Synthetic studies on mitotic kinesin Eg5 inhibitors: synthesis and structure-activity relationships of novel 2,4,5-substituted-1,3,4-thiadiazoline derivatives
| Autor: | Yoji Ino, Yoshihisa Ohta, Tetsuya Tsujita, Seiho Okamoto, Ryuichiro Nakai, Nobuyoshi Amishiro, Takeshi Takahashi, Kazuhiko Kato, Yoshinori Yamashita, Junichiro Yamamoto, Shiro Akinaga, Hideaki Kusaka, Mitsuharu Araki, Chikara Murakata |
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| Rok vydání: | 2014 |
| Předmět: |
Antitumor activity
Dose-Response Relationship Drug Molecular Structure Organic Chemistry Clinical Biochemistry Pharmaceutical Science Kinesins Optically active Inhibitory postsynaptic potential Biochemistry chemistry.chemical_compound Structure-Activity Relationship chemistry Oral administration Drug Discovery Side chain Molecular Medicine Kinesin Humans Thiazolidines Enzyme Inhibitors Molecular Biology Mitosis Acyl group |
| Zdroj: | Bioorganicmedicinal chemistry letters. 24(16) |
| ISSN: | 1464-3405 |
| Popis: | The 2,4,5-substituted-1,3,4-thiadiazoline derivative 1a has been identified as a new class of mitotic kinesin Eg5 inhibitor. With the aim of enhancement of the mitotic phase accumulation activity, structure optimization of side chains at the 2-, 4-, and 5-positions of the 1,3,4-thiadiazoline ring of 1a was performed. The introduction of sulfonylamino group at the side chain at the 5-position and bulky acyl group at the 2- and 4-position contributed to a significant increase in the mitotic phase accumulation activity and Eg5 inhibitory activity. As a result, a series of optically active compounds exhibited an increased antitumor activity in a human ovarian cancer xenograft mouse model that was induced by oral administration. |
| Databáze: | OpenAIRE |
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