PF-05085727

• CAT Number: I014562
• CAS Number: 1415637-72-7
• Molecular Formula: C20H18F3N7
• Molecular Weight: 413.40
• Purity: ≥95%
• Synonyms: 4-(azetidin-1-yl)-1-methyl-3-[1-methyl-5-[4-(trifluoromethyl)phenyl]pyrazol-4-yl]pyrazolo[3,4-d]pyrimidine
• InChI: InChI=1S/C20H18F3N7/c1-28-17(12-4-6-13(7-5-12)20(21,22)23)14(10-26-28)16-15-18(29(2)27-16)24-11-25-19(15)30-8-3-9-30/h4-7,10-11H,3,8-9H2,1-2H3
• InChIKey: SHAVEYUXRBIMLA-UHFFFAOYSA-N
• SMILES: CN1C(=C(C=N1)C2=NN(C3=C2C(=NC=N3)N4CCC4)C)C5=CC=C(C=C5)C(F)(F)F

PF-05085727 is a potent, selective and brain penetrant inhibitor of cGMP-dependent PDE2A (IC50=2 nM). PF-05085727 inhibits PDE2A >4,000-fold selectivity over PDE1 and PDE3-11[1].
PF-05085727 shows weak activity with IC50 of 162 μM to induce cell death in a cellular toxicity assay using transformed human liver endothelial (THLE) cells[1].PF-05085727 (3 μM) shows a minimal inhibition of cytochrome P450 enzymes (CYPs), inhibits 1A2, 2C8, 2C9, 2D6 and 3A4 with percentage% of 16%, 18%, 7%, 4%, and 30%, respectively[1].PF-05085727 (10 μM) inhibits PDE1B, PDE4B, PDE7B and PDE10A with IC50 values of 12.146 μM, 22,503 μM, 13.157 μM and 6.515 μM, respectively[1].
PF-05085727 (subcutaneous injection; 3.2 mg/kg/mice; 3 mg/kg/rat) gives a ratio of unbound brain (Cbu) to unbound plasma (Cpu) of ca. 0.27 and 0.37, respectively[1].PF-05085727 in mice leads to an acute and exposure-dependent elevation in the accumulation of bulk levels of cGMP in cortex, striatum, and hippocampus as measured by enzyme-linked immunosorbent assay[1].

Reference

[1]. Helal CJ, et al. Application of Structure-Based Design and Parallel Chemistry to Identify a Potent, Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor. J Med Chem. 2017 Jul 13;60(13):5673-5698.
 [Content Brief]