QUINOXALINE CHEMISTRY - PART 10 - QUINOXALINE 10-OXA-ANALOGS OF TRIMETREXATE (TMQ) AND OF 5,8-DIDEAZAFOLIC ACID - SYNTHESIS AND EVALUATION OF IN-VITRO ANTICANCER ACTIVITY

Among twenty-eight novel compounds (twenty-two ituted-6-[(substituted- phenoxy)methyl-quinoxalines and six 4-[(2,3-disubstituted-quinoxalin-6 -yl) methoxy]benzoylglutamates) only thirteen were selected at NCI for evaluation of their in vitro anticancer activity. The results have sh own that compounds 3l,c,b,e and 4b were endowed with Significantly hig h values of percent tumor growth inhibition on several tumor cell line s at 10(-4) M, while compound 3t was characterized by a high selectivi ty, being still strongly inhibiting on three cell lines at 10(-5) M. C omparison of the presently observed activity with that of the previous ly described aza-analogues confirms that the effected isosteric substi tution is highly valuable in some cases. (C) 1998 Elsevier Science S.A . All rights reserved.