Discovery and pharmacological characterization of a selective delta opiate receptor antagonist (CP-646,777)

Spiros Liras; Stanton F. McHardy; Martin P. Allen; Barb E. Segelstein; Steven D. Heck; Dianne K. Bryce; Anne W. Schmidt; Rebecca O'Connor; Michelle Vanase-Frawley; Ernesto Callegari; Stafford McLean

doi:10.1039/C0MD00249F

Discovery and pharmacological characterization of a selective delta opiate receptor antagonist (CP-646,777)†

Spiros Liras,*^a Stanton F. McHardy,‡^a Martin P. Allen,^a Barb E. Segelstein,^a Steven D. Heck,^a Dianne K. Bryce,^b Anne W. Schmidt,^b Rebecca O'Connor,^b Michelle Vanase-Frawley,^b Ernesto Callegari^c and Stafford McLean^b

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* Corresponding authors

^a Neuroscience Medicinal Chemistry, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT, USA
E-mail: spiros.liras@pfizer.com

^b Neuroscience Biology, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT, USA

^c Pharmacokinetics, Dynamics and Metabolism, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT, USA

Abstract

CP-646,777 (compound 2a) is identified as a potent and selective delta opioid receptor antagonist. The synthesis, pharmacological evaluation, disposition characteristics and pharmacokinetic properties of this compound are reported herein. An approach for reducing clearance as measured by human liver microsomes is demonstrated. The significance of p-glycoprotein efflux on CNS disposition and on the pharmacological action of CP-646,777 is also discussed.

MedChemComm

Discovery and pharmacological characterization of a selective delta opiate receptor antagonist (CP-646,777)†

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Discovery and pharmacological characterization of a selective delta opiate receptor antagonist (CP-646,777)

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