Design, synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 receptor (CRF1R).

Abstract Several tetrahydroimidazopyrimidines were prepared using silver assisted cyclization as the key step. The binding affinities of compounds thus prepared were evaluated in vitro toward hCRF 1 R. Initial lead compound 16 ( K i  = 32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test. Further optimization using parallel synthesis provided compounds with K i ’s