Use of pteridine(s) to sensitise resistant plasmodia - in combination with conventional di:hydro:folate reductase inhibitors and di:hydro-pteroate synthase inhibitors

摘要

The pteridines (which may also be in acid salt form) are of formula (I). Where n = 0 or 1. R3 = 2-6C alkyl, one or two of whose C atoms (except the one adjacent to the N atom) may be substituted by OH. R4 = benzyl or 1-4C alkyl (optionally OH substituted as before). Alternatively, R3 = 1-3C alkyl and R4 = phenyl-(1-3C) alkyl. R2, R7 = independently pyrrolidino, piperidino or morpholino (optionally substituted by 1 or 2 CH3 or C2H5 groups). R5 = H or CH3. (I) is e.g. 4-(N-(2-hydroxy-2-methyl-n-propyl)-ethanolamino)-2,7-bis(2 6-dimethyl-morpholino)-6-phenyl-pteridine. USE/ADVANTAGE - In combination with dihydrofolate reductase inhibitors and dihydropteroate synthase inhibitors in the treatment of malaria (claimed). (I) act by sensitising malarial pathogens to these chemotherpeutics, which include pyrimethamine, proguanil, cycloguanil; and 2,4-diamino-5-(4-(4'-aminophenyl-4-sulphonylamino-propoxy)-3 5-dimethoxy)-pyrimidine. (I) are described in CA-912556-A, US3557105-A, US3574206-A and EP-362645-A. Dose of (I) is 1-50 (3-20) mg/kg.