Boykin DW et al [85] syhthesized and evaluated five O-alkoxyamidine analogues of the prodrug 2,5-bis [4-methoxyamidinophenyl] furan against Trypanosoma brucei rhodesiense in the STIB900 mouse model by oral administration. It was observed that the size of the O-alkyl side-chain determined the metabolic stability of the prodrugs. The prodrugs with the O-methyl analogue were most susceptible to metabolism while the larger O-n-butyl and O-n-hexyl groups were least susceptible to metabolism. The in vivo studies in the STIB900 mouse model for T. b. rhodesiense showed that compounds with an O-methoxy-amidine or O-ethoxyamidine group effectively cured all trypanosome-infected mice, whereas prodrugs with larger side-chains did not completely cure the mice. Therefore the O-alkoxyamidine prodrugs, where the alkyl chain is less than three carbons, could effectively be used as prodrugs for amidines. 