PF-04449613

PDE9A抑制剂(IC50=22nM)；对PDE9A的选择性优于PDE1C(IC50=>1,000nM)，也优于多种其他PDE，在1µM浓度下，可抑制一系列酶、离子通道和转运蛋白中的PDE2-8、-10和-11活性不到30%，但可抑制人类多巴胺转运蛋白(DAT；Ki=293nM)；可提高大鼠的cGMPCSF水平；在10mg/kg剂量下，可提高小鼠体内初级运动皮层锥体神经元树突棘形成和消除的速度；在10mg/kg剂量下，可提高小鼠在加速转棒任务中的平均跑步速度。A PDE9A inhibitor (IC50 = 22 nM); is selective for PDE9A over PDE1C (IC50 = >1,000 nM), as well as over a variety of other PDEs, inhibiting PDE2-8, -10, and -11 activity by less than 30% in a panel of enzymes, ion channels, and transporters at 1 µM but does inhibit the human dopamine transporter (DAT; Ki = 293 nM); increases cGMP CSF levels in rats; increases the rate of dendritic spine formation and elimination in mouse primary motor cortex pyramidal neurons in vivo at 10 mg/kg; increases the average running speed of mice in an accelerating rotarod task at 10 mg/kg.分子式C21H25N5O3分子量395.5O=C1N=C([C@@H](C)N2CC(OC3=CC=CC=C3)C2)NC4=C1C=NN4C5CCOCC5