Synthesis of organophosphates with fluorine-containing leaving groups as serine esterase inhibitors with potential for Alzheimer disease therapeutics

Galina F Makhaeva; Alexey Y Aksinenko; Vladimir B Sokolov; Olga G Serebryakova; Rudy J Richardson

doi:10.1016/j.bmcl.2009.08.065

Synthesis of organophosphates with fluorine-containing leaving groups as serine esterase inhibitors with potential for Alzheimer disease therapeutics

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5528-30. doi: 10.1016/j.bmcl.2009.08.065. Epub 2009 Aug 21.

Authors

Galina F Makhaeva¹, Alexey Y Aksinenko, Vladimir B Sokolov, Olga G Serebryakova, Rudy J Richardson

Affiliation

¹ Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka, 142432, Russia.

PMID: 19717305
DOI: 10.1016/j.bmcl.2009.08.065

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylcholinesterase / chemistry*
Acetylcholinesterase / metabolism
Alzheimer Disease / drug therapy*
Animals
Butyrylcholinesterase / chemistry*
Butyrylcholinesterase / metabolism
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology
Fluorine / chemistry*
Horses
Humans
Neuroprotective Agents / chemical synthesis*
Neuroprotective Agents / chemistry
Neuroprotective Agents / pharmacology
Organophosphates / chemical synthesis*
Organophosphates / chemistry
Organophosphates / pharmacology
Swine

Substances

Cholinesterase Inhibitors
Neuroprotective Agents
Organophosphates
Fluorine
Acetylcholinesterase
Butyrylcholinesterase