4-Thiazolidinones: novel inhibitors of the bacterial enzyme MurB.

4-Thiazolidinones were synthesized and evaluated for their ability to inhibit the bacterial enzyme MurB. Selected 4-thiazolidinones displayed activity against the enzyme in vitro. This activity, coupled with the design principles of the thiazolidinones, supports the postulate that 4-thiazolidinones may be recognized as diphosphate mimics by a biological selector.

A novel cleavage protocol for use with Rf-encoded split pool synthesis technology: product cleavage and collection in standard 96 well format.

A novel protocol which employs commercially available, standard tools and hardware has been developed. This protocol allows for cleavage and collection of IRORI Microkan products in 96 well plate format. Typically, 640 compounds can be cleaved in a 4 hour time period using approximately 3 square feet of space. This protocol has been used successfully for the liberation of thousands of individual compounds, in single compound per well format from the solid phase. Additionally, this protocol is the first example of making IRORI Microkan technology directly compatible with standard 96 position deep well blocks.

Naphtho and benzo analogues of the kappa opioid agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide.

Further elaboration on the structure-activity relationships in our U-50,488 series has revealed that benzologation of this cyclohexane-1,2-diamine derivative provides compounds which either maintain the interaction with the kappa receptor (e.g. compounds 3a and 5a in the phenylacetamido series) or eliminate the mu receptor mediated analgesia (e.g. compounds 3-6 in the benzamido series). Naphthologation also caused the elimination of mu receptor mediated analgesia (e.g. compounds 17a and 17b).