CORRELATION OF MOLECULAR ORBITAL PARAMETERS AND ANTIASTHMATIC ACTIVITY OF SOME α, β- UNSATURATED CYCLOKETONES

It was reported by one of the authors (G. K.) that some of 4-oxo-4H-1-benzopyran-3-carboxaldehydes and trans-3-(4'-oxo-4'H-1'-benzopyran-3') -acrylic acids prepared exhibited significant antiasthmatic activity in guinea pig induced by histamine or acetylcholine. We consider that quantum chemical knowledge is helpful for understanding drug actions. As a start, we have calculated electron charge q, net charge Q, frontier electron density f, bond order P, delocalizability energy S, and free valency F for 19 afore-mentioned compounds by means of Hückel molecular orbital method. Linear correlations have been observed between antiasthmatic activity and the electron density of carbonyl oxygen atoms (q_c=o), the sum of frontier electron density of carbonyl carbon and oxygen atoms (f_c=o) and the delocalizability energy of α-carbon atoms by the carbonyl group (S_a-c). As a result of regression analyses, a correlation between such parameters and antiasthmatic activity can be expressed by four equations.