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

• From rational design to serendipity: Discovery of novel thiosemicarbazones as potent trypanocidal compounds
  作者：Saulo Fehelberg Pinto Braga、Viviane Corrêa Santos、Rafael Pinto Vieira、Elany Barbosa da Silva、Ludovica Monti、Susann H. Krake、Pablo D.G. Martinez、Luiz Carlos Dias、Conor R. Caffrey、Jair L. Siqueira-Neto、Renata Barbosa de Oliveira、Rafaela Salgado Ferreira

  DOI：10.1016/j.ejmech.2022.114876

  日期：2022.12

  Here, we describe the design and synthesis of derivatives of our lead compound. The new thiosemicarbazone derivatives showed potency in the nanomolar concentration range against the two enzymes, but they were later characterized as aggregators. Nevertheless, the thiosemicarbazone derivatives showed promising antiparasitic activities against T. b. brucei (EC50 13–49.7 μM) and T. cruzi (EC50 0.027–0.59 μM)

  恰加斯病是由病原体克氏锥虫引起的主要公共卫生问题，估计有 6-7 百万人受到感染，7000 万人面临感染风险。T. brucei gambiense和T. brucei rhodesiense是导致非洲人类锥虫病的相关寄生虫的两个亚种，这是一种被忽视的热带疾病，也有数百万人面临感染风险。这两种疾病的药物治疗都存在疗效低下、副作用或耐药性等问题。最近，我们报道了 cruzain（IC 50 26 μM ，K i 3 μM）和Tbr CatL（IC 5050 μM），两种半胱氨酸蛋白酶被认为是锥虫病有希望的药物靶点。在这里，我们描述了先导化合物衍生物的设计和合成。新的缩氨基硫脲衍生物在纳摩尔浓度范围内显示出对这两种酶的效力，但它们后来被表征为聚集剂。尽管如此，缩氨基硫脲衍生物显示出对T. b.有希望的抗寄生虫活性。brucei (EC 50 13–49.7 μM) 和T. cruzi (EC 50
• 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.