Patent Evaluation: Adenosines in the Treatment of Sleeping Sickness

Summary

Novelty: 5′-Deoxy-5′-(hydroxyethylthio)adenosine (HETA), 5′-deoxy-5′-(monofluoroethylthio) adenosine (MFETA), 5′-deoxy-5′-(chloro-ethylthio)adenosine (CETA) and 5′-deoxy-5′-(bromoethylthio)adenosine (BETA) are disclosed. 5-Deoxy-5-(hydroxyethylthio)ribose (HETR), 5-deoxy-5-(monofluoroethylthio)ribose (CETR) and 5-deoxy-5-(bromoethylthio)ribose (BETR) are described. These compounds may be useful for treating infections caused by 5′-deoxy-5′-methylthioadenosine (MTA) phosphorylase-containing microorganisms. They may also be effective against pathogenic microorganisms which contain 5′-deoxy-5-methylthioribose (MTR) kinase.

Biology: In vitro antitrypanosomal activity was evaluated. MFETA, CETA, BETA and HETA all exhibited significant activity in sharp constrast to closely related compounds ETA, PTA, MFPTA and HPTA. In vitro antimalarial activity of HETA was demonstrated against P. falciparum. The test compounds were also found to exhibit IC50 values between 60 μM and 1000 μM against murine L1210 and L51787 tumour cell lines.

Chemistry: The syntheses of these compounds are described in detail.

Structure: