Compounds and related methods for inhibition of gamma-aminobutyric acid aminotransferase
(1S, 3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic acid illustrates a novel class of compounds as potent irreversible inhibitors of γ-aminobutyric acid aminotransferase (GABA-AT). The corresponding monofluoro-substituted compounds also are potent time-dependent inhibitors of GABA-AT.
1. A composition comprising a γ-aminobutyric acid aminotransferase inhibitor compound selected from compounds of a formula
wherein R 1 and R 2 are selected from H and F, and at least one of R 1 and R 2 is F; and salts thereof.
2. The composition of claim 1 wherein R 1 and R 2 are F.
3. The composition of claim 2 wherein said NH 2 and COOH substituents have a stereochemical relationship selected from cis and trans.
4. The composition of claim 3 wherein said substituents are cis.
5. The composition of claim 2 selected from an ammonium salt and a carboxylate salt of said compound.
6. The composition of claim 5 wherein said compound is an ammonium salt, and the counter ion is the conjugate base of a protic acid.
7. The composition of claim 5 wherein said compound is a carboxylate, and the counter ion is selected from the conjugate acid of an amine, alkaline and alkaline-earth base.
8. The composition of claim 5 wherein said compound is selected from an ammonium hydrochloride salt and a sodium carboxylate.
9. The composition of claim 1 wherein one of said R 1 and R 2 is F.
10. The composition of claim 9 wherein R 1 is F, and said F and COOH substituents have a Z configuration.
11. The composition of claim 10 wherein said NH 2 and COOH substituents have a stereochemical relationship selected from cis and trans.
12. The composition of claim 9 wherein R 1 is F, and said F and COOH substituents have an E configuration.
13. The composition of claim 12 wherein said NH 2 and said COOH substituents have a stereochemical relationship selected from cis and trans.
14. The composition of claim 9 selected from an ammonium salt and a carboxylate salt of said compound.
15. The composition of claim 1 wherein said compound is in a fluid medium.
16. The composition of claim 15 contacting a γ-aminobutyric acid aminotransferase.
17. The composition of claim 16 wherein said compound is in an amount at least partially sufficient for inhibition of said transferase.