Small molecule combinatorial chemistry has been used in the last ten years to dramatically accelerate the development of biologically interesting scaffolds in drug discovery process. Some of the advantages of solution-phase parallel synthesis (SPPS) include the capability of easy monitoring the reaction and success and the favorable kinetics of homogeneous conditions that decrease the 21 reaction time. As part of an ongoing drug discovery project we are interested in the design and synthesis of small N-benzenesulfonyl-heterocyclic libraries. Because of their broad-spectrum biological activities, the heterocycles have been extensively used in drug design. We selected eight nitrogenated heterocycles that are common moieties in known biologically active molecules. On the other hand, the benzenesulfonyl (BS) moiety is a substituent frequently present in molecules with biological activity. Not only is the p-aminobenzonesulfonyl moiety a known PABA antagonist with antibacterial and antileprotic activity, but the BS group has demonstrated interesting biological
binding properties. The initial library of small molecules generated more than 100 compounds. The methodology used for the SPPS led to pure compounds in a shorter time compared with the classical synthesis. Finally, the characterization and quality control was also performed by high-throughput methodology (LCMS). The characterization was completed by NMR, IR, m.p. for representative compounds. The overall yield for the synthesis of this library was over 80% with an overall purity (by mass spectrometry) of over 90%.