Preparation of leukotriene B(4) inhibitory active 2- and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives and their growth inhibitory activity on human pancreatic cancer cells.
A series of 2-(2-aminothiazol-4-yl)benzo[b]furan and 3-(2-aminothiazol-4-yl)benzo[b]furan derivatives were prepared, and their leukotriene B(4) inhibitory activity and growth inhibitory activity in cancer cell lines were evaluated. Several compounds showed strong inhibition of calcium mobilization in CHO cells overexpressing human BLT(1) and BLT(2) receptors and growth inhibition to human pancreatic cancer cells MIA PaCa-2. 3-(4-Chlorophenyl)-2-[5-formyl-2-[(dimethylamino)methyleneamino]thiazol-4-yl]-5-methoxybenzo[b]furan 8b showed the most potent and selective inhibition for the human BLT(2) receptor, and its IC(50) value was smaller than that of the selected positive control compound, ZK-158252. 3-(4-Chlorophenyl)-2-[2-[(dimethylamino)methyleneamino]-5-(2-hydroxyethyliminomethyl)thiazol-4-yl]-5-methoxybenzo[b]furan 9a displayed growth inhibitory activity towards MIA PaCa-2.
Kuramoto
Mari
M
School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Sakata
Yoko
Y
Terai
Kumi
K
Kawasaki
Ikuo
I
Kunitomo
Jun-Ichi
J
Ohishi
Takahiro
T
Yokomizo
Takehiko
T
Takeda
Seiichi
S
Tanaka
Shuichi
S
Ohishi
Yoshitaka
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D001572:Benzofurans / Q000737:chemistry* / Q000627:therapeutic use; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry*
D000970:Antineoplastic Agents; D001572:Benzofurans; D018102:Receptors, Leukotriene B4; D013844:Thiazoles; C004483:2-aminothiazole