Related Experiment Video
Updated: Aug 6, 2026

Ex Vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents
Published on: May 16, 2022
Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: optimization of the 4-substituted
Christopher S Burgey1, Craig A Stump, Diem N Nguyen
1Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. christopher_burgey@merck.com
Abstract:
In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented.
Related Concept Videos
Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Antianginal Drugs: Calcium Channel Blockers and Ranolazine
CCBs, a diverse class that includes dihydropyridines (nifedipine) and diphenylalkylamines (verapamil and diltiazem), exert their effect by blocking calcium channels in cardiac and smooth muscle cells. This...
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists
Phenothiazines, such as prochlorperazine...
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
GPCRs Regulate Adenylyl Cylase Activity
Two...
