the pyrimidinone MK 0518 has been accepted by the FDA and currently as the first and only HIV 1 IN chemical for treating HIV infection. 6 Although great strides have already been accomplished in the design and discovery of IN inhibitors as Gemcitabine ic50 antiviral agents,7,8 the emergence of viral strains resistant to clinically learned IN inhibitors and the dynamic character of the HIV 1 genome desire an ongoing effort toward the discovery of novel inhibitors to keep a therapeutic advantage over the disease. One method of learn structurally novel classes of IN inhibitors would be to restore formerly determined IN chemical chemical classes, which exhibited potent IN inhibition, but were developmentally stopped due to unrequired pharmacokinetic, pharmacodynamic, or toxicological properties. The polyhydroxyl aromatics and salicylhydrazide were previously described as potent IN inhibitors,9,10 but their therapeutic Lymph node application was limited by the inherently high cytotoxicity in these compounds as antiretroviral agents. Current structural changes around the salicylhydrazide family triggered a significant decrease in the cytotoxicity whilst the IN inhibitory activity was retained,11,12 thus confirming the feasibility of restoring old medications by structural optimization. In this research, we were enthusiastic about creating new IN inhibitors by merging the pharmacophores of the salicylic acid and catechol to generate novel chemical scaffolds. Really, the surrounding carboxylic and hydroxyl groups on salicylic acid could serve while the metal binding pharmacophore. On the other hand, the polyhydroxylated aromatic inhibitors are often active against both 3 control and strand transfer reactions13 that might imply a different mechanism targeting both methods. Because HIV 1 immune stresses BIX01294 Methyltransferase Inhibitors displayed crossresistance to different string transfer specific chemical classes in preclinical and clinical progress studies,5 the optimum integration of catechol pharmacophores and salicylic acid is likely to develop novel inhibitors by chelating a divalent metal on the IN active site. These inhibitors will probably succeed against viral strains that display resistance to string move specific inhibitors. Consequently, by combining the privileged pieces of salicyl and catechol containing IN inhibitors, we developed four classes of 2-hydroxybenzoic acid derivatives with various substitution patterns on the phenyl ring to find out an optimal scaffold. The catechol moiety is prone to oxidation into a quinone species that have a tendency to cross link with cellular proteins, thus resulting in cytotoxicity,14 a result that we tried to mitigate by incorporating alkyoxy groups such as benzyloxy, 4 fluorobenzyloxy and naphthalenylmethoxy into 6 position of the two hydroxybenzoic acid, respectively.