Reactivation of Aged Organophosphorus Inhibited Acetylcholinesterase
Annual summary rept. 1 Aug 1985-31 Jul 1986
TEMPLE UNIV PHILADELPHIA PA DEPT OF CHEMISTRY
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The purpose of this work is to prepare derivatives of 2-PAM that are substituted in the 3-position by groups capable of bonding to, or liganding with, the oxygen on the phosphorus of aged, poisoned by phosphorylation or phosphonylation acetylcholinesterase. The derivatives suggested for preparation are designed to facilitate cleavage of the bond between phosphorus and the oxygen of the serine in the active site of the poisoned acetylcholinesterase and to thus regenerate native enzyme. The major effort in this first year has been development of a general route to these previously unknown oximes. That route, beginning with derivatives of 3-aminocrotonate and acrolein, has now been defined. Additionally, using the successful route, one compound has been prepared and submitted i.e., ethyl pyridine-3-acetate 2-carboxaldehyde oxime methiodide, BL19566, another prepared i.e., t-butyl pyridine-3-carboxylate 2- carboxaldehyde oxime methiodide but not submitted because the methochloride, not the methiodide as originally anticipated, is desired and anion exchange has not yet succeeded, and significant quantities of intermediates for other proposed compounds have been generated. Keywords Pyridine oximes.