A versatile and inexpensive apparatus for rapid parallel synthesis on solid support: description and synthesis illustration.

A new inexpensive and practical apparatus for solid-phase chemistry and parallel synthesis is described. This new apparatus fills an important void in the availability of portable tools for the synthesis of libraries of compounds in multi-milligram amounts. Individual reaction tube capacities range in size from 4 mL to 500 mL of operating liquid volume. Reaction blocks of 36 tubes x 4 mL or 24 tubes x 150 mL allow flexibility of operation. Insert tubes with frit ends function as filter sticks for resin wash and for maintenance of inert atmosphere. An electronic controller device connects to the reaction tubes for programmable entry of pulses of inert gas for resin mixing or vacuum for resin wash. The utility of this apparatus is illustrated by the synthesis of libraries based on 4-methaneamine imidazoles.

Novel antifungals based on 4-substituted imidazole: a combinatorial chemistry approach to lead discovery and optimization.

A series of 4-substituted imidazole sulfonamides has been prepared by solid-phase chemistry. These compounds were found to have good in vitro antifungal activity and constitute the first examples of C-linked azoles with such activity. The most potent inhibitor (30) demonstrated inhibition of key Candida strains at an in vitro concentration of < 100nM and compared favorably with in vitro potency of itraconazole.