Selective JAK1 inhibitor and selective Tyk2 inhibitor patents

Abstract

The recent disclosure of the clinical efficacy of a selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed disclosure of the some potent and highly selective JAK1 inhibitors provide a clear stimulus for further activity in this area. The availability of a selective Tyk2 inhibitor will provide the opportunity for better understanding of the physiological role of this kinase. Recent patent applications indicate that Tyk2 selectivity is achievable and Tyk2 inhibitors have potential in the treatment of multiple sclerosis.

Evaluation of WO2013125543, WO2013146963 and EP2634185: the first Tyk2 inhibitors from Takeda and Sareum

“…Compound (9) was prepared via a convergent sequence, illustrated for compound (6) in Figure 3. Chiralpak HPLC was used to resolve chiral pyrrolidone derivatives in a number of cases.…”

“…The bulk of this activity has focused upon the identification of inhibitors of JAK2 and JAK3 [5]. In contrast, much less interest has been evident in the identification of selective inhibitors of JAK1 and, especially, Tyk2 [6]. The latter review identified just seven patents claiming Tyk2 inhibitors, four from Roche, two from Cellzome and the single filing from Bayer.…”

“…Sareum claims novel 2-phenyl-5-phenylamino-oxazole-4-carboxamide derivatives such as SAR-T24 [12]. Takeda's first filing claims 1,5-dihydro-4H-pyrazolo [4,3-c] pyridine-4-ones such as (5) [13] and the second claims (2-arylaminopyrimidin-4-yl)-2-oxo-pyrrolidin derivatives such as (6) [14].…”

Selective JAK Inhibitors

“…Pertinent examples will be summarized with key highlights discussed, allowing the reader to compare and contrast the subtleties of JAK family selectivity from a molecular as well as a pharmacological point of view. Patents have not been covered -the reader is referred to other reviews and discussions covering patent publications of JAK inhibitors [2, [20][21][22][23]. Detailed reviews of JAK biology have been adequately presented elsewhere [1,2] and will not be covered here.…”

Discovering What Makes STAT Signaling TYK in T-ALL

“…New inhibitors more specifi c to TYK2 are needed, and, indeed, some have already been identifi ed ( 9 ) and need to be translated for use in humans. Along with TYK2 inhibition, addiction to IL-10 signaling and BCL2 expression can also be exploited therapeutically in T-ALL treatment.…”