Synthesis and biological activity of 2-aminothiazoles as novel inhibitors of PGE2 production in cells.

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Smith B, Chang HH, Medda F, Gokhale V, Dietrich J, Davis A, Meuillet EJ, Hulme C

Synthesis and biological activity of 2-aminothiazoles as novel inhibitors of PGE2 production in cells.

Bioorg Med Chem Lett. 2012 May 15;22(10):3567-70. doi: 10.1016/j.bmcl.2012.03.013. Epub 2012 Mar 28.

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22516282 [ View in PubMed

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Abstract

This Letter presents the synthesis and biological evaluation of a collection of 2-aminothiazoles as a novel class of compounds with the capability to reduce the production of PGE(2) in HCA-7 human adenocarcinoma cells. A total of 36 analogs were synthesized and assayed for PGE(2) reduction, and those with potent cellular activity were counter screened for inhibitory activity against COX-2 in a cell free assay. In general, analogs bearing a 4-phenoxyphenyl substituent in the R(2) position were highly active in cells while maintaining negligible COX-2 inhibition. Specifically, compound 5l (R(1)=Me, R(2)=4-OPh-Ph, R(3)=CH(OH)Me) exhibited the most potent cellular PGE(2) reducing activity of the entire series (EC(50)=90 nM) with an IC(50) value for COX-2 inhibition of >5 muM in vitro. Furthermore, the anti-tumor activity of analog 1a was analyzed in xenograft mouse models exhibiting promising anti-cancer activity.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Celecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	30	N/A	N/A	Details