5-(4-bromo-2-chlorophenyl)furan-2-carbaldehyde

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-bromo-2-chlorophenyl)furan-2-carbaldehyde
• 化学式: C₁₁H₆BrClO₂
• mdl: MFCD01764251
• 分子量: 285.524
• InChiKey: CTUROMWIRNCANZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-bromo-2-chlorophenyl)furan-2-carbaldehyde 在 palladium diacetate 、 三苯基膦 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 24.5h， 生成
  参考文献：
  名称：

  Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues

  摘要：

  Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba2+ current through Ca(v)1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.024
• 作为产物：
  描述：

  糠醛 、 4-溴-2-氯苯胺 在 盐酸 、 sodium nitrite 、 copper(II) choride dihydrate 作用下， 以 水 为溶剂， 反应 0.67h， 以51%的产率得到5-(4-bromo-2-chlorophenyl)furan-2-carbaldehyde
  参考文献：
  名称：

  从“疟疾盒子”中发现锥虫半胱氨酸蛋白酶抑制剂的特性

  摘要：

  南美锥虫病，人类非洲锥虫病和血吸虫病是被忽视的寄生虫病，迫切需要新的治疗方法。为了确定新的化学线索，我们针对半胱氨酸蛋白酶，克鲁萨因（Trypanosoma cruzi），罗得沙因（Trypanosoma brucei）和SmCB1（Schistosoma mansoni）筛选了开放获取疟疾框的400种化合物，是这些疾病的治疗目标。尽管仅对SmCB1命中了3次，但在5μM时，有70种化合物抑制了Cruzain或Rhodesain至少50％。在这些化合物中，选择了15种可商购的化合物进行验证性分析，因为它们的功效，随时间变化的抑制曲线和已报道的抗寄生虫活性。另外的测定导致的四种新型类cruzain和rhodesain抑制剂的确认，并在由低到中档微摩尔对酶和效力锥虫。对哺乳动物组织蛋白酶S和B的分析表明抑制剂对寄生蛋白酶具有选择性。对于确定的两种竞争性抑制剂（化合物7和12），通过对接预测它们

  DOI：

  10.1016/j.ejmech.2019.06.062

文献信息

• Discovery and characterization of trypanocidal cysteine protease inhibitors from the ‘malaria box’
  作者：Glaécia A.N. Pereira、Elany B. da Silva、Saulo F.P. Braga、Paulo Gaio Leite、Luan C. Martins、Rafael P. Vieira、Wai Tuck Soh、Filipe S. Villela、Francielly M.R. Costa、Debalina Ray、Saulo F. de Andrade、Hans Brandstetter、Renata B. Oliveira、Conor R. Caffrey、Fabiana S. Machado、Rafaela S. Ferreira

  DOI：10.1016/j.ejmech.2019.06.062

  日期：2019.10

  parasites. Additional assays led to the confirmation of four novel classes of cruzain and rhodesain inhibitors, with potency in the low-to mid-micromolar range against enzymes and T. cruzi. Assays against mammalian cathepsins S and B revealed inhibitor selectivity for parasitic proteases. For the two competitive inhibitors identified (compounds 7 and 12), their binding mode was predicted by docking, providing

  南美锥虫病，人类非洲锥虫病和血吸虫病是被忽视的寄生虫病，迫切需要新的治疗方法。为了确定新的化学线索，我们针对半胱氨酸蛋白酶，克鲁萨因（Trypanosoma cruzi），罗得沙因（Trypanosoma brucei）和SmCB1（Schistosoma mansoni）筛选了开放获取疟疾框的400种化合物，是这些疾病的治疗目标。尽管仅对SmCB1命中了3次，但在5μM时，有70种化合物抑制了Cruzain或Rhodesain至少50％。在这些化合物中，选择了15种可商购的化合物进行验证性分析，因为它们的功效，随时间变化的抑制曲线和已报道的抗寄生虫活性。另外的测定导致的四种新型类cruzain和rhodesain抑制剂的确认，并在由低到中档微摩尔对酶和效力锥虫。对哺乳动物组织蛋白酶S和B的分析表明抑制剂对寄生蛋白酶具有选择性。对于确定的两种竞争性抑制剂（化合物7和12），通过对接预测它们
• WO2020069625A5
  申请人：——

  公开号：WO2020069625A5

  公开（公告）日：2022-10-11
• TRANSCRIPTION FACTOR BRN2 INHIBITORY COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE
  申请人：The University of British Columbia

  公开号：EP3860994A1

  公开（公告）日：2021-08-11
• [EN] TRANSCRIPTION FACTOR BRN2 INHIBITORY COMPOUNDS AS THERAPEUTICS AND METHODS FOR THEIR USE<br/>[FR] COMPOSÉS INHIBITEURS DU FACTEUR DE TRANSCRIPTION BRN2 UTILISÉS EN TANT QU'AGENTS THÉRAPEUTIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV BRITISH COLUMBIA

  公开号：WO2020069625A1

  公开（公告）日：2020-04-09

  The invention provides a variety of compounds having the structure of Formula I and uses of such compounds for treatment of various indications, including cancer as well as methods of treatment involving such compounds are also provided. The uses of the compounds may specifically include: bladder cancer, cholangiocarcinoma; colorectal cancer; diffuse large B-cell lymphoma (DLBC); liver cancer; ovarian cancer; thymoma; thyroid cancer; clear cell renal cell carcinoma (CCRCC); chromophobe renal cell carcinoma (ChRCC); prostate cancer; breast cancer; uterine cancer; pancreatic cancer; cervical cancer; uveal melanoma; acute myeloid leukemia (AML); head and neck cancer; small cell lung cancer (SCLC); lung adenocarcinoma sarcoma; mesothelioma; adenoid cystic carcinoma (ACC), sarcoma; testicular germ cell cancer; uterine cancer; pheochromocytoma and paraganglioma (PCPG); melanoma; glioma; glioblastoma multiforme; T-cell Acute Lymphoblastic Leukemia; T-cell Lympohoma, medulloblastoma; and neuroblastoma.
• Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues
  作者：Alessandra Vallone、Sarah D'Alessandro、Simone Brogi、Margherita Brindisi、Giulia Chemi、Gloria Alfano、Stefania Lamponi、Soon Goo Lee、Joseph M. Jez、Karin J.M. Koolen、Koen J. Dechering、Simona Saponara、Fabio Fusi、Beatrice Gorelli、Donatella Taramelli、Silvia Parapini、Reto Caldelari、Giuseppe Campiani、Sandra Gemma、Stefania Butini

  DOI：10.1016/j.ejmech.2018.03.024

  日期：2018.4

  Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba2+ current through Ca(v)1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. (C) 2018 Elsevier Masson SAS. All rights reserved.