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-phenyl-acetamide 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.

中文翻译：

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作为谷氨酰胺酶抑制剂的双-2-(5-苯基乙酰氨基-1,2,4-噻二唑-2-基)乙基硫醚 3 (BPTES) 类似物的设计、合成和药理学评价

Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) 是一种有效的选择性肾型谷氨酰胺酶 (GLS) 变构抑制剂，可作为分子探针来确定GLS抑制的治疗潜力。为了鉴定具有改进的药物样分子特性的更有效的 GLS 抑制剂，合成并评估了一系列 BPTES 类似物。我们的构效关系 (SAR) 研究表明，一些截短的类似物保留了 BPTES 的效力，为提高其水溶性提供了机会。类似物之一，N- (5-{2-[2-(5-氨基-[1,3,4]噻二唑-2-基)-乙基硫基]-乙基}-[1,3,4]噻二唑- 2-yl)-2-苯基-乙酰胺6，与 BPTES 相比，表现出相似的效力和更好的溶解性，并在体外和小鼠异种移植模型中减弱了 P493 人淋巴瘤 B 细胞的生长。