PYRAN DERIVATIVES - XX - 2-AMINOCHROMONE BENZO-FUSED DERIVATIVES WITHANTIPROLIFERATIVE PROPERTIES

The N-substituted 2-aminochromones 1 and their benzo-fused derivatives 2-4 described herein were mostly prepared by treating the correspondi ng (methylthio) derivatives 10-13 with an excess of the proper amines. Only the morpholino derivatives 3d and 4c were obtained from the reac tion of the ethyl 3-morpholino-3-oxopropanoate/POCl3 reagent with 1-na phthol or 1-methyl-2-naphthol, respectively. The amino derivatives 1-4 , as well as their methylthio analogues 10-13, were tested in vitro fo r their inhibitory activity on the infectivity of T2 bacteriophage, on the macromolecular synthesis in Ehrlich cells and on the clonal growt h capacity of HeLa cells. Several of the angular or linear aminonaphth opyranones 2 and 3 or 4, respectively, and the (methylthio) derivative s 10, 11 and 13 induced a significant inhibition of DNA synthesis, but usually a clearly lower inhibition of clonal growth. Only the Linear 2-amino-10-methyl-4H-naphtho [2,3-b]pyran-4-ones 4a and 4b significant ly inhibited the clonal growth in HeLa cells and T2 bacteriophage infe ctivity, respectively. (C) 1998 Elsevier Science S.A. All rights reser ved.