| Identification | Back Directory | [Name]
Urea, N-[2-[4-hydroxy-4-(phenylMethyl)-1-piperidinyl]ethyl]-N'-(2-Methyl-4-quinolinyl)- | [CAS]
540769-28-6 | [Synonyms]
Palosuran
ACT 058362
PALOSURAN,, >98%
ACT058362;ACT-058362
ACT 058362; PALOSURAN,
ACT 058362; PALOSURAN,, >98%
1-[2-(4-Benzyl-4-hydroxypiperidin-1-yl)ethyl]-3-(2-methylquinolin-4-yl)urea
N-[2-[4-Hydroxy-4-(phenylmethyl)-1-piperidinyl]ethyl]-N'-(2-methyl-4-quinolinyl)urea
Urea, N-[2-[4-hydroxy-4-(phenylMethyl)-1-piperidinyl]ethyl]-N'-(2-Methyl-4-quinolinyl)- | [Molecular Formula]
C25H30N4O2 | [MDL Number]
MFCD07772352 | [MOL File]
540769-28-6.mol | [Molecular Weight]
418.53 |
| Chemical Properties | Back Directory | [Boiling point ]
612.9±55.0 °C(Predicted) | [density ]
1.235±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 10 mg/ml; DMSO: 10 mg/ml; DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml; Ethanol: 0.5 mg/ml | [form ]
A crystalline solid | [pka]
12.95±0.43(Predicted) | [color ]
White to pink |
| Hazard Information | Back Directory | [Description]
Palosuran is an antagonist of the urotensin II receptor (UTR; IC50s = 3.6 and 1,475 nM for CHO cell membranes expressing human and rat recombinant receptors, respectively).1 It inhibits contraction of isolated rat aortic rings induced by urotensin II (Item Nos. 24711 | 24753) in a concentration-dependent manner. Palosuran (300 mg/kg twice per day) reduces plasma endothelin-1 (Item No. 24127), urotensin II, and TGF-β1 levels, as well as the main pulmonary arterial pressure and right ventricular hypertrophy index in a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (Item No. 16666).2 Palosuran (300 mg/kg per day) reduces serum glucose, cholesterol, and triglyceride levels and increases survival in a rat model of diabetes induced by streptozotocin (STZ; Item No. 13104).3 It also decreases albuminuria and global kidney lesion scores in STZ-induced diabetic rats. | [Uses]
Palosuran (ACT-058362) is a potent, selective, and orally active antagonist of urotensin II receptor, with an IC50 of 3.6 nM for CHO cell membranes expressing human recombinant receptors. Palosuran can improves pancreatic and renal function in diabetic rats[1][2]. | [in vivo]
ACT-058362 (10 mg/kg/h; i.v.) fully prevents the decrease in renal blood flow after ischemia in rats without decreasing blood pressure[1].
Palosuran (300 mg/kg/d; p.o. for 16 weeks) improves the survival, increases insulin, and slows the increase in glycemia, glycosylated hemoglobin, and serum lipids in streptozotocin-induced diabetic rats[2]. | Animal Model: | Male Wistar rats with renal ischemia and reperfusion[1] | | Dosage: | 20 mg/kg/h for 135 min | | Administration: | I.v. (continuous infusion) for 135 min | | Result: | Restored renal blood flow to baseline values at 30 min after reperfusion and by 60 min increased renal blood flow by 12% above baseline values.
Did not significantly alter mean arterial blood pressure (MAP) and heart rate (HR).
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| [References]
[1] Clozel M, et al. Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System. J Pharmacol Exp Ther. 2004 Oct;311(1):204-12. DOI:10.1124/jpet.104.068320
[2] Clozel M, et al. The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1115-21. DOI:10.1124/jpet.105.094821 |
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| Company Name: |
SPIRO PHARMA
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| Tel: |
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| Website: |
www.spiropharma.com.cn |
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