|
|||||
|
|
1-Thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives as antitumor agents |
|
| Authors: | Alan B Cooper Stephane Ciblat Gerald Shipps Jedd Levine Matthew Kostura Vibha Oza Lea Constantineau-Forget Martin Dery Chantal Grand-Maitre Nicolas Bruneau-Latour Edith Bellavance Michael Patane Arshad Siddiqui Michael Luther |
| Institution: | 1. Bantam Pharmaceutical, New York, NY, United States;2. Paraza Pharma, Montreal, QC, Canada;3. Shire PLC, Lexington, MA, United States;4. Mitobridge, Cambridge, MA, United States |
| 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. |
| Keywords: | Tumor cell inhibitor Hemaopoietic cell lines BJAB G0/G1 cell cycle B-cell lymphoma SAR 1-Thiazol-2-yl-N-3-methyl-1H-pyrazole-5-carboxylic acid |
| 本文献已被 ScienceDirect 等数据库收录！ | |