Retinoid-related orphan receptor γ t modulators: comparison of Glenmark's me-too patent application (WO2015008234) with the originator application from Merck Sharp and Dohme (WO2012106995).

Retinoic acid receptor-related orphan nuclear receptor γ t (RORγt) is a key transcription factor for the development of TH17 cells. Inhibiting RORγt activity is thought to be beneficial in targeting a variety of inflammatory and autoimmune disorders. In their patent application WO2015008234, Glenmark applied a scaffold-hop approach regarding to the originator application from Merck Sharp & Dohme (WO2012106995): a 6-membered annelated aromatic moiety is replaced by an annelated 5-membered heteroaryl (exemplified and claimed is however only thiophene), resulting in potent RORγt inverse agonists with a thieno[3,2-b]pyrrole or thieno[3,2-c]pyrazole core. Based on the patent disclosure, the novelty and utility of these me-too compounds is discussed.