Solid-phase synthesis of 5'-deoxy-5'-amino-clitocine analogues.

Several 6-substituted-amino-5'-deoxy-5'-amino-clitocine analogues were synthesized in a parallel fashion in solid phase. The desired scaffold was generated by coupling 2,3-O-bis-(t-butyldimethylsilyl)-5-N-(monomethoxytrityl-polystyrene-resin)-1,5-diamino-5-deoxy-beta-D-ribofuranose and 4, 6-dichloro-5-nitropyrimidine. The scaffold was then reacted with a variety of amines to generate a small library of 14 analogues of 5'-deoxy-5'-amino-clitocine following a protocol developed earlier.

Synthesis of thiazolone-based sulfonamides as inhibitors of HCV NS5B polymerase.

Several thiazolone-based sulfonamides were prepared, utilizing various hetero-aryl sulfonyl chlorides and different aldehydes, as inhibitors of NS5B polymerase, to target HCV. The best compound showed 0.6 microM [corrected] of IC50 inhibitory activity.

Synthesis of pyrrolo[2,3-d]pyrimidine nucleoside derivatives as potential anti-HCV agents.

Several Toyocamycin (4) analogues were examined for their ability to inhibit HCV RNA in a replicon assay. Among the compounds examined 4-methylthio (18) and 5-carboxamide oxime derivatives (23 and 27) of Toyocamycin were found to have good activity and selectivity.

Identification of isothiazole-4-carboxamidines derivatives as a novel class of allosteric MEK1 inhibitors.

The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. Optimization of the carboxamidine and the phenoxyaniline group led to the identification of 55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat.

Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors.

3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles were discovered as potent in vitro MEK1 inhibitors.