Amino- and hydroxy-functionalized 11-azaartemisinins and their derivatives.
An efficient conversion of artemisinin 1 into three new amino- and hydroxy-functionalized 11-aza prototypes 9, 11, and 12 has been achieved on a multigram scale by reaction with hydrazine, hydroxylamine, and 2-amino ethanol, respectively. Of these, 9 has been further diversified into a wide range of derivatives including imines, amines, amides, and linker based dimers. Prototypes 11 and 12 have been converted into the corresponding ethers in high yields. Some of these compounds have shown a high order of activity against multidrug-resistant malaria in mice by oral route.
Singh
Ajit Shankar
AS
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow-226001, India.
Verma
Ved Prakash
VP
Hassam
Mohammad
M
Krishna
Naikade Niraj
NN
Puri
Sunil K
SK
Singh
Chandan
C
D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D037621:Artemisinins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001372:Aza Compounds / Q000737:chemistry*; D018432:Drug Resistance, Multiple; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects
D000981:Antiprotozoal Agents; D037621:Artemisinins; D001372:Aza Compounds; C031327:artemisinin