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Updated: May 28, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Identification of a novel RAMP-independent CGRP receptor antagonist
C Blair Zartman1, Ian M Bell, Steven N Gallicchio
1Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. blair_zartman@merck.com
Abstract:
Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both rat and dog. In contrast to other nonpeptide antagonists, the activity of 16 was affected by the presence of divalent cations and showed evidence of an alternative, RAMP-independent CGRP receptor binding site.
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