5-(5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl)pentanoic acid | 1415397-86-2

• 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-(5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl)pentanoic acid
• 英文别名: 5-[5-[(2-Phenylacetyl)amino]-1,3,4-thiadiazol-2-yl]pentanoic acid；5-[5-[(2-phenylacetyl)amino]-1,3,4-thiadiazol-2-yl]pentanoic acid
• CAS: 1415397-86-2
• 化学式: C₁₅H₁₇N₃O₃S
• 分子量: 319.384
• InChiKey: YBRITRTUIVRJSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl)pentanoic acid 在 copper(l) iodide 、 sodium azide 、 三乙胺 、 三氯氧磷 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 2-(4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)-N-(5-(4-(5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl)butyl)-1,3,4-thiadiazol-2-yl)acetamide
  参考文献：
  名称：

  Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors

  摘要：

  Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Because of its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast, and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors.

  DOI：

  10.1021/acs.jmedchem.9b01035
• 作为产物：
  描述：

  己二酸单乙酯 在 三乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 31.0h， 生成 5-(5-(2-phenylacetamido)-1,3,4-thiadiazol-2-yl)pentanoic acid
  参考文献：
  名称：

  含有三氮唑结构的谷氨酰胺酶GLS1抑制剂或其可药用的盐、其制备方法及用途

  摘要：

  本发明公开了含有三氮唑结构的谷氨酰胺酶GLS1抑制剂或其可药用的盐、其制备方法及用途，本发明的一系列含有三氮唑结构的化合物具有谷氨酰胺酶抑制活性，并可用于治疗与谷氨酰胺酶功能异常或谷氨酰胺酶活性升高相关的疾病和病症。这些化合物可有效结合在谷氨酰胺酶的变构位点，导致谷氨酰胺酶的构象发生变化，阻断其发挥生物学功能。体外实验表明：本发明化合物对于各类谷氨酰胺依赖的癌细胞，如结肠癌、三阴性乳腺癌、肺癌等均具有良好的抑制活性

  公开号：

  CN110746416A

文献信息

• 含有三氮唑结构的谷氨酰胺酶GLS1抑制剂或其可药用的盐、其制备方法及用途
  申请人：中国药科大学

  公开号：CN110746416A

  公开（公告）日：2020-02-04

  本发明公开了含有三氮唑结构的谷氨酰胺酶GLS1抑制剂或其可药用的盐、其制备方法及用途，本发明的一系列含有三氮唑结构的化合物具有谷氨酰胺酶抑制活性，并可用于治疗与谷氨酰胺酶功能异常或谷氨酰胺酶活性升高相关的疾病和病症。这些化合物可有效结合在谷氨酰胺酶的变构位点，导致谷氨酰胺酶的构象发生变化，阻断其发挥生物学功能。体外实验表明：本发明化合物对于各类谷氨酰胺依赖的癌细胞，如结肠癌、三阴性乳腺癌、肺癌等均具有良好的抑制活性
• [EN] GLUTAMINASE GLS1 INHIBITOR CONTAINING TRIAZOLE STRUCTURE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF<br/>[FR] INHIBITEUR DE GLUTAMINASE GLS1 CONTENANT UNE STRUCTURE TRIAZOLE OU UN SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, PROCÉDÉ DE PRÉPARATION CORRESPONDANT ET UTILISATION ASSOCIÉE<br/>[ZH] 含有三氮唑结构的谷氨酰胺酶GLS1抑制剂或其可药用的盐、其制备方法及用途
  申请人：UNIV CHINA PHARMA

  公开号：WO2021042723A1

  公开（公告）日：2021-03-11

  本发明公开了含有三氮唑结构的谷氨酰胺酶GLS1抑制剂或其可药用的盐、其制备方法及用途，本发明的一系列含有三氮唑结构的化合物具有谷氨酰胺酶抑制活性，并可用于治疗与谷氨酰胺酶功能异常或谷氨酰胺酶活性升高相关的疾病和病症。这些化合物可有效结合在谷氨酰胺酶的变构位点，导致谷氨酰胺酶的构象发生变化，阻断其发挥生物学功能。体外实验表明：本发明化合物对于各类谷氨酰胺依赖的癌细胞，如结肠癌、三阴性乳腺癌、肺癌等均具有良好的抑制活性
• Design, Synthesis, and Pharmacological Evaluation of Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl Sulfide 3 (BPTES) Analogs as Glutaminase Inhibitors
  作者：Krupa Shukla、Dana V. Ferraris、Ajit G. Thomas、Marigo Stathis、Bridget Duvall、Greg Delahanty、Jesse Alt、Rana Rais、Camilo Rojas、Ping Gao、Yan Xiang、Chi V. Dang、Barbara S. Slusher、Takashi Tsukamoto

  DOI：10.1021/jm301191p

  日期：2012.12.13

  Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a potent and selective allosteric inhibitor of kidney-type glutaminase (GLS) that has served as a molecular probe to determine the therapeutic potential of GLS inhibition. In an attempt to identify more potent GLS inhibitors with improved drug-like molecular properties, a series of BPTES analogs were synthesized and evaluated. Our structure activity relationship (SAR) studies revealed that some truncated analogs retained the potency of BPTES, presenting an opportunity to improve its aqueous solubility. One of the analogs, N-(5-2-[2-(5-amino-[1,3,4]thiadiazol-2-yl)-ethylsulfanyl]-ethyl}-[1,3,4]thiadiazol-2-yl)-2-phenylacetamide 6, exhibited similar potency and better solubility relative to BPTES and attenuated the growth of P493 human lymphoma B cells in vitro as well as in a mouse xenograft model.
• Development and Characterization of a Fluorescent Probe for GLS1 and the Application for High-Throughput Screening of Allosteric Inhibitors
  作者：Xi Xu、Zijian Kuang、Jie Han、Ying Meng、Lei Li、Hongyu Luan、Pengfei Xu、Jubo Wang、Cheng Luo、Hong Ding、Zhiyu Li、Jinlei Bian

  DOI：10.1021/acs.jmedchem.9b01035

  日期：2019.11.14

  Glutaminase (GLS1) is a cancer energy metabolism protein which plays a predominant role in cell growth and proliferation. Because of its major involvement in malignant tumor, small-molecule GLS1 inhibitors are urgently needed to assess its therapeutic potential and for probing their underlying biology function. Recent studies showed that targeting the allosteric binding site represented a promising strategy for identifying potent and selective GLS1 inhibitors. Herein, we present the synthesis of two fluorescent probes targeting the allosteric binding site of GLS1 and their usage as mechanistic tools in multiple applicable assay platform. The fluorescence polarization (FP)-based binding assay enables easy, fast, and reliable screen of allosteric inhibitors from our in-house compound library obtained through click chemistry method. The obtained compound C147 (named as CPU-L1) has been proved to be more potent and with greater solubility than the control compound CB839, which could serve as promising leads for further optimization as novel GLS1 inhibitors.