Synthesis of organophosphates with fluorine-containing leaving groups as serine esterase inhibitors with potential for Alzheimer disease therapeutics.
Acetylcholinesterase and butyrylcholinesterase inhibitors are potential cognition enhancers in Alzheimer disease. O,O-Dialkylphosphate inhibitors with 1-substituted 2,2,2-trifluoroethoxy leaving groups were synthesized by phosphonate-phosphate rearrangement. Substituents in the 1-position of the leaving group along with the O-alkyl groups modulated potency and selectivity against acetylcholinesterase, butyrylcholinesterase, and carboxylesterase.
Makhaeva
Galina F
GF
Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.
Aksinenko
Alexey Y
AY
Sokolov
Vladimir B
VB
Serebryakova
Olga G
OG
Richardson
Rudy J
RJ
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005461:Fluorine / Q000737:chemistry*; D006736:Horses; D006801:Humans; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010755:Organophosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013552:Swine
D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010755:Organophosphates; D005461:Fluorine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase