Peptidyl-prolyl cis-trans isomerases (PPIases) are a class of enzymes that convert the cis isoform of a proline residue within a peptide to its more stable trans isoform. PPIases are divided into three families: cyclophilins, FK506 binding proteins (FKBP's), and parvulins. There are 17 isoforms of cyclophilins present in humans which mediate a variety of biological functions. Cyclophilin A has been studied as a potential target to prevent human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection and virion packaging. Acylureas,are literature compounds presented as potent (single digit nanomolar) cyclophilin A inhibitors. The 2,6-dichlorobenzene ring is perpendicular to the acyl urea due to a large rotational barrier resulting from the two chlorine atoms. Design, synthesis, and testing of these rotationally restricted amides will be presented.

Development of small molecule cyclophilin inhibitors

245th National Meeting (2013)

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