Synthesis and pharmacological evaluation of cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine: A structural analogue of the GABA agonist THIP

Article abstract of DOI:10.1021/jm00146a024

The pharmacological activities of the GABA agonist muscimol and its dihydro analogue have been shown to be almost identical. The closely related 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) although biologically less active than muscimol, was selected for clinical trials. We report the synthesis of the so far elusive cis-2,3,3a,4,5,6,7,7a-octahydro-3-oxoisoxazolo[5,4-c]pyridine (cis-DH-THIP), which - surprisingly - is devoid of any GABAergic activity.