Convenient access both to highly antimalaria-active 10-arylaminoartemisinins, and to 10-alkyl ethers including artemether, arteether, and artelinate.
An economical phase-transfer method is used to prepare 10-arylaminoartemisinins from DHA and arylamines, and artemether, arteether, and artelinate from the corresponding alcohols. In vivo sc screens against Plasmodium berghei and P. yoelii in mice reveal that the p-fluorophenylamino derivative 5 g is some 13 and 70 times, respectively, more active than artesunate; this reflects the very high sc activity of 10-alkylaminoartemisinins. However, through the po route, the compounds are less active than the alkylaminoartemisinins, but still approximately equipotent with artesunate.
Haynes
Richard K
RK
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, PR China. haynes@ust.hk
Chan
Ho-Wai
HW
Ho
Wing-Yan
WY
Ko
Cliff Ki-Fung
CK
Gerena
Lucia
L
Kyle
Dennis E
DE
Peters
Wallace
W
Robinson
Brian L
BL
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077549:Artemether; D037621:Artemisinins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D010967:Plasmodium yoelii / Q000187:drug effects; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C062768:artelinic acid; D000077549:Artemether; C055141:artemotil