Introduction:: The present study reveals the 2D, 3D-QSAR analysis of Thieno[3,2-d]pyrimidine to express the biological activity against Cholesterol, structurally different ligands can fit the common receptor site, and Pharmacophore models well describe safety considerations of the said chemical entities Methods:: The organic exercises of the atoms were changed over into log IC50. The measurably huge of 2D-QSAR and 3D QSAR models are r2 = 0 .9762, q2 = 0.9379 and internal (q2 = 0.8837) and external (predictive r2 = 0.9162) respectively. 2D QSAR studies revealed that the Positive coefficient value of Quadrupole2 and Negative coefficient value of T_2_Cl_7 descriptors were major contributing descriptors. Results:: The 3D QSAR models indicate that steric and electrostatic effects primarily determine binding affinities. Conclusion:: From the best model obtained from the QSAR analyses, some newer compounds of the same series were developed, having better activity than the earlier compounds that have been reported.