4-溴-6-氟喹啉-3-羧酸乙酯 | 1242260-48-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 4-溴-6-氟喹啉-3-羧酸乙酯
• 英文名称: ethyl 4-bromo-6-fluoroquinoline-3-carboxylate
• 英文别名: 4-Bromo-6-fluoroquinoline-3-carboxylic acid ethyl ester
• CAS: 1242260-48-5
• 化学式: C₁₂H₉BrFNO₂
• 分子量: 298.111
• InChiKey: LTRNAUFYDOWTMH-UHFFFAOYSA-N

物化性质

• 沸点：
  358.4±37.0 °C(Predicted)
• 密度：
  1.556±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-溴-6-氟喹啉-3-羧酸乙酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.5h， 生成 4-(4-(4-(1-cyanocyclopropyl)phenyl)-6-fluoroquinoline-3-carbonyl)-N,N-dimethylpiperazine-1-carboxamide trifluoroacetate
  参考文献：
  名称：

  Discovery of Orally Bioavailable, Quinoline-Based Aldehyde Dehydrogenase 1A1 (ALDH1A1) Inhibitors with Potent Cellular Activity

  摘要：

  Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiological and toxicological functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g., ALDHIAI) is an important biomarker in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small molecule ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described. Extensive medicinal chemistry optimization and biological characterization led to the identification of analogs with significantly improved enzymatic and cellular ALDH inhibition. Selected analogs, e.g., 86 (NCT-505) and 91 (NCT-506), demonstrated target engagement in a cellular thermal shift assay (CETSA), inhibited the formation of 3D spheroid cultures of OV-90 cancer cells, and potentiated the cytotoxicity of paclitaxel in SKOV-3-TR, a paclitaxel resistant ovarian cancer cell line. Lead compounds also exhibit high specificity over other ALDH isozymes and unrelated dehydrogenases. The in vitro ADME profiles and pharmacokinetic evaluation of selected analogs are also highlighted.

  DOI：

  10.1021/acs.jmedchem.8b00270

文献信息

• [EN] SUBSTITUTED QUINOLINE ANALOGS AS ALDEHYDE DEHYDROGENASE 1A1 (ALDH1A1) INHIBITORS<br/>[FR] ANALOGUES DE QUINOLÉINE SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS D'ALDÉHYDE DÉSHYDROGÉNASE 1A1 (ALDH1A1)
  申请人：US HEALTH

  公开号：WO2019089626A1

  公开（公告）日：2019-05-09

  The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R4, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumorsbreast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis. The disclosure also includes pharmaceutical compositions containing a compound or salt of Formula I.

  该披露提供了式I的化合物及其药物可接受的盐，可用作醛脱氢酶抑制剂。其中变量J，R4，G，Q和环A在此处定义。式I的醛脱氢酶抑制剂可用于治疗多种疾病，包括癌症和炎症。该披露包括使用式I的化合物和盐治疗结肠癌、胰腺癌、鼻咽癌、甲状腺癌、前列腺癌、卵巢癌、头颈部鳞状细胞癌、肺癌、肝细胞癌、白血病、脑肿瘤、乳腺癌、动脉粥样硬化、缺血性心脏病、痤疮、哮喘、自身免疫疾病、自身炎症性疾病、慢性前列腺炎、肾小球肾炎、炎症性肠病、盆腔炎症、再灌注损伤、类风湿性关节炎、结节病、移植排斥、血管炎和间质性膀胱炎的方法。该披露还包括含有式I的化合物或盐的制药组合物。
• SUBSTITUTED QUINOLINE ANALOGS AS ALDEHYDE DEHYDROGENASE 1A1 (ALDH1A1) INHIBITORS
  申请人：The U.S.A. as represented by the Secretary, Department of Health and Human Services

  公开号：EP3704102A1

  公开（公告）日：2020-09-09