the piperidin 1 ylsulfonyl substituent at 5 position of dihydroxyphenyl ring may potentiate the conversation with the LEDGF binding site of IN when precisely focused, which was depicted in the following molecular modeling. Instead of targeting the catalytic action of IN, the consequent inhibition of HIV replication, and the disruption of the Foretinib clinical trial integrase LEDGF/p75 connection, represents a fresh frontier for the look and development of novel anti HIV agents for AIDS therapy. However, not many small molecule inhibitors of the IN LEDGF/p75 conversation have been reported currently. 17,22 25 Considering that the specific protein protein interaction between IN catalytic core domain and the LEDGF/p75 IN binding domain was seen as a IBD derivatives Ile365, Asp366, Phe406 and Val408,26 we were enthusiastic about testing these salicylate and catechol combined materials in the inhibition of IN LEDGF/p75 interaction, since our chemical shape included both the aromatic moiety and the carboxylic efficiency. Interestingly, nearly all of our 2,3 dihydroxybenzamide derivatives were able to inhibit the INLEDGF/ p75 interaction at micromolar concentrations in the AlphaScreen analysis. As shown in Table 2, the effective Latin extispicium IN strand exchange inhibitors exhibited steady potency in inhibiting the interaction of IN LEDGF/p75, among which the greatest potency was exhibited by 5u bearing the buildings on both sides. The early SAR study indicated the substituent attached about the percentage played an essential role in the disruption of IN LEDGF/p75 conversation. In this situation, the lipophilic structure in addition to the heteroaromatics was desired. Nevertheless, the catechol structure was not needed for inhibiting IN LEDGF/p75 interaction, exemplified by 6c and 6d which were very nearly inactive contrary to the transfer but mildly effective in preventing INLEDGF/ p75 interaction. Our research provides new crucial chemical frames to interrupt the protein protein interaction between natural product library IN and its cellular cofactor LEDGF/p75, which may advance the discovery and design of anti-hiv agents possessing a novel mechanism of action. Molecular Modeling Studies We picked 5p, 5t and 5u as active and 6c as inactive consultant structures to dock against an HIV 1 IN product that has been built from the crystal structure of model foamy virus intasome. Materials were then docked into the binding site using Standard Precision approach to Glide from Schrodinger, Inc. The binding modes of substances 5p, 5t, 5u and 6c in the IN lively website are shown in Figures 3 and 4. The settings in PVF IN of all active compounds resemble that of raltegravir. Both hydroxyl groups of 5p form material chelating communications with the two Mg2 ions along with the amino acid residues Asp64, Asp116 and Glu152.