Potent phthalate inhibitors of aspartate N-acetyltransferase and selective aspartate pathway inhibitors

1. A composition comprising Formula II:

wherein:

n is either 1 or 2, and

R 1 is substituted or unsubstituted aryl, alkyl, aralkyl, or aryloxy;

and salts, stereoisomers, racemates, solvates, and hydrates thereof.

2. The composition of claim 1 , wherein R 1 is benzyl.

3. The composition of claim 1 , wherein R 1 is naphthyl.

4. The composition of claim 1 , wherein n is 1, and R 1 is aryl or aryloxy.

5. The composition of claim 1 , wherein n is 2, and R 1 is aryl or aryloxy.

6. The composition of claim 1 , wherein R 1 is biphenyl.

7. A composition comprising Formula III:

wherein

R 2 is H, halo or substituted or unsubstituted aryl, alkyl, or carboxyl,

provided, however, that when R 2 is aryl, the aryl forms a fused bicyclic ring.

8. A composition comprising Formula III:

wherein R 2 is hydrogen, a straight or branched alkyl having from 1 to 6 carbons, a halogen, a halogenated alkyl having from 1 to 6 carbons, a halogenated alkoxy, or a substituted or unsubstituted cyclic alkyl.

9. The composition of claim 8 , wherein R 2 is selected from the group consisting of: H, 4-bromo, 4-methyl, 4-trifluoromethyl, 4-trifluoromethoxy, 4-difluoromethoxy, 4-tert-butyl, 4-(2-perfluoropropyl), 4-phenyl, 4-((2-benzyl)vinyl), and 4-trifluoromethyl.

10. The composition of claim 1 , wherein the composition consists essentially of a sodium salt of Formula II.

11. A pharmaceutical composition comprising:

a composition of claim 1 ; and

a pharmaceutically acceptable excipient, diluent, or carrier.

12. A method of making a composition of claim 1 , the method comprising:

i) esterifying a dicarboxylic methylphthalate to produce a methylphthalate dimethyl ester;

ii) bromonating the methylphthalate dimethyl ester to produce a bromomethylphthalate dimethyl ester by either:

a) coupling the bromomethylphthalate dimethyl ester with glycine methyl ester to produce an esterified N-carboxymethyl dicarboxybenzylamine; or,

b) coupling the bromomethylphthalate dimethyl ester with β-alanine methyl ester to produce an esterified N-carboxyethyl dicarboxybenzylamine;

and,

iii) reacting the bromomethylphthalate dimethyl ester with an alkyl halide or a benzyl halide to produce an ester compound.

13. A method of inhibiting ANAT activity in a cell, the method comprising:

administering a composition of claim 1 to a cell, and inhibiting ANAT activity in the cell.

14. The composition of claim 1 , wherein the compound is selected from:

N-carboxymethyl-3,4-dicarboxybenzylamine;

N-carboxyethyl-3,4-dicarboxybenzylamine;

N-((2-methyl)carboxymethyl)-3,4-dicarboxybenzylamine;

N-((2-hydroxymethyl)carboxymethyl)-3,4-dicarboxybenzylamine;

N-methyl, N-carboxymethyl-2,3-dicarboxybenzylamine;

N-methyl, N-carboxymethyl-3,4-dicarboxybenzylamine;

N-allyl, N-carboxymethyl-3,4-dicarboxybenzylamine;

N-acetonitrile, N-carboxymethyl-3,4-dicarboxybenzylamine;

N-benzyl, N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(1-naphthyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(2-naphthyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(ethylmorpholino)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-biphenyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(2-bromobenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(3-bromobenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-bromobenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(2-methylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(3-methylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-methylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(2-trifluoromethylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(3-trifluoromethylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-trifluoromethylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(2-trifluoromethyoxybenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(3-trifluoromethoxybenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-trifluoromethoxybenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-difluoromethoxybenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-carboxybenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-carboxamidebenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-t-butylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-(2-perfluoropropyl))-N-carboxymethyl-3,4-dicarboxybenzylamine;

N-(4-bromobenzyl)-N-carboxyethyl-3,4-dicarboxybenzylamine;

N-(4-trifluoromethylbenzyl)-N-carboxymethyl-3,4-dicarboxybenzylamine; or,

N-acetal-N-carboxymethyl-3,4-dicarboxybenzylamine.