N-[5-[4-(5-amino-1,3,4-thiadiazol-2-yl)butyl]-1,3,4-thiadiazol-2-yl]-3-phenylpropanamide | 1415397-20-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[5-[4-(5-amino-1,3,4-thiadiazol-2-yl)butyl]-1,3,4-thiadiazol-2-yl]-3-phenylpropanamide
• CAS: 1415397-20-4
• 化学式: C₁₇H₂₀N₆OS₂
• 分子量: 388.517
• InChiKey: HKPOSUQQVVQZDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  163
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-(5-amino-1,3,4-thiadiazol-2-yl)pentanoic acid 在 硫酸 、 三乙胺 、 lithium hydroxide 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 100.0h， 生成 N-[5-[4-(5-amino-1,3,4-thiadiazol-2-yl)butyl]-1,3,4-thiadiazol-2-yl]-3-phenylpropanamide
  参考文献：
  名称：

  Design, Synthesis, and Pharmacological Evaluation of Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl Sulfide 3 (BPTES) Analogs as Glutaminase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm301191p

文献信息

• [EN] COMBINATION THERAPY WITH GLUTAMINASE INHIBITORS<br/>[FR] POLYTHÉRAPIE AVEC DES INHIBITEURS DE GLUTAMINASE
  申请人：CALITHERA BIOSCIENCES INC

  公开号：WO2015138902A1

  公开（公告）日：2015-09-17

  The invention relates to methods of treating cancer, myeloproliferative disorders or immunological diseases with a combination of an immunomodulatory agent and a glutaminase inhibitor. The invention further relates to methods of treating cancer, myeloproliferative disorders, or immunological diseases that are resistant to one or more immunomodulatory agents.
• 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.