Crystal structure of the alcoholates and the ansolvate of PNU-97018, an angiotensin II receptor antagonist.

The title compound, PNU-97018 [systemic name: 2-butyl-3,6,7,8,9,11-hexahydro-6,9-dimethyl-3-([2'-(2H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl)-6,9-ethano-4H-imidazo[4,5-d]-pyridazino[1,2-a]pyridazin-4-one] is a newly developed angiotensin II receptor antagonist. The compound and its methanolate and ethanolate were characterized by X-ray crystallography and thermal analysis. The methanolate and ethanolate crystals have an almost identical molecular conformation and crystal packing. In both alcoholates, each alcohol molecule is fixed to the compound with a molar ratio of 1 : 1 by a hydrogen bond between the hydroxyl group of the alcohol molecule and the tetrazole group of the compound. The hydroxyl group of each alcohol molecule further links with the imidazole ring of the neighboring compound by hydrogen bond to form a hydrogen-bond network in both alcoholates. A tunnel-like structure that includes alcohol molecules is formed in each alcoholate. The ansolvate crystal showed completely different thermal and X-ray crystallographic characteristics from the alcoholates, where the compound molecules were directly linked by hydrogen bonds between the tetrazole group of a molecule and the imidazole ring of the neighboring molecule. The position of the hydrogen atom in the tetrazole ring was different between the ansolvate and alcoholates. Unlike alcoholates, a layer structure stacked on the b-c plane was observed in the ansolvate crystal. It was concluded that the molecular conformation and the arrangement of the compound molecules were largely different between ansolvate and alcoholate crystals.