Cooper Alan B, Ciblat Stephane, Shipps Gerald, Levine Jedd, Kostura Matthew, Oza Vibha, Constantineau-Forget Lea, Dery Martin, Grand-Maitre Chantal, Bruneau-Latour Nicolas, Bellavance Edith, Patane Michael, Siddiqui Arshad, Luther Michael
Bantam Pharmaceutical, New York, NY, United States.
Paraza Pharma, Montreal, QC, Canada.
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4471-4477. doi: 10.1016/j.bmcl.2017.08.003. Epub 2017 Aug 2.
A class of substituted 1-thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives was found to have potent anti-proliferative activity against a broad range of tumor cell lines. A compound from this class (14) was profiled across a broad panel of hematologic and solid tumor cancer cell lines demonstrating cell cycle arrest at the G0/G1 interphase and has potent anti-proliferative activity against a distinct and select set of cancer cell types with no observed effects on normal human cells. An example is the selective inhibition of human B-cell lymphoma cell line (BJAB). Compound 14 was orally bioavailable and tolerated well in mice. Synthesis and structure activity relationships (SAR) in this series of compounds are discussed.
发现一类取代的1-噻唑-2-基-N-3-甲基-1H-吡唑-5-羧酸衍生物对多种肿瘤细胞系具有强大的抗增殖活性。该类中的一种化合物（14）在广泛的血液学和实体瘤癌细胞系中进行了分析，显示在G0/G1间期使细胞周期停滞，并且对一组独特且特定的癌细胞类型具有强大的抗增殖活性，对正常人类细胞无明显影响。例如对人B细胞淋巴瘤细胞系（BJAB）的选择性抑制。化合物14口服具有生物利用度，在小鼠中耐受性良好。讨论了该系列化合物的合成及构效关系（SAR）。
