Download Mendeley1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile.
Fancelli, D., Moll, J., Varasi, M., Bravo, R., Artico, R., Berta, D., Bindi, S., Cameron, A., Candiani, I., Cappella, P., Carpinelli, P., Croci, W., Forte, B., Giorgini, M.L., Klapwijk, J., Marsiglio, A., Pesenti, E., Rocchetti, M., Roletto, F., Severino, D., Soncini, C., Storici, P., Tonani, R., Zugnoni, P., Vianello, P.(2006) J Med Chem 49: 7247-7251
- PubMed: 17125279
- DOI: https://doi.org/10.1021/jm060897w
- Primary Citation of Related Structures:
2J4Z, 2J50 - PubMed Abstract:
The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora kinases that also shows low nanomolar potency against additional anticancer kinase targets. Based on its high antiproliferative activity on different cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.
Organizational Affiliation:
Nerviano Medical Sciences S.r.l. viale Pasteur 10, 20014 Nerviano, Milan, Italy.
