952521-75-4

Upstream product

• 552846-17-0 tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate 
• 906092-45-3 4-iodo-7-tosyl-7H-pyrrolo[2,3-d]-pyrimidine 
• 1146629-77-7 [4-(1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl]methyl 2,2-dimethylpropanoate 
• 98-59-9 p-toluenesulfonyl chloride 

Downstream Products

• 1246751-98-3 4-(1-(hexan-3-yl)-1H-pyrazol-4-yl)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine 

Relevant academic research and scientific papers

PROCESS FOR PREPARING ENANTIOMERICALLY ENRICHED JAK INHIBITORS

Certain aspects of the present invention are directed to improved processes for preparing enantiomerically enriched intermediates for the synthesis of ruxolitinib and deuterated forms of ruxolitinib. Certain aspects are also directed to deuterated intermediates useful in the synthesis of deuterated forms of ruxolitinib. Certain aspects are also directed to reaction mixtures for preparing enantiomerically enriched intermediates useful in the synthesis of ruxolitinib and deuterated forms of ruxolitinib.

Design and Synthesis of Ligand Efficient Dual Inhibitors of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Based on Ruxolitinib and Vorinostat

Concomitant inhibition of multiple oncogenic pathways is a desirable goal in cancer therapy. To achieve such an outcome with a single molecule would simplify treatment regimes. Herein the core features of ruxolitinib (1), a marketed JAK1/2 inhibitor, have been merged with the HDAC inhibitor vorinostat (2), leading to new molecules that are bispecific targeted JAK/HDAC inhibitors. A preferred pyrazole substituted pyrrolopyrimidine, 24, inhibits JAK1 and HDACs 1, 2, 3, 6, and 10 with IC50 values of less than 20 nM, is 100 nM potent against JAK2 and HDAC11, and is selective for the JAK family against a panel of 97 kinases. Broad cellular antiproliferative potency of 24 is supported by demonstration of JAK-STAT and HDAC pathway blockade in hematological cell lines. Methyl analogue 45 has an even more selective profile. This study provides new leads for assessment of JAK and HDAC pathway dual inhibiton achieved with a single molecule.

DEAZAPURINES USEFUL AS INHIBITORS OF JANUS KINASES

The present invention relates to compounds of formula (I): useful as inhibitors of protein kinases, particularly of JAK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the