TY - JOUR
T1 - Design, synthesis, and biological evaluation of a new class of small molecule peptide mimetics targeting the melanocortin receptors
AU - Cain, James P.
AU - Mayorov, Alexander V.
AU - Cai, Minying
AU - Wang, Hui
AU - Tan, Bahar
AU - Chandler, Kevin
AU - Lee, Yeon Sun
AU - Petrov, Ravil R.
AU - Trivedi, Dev
AU - Hruby, Victor J
PY - 2006/10/15
Y1 - 2006/10/15
N2 - A new bicyclic template has been developed for the synthesis of peptide mimetics. Straightforward synthetic steps, starting from amino acids, allow the facile construction of a wide range of analogs. This system was designed to target the melanocortin receptors (MCRs), with functional group selection based on a known pharmacophore and guidance from molecular modeling to rationally identify positional and stereochemical isomers likely to be active. The functions of hMCRs are critical to myriad biological activities, including pigmentation, steroidogenesis, energy homeostasis, erectile activity, and inflammation. These G-protein-coupled receptors (GPCRs) are targets for drug discovery in a number of areas, including cancer, pain, and obesity therapeutics. All compounds from this series tested to date are antagonists which bind with high affinity. Importantly, many are highly selective for a particular MCR subtype, including some of the first completely hMC5R-selective antagonists reported.
AB - A new bicyclic template has been developed for the synthesis of peptide mimetics. Straightforward synthetic steps, starting from amino acids, allow the facile construction of a wide range of analogs. This system was designed to target the melanocortin receptors (MCRs), with functional group selection based on a known pharmacophore and guidance from molecular modeling to rationally identify positional and stereochemical isomers likely to be active. The functions of hMCRs are critical to myriad biological activities, including pigmentation, steroidogenesis, energy homeostasis, erectile activity, and inflammation. These G-protein-coupled receptors (GPCRs) are targets for drug discovery in a number of areas, including cancer, pain, and obesity therapeutics. All compounds from this series tested to date are antagonists which bind with high affinity. Importantly, many are highly selective for a particular MCR subtype, including some of the first completely hMC5R-selective antagonists reported.
KW - GPCRs
KW - Melanocortins
KW - Peptide mimetics
UR - http://www.scopus.com/inward/record.url?scp=33748324542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748324542&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2006.07.015
DO - 10.1016/j.bmcl.2006.07.015
M3 - Article
C2 - 16931008
AN - SCOPUS:33748324542
SN - 0960-894X
VL - 16
SP - 5462
EP - 5467
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 20
ER -