[(11)C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin Gene-Related Peptide Receptor

Ian M Bell; Steven N Gallicchio; Craig A Stump; Joseph G Bruno; Hong Fan; Liza T Gantert; Eric D Hostetler; Amanda L Kemmerer; Melody McWherter; Eric L Moore; Scott D Mosser; Mona L Purcell; Kerry Riffel; Christopher A Salvatore; Sandra Sanabria-Bohórquez; Donnette D Staas; Rebecca B White; Mangay Williams; C Blair Zartman; Jacquelynn J Cook; Richard J Hargreaves; Stefanie A Kane; Samuel L Graham; Harold G Selnick

doi:10.1021/ml400199p

[(11)C]MK-4232: The First Positron Emission Tomography Tracer for the Calcitonin Gene-Related Peptide Receptor

ACS Med Chem Lett. 2013 Jul 18;4(9):863-8. doi: 10.1021/ml400199p. eCollection 2013 Sep 12.

Authors

Ian M Bell¹, Steven N Gallicchio¹, Craig A Stump¹, Joseph G Bruno¹, Hong Fan¹, Liza T Gantert¹, Eric D Hostetler¹, Amanda L Kemmerer¹, Melody McWherter¹, Eric L Moore¹, Scott D Mosser¹, Mona L Purcell¹, Kerry Riffel¹, Christopher A Salvatore¹, Sandra Sanabria-Bohórquez¹, Donnette D Staas¹, Rebecca B White¹, Mangay Williams¹, C Blair Zartman¹, Jacquelynn J Cook¹, Richard J Hargreaves¹, Stefanie A Kane¹, Samuel L Graham¹, Harold G Selnick¹

Affiliation

¹ Departments of Medicinal Chemistry, Pain & Migraine, Imaging, In Vitro Pharmacology, Neuroscience & Ophthalmology, and Pharmacokinetics Pharmacodynamics & Drug Metabolism, Merck Research Laboratories , West Point, Pennsylvania 19486, United States.

Abstract

Rational modification of the potent calcitonin gene-related peptide (CGRP) receptor antagonist MK-3207 led to a series of analogues with enhanced CNS penetrance and a convenient chemical handle for introduction of a radiolabel. A number of (11)C-tracers were synthesized and evaluated in vivo, leading to the identification of [(11)C]8 ([(11)C]MK-4232), the first positron emission tomography tracer for the CGRP receptor.

Keywords: MK-4232; calcitonin gene-related peptide receptor; positron emission tomography.