Application of a novel design paradigm to generate general nonpeptide combinatorial scaffolds mimicking beta turns: synthesis of ligands for somatostatin receptors.
Nonpeptide compounds that mimic bioactive peptides are desirable for a number of clinical indications. We report a new practical method for the design of scaffolds exhibiting drug-like properties that are suitable for the display of peptide pharmacophores. The synthesis of various synthons of 7'-hydroxy-2',3'-dihydro-1'H,2H,5H-spiro[imidazolidine-4,4'-quinoline]-2,5-dione (1) and methods for the introduction of several mimics of amino acid side-chains are described. This method is exemplified by derivatives that show agonist activity for the somatostatin type 2 receptor.
Chianelli
Dona
D
ChemBridge Research Labs., LLC, 16981 Via Tazon, San Diego, CA 92127, USA.
Kim
Yong-Chul
YC
Lvovskiy
Dmitriy
D
Webb
Thomas R
TR
D020650:Combinatorial Chemistry Techniques; D006827:Hydantoins / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D017481:Receptors, Somatostatin / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000737:chemistry
C488095:7'-hydroxy-2',3'-dihydro-1'H,2H,5H-spiro(imidazolidine-4,4'-quinoline)-2,5-dione; D006827:Hydantoins; D017481:Receptors, Somatostatin; D013141:Spiro Compounds; C093733:somatostatin receptor 2