N-[2-Methoxy-4-(4-morpholinyl)phenyl]-2-(3-pyridinyl)-4-thiazolecarboxamide

Biological Activity

irak inhibitor 6 is an interleukin-1 receptor associated kinase 4 (irak-4) inhibitor.the interleukin-1 receptor associated kinases (iraks) are a family of serine/threonine kinases related with regulating cellular signalling downstream of the il-18, il-1 and various toll-like receptors. irak-4 is reported to be essential for the activation of the intracellular signalling cascades including nfкb and mapk pathways, which are critical for the production of inflammatory cytokines.

in vitro

a quantitative structure–activity relationship (qsar) study of irak inhibitor 6 and its analogs were conducted by using the genetic algorithm and multiple linear regression (ga-mlr) method [1]. in vitro study showed that compared with its unsubstituted phenyl amide analog, the ortho-substitution with chloro, methoxy and difluoromethoxy analogs of irak inhibitor 6 improved potency against irak-4 significantly. these potency effects were additive, with the most active example in the set being irak inhibitor 6, in which the presence of nitrogen-linked substituents at the para position had a beneficial effect on the rate of turnover by human microsomes (20 μl/min/mg protein) [2].

IC 50

0.16 μm for irak-4

References

[1] pourbasheer e, riahi s, ganjali mr, norouzi p. quantitative structure-activity relationship (qsar) study of interleukin-1 receptor associated kinase 4 (irak-4) inhibitor activity by the genetic algorithm and multiple linear regression (ga-mlr) method. j enzyme inhib med chem. 2010 dec;25(6):844-53.
[2] buckley gm, gowers l, higueruelo ap, jenkins k, mack sr, morgan t, parry dm, pitt wr, rausch o, richard md, sabin v, fraser jl. irak-4 inhibitors. part 1: a series of amides. bioorg med chem lett. 2008 jun 1;18(11):3211-4.