Georgia Tech Research Corporation

University of Georgia Research Foundation Inc

Medical College of Georgia Research Institute, Inc.

Jerry J Buccafusco

James C Powers

J Warren Beach

Rammamohanna R Jonnala

Kenneth M Starks

Alvin V Terry

The present invention relates to novel analogs of choline and methods of use or treatment of neurodegenerative disorders and/or conditions such as Parkinson's disease, Huntington disease, Alzheimer's disease and related disorders such as amyotrophic lateral sclerosis, spinal muscular atrophy, Friedrich's ataxia, Pick's disease, Bassen-Kornzweig syndrome, Refsom's disease, retinal degeneration, Cruetzfelt-Jacob syndrome or prion disease (mad cow disease), dementia with Lewy bodies, schizophrenia, paraneoplastic cerebellar degeneration and neurodegenerative conditions caused by stroke. The present compounds are effective to treat any neurological condition where acetylcholine transmission neurons and their target cells are affected. Compounds according to the present invention are effective to alleviate and/or reverse the effects of a neurodegenerative condition, prevent further deterioration and/or enhance cognition and memory in patients suffering from neurodegenerative disorders, especially Alzheimer's disease.

Analogs of choline for neuroprotection and cognitive enhancement in neurodegenerative disorders

Novel quaternary pyridinium compounds useful in inhibiting acetylcholinesterase in mammals of the general structure: ##STR1## or pharmaceutically acceptable salts thereof, where R.sub.5 is pentafluorophenyl, phenyl monosubstituted with K, phenyl disubstituted with K, phenyl trisubstituted with K, or naphthyl; R.sub.6 is H, C.sub.1-6 alkyl, phenyl, pentafluorophenyl, phenyl mono, di, or trisubstituted with K, C.sub.1-6 alkyl with an attached phenyl group, C.sub.1-6 alkyl with an attached phenyl group mono, di, or trisubstituted with K; K is halogen, COOH, OH, CN, NO.sub.2, NH.sub.2, C.sub.1-6 alkyl, C.sub.1-6 fluorinated alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylamine, C.sub.1-6 alkyl--O--CO--, C.sub.1-6 alkyl--CO--NH--, C.sub.1-6 alkyl--NH--CO--NH--, C.sub.1-6 alkyl--NH--CO--O--, C.sub.1-6 alkyl--NH--CO--, or (C.sub.1-6 alkyl).sub.2 N--CO--; X is OH, C.sub.1-6 alkyl--NH--CO--O--, (C.sub.1-6 alkyl).sub.2 --N--CO--O--, C.sub.1-6 fluoroalkyl--NH--CO--, or (C.sub.1-6 fluoroalkyl).sub.2 --NH--CO--O--; and B is H or C.sub.1-6 alkyl.

Pyridinium compounds

Methods for using novel quaternary pyridinium compounds in inhibiting acetylcholinesterase in mammals, specifically using the quaternary pyridinium compounds in the prophylaxis and treatment of organophosphate poisoning and mammalian dementia by mimicking or opposing the actions of the natural neurotransmitter acetylcholine.

Growing community of inventors

Evans, GA, United States of America

Jerry J Buccafusco