jm049161u_si_001.pdf (28.65 kB)
Design, Synthesis, and Biological Activity of Novel Polycyclic Aza-Amide FKBP12 Ligands
journal contribution
posted on 2006-02-09, 00:00 authored by Raymond A. Hudack,, Nancy S. Barta, Chuangxing Guo, Judith Deal, Liming Dong, Lorraine K. Fay, Bradley Caprathe, Arindam Chatterjee, Darin Vanderpool, Christopher Bigge, Richard Showalter, Steve Bender, Corinne E. Augelli-Szafran, Elizabeth Lunney, Xinjun HouSince the discovery that FK-506 promotes neurite outgrowth, considerable attention has been focused on
the development of potent nonimmunosuppressive ligands for FK-506 binding proteins (FKBPs). Such
neuroimmunophilin agents have been reported to show neuroregenerative activity in a variety of cell and
animal models including neurite outgrowth, age-related cognitive decline, Parkinson's disease, peripheral
nerve injury, optic nerve degeneration, and diabetic neuropathy. We have designed and synthesized a unique
series of tetracyclic aza-amides that have been shown to be potent FKBP12 rotamase inhibitors. The structure−activity relationships established in this study have demonstrated diverse structural modifications that result
in potent rotamase inhibitory activity.