Structural modification of the isocoumarin moiety (A and B rings) of 1'-benzylspiro-[isocoumarin-piperidines] (1a and 2a), which inhibit the compound 48/80-induced release of histamine from isolated rat peritoneal mast cells, was undertaken to clarify the structure-activity relationship. Chromanone (3), chroman (4), 1, 3-benzoxazine (5), 1, 3-benzothiazine (6), and 4-quinazolinone (7) analogs were active, although there were differences in potency. Substituent effects on the benzene moiety (A ring) of 3 were examined.