Design, synthesis and evaluation of constrained tetrahydroimidazopyrimidine derivatives as antagonists of corticotropin-releasing factor type 1 recept...

Basic Information

ID: ALA1155435

Journal: Bioorg Med Chem Lett

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

Authors: Vrudhula VM, Dasgupta B, Pin SS, Burris KD, Balanda LA, Fung LK, Fiedler T, Browman KE, Taber MT, Zhang J, Macor JE, Dubowchik GM.

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 <50 nM.

CiteXplore: 20185312

DOI: 10.1016/j.bmcl.2010.01.127

Patent ID: