Labile quaternary ammonium salts as prodrugs

Abstract

Abstract Labile quaternary ammonium salts of the following formula (I) and (II) are provided: <IMAGE> (I) <IMAGE> (II) wherein N represents a tertiary aliphatic amine; wherein N represents an unsaturated amine; wherein R represents a member selected from the group consisting of a hydrogen atom, a C1-C8 open chain or cyclo alkyl group, a C1-C8 alkoxyalkyl group, a C1-C8 acyloxyalkyl group, a C1-C8 haloalkyl group, a C1-C8 carboxyalkyl group, a C2-C8 alkenylphenyl group, an aryl group, and a substituted aryl group, whose substituents are selected from the group consisting of a halogen atom, an O-lower alkyl (C1-C4) group, an O-acyl group, a nitro group, a carboxyl group, and a carboethoxy group; wherein R1 which may be the same or different, represents any member defined by R above with the proviso that R1 cannot be a hydrogen atom; wherein X is -O- or -S-; and wherein Y represents a member selected from the group consisting of a halogen atom or any other organic or inorganic monovalent equivalent anion; with the further proviso that N and N, respectively cannot represent trimethylamine and pyridine or quinoline when R represents a hydrogen atom and R1 represents a methyl group or a phenyl group. The compounds described above are characterized by their extreme solubility and resistance to oxidation, dealkylation, and protonation prior to chemical and/or enzymatic hydrolysis. Upon chemical and/or enzymatic hydrolysis, these compounds will "cleave," thus releasing their active constituent or constituents, according to the following general scheme(s): <IMAGE> +TR <IMAGE> <IMAGE> +TR <IMAGE> In other words, the title compounds hydrolyze (chemically or enzymatically) releasing a tertiary amine or unsaturated amine derivative, an aldehyde, a carboxylic acid and a hydrogen halide (HX) per the above reaction scheme.

Inventors

• 👤 Nicolae S. Bodor

Bibliographic Details