SYNTHESIS AND ANALYSIS OF POSITIVE INOTROPIC EFFECTS OF 3-SUBSTITUTED-2H-CYCLOHEPTA[B]FURAN-2-ONE DERIVATIVES

Several 3-substituted-2H-cyclohepta[b]furan-2-one derivatives were pre pared and tested in vitro for positive inotropic character. Introducti on of an isopropyl group at the 5-position of compound 8a caused an in crease of PIC50 (negative logarithm of the dosage which increases the contractile force by 50%) from 4.48 to 5.10. Among the 5-isopropyl-8-a lkoxy compounds, the isopropoxy compound 12f had the most potent activ ity with a PIC50 value of 5.99. Conversion of the ester group at the 3 -position to a methylene group and of the alkoxy group at the 8-positi on to a substituted amino group caused a decrease in activity. The mos t active compound, 12f, was also found to have a weaker heart rate (HR )-increasing effect compared to milrinone and amrinone.