Thiourea and thioether derivatives of sorafenib: synthesis, crystal structure, and antiproliferative activity

A series of novel sorafenib derivatives containing diaryl thiourea and thioether, 9a–u, was designed and synthesized, and their antiproliferative activities against HCT116 and MDA-MB-231 cell lines were also evaluated and described. Most compounds exhibited potent antiproliferative activity against HCT116 cells with IC50 = 1.8–80.4 μM. Compounds 9p, 9r, and 9s demonstrated competitive antiproliferative activities to sorafenib, against all two cancer cell lines. The structures of all the newly synthesized compounds were determined by 1H NMR, 13C NMR, and HRMS, and compound 9n was characterized by single-crystal X-ray diffraction. Primary structure–activity relationships (SAR) have also been established.