Compounds and Methods for Altering Lifespan of Eukaryotic Organisms
AssigneesSouthern Research Institute, University of Rochester
InventorsDavid S. Goldfarb, Joseph A. Maddry, Lynn Rasmussen, Ellie Lucile White, Krister Wennerberg
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Abstract
Provided are compounds which generally have a triketone structure. Examples of the compounds include derivatives of 1,3-cyclohexanedione, such as: 1,3-cyclohexanedione, 2-propanoyl-5-cyclohexyl-; 1,3-cyclohexanedione, 2-propanoyl-5-[4-fluorophenyl]-; 1,3-cyclohexanedione, 2-acetyl-5-[thien-2-yl]-; 1,3-cyclohexanedione, 2-acetyl-5-butyl-; and 1,3-cyclohexanedione, 2-propanoyl-5-[bicyclo[2.2.1]hept-2-en-5-yl]-. The compounds can be used to alter the lifespan of eukaryotic organisms and treat inflammation.
Claims15
) A compound with the following structure:
- wherein R1 and R2 are independently
- an aliphatic alkyl group having 1 carbon to 8 carbons, wherein the aliphatic alkyl group is linear or branched, saturated or has one or more carbon-carbon multiple bonds, and is, optionally, substituted with one or more halogens,
- a cyclic alkyl group having 3 carbons to 8 carbons, wherein the cyclic alkyl group is saturated or has one or more carbon-carbon multiple bonds, and is, optionally, substituted with one or more alkyl groups having 1 carbon to 6 carbons,
- an aryl group, wherein the aryl group has a single, multiple-ring or fused-ring structure, and each ring is, optionally, independently substituted with one or more groups selected from halogen, hydroxy, alkoxy group having 1 carbon to 6 carbons, wherein if the compound is substituted with two adjacent alkoxy groups the groups are, optionally, linked by an alkyl group having 1 carbon to 4 carbons, amino group, alkylamino group having one alkyl group or two alkyl groups, wherein each alkyl group has 1 carbon to 6 carbons, arylamino group having one aromatic group or two aromatic groups, wherein each aryl group has 4 carbons to 6 carbons, alkyloxy group, wherein the alkyl group has 1 carbon to 6 carbons and is linear, branched or cyclic, and aryloxy group, wherein the aryl group has 4 carbons to 6 carbons,
- an aralkyl group, wherein the araalkyl group is attached via the aliphatic moiety having 1 carbon to 8 carbons and an aromatic moiety having 4 carbons to 8 carbons,
- or a heterocyclic group having 3 carbons to 8 carbons, wherein the heterocyclic group is saturated or comprises one or more carbon-carbon multiple bonds, and
- wherein R3 is an optional substitution and is any of the R1 and R2 groups.
) The compound of claim 1, wherein the compound has the following structure:
- wherein the compound has at least one of R4, R5 and R6, and R4, R5 and R6 are independently selected from halogen, hydroxy, alkoxy group having 1 carbon to 6 carbons, wherein if the compound is substituted with two adjacent alkoxy groups the groups are, optionally, linked by an alkyl group having from 1 carbon to 4 carbons, amino group, alkylamino group having one or two alkyl groups, wherein each alkyl group has 1 carbon to 6 carbons, alkyloxy group, wherein the alkyl group has 1 carbon to 6 carbons and is linear, branched or cyclic, and aryloxy group, wherein the alkyl group has 4 carbons to 6 carbons.
) The compound of claim 2, wherein the compound has one of the following structures:
) The compound of claim 1, wherein the compound has the following structure:
- wherein X is O, N, or S.
) The compound of claim 4, wherein the compound has one of the following structures:
) The compound of claim 1, wherein the compound has the following structure:
) The compound of claim 1, wherein the compound has the following structure:
) The compound of claim 7, wherein the compound has one of the following structures:
- wherein the compound has at least one of R4, R5 and R6, and R4, R5 and R6 are independently selected from halogen, hydroxy, alkoxy group having 1 carbon to 6 carbons, wherein if the compound is substituted with two adjacent alkoxy groups the groups are, optionally, linked by an alkyl group having from 1 carbon to 4 carbons, amino group, alkylamino group having one or two alkyl groups, wherein each alkyl group comprises 1 carbon to 6 carbons, alkyloxy group, wherein the alkyl group comprises 1 carbon to 6 carbons and is linear, branched or cyclic, and aryloxy group, wherein the alkyl group comprises 4 carbons to 6 carbons, or
- or
- wherein X is O, N or S.
) The compound of claim 1, wherein the compound has one of the following structures:
) The compound of claim 1, where the compound is selected from:
) The compound of claim 1, wherein the compound is selected from the following:
- 1,3-cyclohexanedione, 2-acetyl-5-[4-(N,N-dimethylamino)phenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[4-methylphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[4-(1-methylethyl)phenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[4-chlorophenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-[2-chloro-6-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[4-methoxyphenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[3,4-dimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-[3,4-dimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[naphth-2-yl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-[2,4-dichlorophenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[2,4,5-trimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-[4-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-[4-methoxyphenyl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[4-methoxyphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[4-methoxyphenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[4-methoxyphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-phenyl-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[4-(N,N-dimethylamino)phenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[4-(N,N-dimethylamino)phenyl]-;
- 1,3-cyclohexanedione, 2-isobutyrylyl-5-[4-(N,N-dimethylamino)phenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[2,4,6-trimethylphenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[2,4,6-trimethylphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[3,4-dimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[3,4-dimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[3,4-dimethoxyphenyl]-;
- N, 5-diphenylcyclohexane-1,3-dione-2-carboxamide;
- N-phenyl-5-[4-fluorophenyl]-cyclohexane-1,3-dione-2-carboxamide;
- N-phenyl-5-[2,4-dichlorophenyl]-cyclohexane-1,3-dione-2-carboxamide;
- N-phenyl-5-[fur-2-yl]-cyclohexane-1,3-dione-2-carboxamide;
- N-phenyl-5-[2,4,6-trimethylphenyl]-cyclohexane-1,3-dione-2-carboxamide;
- N-phenyl-5-[3,4-dimethoxyphenyl]-cyclohexane-1,3-dione-2-carboxamide;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[4-(cyclopropanecarboxy)phenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-methyl-;
- 1,3-cyclohexanedione, 2-acetyl-5-methyl-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[indol-3-yl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-ethyl-;
- 1,3-cyclohexanedione, 2-butyryl-5-[4-hydroxyphenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-cyclohexyl-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[2-chloro-6-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[4-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[2,4,6-trimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[2,4,6-trimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[2,4,6-trimethoxyphenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[4-methylphenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[4-methylphenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[4-(1-methylethyl)phenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[4-chlorophenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[4-chlorophenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[4-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-cyclopentanecarbonyl-5-[4-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[4-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[2,4-dichlorophenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[2,4-dichlorophenyl]-;
- 1,3-cyclohexanedione, 2-butyryl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-benzoyl-5-cyclohexyl-;
- 1,3-cyclohexanedione, 2-acetyl-5-[2-chloro-6-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[fur-2-yl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[4-fluorophenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[4(N,N-dimethylamino)phenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[bicyclo[2.2.1]hept-2-en-5-yl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[(3,4-ethylenedioxy)phenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-phenyl-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-phenyl-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[2,4-dichlorophenyl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[2,4-dichlorophenyl]-;
- 1,3-cyclohexanedione, 2-cyclopropanecarbonyl-5-[thien-2-yl]-;
- 1,3-cyclohexanedione, 2-isobutyryl-5-[thien-2-yl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-hexyl-;
- 1,3-cyclohexanedione, 2-propanoyl-5-hexyl-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[thien-2-yl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-(1-methylethyl)-;
- 1,3-cyclohexanedione, 2-propanoyl-5-(1-methylethyl)-;
- 1,3-cyclohexanedione, 2-acetyl-5-[thien-2-yl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[4-hydroxyphenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[3,4-methylenedioxyphenyl]-;
- 1,3-cyclohexanedione, 2-propanoyl-5-[3,4-methylenedioxyphenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[3,4-ethylenedioxyphenyl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-[N-methylindol-3-yl]-;
- 1,3-cyclohexanedione, 2-acetyl-5-ethyl-;
- 1,3-cyclohexanedione, 2-acetyl-5-butyl-;
- 1,3-cyclohexanedione, 2-propanoyl-5-butyl-;
- 1,3-cyclohexanedione, 2-acetyl-5-pentyl-;
- 1,3-cyclohexanedione, 2-propanoyl-5-pentyl-;
- 1,3-cyclohexanedione, 2-butyryl-5-[N-methylindol-3-yl]-;
- and 1,3-cyclohexanedione, 2-propanoyl-5-[bicyclo[2.2.1]hept-2-en-5-yl]-.
) A method for altering the lifespan of a eukaryotic organism comprising administering a composition comprising a compound of claim 1 to the organism, wherein the lifespan of the eukaryotic organism is altered subsequent to the administration.
) The method of claim 12, wherein the altering of the lifespan comprises extending the lifespan of the organism.
) A method for prophylaxis and/or therapy of inflammation in an individual comprising administering a composition comprising a compound of claim 1 to the individual, wherein inflammation in the organism is reduced subsequent to the administration.
) The method of claim 14, wherein the inflammation is positively correlated with an age-related disease.