title: Novel substituted aminothiazoles as potent and selective anti-hepatocellular carcinoma agents.
abstract: Based on our previous identification of a disubstituted aminothiazole termed HBF-0079 with promising selective toxicity for HCC-derived cell lines versus non-HCC liver lines, a series of tri-substituted aminothiazole derivatives were prepared and evaluated. This work resulted in the discovery of isopropyl 4-(pyrazin-2-yl)-2-(pyrimidin-2-ylamino)thiazole-5-carboxylate, 14, which displayed EC50value of 0.11μM and more than 450times of selectivity, and its methyl carbonate prodrug 24 with improved solubility in organic solvents. Furthermore, 14, was shown to reduce the proliferation of several liver cancer cells derived directly from patients.
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: Huagang
authors: H
authors: Lu
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: John
authors: J
authors: Rogowskyj
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: Wenquan
authors: W
authors: Yu
authors: Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Anu
authors: A
authors: Venkatesh
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: Noshena
authors: N
authors: Khan
authors: Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Shigeki
authors: S
authors: Nakagawa
authors: Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Nicolas
authors: N
authors: Goossens
authors: Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Anna P
authors: AP
authors: Koh
authors: Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Takaaki
authors: T
authors: Higashi
authors: Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Ganesh
authors: G
authors: Gunasekaran
authors: Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Myron E
authors: ME
authors: Schwarz
authors: Division of Surgical Oncology, Department of Surgery, Icahn School of Medicine at Mount Sinai, United States.
authors: Spiros P
authors: SP
authors: Hiotis
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: Xiaodong
authors: X
authors: Xu
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: William
authors: W
authors: Kinney
authors: Division of Liver Diseases, Department of Medicine, Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, United States.
authors: Yujin
authors: Y
authors: Hoshida
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States.
authors: Timothy
authors: T
authors: Block
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States. Electronic address: acuconati@arbutusbio.com.
authors: Andrea
authors: A
authors: Cuconati
authors: Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, United States. Electronic address: yanming.du@bblumberg.org.
authors: Yanming
authors: Y
authors: Du
mesh_terms: D000586:Amination; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002254:Carbonates / Q000737:chemistry / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D002254:Carbonates; D011355:Prodrugs; D013844:Thiazoles
keywords: Hepatocellular carcinoma (HCC); Prodrug; Substituted aminothiazole