High Affinity Agonists of the Neuropeptide Y (NPY) Y-4 Receptor Derived from the C-Terminal Pentapeptide of Human Pancreatic Polypeptide (hPP): Synthesis, Stereochemical Discrimination, and Radiolabeling

• Published in: Journal of medicinal chemistry Vol. 59; no. 13; pp. 6045 - 6058
• Main Authors: Kuhn, Kilian K., Ertl, Thomas, Dukorn, Stefanie, Keller, Max, Bernhardt, Guenther, Reiser, Oliver, Buschauer, Armin
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 14.07.2016
• Subjects: Chemistry, Medicinal; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Science & Technology; ACID-DERIVATIVES; POTENT; HYDROGENATION; PEPTIDES; LIGANDS; LUMINESCENCE; ANTAGONISTS; EXPRESSION; METATHESIS; FAMILY

The diastereomeric mixture of D/L-2,7-diaminooctanedioyl-bis(YRLRY-NH2) (BVD-74D, 2) was described in the literature as a high affinity Y-4 receptor agonist. Here we report on the synthesis and pharmacological characterization of the pure diastereomers (2R,7R)- and (2S,7S)-2 and a series of homo- an...