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Mirabegron 223673-61-8 Selective β 3-adrenergic receptor agonist
Product Specification
| Appearance: | White or almost white crystalline powder |
| Identification: | The retention time ofthe main peak should beconsistent with the RS、The infrared absorption spectrum is concordant withthat of RS |
| Related substances： | Impurity D≤0.15%、Unspecified impurities≤0.10%、Total impurities (including impurity B)≤0.2% |
| Enantiomeric purity andimpurity B： | Impurity B≤0.10%、Enantiomeric purity≤0.2% |
| Residual solvents： | Methanol ≤3000ppm、Ethanol ≤5000ppm、Isopropanol ≤5000ppm、Tetrahydrofuran ≤720ppm、Triethylamine≤5000ppm |
| Impurities E, F, G： | Impurity E ≤18ppm、lmpurity F ≤18ppm、Impurity G ≤18ppm |
| Impurity I： | Impurity I ≤18ppm |
| Water： | ≤0.2% |
| Sulfated ash： | ≤0.1% |
| Assay： | 98.0%~102.0%(anhydrous substance) |
description1
PRODUCT DESCRIPTION
Betanis (Mirabegron) was approved in July 2011 by the Japanese Ministry of Health, Labour, and Welfare for the treatment of urgency, urinary frequency, and urinary urge urinary incontinence associated with overactive bladder (OAB). Mirabegron is synthesized by coupling 4-nitrophenethyl amine to (R)-2-hydroxy-2-phenylacetic acid. The resulting amide is reduced to an amine. The nitro group is then reduced and the resulting aniline is coupled to 2-(2-aminothiazol-4-yl) acetic acid to give mirabegron. Mirabegron has an EC50 of 22 nM (intrinsic activity=0.8) for β3-AR with no detectable activity for β1- andβ2-AR (EC50>10,000 nM). In an anesthetized rat rhythmic bladder contraction model in which bladder contractions are induced by saline, mirabegron at 3 mg/kg iv decreased the frequency of rhythmic bladder contraction without suppressing contraction amplitude. These data suggest that the activation of β3-AR increases bladder capacity without influencing the frequency of bladder contraction.
Mirabegron is an orally active β3-adrenoceptor agonist currently in development by Astellas Pharma for the treatment of overactive bladder (OAB). The drug is a nanomolar EC50 antagonist against human β3-AR biochemical assays with good selectivity over b1- and β2-ARs. Mirabegron demonstrates a novel mechanism by targeting the β3-AR for bladder relaxation to help manage OAB symptoms such as increased urinary urgency and frequency and urgency incontinence. However, mirabegron is a cytochrome P450 2D6 inhibitor, and it raises a concern for drug–drug interaction with concomitant administration of other cytochrome P450 2D6 substrates.
Metabolised via multiple pathways involving dealkylation, oxidation, (direct) glucuronidation, and amide hydrolysis. Renal elimination of mirabegron is primarily through active tubular secretion along with glomerular filtration.
Metabolised via multiple pathways involving dealkylation, oxidation, (direct) glucuronidation, and amide hydrolysis. Renal elimination of mirabegron is primarily through active tubular secretion along with glomerular filtration.