure Biotech GmbH

  公开号：US10322110B2

  公开（公告）日：2019-06-18

  The present invention relates to therapeutic agents suitable for use in the treatment of microbial infection in mammals. The present invention further relates to the use of pharmaceutical compositions comprising said agents in the treatment of medical conditions in mammals, in particular in the treatment of microbial infection. The agents and pharmaceutical compositions of the invention are of particular relevance in the treatment of diseases associated with antibiotic-resistant microbes. In one particular embodiment, the pharmaceutical composition can have the structural moiety of formula (I) or a pharmaceutically-acceptable salt of said compound: wherein group A is selected from the formulae Group B is aryl, R1 is an optionally substituted aryl ring, an optionally substituted benzyl ring, CH3, or C2 to 6 alkyl, and R2 is hydrogen, an alkyl group, a halogen, or —(CH2)nN(CH3)2 where n is an integer from 1 to 3.

  本发明涉及适用于治疗哺乳动物微生物感染的治疗剂。本发明还涉及包含上述制剂的药物组合物在治疗哺乳动物的病症，特别是治疗微生物感染中的用途。本发明的制剂和药物组合物在治疗与抗生素耐药微生物相关的疾病方面具有特殊意义。在一个特定的实施方案中，药物组合物可以具有式（I）的结构分子或所述化合物的药学上可接受的盐： 其中 A 组选自式 B 组为芳基，R1 为任选取代的芳基环、任选取代的苄基环、CH3 或 C2 至 6 烷基，R2 为氢、烷基、卤素或-(CH2)nN( )2，其中 n 为 1 至 3 的整数。
• IMIDAZOLE-BASED ANTIMICROBIAL AGENTS
  申请人：Procomcure Biotech GmbH

  公开号：EP3226858A1

  公开（公告）日：2017-10-11
• Imidazole-Based Antimicrobial Agents
  申请人：Procomcure Biotech GmbH

  公开号：US20170368032A1

  公开（公告）日：2017-12-28

  The present invention relates to novel therapeutic agents suitable for use in the treatment of mammalian disease and in particular to novel therapeutic agents suitable for use in the treatment of microbial infection in mammals. The present invention further relates to the use of pharmaceutical compositions comprising said agents in the treatment of medical conditions in mammals, in particular in the treatment of microbial infection. The agents and pharmaceutical compositions of the invention are of particular relevance in the treatment of diseases associated with antibiotic-resistant microbes.