Cortisol, Dehydroepiandrosterone (DHEA) and Pregnenolone are the most clinically significant adrenal hormones. Among them, Pregnenolone is a precursor for sex steroidal hormones and also acts as a neuroprotective agent. Dis-regulation of their balance is observed at the stress conditions which result in the pathological state, pregnenolone steal. In this study we have computationally investigated the key enzyme CYP17A1 interaction with pregnenolone and its structural analogues. We first explored the active sites of the enzyme (PDBid: 3RUK) using CASTp and POCKET FINDER and was found to be consistent with the interaction residues. Next, fragment based search was performed to generate pregnenolone like compounds through Enchanced NCI server. Then the most potential competitive ligands were filtered by applying PASS Prediction tool, Lipinsky rule and ADME properties. The array of ligand along with pregnenolone was docked to enzyme structure using AUTODOCK 4.0 software. The prospective ligands were ranked according to the highest binding energy as the best conformers. The compounds such as pregnenolone-3acetate, 16-Dehydropregnenolone and Pregnenolone 3-methyl ether were identified as the significant ligands that can compete with pregnenolone in maintaining the balance during the stressed conditions. These compounds can be tried for such pathological states as a competitive binder for endogenous ligand, pregnenolone. However, further experimental evidence is required to support this study.