Quaternary Ammonium Salt Prodrugs
First Claim
1. A method for sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering a prodrug compound having the formula:
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Abstract
The invention provides a method of sustained delivery of a tertiary amine-containing parent drug comprising administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile quaternary ammonium salts of tertiary amine-containing parent drugs (or tertiary imine-containing parent drugs) that are derivatized through aldehyde-linked prodrug moieties that reduce the solubility of the prodrug compound at a reference pH as compared to the parent drug. The physical, chemical and solubility properties of these derivatives can be further modulated by the choice of counterion X−. In one embodiment, the present invention provides a prodrug compound of Formula I:
where R1-R5 are defined in the written description of the invention. The prodrug compounds of the invention can be used to treat any condition for which the tertiary amine-containing parent drug or tertiary imine-containing parent drug is useful as a treatment.
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Citations
34 Claims
- 1. A method for sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering a prodrug compound having the formula:
- 10. A method for producing a prodrug compound of a tertiary amine-containing or tertiary imine-containing parent drug compound comprising the step of reacting a parent drug compound having the formula:
- 12. A prodrug compound of a tertiary amine-containing parent drug wherein said prodrug compound is represented by the formula:
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18. A compound of the formula:
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19. A method for sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering a prodrug compound of the parent drug having the formula:
- 20. A method for sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering a prodrug compound of the parent drug having the formula:
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28. A prodrug compound of a tertiary amine-containing parent drug or a tertiary imine-containing parent drug wherein the prodrug compound has the formula represented by:
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29. A prodrug compound of a tertiary amine-containing parent drug or a tertiary imine-containing parent drug wherein the prodrug compound has the formula represented by:
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30. A prodrug compound of a tertiary amine-containing parent drug wherein the prodrug compound has the formula represented by:
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31. A method for sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering a prodrug compound of the parent drug having the formula:
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32. A method for pH-independent sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering to the patient, a prodrug compound of the parent drug having the Formula III:
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33. A method for pH-independent sustained delivery of a tertiary amine-containing parent drug to a patient comprising administering to the patient, a prodrug compound and an optional biocompatible delivery system for delivering the prodrug wherein the optional delivery system is capable of minimizing accelerated hydrolytic cleavage of the prodrug wherein the prodrug has the Formula III:
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34. A method of reducing the side effect of sedation or coma in the patient as compared to sedation or coma caused by administration of the parent drug of formula IV comprising administering to the patient, a prodrug compound of the parent drug having the Formula III:
Specification