Facile and efficient preparation of hybrid phenylthiazolyl-1,3,5-triazines and their antidepressant-like effect in mice

High safety, robust efficacy, and rapid onset of action remain the key challenges for improving antidepressant drug discovery. We report a facile and efficient synthetic strategy to structurally encompass mono-, di-, or tri-substituted derivatives using cyanuric chloride and various substituted phenylthiazole-2-amines. The predicted physicochemical property precisely state their specificity as CNS acting agent and antidepressant-like effect of the most promising compound 10 after oral administration significantly reduced immobility in mice behavior models, especially TST from 63 s. In addition, good safety features of 10 highlight its ability to modulate hallmarks for antidepressant discovery. These insights are useful in generalization and systematization of CRF1 antagonist design to develop future biological end points.