Preparation of furano- and pyrrolo- pyrimidine and pyridine compounds as IRAK inhibitors and therapeutic uses thereof.

Abstract

The present invention provides furano- and pyrrolo- pyrimidine and pyridine compds. of general formula I (wherein Ring A is a 3-7 membered carbocyclic ring or a 4-7 membered heterocyclic ring; n = 0-4; each R1 is independently halo, CN, alkoxy, etc., or two R1 groups form part of a bicyclic ring system; each Rx and Ry is independently halo, CN, alkoxy, etc., or together they form part of a ring system; Rz is CN, NO2, halo, etc.; W is N or (un)substituted CH; Q is o or (un)substituted NH; L1 is a bond or a C1-6 bivalent hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by O, S, etc.), compns. thereof, and methods of using the same. for therapy. Synthetic procedures for prepg. I are exemplified. Example compd. II was prepd. by reacting 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile and trans-N,N-dimethylcyclohexane-1,4-diamine. In an IRAK-4 inhibition assay, II had an IC50 of 0.1-1 μM. [on SciFinder(R)]