One-Pot Synthesis of New (1,3-Thiazolo[5,4-b]pyridin-2-yl)benzenediols and Their Antiproliferative Activities against Human Cancer Cell Lines by Joanna Matysiak* a ), Monika M. Karpin ´ ska b ), Andrzej Niewiadomy a ) b ), Joanna Wietrzyk c ), and Dagmara Klopotowska c ) a ) Department of Chemistry, University of Life Sciences, Akademicka 15, PL-20-950 Lublin (phone: þ 48-81-4456816; fax: þ 48-81-5333549; e-mail: joanna.matysiak@up.lublin.pl) b ) Institute of Industrial Organic Chemistry, Annopol 6, PL-03-236 Warszawa c )Department of Experimental Onkology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, R. Weigla 12, PL-53-114 Wrocław A one-pot synthesis of new 4-(1,3-thiazolo[5,4-b]pyridin-2-yl)benzene-1,3-diols has been described. The compounds were prepared by the reaction of sulfinylbis[(2,4-dihydroxyphenyl)methanethione] derivatives, with various substituents in the aryl rings, with 2-chloropyridin-3-amines. Their structures were deduced from IR and, 1 H- and 13 C-NMR spectroscopic, mass spectrometric, and elemental analyses. The antiproliferative properties of some of the products against human cancer cell lines were comparable to those of cisplatin. Structure activity analysis showed that the presence of hydrophobic substituents in both heterocyclic fused and phenyl rings of the compounds improves their biological effects. Further, an additional OH group in the resorcinol moiety reduced the antiproliferative activity. Introduction. – The thiazole and fused-thiazole heterocycles are important structural components of biologically active molecules, and, as a result, they serve as attractive targets for developing new, effective synthesis methods [1] [2]. Because of their pharmaceutical importance in the area of drug discovery, we have been interested in developing an efficient protocol to prepare fused-thiazole scaffolds of 1,3- thiazolo[5,4-b]pyridine that is relatively unexplored with regard to its biological activity. Several synthetic methods for the preparation of 1,3-thiazolo[5,4-b]pyridine derivatives have been well-documented, but all approaches have some restraints. The most common route involves the reaction of 2-chloropyridin-3-amine with alkyl, aralkyl, or aryl isothiocyanate in absolute EtOH [3] [4]. Krayushkin and co-workers described the oxidation of compounds, in which a monothioxamide fragment is linked to a heterocyclic ring leading to the formation of fused thiazole derivatives with a carboxamide group. This approach was applied to the synthesis of previously unknown derivatives, and its sensitivity to electronic factors was noticed [5 – 8] . 1,3-Thiazolo[5,4- b]pyridine-2-carboxamides were also prepared by the reaction of 2-nitropyridin-3- amine with dithioesters containing a carbamoyl group [9]. A one-step synthesis from appropriately substituted chloro-nitro-pyridine, and thioamide or thiourea has been recently described by Sahasrabudhe et al. In particular, the reaction was used to prepare a large number of 6-nitrothiazolo[5,4-b]pyridine derivatives with various substituents in 2-position [10]. Treatment of 4-chloro-N-(2-chloropyridin-3-yl)- or 4- chloro-N-(4-chloropyridin-3-yl)-1,2,3-dithiazol-5H-imines with catalytic amounts of tetraalkylammonium iodide gave 1,3-thiazolo[5,4-b]pyridine-2-carbonitriles [11]. CHEMISTRY & BIODIVERSITY – Vol. 9 (2012) 48  2012 Verlag Helvetica Chimica Acta AG, Zürich