| Identification | Back Directory | [Name]
2,8-Diazaspiro[4.5]decan-1-one, 2-(2,5-dihydro-4-methyl-5-oxo-3-furanyl)-8-[(2R)-2-(1,3-dihydro-4-methyl-1-oxo-5-isobenzofuranyl)-2-hydroxyethyl]- | [CAS]
1548286-45-8 | [Synonyms]
2,8-Diazaspiro[4.5]decan-1-one, 2-(2,5-dihydro-4-methyl-5-oxo-3-furanyl)-8-[(2R)-2-(1,3-dihydro-4-methyl-1-oxo-5-isobenzofuranyl)-2-hydroxyethyl]- | [Molecular Formula]
C24H28N2O6 | [MOL File]
1548286-45-8.mol | [Molecular Weight]
440.49 |
| Hazard Information | Back Directory | [Uses]
MK-8153 is a potent, selective and orally active inhibitor of renal outer medullary potassium channel (ROMK), with IC50s of 5 nM, 34 μM for ROMK electrophysiology (EP) and hERG EP, respectively. MK-8153 can be used as the diuretic/atriuretic[1]. | [in vivo]
MK-8153 (0.1-10 mg/kg/d, p.o. once daily for 3 days) causes a dose-dependent decrease in systolic blood pressure of aged SHRs. MK-8153 shows diuretic effects in SHRs[1].
MK-8153 (2 mg/kg; p.o.) exhibits terminal elimination half-lives (rat 3.6, dog 9.1, Rhesus 3.3 h), bioavailability (rat 53%, dog ~100%, Rhesus 3.4%), and plasma clearance (rat 29.4, dog 8.7, Rhesus 58.3 mL/min/kg)[1]. | Animal Model: | Aged spontaneously hypertensive rats (SHRs)[1] | | Dosage: | 0.1, 0.3, 1, 3, 10 mg/kg | | Administration: | P.o. once daily for 3 days | | Result: | Observed the maximal lowering of systolic blood pressure (～24 mm Hg) by day 3 at the 3 mg/kg.
Dose-dependently increased the sodium excretion.
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| [References]
[1] Jiang J, et, al. Discovery of MK-8153, a Potent and Selective ROMK Inhibitor and Novel Diuretic/Natriuretic. J Med Chem. 2021 May 26. DOI:10.1021/acs.jmedchem.1c00406 |
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