2-Methyl-4,5,6,7-tetrahydropyrazolo[3,4-c]pyridin-3-ol monohydrate, a structural analogue of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol)

CTHIIN30 .H20 , M r = 171.21, monoclinic, e2~/c, a = 8.204 (4), b -7.352 (3), c = 15.320 (7) A, ,8= 118.52 (5) °, V = 811.9 (6) A 3, D m (flotation) = 1.40, D,.= 1.401 Mg m -s, Z = 4. The structure was solved by direct methods and refined by full-matrix least-squares methods. The final R value for 1309 observed reflections is 0.044. The molecule is a zwitterion, and the crystal structure is stabilized by a system of hydrogen bonds. Introduction. Muscimol [5-(aminomethyl)-3-isoxazolol] is a very active and selective GABA (~,-aminobutyric acid) agonist (Johnston, Curtis, DeGroat & Duggan, 1968; Curtis, Duggan, Felix & Johnston, 1971; Krogsgaard-Larsen, Johnston, Curtis, Game & McCulloch, 1975). Using muscimol as a model 0567-7408/82/102741-04501.00 compound, a comprehensive series of heterocyclic GABA analogues has been developed (KrogsgaardLarsen, 1978; Krogsgaard-Larsen, Honor6 & Thyssen, 1979; Brehm, Krogsgaard-Larsen & Jacobsen, 1979) and studied with respect to various GABA synaptic processes (Krogsgaard-Larsen, Johnston, Curtis, Game & McCulloch, 1975; Krogsgaard-Larsen & Johnston, 1975, 1978). Some muscimol analogues including THIP are very potent GABA agonists in vivo and in vitro (Krogsgaard-Larsen, Johnston, Lodge & Curtis, 1977). However, 2-methyl-4,5,6,7-tetrahydropyrazolo[3,4-c]pyridin-3-ol (2), which is a structural analogue of THIP in which the 3-isoxazolol moiety has been replaced by a related heterocyclic ring, showed no affinity for the GABA receptors in vitro (Krogsgaard-Larsen & Roldskov Christiansen, 1979). © 1982 International Union of Crystallography