Novel pyrrole carboxamide inhibitors of JAK2 as potential treatment of myeloproliferative disorders. Issue 10 (15th May 2015) - Brasca, Maria Gabriella
Graphical abstract: Deconstruction of compound1 led to the identification of the potent and orally bioavailable JAK2 inhibitor16 (NMS-P830). Abstract: Compound1, a hit from the screening of our chemical collection displaying activity against JAK2, was deconstructed for SAR analysis into three regions, which were explored. A series of compounds was synthesized leading to the identification of the potent and orally bioavailable JAK2 inhibitor16 (NMS-P830), which showed an encouraging tumour growth inhibition in SET-2 xenograft tumour model, with evidence for JAK2 pathway suppression demonstrated by in vivo pharmacodynamic effects.