1. Synthesis of Tic-d-Phe Ψ[CH2–CH2] isostere and its use in the development of melanocortin receptor agonists
- Author
-
Beth B. Pinney, Jeffery C. Hayes, Xinrong Tian, Russell James Sheldon, Mark Gregory Solinsky, Adrian Gregory Switzer, Frank H. Ebetino, Doreen Crossdoersen, John August Wos, Julie A. Farmer, Xuemei Chen, and Lixian Gan
- Subjects
Models, Molecular ,Agonist ,Alkylation ,Lactams ,medicine.drug_class ,Stereochemistry ,Isostere ,Peptidomimetic ,Phenylalanine ,Clinical Biochemistry ,Pharmaceutical Science ,Ligands ,Biochemistry ,Chemical synthesis ,Structure-Activity Relationship ,chemistry.chemical_compound ,Melanocortin receptor ,Drug Discovery ,medicine ,Humans ,Molecular Biology ,Dipeptide ,Molecular Structure ,Chemistry ,Molecular Mimicry ,Organic Chemistry ,Stereoisomerism ,Dipeptides ,Combinatorial chemistry ,Lactam ,Receptor, Melanocortin, Type 4 ,Molecular Medicine ,Melanocortin ,Receptor, Melanocortin, Type 3 - Abstract
The first synthesis of Tic-D-Phe Psi[CH(2)-CH(2)] isostere is described, which features diastereoselective alkylation of the tricyclic lactam 14. The use of this novel dipeptide isostere in the development of melanocortin agonists has been demonstrated by the synthesis of peptidomimetic 7 and non-peptidic ligand 27. Both compounds displayed significant binding and agonist potency at the MC4R.
- Published
- 2006
- Full Text
- View/download PDF