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- W2031688196 abstract "Several categories of neuromuscular blocking bisquaternary tropine and tropane derivatives were synthesized and studied in the past five decades, mainly with the purpose of arriving at meaningful information about structure-activity relationships. Such a structure-activity relationship database is important in the development of new muscle relaxants with improved pharmacological characteristics. Although quaternary tropine diesters were explored since 1952, most of them were developed in the last decade. Over 250 such agents are being reviewed here. The skeleton of the majority of them consists of two tropines, connected through their 3-OH group with various dicarboxylic acid ester linkages and quaternized by several mostly di- and trisubstituted benzyl groups. The significance of changing the quaternizing group; the diester linker; and, to a smaller extent, the substituents and their steric orientation on the tropane ring and some alterations of the tropane ring itself have been explored in in vivo experiments on anesthetized rats. Di- or trisubstituted alkoxy and/or acyloxybenzyl quaternaries of certain tropinyl diesters, e.g., glutaryl, fumaryl, and cyclobutane-1,2-dicarboxylyl, showed an optimal profile with respect to desirable neuromuscular blocking actions and side effects, which was confirmed on other experimental animal species. The details of the structural changes toward obtaining new ultrashort-acting nondepolarizing muscle relaxants are discussed." @default.
- W2031688196 created "2016-06-24" @default.
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- W2031688196 date "2002-10-01" @default.
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- W2031688196 title "Structure-activity relationships among derivatives of dicarboxylic acid esters of tropine" @default.
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- W2031688196 doi "https://doi.org/10.1016/s0163-7258(02)00296-6" @default.
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