CAS 898562-94-2|PF-2545920

Introduction：Basic information about CAS 898562-94-2|PF-2545920, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. PF-2545920 BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Synonyms

Common Name	PF-2545920
CAS Number	898562-94-2	Molecular Weight	392.453
Density	1.2±0.1 g/cm3	Boiling Point	568.6±50.0 °C at 760 mmHg
Molecular Formula	C₂₅H₂₀N₄O	Melting Point	/
MSDS	/	Flash Point	297.7±30.1 °C

Names

Name	Quinoline, 2-[[4-[1-methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxy]methyl]
Synonym	More Synonyms

PF-2545920 BiologicalActivity

Description	PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE. IC50 value: 0.37 nM [1]Target: PDE10APDE10A subcutaneously administrated at dose of 1 mg/kg elevates striatal cGMP about 3 fold in male CD-1 mice, while PDE10A subcutaneously administrated at dose of 3.2 mg/kg displays a maximal elevation of striatal cGMP approximately a 5-fold increase in male CD-1 mice. PDE10A intravenous injected at a dose of 0.1 mg/kg in Sprague-Dawley rats displays clearance of 36 ml/min/Kg, DE10A intravenous injected at a dose of 0.3 mg/kg in Dog Beagle displays clearance of 7.2 ml/min/Kg in vivo clearance with a moderate volume of distribution, DE10A intravenous injected at a dose of 0.03 mg/kg in Monkey Cynomolgus displays clearance of 13.9 ml/min/Kg in vivo clearance with a moderate volume of distribution. PDE10A is active with an ED50 of 1 mg/kg at a significantly lower total plasma exposure (115 nM) in the conditioned avoidance response assay (CAR) in Sprague-Dawley rats [1]. MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice causes striking increases in GluR1 phosphorylation levels of 3-, 5.4-, and 4.1-fold , respectively. MP-10 at concentration of 1 μM treats Rat striatal slices for 30 min, the level of GluR1S845 phosphorylation at the cell surface is significantly increased 2-fold, without change the level of total GluR1 on the cell surface. MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice results in robust, statistically significant increases in CREBS133 phosphorylation of 3-, 4-, and 2.6-fold, respectively. MP-10 intraperitoneally administrated at dose of 3 mg/kg increases both enkephalin and substance-P mRNA levels in striatum of CF-1 mice. MP-10 intraperitoneally administrated at dose of 0.3-1 mg/kg decreases avoidance responding with a significant treatment effect in the mouse CAR model. Mice treated with MP-10 at dose of 0.03 mg/kg spents more time in the empty than social side in the mice, MP-10 also dose-dependently decreased locomotor activity [2].
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Neurological Disease
References	[1]. Verhoest PR, et al. Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. J Med Chem, 2009, 52(16), 5188-5196. [2]. Grauer SM, et al. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther, 2009, 331(2), 574-590.

Description

PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE. IC50 value: 0.37 nM [1]Target: PDE10APDE10A subcutaneously administrated at dose of 1 mg/kg elevates striatal cGMP about 3 fold in male CD-1 mice, while PDE10A subcutaneously administrated at dose of 3.2 mg/kg displays a maximal elevation of striatal cGMP approximately a 5-fold increase in male CD-1 mice. PDE10A intravenous injected at a dose of 0.1 mg/kg in Sprague-Dawley rats displays clearance of 36 ml/min/Kg, DE10A intravenous injected at a dose of 0.3 mg/kg in Dog Beagle displays clearance of 7.2 ml/min/Kg in vivo clearance with a moderate volume of distribution, DE10A intravenous injected at a dose of 0.03 mg/kg in Monkey Cynomolgus displays clearance of 13.9 ml/min/Kg in vivo clearance with a moderate volume of distribution. PDE10A is active with an ED50 of 1 mg/kg at a significantly lower total plasma exposure (115 nM) in the conditioned avoidance response assay (CAR) in Sprague-Dawley rats [1]. MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice causes striking increases in GluR1 phosphorylation levels of 3-, 5.4-, and 4.1-fold , respectively. MP-10 at concentration of 1 μM treats Rat striatal slices for 30 min, the level of GluR1S845 phosphorylation at the cell surface is significantly increased 2-fold, without change the level of total GluR1 on the cell surface. MP-10 intraperitoneally administrated at dose of 0.3, 3, and 5 mg/kg in male CF-1 mice results in robust, statistically significant increases in CREBS133 phosphorylation of 3-, 4-, and 2.6-fold, respectively. MP-10 intraperitoneally administrated at dose of 3 mg/kg increases both enkephalin and substance-P mRNA levels in striatum of CF-1 mice. MP-10 intraperitoneally administrated at dose of 0.3-1 mg/kg decreases avoidance responding with a significant treatment effect in the mouse CAR model. Mice treated with MP-10 at dose of 0.03 mg/kg spents more time in the empty than social side in the mice, MP-10 also dose-dependently decreased locomotor activity [2].

Related Catalog

Signaling Pathways >>Metabolic Enzyme/Protease >>Phosphodiesterase (PDE)Research Areas >>Neurological Disease

References

[1]. Verhoest PR, et al. Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. J Med Chem, 2009, 52(16), 5188-5196.

[2]. Grauer SM, et al. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther, 2009, 331(2), 574-590.

Chemical & Physical Properties

Density	1.2±0.1 g/cm3
Boiling Point	568.6±50.0 °C at 760 mmHg
Molecular Formula	C₂₅H₂₀N₄O
Molecular Weight	392.453
Flash Point	297.7±30.1 °C
Exact Mass	392.163696
PSA	52.83000
LogP	3.52
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.661
InChIKey	AZEXWHKOMMASPA-UHFFFAOYSA-N
SMILES	Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ccccc4n3)cc2)n1

Safety Information

HS Code	2933990090

Customs

HS Code	2933990090
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Synonyms

2-({4-[1-Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxy}methyl)chinolin

2-({4-[1-Methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline

2-{4-[1-methyl-4-(pyridin-4-yl)pyrazol-3-yl]phenoxymethyl}quinoline

2-{4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxymethyl}quinoline

UNII:R9Y8EY0G42

Quinoline, 2-[[4-[1-methyl-4-(4-pyridinyl)-1H-pyrazol-3-yl]phenoxy]methyl]-

2-({4-[1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl]phenoxy}methyl)quinoline

2-[(4-(1-Methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenoxy)methyl]quinoline

MP 10

PF-2545920

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