Ring deuterated gaboxadol and its use for the treatment of psychiatric disorders
AssigneeCertego Therapeutics
InventorsPavel Osten, Kristin K. Baldwin, Robert DeVita, Samuel Desjardins, Jeffrey Albert
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Abstract
Ring deuterated gaboxadol is provided. The ring deuterated gaboxadol is useful in the treatment of psychiatric disorders and is more effective than non-deuterated gaboxadol in such treatments. Deuterated gaboxadol is useful in combinations with other compounds to provide additive and synergistic effects for patient therapies. In a specific embodiment, the deuterated gaboxadol is d6-gaboxadol.
Claims54
A ring carbon deuterated gaboxadol compound of Formula I
- or a pharmaceutically acceptable salt thereof,
- wherein all of R4, R4′, R5, R5′, R7 and R7′ are D, and wherein the percentage of incorporation of deuterium is at least 1%.
A method of making d6-gaboxadol, said method comprising:
- (a) treating 3-hydroxypyridine-4-carboxylic acid with deuterium oxide under catalytic hydrogenation conditions to provide 2,3,6-trideuterio-5-hydroxy-pyridine-4-carboxylic acid;
- (b) treating 2,3,6-trideuterio-5-hydroxy-pyridine-4-car boxylic acid from step (a) above with a methylating agent, to provide methyl 2,3,6-trideuterio-5-hydroxy-pyridine-4-carboxylate;
- (c) treating methyl 2,3,6-trideuterio-5-hydroxy-pyridine-4-carboxylate from step (b) above with hydroxylamine hydrochloride, to provide 2,3,6-trideuterio-5-hydroxy-pyridine-4-carbohydroxamic acid;
- (d) treating 2,3,6-trideuterio-5-hydroxy-pyridine-4-carbohydroxamic acid from step (c) above with an activating agent, to provide 4,5,7-trideuterioisoxazolo[5,4-c]pyridin-3-one;
- (e) treating 4,5,7-trideuterioisoxazolo[5,4-c]pyridin-3-one from step (d) above with a brominating agent to provide 6-benzyl-4,5,7-trideuterio-isoxazolo[5,4-c]pyridin-6-ium-3-ol bromide;
- (f) treating 6-benzyl-4,5,7-trideuterio-isoxazolo[5,4-c]pyridin-6-ium-3-ol bromide from step (e) above with a reducing agent, to provide 6-benzyl-4,4,5,5,7,7-hexadeuteri o-isoxazolo[5,4-c]pyridin-3-ol;
- and
- (g) deprotecting 6-benzyl-4,4,5,5,7,7-hexadeuterio-isoxazolo[5,4-c]pyridin-3-ol from step (f) above to remove the benzyl group to provide d6-gaboxadol.
A method for treating a psychiatric disorder comprising administering to a human patient in need thereof a therapeutically effective amount of ring carbon deuterated gaboxadol or a pharmaceutically acceptable salt thereof, wherein the psychiatric disorder is bipolar disorder, depression, treatment-resistant depression, major depressive disorder, postpartum depression, or suicidality.
A method for treating major depressive disorder comprising administering to a human patient in need thereof a therapeutically effective amount of ring carbon deuterated gaboxadol or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.