| Identification | Back Directory | [Name]
GSK-356278 | [CAS]
720704-34-7 | [Synonyms]
GSK-356278
GSK356278,anti-inflammatory,Phosphodiesterase (PDE),anxiolytic,cognition,Inhibitor,phosphodiesterase,PDE4,inhibit
5-[5-[(2,4-dimethyl-5-thiazolyl)methyl]-1,3,4-oxadiazol-2-yl]-1-ethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-Pyrazolo[3,4-b]pyridin-4-amine
5-(5-((2,4-Dimethylthiazol-5-yl)methyl)-1,3,4-oxadiazol-2-yl)-1-ethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine
1H-Pyrazolo[3,4-b]pyridin-4-amine, 5-[5-[(2,4-dimethyl-5-thiazolyl)methyl]-1,3,4-oxadiazol-2-yl]-1-ethyl-N-(tetrahydro-2H-pyran-4-yl)- | [Molecular Formula]
C21H25N7O2S | [MDL Number]
MFCD27987927 | [MOL File]
720704-34-7.mol | [Molecular Weight]
439.53 |
| Chemical Properties | Back Directory | [Boiling point ]
683.6±65.0 °C(Predicted) | [density ]
1.50±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C, stored under nitrogen | [solubility ]
Chloroform: 30 mg/ml | [form ]
A crystalline solid | [pka]
3.33±0.10(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory activity, and exhibits anxiolytic and cognition-enhancing effects[1]. | [in vivo]
GSK356278 (0.003-30 mg/kg; p.o.) shows anti-inflammatory activity in rodents at exposures that does not induce pica feeding[1].
GSK356278 (0.1-0.1 mg/kg; p.o.) demonstrates efficacy in a nonhuman primate model of anxiety at exposures that do not induce emesis[1].
GSK356278 (4 doses at 0.03, 0.1, 0.3, and 1.0 mg/kg for 6 weeks; p.o.) enhances performance in a nonhuman primate object retrieval test[1]. GSK356278 exhibits oral bioavailability (rat 91%, monkey 23%) and Cmax (rat 205, monkey 41 nM) following oral administration (rat 1, monkey 0.2 mg/kg)[1].
GSK356278 exhibits terminal elimination half-lives (rat 2.2, monkey 1.5 h) due to moderate blood clearance (rat 40, monkey 16 mL/min/kg) combined with volumes of distribution (rat 6.3, monkey 2.1 L/kg) following intravenous administration (rat 1, monkey 0.2 mg/kg)[1]. | Animal Model: | Male Lewis rats (320-400 g) are treated with lipopolysaccharide (LPS)[1] | | Dosage: | 0.003-3 mg/kg | | Administration: | P.o. administration 30 minutes prior to the LPS challenge | | Result: | Reduced the level of neutrophilia in a dose-dependent manner, with an ED50 of 0.09 mg/kg. |
| Animal Model: | Male CD rats[1] | | Dosage: | 1 mg/kg (Pharmacokinetic Analysis) | | Administration: | I.v. and p.o. administration | | Result: | Oral bioavailability (91%), Cmax (205 nM), T1/2 (2.2 h). |
| [IC 50]
PDE4A: 8.6 (pIC50); PDE4B: 8.8 (pIC50); PDE4D: 8.7 (pIC50) | [References]
[1] Rutter AR, et, al. GSK356278, a potent, selective, brain-penetrant phosphodiesterase 4 inhibitor that demonstrates anxiolytic and cognition-enhancing effects without inducing side effects in preclinical species. J Pharmacol Exp Ther. 2014 Jul;350(1):153-63. DOI:10.1124/jpet.114.214155 |
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