ANTIDOTES CENTRALEMENT ACTIFS ET BIO-DISPONIBLES PAR VOIE ORALE UTILISABLES EN CAS D'EXPOSITION AUX ORGANOPHOSPHATES ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
THE REGENTS OF THE UNIVERSITY OF CALIFORNIA;THE SCRIPPS RESEARCH INSTITUTE
发明人:
TAYLOR,PALMER,RADIC, ZORAN,SHARPLESS, K., BARRY,FOKIN, VALERY,SIT, RAKESH
申请号：
EP14751631
公开号：
EP2956451A4
申请日:
2014.02.15
申请国别(地区):
EP
年份:
2016
代理人:
摘要：
In alternative embodiments, the invention provides nucleophilic hydroxyimino-acetamido alkylamine antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). The hydroxyimino-acetamido alkylamines of the invention are designed to fit within AChE active center gorge dimensions, bind with reasonable affinity, and react with the conjugated phosphate atom in the gorge. The hydroxyimino-acetamido alkylamines of the invention are also designed to possess ionization states that govern affinity and reactivity for the two linked hAChE re-activation steps. In alternative embodiments, the invention provides pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound of the invention.
