| Identification | Back Directory | [Name]
Zamicastat | [CAS]
1080028-80-3 | [Synonyms]
Zamicastat
BIA 5-1058
Zamicastat USP/EP/BP
Zamicastat (BIA 5-1058)
2H-Imidazole-2-thione, 1-[(3R)-6,8-difluoro-3,4-dihydro-2H-1-benzopyran-3-yl]-1,3-dihydro-5-[2-[(phenylmethyl)amino]ethyl]- | [Molecular Formula]
C21H21F2N3OS | [MDL Number]
MFCD28502160 | [MOL File]
1080028-80-3.mol | [Molecular Weight]
401.47 |
| Chemical Properties | Back Directory | [Boiling point ]
525.8±60.0 °C(Predicted) | [density ]
1.36±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 150 mg/mL (373.63 mM);Water : < 0.1 mg/mL (insoluble) | [form ]
Solid | [pka]
11.74±0.70(Predicted) | [color ]
White to yellow | [InChIKey]
ZSSLCFLHEFXANG-GOSISDBHSA-N | [SMILES]
C1(=S)N([C@@H]2CC3=CC(F)=CC(F)=C3OC2)C(CCNCC2=CC=CC=C2)=CN1 |
| Hazard Information | Back Directory | [Uses]
Zamicastat (BIA 5-1058) is a dopamine β-hydroxylase (DBH) inhibitor and can cross the blood-brain barrier (BBB) to cause central as well as peripheral effects. Zamicastat is also a concentration-dependent dual P-gp and BCRP inhibitor with IC50 values of 73.8 μM and 17.0 μM, respectively[1]. Zamicastat reduces high blood pressure[2]. | [in vivo]
Zamicastat (10, 30 and 100 mg/kg/day; oral bolus, 7 days) is tested acutely against salt-induced hypertension in the Dahl SS rat. Zamicastat produces a dose-dependent decrease in blood pressure. 24 h after Zamicastat administration mean systolic blood pressure (SBP) decrease is -12.6±4.1 mm Hg (P=0.0284), -15.2±2.7 mm Hg (P=0.0026) and -19.0±3.7 mm Hg (P=0.0036) for the 10, 30, and 100 mg/kg body weight dose, respectively. Zamicastat administration also produces a significant 24-h average decrease in diastolic blood pressure (DBP) of - 14.6±3.4 mm Hg (P=0.0073) with 10 mg/kg body weight dose, -13.0±4.5 mm Hg (P=0.0347) with 30 mg/kg body weight dose and -15.0±3.1 mm Hg (P=0.0046) with 100 mg/kg body weight dose. Zamicastat administration leads to a decrease in the 24h post-dose mean arterial pressure (MAP) of -13.4±3.8 mm Hg (P=0.0162), -14.0±3.5 mm Hg (P=0.0101) and -20.6±3.7 mm Hg (P=0.0026) for the 10, 30, and 100 mg/kg body weight dose, respectively. There is a small, but significant, effect of Zamicastat on the 24-h mean heart rate (HR) post-dose for all tested doses (10 mg/kg: -19.1±3.2 beats/min, P=0.0019; 30 mg/kg: -13.0±4.5 beats/min, P=0.0347; 100 mg/kg: -21.6±6.6 beats/min, P=0.0235)[2]. | Animal Model: | Six-week-old male inbred male Dahl SS rats[2] | | Dosage: | 10, 30, or 100 mg/kg; 4 mL/kg | | Administration: | Oral bolus, daily, seven days | | Result: | Treatment produced a dose-dependent decrease in blood pressure. Twenty four hours after administration mean SBP decrease was -12.6±4.1 mm Hg (P=0.0284), -15.2±2.7 mm Hg (P=0.0026) and -19.0±3.7 mm Hg (P=0.0036) for the 10, 30, and 100 mg/kg body weight dose, respectively. |
| Animal Model: | ten-week-old male Wistar Han rats[2] | | Dosage: | 30 mg/kg/day | | Administration: | in animal feedings (mixed in meal rodent food) everyday | | Result: | lead to a significant 51% decrease in noradrenaline levels excreted in urine |
| [storage]
Store at -20°C | [References]
[1] Bicker J, et al. In vitro assessment of the interactions of dopamine β-hydroxylase inhibitors with human P-glycoprotein and Breast Cancer Resistance Protein. Eur J Pharm Sci. 2018 May 30;117:35-40. DOI:10.1016/j.ejps.2018.02.006
[2] Igreja B, et al. Effects of Zamicastat treatment in a genetic model of salt-sensitive hypertension and heart failure. Eur J Pharmacol. 2019 Jan 5;842:125-132. DOI:10.1016/j.ejphar.2018.10.030 |
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DC Chemicals Gold
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021-58447131 13564518121 |
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www.chemicalbook.com/showsupplierproductslist927327/0_en.htm |
| Company Name: |
InvivoChem
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13549236410 |
| Website: |
https://www.invivochem.cn/ |
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