Background: A 3D-QSAR model of KATP channel activation by benzopyran derivatives has been developed using molecular field alignment method. The model based on pED50 values required for myorelaxant activity by 4, 6 disubstituted benzopyrans has been explored.Discussion: The results are critically discussed based on molecular field of the structures and their alignment with the most potent compound of the series, i.e. Cromakalim. The model had an R2 of 0.99 and the training set of 25 compounds. A Leave-Many-Out (LMO) cross-validated value (Q2) of 0.496 with RMSETraining of 0.020 indicated that the model had optimum predictive ability on structurally diverse 4, 6 di-substituted benzopyrans. Conclusion: The developed model and the participating molecular field suggest the potential of replacement groups of 4, 6 di-substituted benzopyrans for structural optimization for the enhancement of biological activity.