11 beta-Hydroxysteroid dehydrogenase type1 (11 beta HSD1) regulates the conversion from inactive cortisone to active cortisol. Increased cortisol results in diabetes, hence quelling the activity of 11 beta HSD1 has been thought of as an effective approach for the treatment of diabetes. Quantitative hypotheses were developed and validated to identify the critical chemical features with reliable geometric constraints that contribute to the inhibition of 11 beta HSD1 function. The best hypothesis, Hypo1, which contains one-HBA; one-Hy-Ali, and two-RA features, was validated using Fischer's randomization method, a test and a decoy set. The well validated, Hypo1, was used as 3D query to perform a virtual screening of three different chemical databases. Compounds selected by Hypo1 in the virtual screening were filtered by applying Lipinski's rule of five, ADMET, and molecular docking. Finally, five hit compounds were selected as virtual novel hit molecules for 11 beta HSD1 based on their electronic properties calculated by Density functional theory.