Design and Discovery of 6-[(3 S, 4 S)-4-Methyl-1-(pyrimidin-2-ylmethyl) pyrrolidin-3-yl]-1-(tetrahydro-2 H-pyran-4-yl)-1, 5-dihydro-4 H-pyrazolo [3, 4-d] pyrimidin-4-one …

…, C Proulx-LaFrance, M Corman, CJ Helal…

Index: Verhoest, Patrick R.; Fonseca, Kari R.; Hou, Xinjun; Proulx-Lafrance, Caroline; Corman, Michael; Helal, Christopher J.; Claffey, Michelle M.; Tuttle, Jamison B.; Coffman, Karen J.; Liu, Shenpinq; Nelson, Frederick; Kleiman, Robin J.; Menniti, Frank S.; Schmidt, Christopher J.; Vanase-Frawley, Michelle; Liras, Spiros Journal of Medicinal Chemistry, 2012 , vol. 55, # 21 p. 9045 - 9054

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Citation Number: 29

Abstract

6-[(3 S, 4 S)-4-Methyl-1-(pyrimidin-2-ylmethyl) pyrrolidin-3-yl]-1-(tetrahydro-2 H-pyran-4-yl)- 1, 5-dihydro-4 H-pyrazolo [3, 4-d] pyrimidin-4-one (PF-04447943) is a novel PDE9A inhibitor identified using parallel synthetic chemistry and structure-based drug design (SBDD) and has advanced into clinical trials. Selectivity for PDE9A over other PDE family members was achieved by targeting key residue differences between the PDE9A and PDE1C catalytic ...