Discovery and evaluation of pyrazolo [1, 5-a] pyrimidines as neuropeptide Y1 receptor antagonists

…, S De Lombaert, JK Inthavongsay, LE Klade…

Index: Griffith, David A.; Hargrove, Diane M.; Maurer, Tristan S.; Blum, Charles A.; De Lombaert, Stephane; Inthavongsay, John K.; Klade, Lee E.; MacK, Christine M.; Rose, Colin R.; Sanders, Martin J.; Carpino, Philip A. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 9 p. 2641 - 2645

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Citation Number: 9

Abstract

A novel series of pyrazolo [1, 5-a] pyrimidine derivatives was synthesized and evaluated as NPY Y1R antagonists. High binding affinity and selectivity were achieved with C3 trisubstituted aryl groups and C7 substituted 2-(tetrahydro-2H-pyran-4-ylamino) ethylamine moieties. Efforts to find close analogs with low plasma clearance in the rat and minimal p- glycoprotein efflux in the mouse were unsuccessful. Compound 2f (CP-671906) inhibited ...