N-terminal D(-)-penicillamine peptides as aldehyde sequestration agents
AssigneeFederal Government as represented by the Department of Veterans Affaires
InventorHerbert T. Nagasawa
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Abstract
The invention provides a compound of formula I: 1 wherein R1-R3 have any of the values described in the specification; or a salt thereof. The compounds are useful as aldehyde sequestration agents (e.g., in the treatment of alcohol-related diseases). The invention also provides compositions comprising such compounds as well as therapeutic methods comprising their administration.
Claims26
A compound of formula I:
- 4
- wherein
- R1 is an amino acid or peptide;
- and
- R2 and R3 are each independently, hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, or (C3-C6)cycloalkyl(C1-C6)alkyl;
- or R2 and R3 together to which the carbon to which they are attached form a 3, 4, 5, or 6-membered carbocyclic or heterocyclic ring, optionally substituted on carbon with (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C1-C6)alkoxy, or (C3-C6)cycloalkyl(C1-C6)alkoxy;
- or a salt thereof,
- provided that R2 and R3 are not both hydrogen.
The compound D-penicillamyl-β-alanine hydrochloride, D-penicillamylglycine hydrochloride, D-penicillamyl-L-valine hydrochloride, or D-penicillamyl-α-aminoisobutyric acid hydrochloride;
- or a pharmaceutically acceptable salt thereof.
A compound of formula II:
- 5
- wherein
- R1 is an amino acid or peptide;
- R2 and R3 are each independently, hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, or (C3-C6)cycloalkyl(C1-C6)alkyl;
- or R2 and R3 together with the carbon to which they are attached form a 3, 4, 5, or 6-membered carbocyclic or heterocyclic ring, optionally substituted on carbon with (C1-C6)alkyl, (C1C6)haloalkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1 -C6)alkyl, (C1-C6)alkoxy, or (C3-C6)cycloalkyl(C1-C6)alkoxy, provided R2 and R3 are not both hydrogen;
- R4 and R5 are each independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, or (C3-C6)cycloalkyl(C1-C6)alkyl;
- or R4 and R5 together with the carbon to which they are attached form a 3, 4, 5, or 6-membered carbocyclic or heterocyclic ring, optionally substituted on carbon with (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C1-C6)alkoxy, or (C3-C6)cycloalkyl(C1-C6)alkoxy, provided R4 and R5 are not both hydrogen;
- and
- R6 is Ra—C═O—), wherein Ra hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, or aryl.
The compound N-(3-formyl-2,2,5,5-tetramethylthiazolidine-4S-carbonyl)-β-alanine ethyl ester, N-(3-formyl-2,2,5,5-tetramethylthiazolidine-4S-carbonyl)-glycine t-butyl ester, N-(3-formyl-2,2,5,5-tetramethylthiazolidine-4S-carbonyl)-valine t-butyl ester, or N-(3-formyl-2,2,5,5-tetramethylthiazolidine-4S-carbonyl)-α-amino isobutyric acid t-butyl ester.
Dependencies are inferred from the claim text.