The title compound 1 was prepared from 1-bromonaphthalene and cyclobutanone in 11 steps, and its structure was determined by single-crystal X-ray diffraction for its monohydrate. The title compound 1 crystallizes as its monohydrate (C19H18BrN3O2S center dot H2O, M-r = 450.35) in triclinic, space group P1 with a = 8.195(3), b = 8.703(3), c = 14.610(4) angstrom, alpha = 90.290(4), beta = 93.764(9), gamma = 116.435(10)degrees, V = 930.3(5) angstrom(3), Z = 2, D-c = 1.608 g/cm(3), F(000) = 460, mu = 2.347 mm(-1), the final R = 0.0314 and wR = 0.0746 for 3368 observed reflections (I > 2 sigma(I)). The cyclobutane ring adopts a puckered conformation. The crystal lattice is stabilized by three intermolecular hydrogen bonds involving the existing water molecule. 1 was a highly active urate transporter 1 (URAT1) inhibitor as it was 14-fold more active in in vitro human URAT1 inhibitory assay versus positive control lesinurad (IC50 = 0.51 mu M for 1 vs. 7.18 mu M for lesinurad against human URAT1). The single-crystal structure for the monohydrate of 1 reported herein represents the first unambiguous structural determination of a novel flexible molecular scaffold we discovered earlier that was very promising for the design of highly active URAT1 inhibitors.
