Design and Discovery of 6‑[(3S,4S)‑4-Methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro‑2H‑pyran-4-yl)-1,5-dihydro‑4H‑pyrazolo[3,4‑d]pyrimidin-4-one (PF-04447943), a Selective Brain Penetrant PDE9A Inhibitor for the Treatment of Cognitive Disorders - 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; et al. (Journal of medicinal chemistry, 2012)
Keywords: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Amyloid beta-Protein Precursor - genetics; Animals; Brain - metabolism; Catalytic Domain; Chemistry, Medicinal; Cognition Disorders - drug therapy; Crystallography, X-Ray; Cyclic GMP - metabolism; Dogs; Drug Design; Hippocampus - drug effects; Hippocampus - physiology; Humans; Life Sciences & Biomedicine; Long-Term Potentiation - drug effects; Maze Learning - drug effects; Mice; Mice, Transgenic; Microsomes, Liver - metabolism; Models, Molecular; Pharmacology & Pharmacy; Protein Conformation; Pyrazoles - chemical synthesis; Pyrazoles - pharmacokinetics; Pyrazoles - pharmacology; Pyrimidinones - chemical synthesis; Pyrimidinones - pharmacokinetics; Pyrimidinones - pharmacology; Rats; Science & Technology; Stereoisomerism; Structure-Activity Relationship; Synapses - drug effects; Synapses - physiology; CGMP-SPECIFIC PHOSPHODIESTERASE; RODENTS; MILRINONE; ALIGNMENT; ADME; DRUGS; CNS; CENTRAL-NERVOUS-SYSTEM; SYNAPTIC PLASTICITY; BINDING