THIAZOLYL AND BENZOTHIAZOLYL HYDRAZONES DERIVED FROM ALPHA-(N)-ACETYLPYRIDINES AND DIAZINES - SYNTHESIS, ANTIPROLIFERATIVE ACTIVITY AND COMFA STUDIES

The synthesis of a series of thiazolyl and benzothiazolyl hydrazones d erived from alpha-(N)-acylpyridines,-quinolines, -isoquinolines, -pyri dazines, -pyrimidines, and -pyrazines is reported. The stereochemistry of these compounds was determined by NMR spectroscopic methods. The a ntiproliferative activity of the novel compounds was quantified in tis sue culture (melanoma, breast carcinoma, colon adenocarcinoma, epithel oid cervix carcinoma, Burkitt's lymphoma, leukemia, and hydroxyurea se nsitive and resistant myelogenous leukemia sublines). All compounds ex hibited profound antiproliferative activity, in particular against Bur kitt's lymphoma cells. Out of this series, compounds 6b, 7b, 7c, 8c an d 8i were found to be 13-900 times more potent than hydroxyurea and no cross-resistance to hydroxyurea was observed. A predictive 3D-QSAR mo del using the CoMFA approach was established.