可逆性胆碱酯酶抑制剂:N,N-二甲胺基甲酸-5-(1,3,3-三取代二氢吲(口朶))酯的合成

SYNTHESIS OF 5-(1, 3, 3-TRISUBSTITUTED) INDOLINYL-N,N-DIMETHYLCARBAMATES AS REVERSIBLE CHOLINESTERASE INHIBITORS

摘要: 为了进一步研究胺甲酸酯类胆碱酯酶抑制剂的化学结构与胆碱酯酶抑制作用间的关系,在催醒宁的化学结构基础上合成了9个N,N-二甲胺基甲酸-5-二氢吲哚酯化合物。化合物Ⅰ～Ⅴ的pI₅₀值在6.72以上,其中Ⅱ(R=C₄H₉)的pI₅₀值高达8.26,较催醒宁(R=CH₃)高一个数量级。在这些化合物的合成过程中,成功地应用了相转移催化反应于2-二氢吲哚酮的N-烷化及5-羟基-二氢吲哚的胺甲酰化。

Abstract: In order to study the structure-activity relationship of cholinesterase inhibitor-carbamates, nine 5-indolinyl N,N-dimethylcarbamates have been synthesized as anticholinesterase agents. All compounds tested are strong cholinesterase inhibitors. The pI₅₀ of compound Ⅱa (R=C₄H₉) is 8.26, more potent than CUI XING NING (R=CH₃). For synthesizing these compounds, the technique of phase transfer catalysis was successfully applied in the N-alkylation of oxindoles and the carbamylation of 5-hydroxyindolines.