Quaternary anticholinesterase therapeutics. Annual report, 22 July 1986-21 July 1987

Technical Report · Fri Apr 01 00:00:00 EST 1988

OSTI ID:6737293

Harris, R N; Koolpe, G A; Lovejoy, S M; Kelson, A B; Vu, H M

Ninety-five new imidazolium, pyridinium, and 1,2,4-triazolium salts were prepared, characterized, and submitted to WRAIR for in-vivo evaluation as antidotes against the nerve agent soman. Many of the salts were evaluated at the U.S. Army Institute of Chemical Defense (ICD) in the mouse as treatment therapeutics for organophosphonate nerve agent intoxication. Of the effective type I compounds, those that provided the greatest protective ability incorporated side chains functionalized with nitro, sulfone, and amino groups. In an effort to prepare type I and II compounds that have the potential to reactivate aged, inhibited acetylcholinesterase by means of a chelated metal ion, several new phosphatase simulant ligands were prepared and characterized. Unfortunately, the ligands could not be induced to form stable metal complexes. Finally, a methodology for preparing 4(5)-substituted imidazoles was established and subsequently applied to the preparation of several new 4(5)-substituted type I salts.

• Research Organization: SRI International, Menlo Park, CA (USA)
• OSTI ID: 6737293
• Report Number(s): AD-A-195868/5/XAB
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHEMICAL WARFARE AGENTS
ANTITOXINS
AMINES
CHEMICAL REACTIONS
CHOLINESTERASE
LIGANDS
MICE
OXIMES
PROGRESS REPORT
STABILITY
ANIMALS
ANTIBODIES
CARBOXYLESTERASES
DOCUMENT TYPES
ENZYMES
ESTERASES
HYDROLASES
HYDROXY COMPOUNDS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RODENTS
VERTEBRATES
WEAPONS
550200* - Biochemistry
550900 - Pathology