Novel pro-drug derivatives of pyridinium aldoxime type cholinesterase reactivators and method of using same
First Claim
1. A pharmaceutical composition for reactivating blocked cholinesterase in a warm-blooded animal and suitable for oral administration and absorption through the small intestine of said warm-blooded animal, comprising an effective cholinesterase reactivating amount of a pro-drug compound of the pyridine aldoxime-(hydroxyiminomethyl pyridinium) type capable of reactivating blocked cholinesterase having the formula:
- ##SPC17##wherein R represents a member selected from the group consisting of an alkyl (C1 -C4) group, a ##SPC18##group, a ##SPC19##group, ##SPC20##group, and a ##SPC21##group, wherein Z represents a member selected from the group consisting of a --CH2 --CH2 -- group, a --CH2 --O--CH2 -- group, a --CH2 CH2 OCH2 CH2 -- group, and a --CH2 O--CH2 --CH2 --O--CH2 -- group;
wherein R1 represents a member selected from the group consisting of a hydrogen atom, a methyl group, an acyl group and a ##EQU3## group; and
wherein X- represents an anion derived from a pharmaceutically acceptable acid addition salt in combination with a pharmaceutically acceptable enteric carrier.
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Abstract
There is provided, novel pro-drug forms of pyridinium aldoxime type cholinesterase reactivators, namely, dihydropyridinium aldoximes, having the formula: ##SPC1##
Wherein R represents a member selected from the group consisting of an alkyl (C1 -C4) group, a ##SPC2##
Group, a ##SPC3##
Group, ##SPC4##
Group, and a ##SPC5##
Wherein Z represents a member selected from the group consisting of a --CH2 --CH2 -- group, a --CH2 --O--CH2 -- group, a --CH2 CH2 OCH2 CH2 -- group, and a --CH2 O--CH2 --CH2 --O--CH2 -- group; wherein R1 represents a member selected from the group consisting of a hydrogen atom, a methyl group, an acyl group and a ##EQU1## group; and wherein X- represents an anion derived from a pharmaceutically acceptable acid addition salt.
These compounds are useful in reactivating cholinesterase, inhibited following exposure to and/or ingestion of conventional anti-cholinesterase agents, especially in the brain.
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Citations
32 Claims
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1. A pharmaceutical composition for reactivating blocked cholinesterase in a warm-blooded animal and suitable for oral administration and absorption through the small intestine of said warm-blooded animal, comprising an effective cholinesterase reactivating amount of a pro-drug compound of the pyridine aldoxime-(hydroxyiminomethyl pyridinium) type capable of reactivating blocked cholinesterase having the formula:
- ##SPC17##
wherein R represents a member selected from the group consisting of an alkyl (C1 -C4) group, a ##SPC18## group, a ##SPC19## group, ##SPC20## group, and a ##SPC21## group, wherein Z represents a member selected from the group consisting of a --CH2 --CH2 -- group, a --CH2 --O--CH2 -- group, a --CH2 CH2 OCH2 CH2 -- group, and a --CH2 O--CH2 --CH2 --O--CH2 -- group;
wherein R1 represents a member selected from the group consisting of a hydrogen atom, a methyl group, an acyl group and a ##EQU3## group; and
wherein X- represents an anion derived from a pharmaceutically acceptable acid addition salt in combination with a pharmaceutically acceptable enteric carrier. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15)
- ##SPC17##
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16. A method for reactivating blocked cholinesterase in a warm-blooded animal as a result of anticholinesterase compound poisoning, which comprises:
administering thereto, an effective cholinesterase reactivating amount of a pro-drug compound of the pyridine aldoxime (hydroxyiminomethyl pyridinium) type capable of reactivating blocked cholinesterase having the formula;
##SPC22##wherein R represents a member selected from the group consisting of an alkyl (C1 -C4) group, a ##SPC23## group, a ##SPC24## group, ##SPC25## group and a ##SPC26## group, wherein Z represents a member selected from the group consisting of a --CH2 --CH2 -- group, a --CH2 --O--CH2 -- group, a --CH2 CH2 OCH2 CH2 -- group, and a --CH2 O--CH2 --CH2 --O--CH2 -- group;
wherein R1 represents a member selected from the group consisting of a hydrogen atom, a methyl group, an acyl group and a ##EQU4## group; and
wherein X- represents an anion derived from a pharmaceutically acceptable acid addition salt.- View Dependent Claims (17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32)
Specification