Labile quaternary ammonium salts as prodrugs
First Claim
1. A labile quaternary ammonium salt being capable of cleavage upon chemical or enzymatic hydrolysis to deliver a pharmacologically active tertiary amine and having the structural formulas (I) ##STR310## wherein N.sup.⊕
- -- is a pharmacologically active tertiary amine moiety selected from the group consisting oflidocaine;
1 Assignment
0 Petitions
Accused Products
Abstract
Labile quaternary ammonium salts of the following formula (I) and (II) are provided: ##STR1## 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): ##STR2## 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.
-
Citations
3 Claims
-
1. A labile quaternary ammonium salt being capable of cleavage upon chemical or enzymatic hydrolysis to deliver a pharmacologically active tertiary amine and having the structural formulas (I) ##STR310## wherein N.sup.⊕
- -- is a pharmacologically active tertiary amine moiety selected from the group consisting of
lidocaine; - View Dependent Claims (3)
- -- is a pharmacologically active tertiary amine moiety selected from the group consisting of
-
2. 8-Dichloro-α
- -[dibutylaminomethyl]-2-[3'"'"',4'"'"'-dichlorophenyl]-4-quinolinemethyl-N,N-dimethyl glycinate;
3-[Dibutylamino]-1-[2,6-bis-trifluoromethylphenyl)-4-pyridyl]propanol-N,N-dimethylglycinate; N,N-Dimethyl-N'"'"'-phenyl-N'"'"'-(2-thienyl)-ethylenediammonium; β
-Dimethylaminoethyl(p-chloro-α
-methyl benzhydryl)ether;N-Ethylephedrine; 2-Diethylaminopropiophenone; (Bicyclohexyl)-1-carboxylic acid 2-(diethylamino)-ethyl ester; Diphenylthioacetic acid 5-(2-diethylaminoethyl)ester; 6-Dimethylamino-4,4-diphenyl-3-heptanone; chlorcyclizine; methapheniline; pyrathiazine; pyrilamine; chlorophenoxamine; clemastine; diphenylpyraline; doxylamine; phenindamine; cyclizine; etafedrine acetate; benzphetamine; phendimetrazine; cinnamedrine acetate; piperoxan; arecoline; physostigmine; adiphenine; dicylomine; piperidolate; thiphenamil; pipoxolan; tremorine; nicotine; cocaine; piperocaine; dibucaine; mepivacaine; pyrrocaine; fentanyl; benzydamine; methadone; propoxyphene; chlorpromazine; diazepam;
orcotinine; R is hydrogen C1 -C8 alkyl, C3 -C8 cycloalkyl, C2 -C8 alkoxyalkyl, C1 -C8 haloalkyl, C6 -C10 aryl or substituted C6 -C10 aryl whose substituents are selected from the group consisting of halogen, C1 -C4 alkoxy, nitro, carboxyl, and carboethoxy; R1 which can be the same as or different from R, is any member of the group defined by R above, with he proviso that R1 cannot be a hydrogen atom; X is --O-- or --S--; and Y is halogen or an equivalent nontoxic pharmaceutically acceptable organic or inorganic monovalent anion.
- -[dibutylaminomethyl]-2-[3'"'"',4'"'"'-dichlorophenyl]-4-quinolinemethyl-N,N-dimethyl glycinate;
Specification