Baylis-Hillman reaction assisted parallel synthesis of 3, 5-disubstituted isoxazoles and their in vivo bioevaluation as antithrombotic agents

The solution phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detailed evaluation of one of the compounds as an inhibitor of platelet aggregation are also presented.

Combinatorial synthesis and biological evaluation of isoxazole-based libraries as antithrombotic agents

The 3-substitutedphenyl-5-isoxazolecarboxaldehydes have been identified as activated aldehydes for the generation of isoxazole-based combinatorial libraries on solid phase through automation. Three highly functionalized isoxazole-based libraries comprising of 32, 96 and 45 compounds each have been synthesized in parallel format using Baylis Hillman reaction, Michael addition, reductive amination and alkylation reactions. With an objective of lead generation all the three libraries were evaluated for their antithrombin activity in vivo.

Medicinal Chemistry of ureido derivatives as Antiinfectives

Ureides are compounds, which essentially incorporate urea as a substructural component either in open or cyclic form. Ureido derivatives are one of the oldest classes of bioactives, widely used as antiinfective agents. Several of these compounds, including aminoquinuride, aminocarbalide, imidurea, cloflucarban, nitrofurazone, urosulfan, viomycin are used in clinical situations. One of the ureides, the triclocarban is compulsorily used as antibacterial agent in cleansing and disinfecting solutions in hospital, household, cosmetics, toys, textile and plastics. It disables the activity of ENR, an enzyme vital for building the cell wall of the bacteria and fungus. Besides, the ureido-penicillins in clinical use there have been several ureido-lactam derivatives which have been reported to exhibit significant antibacterial activity. A urea containing dipeptide TAN-1057A isolated from Flexibacter spp. has potent bioactivity against MRSA. The metal complexes of sulphonyl ureido derivatives are effective antifungal agents by inhibiting the activity of phosphomannose isomerase, a key enzyme in the biosynthesis of yeast cell walls. There have been number of ureides including the cyclic ureas which are potent HIV protease inhibitors and display significant anti-HIV activity. The urea derivative, merimepodip that has been derived using structure based design, is potent inhibitor of IMPDH and is active against Hepatitis-C infection. This review will primarily focus on the significant work reported for this class of compounds including design, synthesis and biological activity.