Dual Kinase inhibitor for Autoimmune disease

There are lots of JAK/TYK inhibitor project in drug discovery area.
https://www.ncbi.nlm.nih.gov/pubmed/30113844
Here is an article from pfizer. Pfizer discovered and launched JAK inhibitor ‘tofacitinib’.
Tofacitinib inhibits JAK3, JAK1 and JAK3.

It is well known that JAK2 uniquely forms a homodimer, which is important in hematopoiesis via signal transduction associated with erythropoietin (EPO), thrombopoietin (TPO), and IL-3. Inhibition of JAK2 is concerned about reduction in hemoglobin/Amemia.

They focused to obtain JAK1/TYK2 dual inhibitor to block INF alpha. I think the strongest point is that they can use PK/PD relationship of tofacinib’s JAK2 inhibition.
By using their clinical knowledge, they could define the clear criteria of the project.

Their lead compound is pyrimidine derivative with 4 diversity points. They changed R4 group from cyanoacetyl group to cyclopropyamidel group to improve hydrohobic interactions. And finally they found difluoro cyclopropyl amide moiety. Genentec published Tyk2 inhibitor and the compound has cyclopropyl moiety too but different binding mode. Hmm, cyclopropyl group is interesting parts for medicinal chemist.

Finally they found compound 23 and the compound showed good efficacy in vivo AIA model (PF-06700841). And this compound studies in Ph II trials now.

BTW, In fig1 shows Jak inhibitors on the market and in late stage clinical development.

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It is very interesting for me baricitinib and ruxolitinib is quite similar structure. It is because that both compounds are developed by same company Incyte Biopharmaceutical Company. I did not check patents of both compounds. I would like to know claim strategy of them.
https://pdfs.semanticscholar.org/8184/fef3e8864e14aa652f01f237e6b4df9ec86a.pdf?_ga=2.218333145.1597951041.1535025783-1067331720.1532781359
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