Synthesis,Crystal Structure and Anticoagulant Activity of 5-Chloro-N-[[(5S)-2-oxo-3-[4-(2-oxopyridin

• 作 者: 刘巍 袁静 张士俊 徐为人 黄长江 汤立达
• 机 构: Tianjin Key Laboratory of Molecular Design and Drug Discovery,Tianjin Institute of Pharmaceutical Re
• 出 处: 结构化学
• 发表日期: 2014年07期
• 关键词: thiophene absolute intermolecular monoclinic adopt stabilize conformation bonds

The title compound(zifaxaban 2, C20H16ClN3O4 S, Mr = 429.87) was synthesized and its crystal structure was determined by single-crystal X-ray diffraction. Zifaxaban crystallizes in monoclinic, space group P21 with a = 5.7900(12), b = 13.086(3), c = 12.889(3) A, β = 100.86(3)°, V = 959.1(3) A3, Z = 2, Dc = 1.489 g/cm3, F(000) = 444, μ = 0.342 mm-1, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections(I > 2σ(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.

ZIFXABAN crystallizes in monoclinic, space group P21 with a = 5.7900 (12), b = 13.086 (3), c = 12.889 (3) A, β = 100.86 (3) °, V = 959.1 (3) A3, Z = 2, Dc = 1.489 g / cm3, F (000) = 444, μ = 0.342 mm -1, the final R = 0.0320 and wR = 0.0640 for 2717 observed reflections (I> 2σ (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.