1426833-08-0

1426833-08-0 structure

1426833-08-0 structure

Name: PDE2/PDE10-IN-1
Chemical Name: PDE2/PDE10-IN-1
CAS Number: 1426833-08-0
Molecular Formula: C₁₅H₁₀ClN₅
Molecular Weight: 295.73
Catalog: Signaling Pathways Metabolic Enzyme/Protease Phosphodiesterase (PDE)
Create Date: 2018-05-30 04:15:40
Modify Date: 2024-01-08 18:13:09
PDE2/PDE10-IN-1 is a phosphodiesterase 2 (PDE2) and PDE10 inhibitor with IC50s of 29 and 480 nM, respectively.

Name	PDE2/PDE10-IN-1

Description	PDE2/PDE10-IN-1 is a phosphodiesterase 2 (PDE2) and PDE10 inhibitor with IC50s of 29 and 480 nM, respectively.
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE) Research Areas >> Neurological Disease
Target	hPDE2A:29 nM (IC50) rPDE10A:480 nM (IC50) hPDE4D:5890 nM (IC50) hPDE11A:6920 nM (IC50)
In Vitro	PDE2/PDE10-IN-1 (Compound 6) inhibits PDE2 and PDE10, respectively, with an IC50 value of 29 and 480 nM. PDE2/PDE10-IN-1 also inhibits PDE11A and PDE4D with IC50s of 6920 nM and 5890 nM, respectively. In addition PDE2/PDE10-IN-1 does not show significant inhibition of a panel of CYP450 enzymes (CYP1A2, 2C9, 2D6, 2C19, and 3A4). PDE2/PDE10-IN-1 is also inactive up to a concentration of 125 μg/mL in a bacterial mutagenicity assay[1].
In Vivo	The PK properties of PDE2/PDE10-IN-1 are studied in rats after 2.5 mg/kg i.v. and 10 mg/kg p.o. administration. After i.v. administration, a rapid clearance is observed (t1/2=0.47 h), which is not expected based on the in vitro metabolic stability in rat liver microsomes (rLMs). Interestingly, PDE2/PDE10-IN-1 shows much slower clearance after p.o. administration (t1/2=2.36 h), resulting in good bioavailability and a maximum plasma concentration (Cmax) of 997 ng/mL. PDE2/PDE10-IN-1 is assessed for its potential to cross the blood–brain barrier in rats after 10 mg/kg s.c. administration. PDE2/PDE10-IN-1 shows good formulatability with 10 to 20% HPβCD at pH>3.5. The brain concentration for PDE2/PDE10-IN-1 after 1 h administration is in the range of 370-895 ng/g with high brain free fractions and brain/plasma ratios. More specifically, PDE2/PDE10-IN-1, which is orally bioavailable, occupies PDE2 with an ED50 of 21 mg/kg[1].
Animal Admin	Rats[1] Male Sprague-Dawley rats are fed with PDE2/PDE10-IN-1 (i.v., 2.5 mg/kg; p.o., 10 mg/kg). After administration, the clearance is observed.
References	[1]. Rombouts FJ, et al. Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors. ACS Med Chem Lett. 2015 Jan 15;6(3):282-6.

Molecular Formula	C₁₅H₁₀ClN₅
Molecular Weight	295.73