Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice |
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| Authors: | Zhao Wei Xinlei Zhang Huifang Nie Lin Yao Yanqin Liu Zhibing Zheng Qin Ouyang |
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| Affiliation: | 1.Department of Medicinal Chemistry, School of Pharmacy, Air Force Medical University, Xi’an 300071, China; (X.Z.); (H.N.); (L.Y.);2.Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;3.Department of Medicinal Chemistry, School of Pharmacy, Third Military Medical University, Chongqing 400038, China |
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| Abstract: | A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD50 sarin exposure, which is promising for the development of non-oxime reactivators with central efficiency. |
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| Keywords: | organophosphate acetylcholinesterase non-oximes reactivators Mannich phenol |
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