Synthesis, Crystal Structure and Anticoagulant Activity of 5-Chloro-N-[[(5S)-2-oxo-3-[4-(2-oxopyridin-1(2H)-yl)phenyl]oxazolidin-5-ylimethyllthiophene-2-carboxamide

The title compound (zifaxaban 2, C20H16ClN3O4S, M-r = 429.87) was synthesized and its crystal structure was determined by single-crystal X-ray diffiraction. Zifaxaban crystallizes in monoclinic, space group P2(1) with a = 5.7900(12), b = 13.086(3), c = 12.889(3) angstrom, beta = 100.86(3)degrees, V = 959.1(3) angstrom(3), Z = 2, D-c = 1.489 g/cm(3), F(000) = 444, mu = 0.342 mm(-1), the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections (I > 2 sigma(I)). The absolute configuration of the stereogenic center in the title compound was confirmed to be S by single-crystal X-ray diffraction. Four existing intermolecular hydrogen bonds help to stabilize the lattice and the molecule in the lattice to adopt an L-shape conformation. Zifaxaban was slightly more active than rivaroxaban 1 in in vitro assay against human FXa and therefore is promising as a drug candidate.