0000000000760732
AUTHOR
Hemma Schueffl
Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib
Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dr…
CCDC 1944348: Experimental Crystal Structure Determination
Related Article: Bjoern Bielec, Hemma Schueffl, Alessio Terenzi, Walter Berger, Petra Heffeter, Bernhard K. Keppler, Christian R. Kowol|2020|Bioorg.Chem.|99|103778|doi:10.1016/j.bioorg.2020.103778