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ID: ALA4219038

Journal: Bioorg Med Chem Lett

Title: 1-Thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives as antitumor agents.

Authors: Cooper AB, Ciblat S, Shipps G, Levine J, Kostura M, Oza V, Constantineau-Forget L, Dery M, Grand-Maitre C, Bruneau-Latour N, Bellavance E, Patane M, Siddiqui A, Luther M.

Abstract: 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.

CiteXplore: 28844391

DOI: 10.1016/j.bmcl.2017.08.003