In our prior studies, substituted 2-phenyl-4-quinolones (2-PQ) were identified as novel antimitotic agents. The structure-activity relationship were established with many related analogs. Among these analogs, most of potent cytotoxicity compounds were quite lipophilic and there, not optimal for in vivo and clinical studies.
In order to improve the pharmacokinetic properties of antimitotic 2-phenyl-4-quinolone derivatives. Serveral water soluble salts of 6-[(diethylamino)methyl]-2-phenylquinolin-4(1H)-one (3a), 6-[(diethyl- amino)methyl]-2-(2-fluorophenyl)quinolin-4(1H)-one (3b) and 2-{3- [(diethylamino)methyl]phenyl}-6-methoxyquinolin-4(1H)-one (4) were designed and synthesized.
The results of preliminary screening of target compounds and their intermediates demonstrated that 4-(4-methoxy-benzyloxy)-6-methoxy- 2-phenyl-quinoline (1) and 1-(4-methoxybenzyl)-5,7-dimethoxy-2-m- tolylquinolin-4(1H)-one (2) show significant cytotoxicity. These compounds were selected as the new lead compounds for further structure modification.
