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US 2014/0228302 A1Published application
Compounds, compositions and methods for treating or preventing hypoxic or ischemic injury
AssigneeFred Hutchinson Cancer Research Center
InventorsFuqiang Ruan, Edward A. Winter, Thomas L. Deckwerth
Life of this patent
Estimating the term…
Abstract
Compositions and methods of treating or preventing disease or injury to a human patient or biological material undergoing ischemic or hypoxic conditions.
Claims22
A compound represented by the following structure:
- wherein R1 and R2 are independently a branched or straight chain C1-10 alkyl;
- a branched or straight chain C1-10 alkyl substituted with —ONO2;
- or, a branched or straight chain C1-10 alkyl substituted with —OH;
- wherein R3 and R4 are independently a branched or straight chain C1-10 alkanediyl;
- wherein R5 and R6 are independently OH, an amino acid moiety, or, a straight or branched chain C1-10 amine substituted with —ONO2;
- wherein X and Y are independently C═O or SO2;
- and, wherein m is 3 or 4;
- Z is selected from H, CH3, and CH2CH3;
- or, a salt, ester, hydrate, solvate, or stereoisomer thereof, with the proviso that when m is 3, Z is H, X and Y are C═O, R3 and R4 are CH2, and R5 and R6 are OH, then R1 and R2 are not C1-10 alkyl.
6 more elements
A compound represented by the structure:
- wherein R10, R11 and R12 are each independently a side chain of a naturally-occurring or a non-naturally occurring amino acid, a branched or straight chain C1-10 alkyl, a straight or branched chain C1-10 alkyl substituted with —ONO2, or, a straight or branched chain C1-10 alkyl substituted with —OH;
- wherein R13 and R14 are independently a branched or straight chain C1-10 alkanediyl;
- and, wherein X is independently C═O or SO2;
- or a compound represented by the structure:
- wherein R15, R16, R17 and R18 are each independently a side chain of a naturally occurring or a non-naturally occurring amino acid, a branched or straight chain C1-10 alkyl, a straight or branched chain C1-10 alkyl substituted with —ONO2, or, a straight or branched chain C1-10 alkyl substituted with —OH;
- wherein R19 and R20 are each independently a branched or straight chain C1-10 alkanediyl;
- and, wherein each X is independently C═O or SO2;
- or, a salt, ester, hydrate, solvate or stereoisomer thereof.
5 more elements
A pharmaceutical composition comprising a compound selected from the group consisting of
- wherein R1 and R2 are independently a branched or straight chain C1-10 alkyl;
- a branched or straight chain C1-10 alkyl substituted with —ONO2;
- or, a branched or straight chain C1-10 alkyl substituted with —OH;
- wherein R3 and R4 are independently a branched or straight chain C1-10 alkanediyl;
- wherein R5 and R6 are independently OH, an amino acid moiety, or, a straight or branched chain C1-10 amine substituted with —ONO2;
- wherein X and Y are independently C═O or SO2;
- and, wherein m is 3 or 4;
- Z is selected from H, CH3, and CH2CH3;
- wherein R10, R11 and R12 are each independently a side chain of a naturally-occurring or a non-naturally occurring amino acid, a branched or straight chain C1-10 alkyl, a straight or branched chain C1-10 alkyl substituted with —ONO2, or, a straight or branched chain C1-10 alkyl substituted with —OH;
- wherein R13 and R14 are independently a branched or straight chain C1-10 alkanediyl;
- and, wherein X is independently C═O or SO2;
- wherein R15, R16, R17 and R18 are each independently a side chain of a naturally occurring or non-naturally occurring amino acid, a branched or straight chain C1-10 alkyl, a straight or branched chain C1-10 alkyl substituted with —ONO2, or, a straight or branched chain C1-10 alkyl substituted with —OH;
- wherein R19 and R20 are independently a branched or straight chain C1-10 alkanediyl;
- and, wherein X is independently C═O or SO2;
- and
- a salt, ester, hydrate, solvate or stereoisomer thereof;
- and a pharmaceutically acceptable vehicle, wherein the pharmaceutical composition has a pH of 5.0 to 6.5.
14 more elements
A method of making a linear symmetrical or asymmetrical trisulfide compound represented by the structure:
- wherein R1 and R2 are independently a branched or straight chain C1-10 alkyl;
- a branched or straight chain C1-10 alkyl substituted with —ONO2;
- or, a branched or straight chain C1-10 alkyl substituted with —OH;
- wherein R3 and R4 are independently a branched or straight chain C1-10 alkanediyl;
- wherein R5 and R6 are independently OH, an amino acid moiety, or, a straight or branched chain C1-10 amine substituted with —ONO2;
- wherein X and Y are independently C═O or SO2;
- and, wherein Z is selected from H, CH3, and CH2CH3;
- the method comprising:
- reacting a compound represented by the following structure
- wherein R1, X, R3 and R5 are as defined above, with an equal molar amount of 2,2′-thiodiisoindoline-1,3-dione in acetonitrile and water to produce a ((1,3-dioxoisoindolin-2-yl)disulfanyl)-containing intermediate;
- isolating the intermediate;
- and
- reacting the intermediate with a compound represented by the following structure
- wherein R2, X, R4 and R6 are as defined above, in an aqueous alcohol solution, thereby forming the trisulfide compound.
11 more elements
A method of making a cyclic trisulfide compound represented by the structure:
- wherein the method comprises preparing a dilute solution of a first compound represented by the structure
- and 2,2′-thiodiisoindoline-1,3-dione in acetonitrile and water, and reacting the first compound and the 2,2′-thiodiisoindoline-1,3-dione to produce the cyclic trisulfide compound.
A method of treating or preventing injury to biological matter exposed to ischemic or hypoxic conditions comprising administering to a patient in need thereof a therapeutically effective dose of a compound selected from the group consisting of
- wherein R1 and R2 are independently a branched or straight chain C1-10 alkyl;
- a branched or straight chain C1-10 alkyl substituted with —ONO2;
- or, a branched or straight chain C1-10 alkyl substituted with —OH;
- wherein R3 and R4 are independently a branched or straight chain C1-10 alkanediyl;
- wherein R5 and R6 are independently OH, an amino acid moiety, or, a straight or branched chain C1-10 amine substituted with —ONO2;
- wherein X and Y are independently C═O or SO2;
- and, wherein m is 3 or 4;
- Z is selected from H, CH3, and CH2CH3;
- wherein R10, R11 and R12 are each independently a side chain of a naturally-occurring or a non-naturally occurring amino acid, a branched or straight chain C1-10 alkyl, a straight or branched chain C1-10 alkyl substituted with —ONO2, or, a straight or branched chain C1-10 alkyl substituted with —OH;
- wherein R13 and R14 are independently a branched or straight chain C1-10 alkanediyl;
- and, wherein X is independently C═O or SO2;
- wherein R15, R16, R17 and R18 are each independently a side chain of a naturally occurring or a non-naturally occurring amino acid, a branched or straight chain C1-10 alkyl, a straight or branched chain C1-10 alkyl substituted with —ONO2, or, a straight or branched chain C1-10 alkyl substituted with —OH;
- wherein R19 and R20 are independently a branched or straight chain C1-10 alkanediyl;
- and, wherein X is independently C═O or SO2;
- and
- a salt, ester, hydrate, solvate or stereoisomer thereof.
13 more elements
A ((1,3-dioxoisoindolin-2-yl)disulfanyl)-containing compound represented by the following structure:
- wherein R1 is a branched or straight chain C1-10 alkyl;
- a branched or straight chain C1-10 alkyl substituted with —ONO2;
- or, a branched or straight chain C1-10 alkyl substituted with —OH;
- wherein R3 is a branched or straight chain C1-10 alkanediyl;
- wherein R5 is OH, an amino acid moiety, or, a straight or branched chain C1-10 amine substituted with —ONO2;
- wherein X is C═O or SO2;
- and, wherein Z is selected from H, CH3, and CH2CH3.
4 more elements
Dependencies are inferred from the claim text.