Nonpeptide urotensin-II receptor antagonists: a new ligand class based on piperazino-phthalimide and piperazino-isoindolinone subunits

…, DK Luci, S Ghosh, WA Kinney, CH Reynolds, J Qi…

Index: Lawson, Edward C.; Luci, Diane K.; Ghosh, Shyamali; Kinney, William A.; Reynolds, Charles H.; Qi, Jenson; Smith, Charles E.; Wang, Yuanping; Minor, Lisa K.; Haertlein, Barbara J.; Parry, Tom J.; Damiano, Bruce P.; Maryanoff, Bruce E. Journal of Medicinal Chemistry, 2009 , vol. 52, # 23 p. 7432 - 7445

Full Text: HTML

Citation Number: 36

Abstract

We have discovered two related chemical series of nonpeptide urotensin-II (U-II) receptor antagonists based on piperazino-phthalimide (5 and 6) and piperazino-isoindolinone (7) scaffolds. These structure types are distinctive from those of U-II receptor antagonist series reported in the literature. Antagonist 7a exhibited single-digit nanomolar potency in rat and human cell-based functional assays, as well as strong binding to the human U-II receptor. ...