Thiazolyl and benzothiazolyl hydrazones derived from α-(N)-acetylpyridines and diazines: synthesis, antiproliferative activity and CoMFA studies

The synthesis of a series of thiazolyl and benzothiazolyl hydrazones derived from α-(N)-acylpyridines, -quinolines, -isoquinolines, -pyridazines, -pyrimidines, and -pyrazines is reported. The stereochemistry of these compounds was determined by NMR spectroscopic methods. The antiproliferative activity of the novel compounds was quantified in tissue culture (melanoma, breast carcinoma, colon adenocarcinoma, epitheloid cervix carcinoma, Burkitt's lymphoma, leukemia, and hydroxyurea sensitive and resistant myelogenous leukemia sublines). All compounds exhibited profound antiproliferative activity, in particular against Burkitt's lymphoma cells. Out of this series, compounds 6b, 7b, 7c, 8c and 8i were found to be 13–900 times more potent than hydroxyurea and no cross-resistance to hydroxyurea was observed. A predictive 3D-QSAR model using the CoMFA approach was established.