GEIPARVARIN ANALOGS .2. SYNTHESIS AND CYTOSTATIC ACTIVITY OF 5-(4-ARYLBUTADIENYL)-3(2H)-FURANONES AND OF N-SUBSTITUTED 3-(4-OXO-2-FURANYL)-2-BUTEN-2-YL CARBAMATES

In an attempt to determine some of the structural features of geiparvarin (1) that account for its cytostatic activity in vitro, a series of geiparvarin analogues (10a-i, 1, 12, and 14-16) which contain novel modifications in the region of the olefinic double bond and of the coumarin moiety have been designed and synthesized. Among the derivatives containing a carbamate moiety, only the analogues containing a carbamate group linked to an alkyl moiety 10b-i were endowed with potent cytostatic activity, whereas the corresponding benzene derivative 10a was devoid of any antiproliferative activity. 6-Methoxygeiparvarin 101 proved equally effective as geiparvin (1), while compounds containing an additional double bond at the side chain (12 and 14-16) were invariably 5-100-fold less effective than geiparvarin. Diene derivative 15, bearing a coumarin moiety, was essentially inactive against murine (L1210, FM3A) tumor cells but exhibited good activity against human (Molt/4F, MT-4) tumor cells.