ABSTRACT
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.
Subject(s)
Acetylcholinesterase/chemistry , Alzheimer Disease/drug therapy , Butyrylcholinesterase/chemistry , Cholinesterase Inhibitors/chemical synthesis , Fluorine/chemistry , Neuroprotective Agents/chemical synthesis , Organophosphates/chemical synthesis , Acetylcholinesterase/metabolism , Animals , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Horses , Humans , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Organophosphates/chemistry , Organophosphates/pharmacology , SwineABSTRACT
The title compound, C(13)H(16)F(6)NO(5)PS, is of inter-est with respect to inhibition of serine hydro-lases. Its structure contains a 1.8797â (13)â Å P-C bond and two inter-molecular N-Hâ¯O=P hydrogen bonds, resulting in centrosymmetric dimers. An intra-molecular N-Hâ¯O=P hydrogen bond is also present.
