Abstract: Microsomal cytochrome P450 family 1 enzymes (2HI4) play prominent roles in xenobiotic detoxication and procarcinogen activation. P450 1A2 is the principal cytochrome P450 family 1 enzyme expressed in human liver and participates extensively in drug oxidations. This enzyme is also of great importance in the bioactivation of mutagens, including the N-hydroxylation of arylamines. P450-catalyzed reactions involve a wide range of substrates, and this versatility is reflected in a structural diversity evident in the active sites of available P450 structures. Here the presented structure of human P450 1A2 in complex with the inhibitor alpha-naphthoflavone, determined to a resolution of 1.95 A alpha-Naphthoflavone is bound in the active site above the distal surface of the heme prosthetic group. Inhibitors of 2HI4 showed highly adapted for the positioning and oxidation of relatively large, planar substrates and a new series of dimethyl 1,4 – diphenyl naphthalene – 2,3 – dicarboxylate and naphthoflavone which possess good inhibitory activity against 2HI4. This compound showed better binding energy than the compound which has been already co-crystallized with the target protein, (PDB ID 2HI4).