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Updated: Jun 14, 2025

Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
Published on: May 16, 2022
Invention of novel 3-aminopiperidin-2-ones as calcitonin gene-related peptide receptor antagonists
Donnette D Staas1, Ian M Bell1, Christopher S Burgey1
1Department of Discovery Chemistry, Merck & Co., Inc., West Point, PA 19486, USA.
Abstract:
A novel series of 3-amino-piperidin-2-one-based calcitonin gene-related peptide (CGRP) receptor antagonists was invented based upon the discovery of unexpected structure-activity observations. Initial exploration of the structure-activity relationships enabled the generation of a moderately potent lead structure (4). A series of modifications, including ring contraction and inversion of stereocenters, led to surprising improvements in CGRP receptor affinity. These studies identified compound 23, a structurally novel potent, orally bioavailable CGRP receptor antagonist.
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