Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof
AssigneeBoard of Regents, The University of Texas
InventorsStanley Watowich, Harshini Neelakantan, Hua-Yu Wang, Stanton Mchardy
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Abstract
The present invention relates to quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT), the preparation thereof and uses thereof.
Claims30
A cation of Formula I, wherein:
- R1 is C1-4 alkyl;
- R2 is independently selected from the group consisting of:
- H, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R3 is independently selected from the group consisting of:
- H, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R4 and R5 are independently selected from the group consisting of:
- H, C1-4 alkyl, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R6 is H or halogen;
- R7 is H, methyl, or NR11R12;
- and
- R8 is H, C1-4 alkyl, halogen-substituted C1-4 alkyl;
- R9, R10, R11, and R12 are independently selected from H and C1-4 alkyl, wherein R9 and R10, are independently selected from C1-4 alkyl when R4 is NR9R10;
- wherein the cation has at least two non-hydrogen substituents at positions R2-R8;
- and wherein at least one of R2, R3, R5, and R7 is NH2.
A method of providing muscular therapy to a subject comprising administration of a cation, said cation chosen from:
- wherein R5 is H or NH2 and R8 is H or methyl, and wherein the cation includes a non-hydrogen substituent at either of positions R5 and R8.
A method of providing muscular therapy to a subject comprising administering a cation of Formula I, wherein:
- R1 is C1-4 alkyl;
- R2, R3, R4, and R5 are independently selected from the group consisting of:
- H, C1-4 alkyl, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R6 is H or halogen;
- R7 is H, methyl, or NR11R12;
- and
- R8 is H, C1-4 alkyl, halogen-substituted C1-4 alkyl;
- R9, R10, R11, and R12 are independently selected from H and C1-4 alkyl;
- wherein the cation has at least two non-hydrogen substituents at positions R2-R8, and wherein at least one of the non-hydrogen substituents at positions R2-R8 is NH2.
A method of treating obesity or related chronic metabolic conditions by administering a therapeutically effective amount of one or more cations of Formula I, wherein Formula I is represented as:
- wherein:
- R1 is C1-4 alkyl;
- R2, R3, R4, and R5 are independently selected from the group consisting of:
- H, C1-4 alkyl, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R6 is H or halogen;
- R7 is H, methyl, or NR11R12;
- and
- R8 is H, C1-4 alkyl, halogen-substituted C1-4 alkyl;
- R9, R10, R11, and R12 are independently selected from H and C1-4 alkyl;
- wherein the cation has at least two non-hydrogen substituents at positions R2-R8;
- and wherein at least one of the non-hydrogen substituents at positions R2-R8 is NH2.
A method of treating a disease, said method comprising administering a therapeutically effective amount of a cation of the following formula:
- wherein:
- R5 is selected from the group consisting of:
- H, C1-4 alkyl, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R6 is H or halogen;
- and
- R9, and R10 are independently selected from H and C1-4 alkyl;
- wherein said disease is chosen from obesity or related chronic metabolic conditions.
A cation of the following formula:
- wherein:
- R5 is selected from the group consisting of:
- H, C1-4 alkyl, halogen-substituted C1-4 alkyl, NR9R10, and CN;
- R6 is H or halogen;
- and
- R9, and R10 are independently selected from H and C1-4 alkyl.
Dependencies are inferred from the claim text.