223673-61-8 Usage
Description
Mirabegron, also known as Betanis, is a selective β3-adrenoceptor agonist with an EC50 of 22.4 nM. It 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, followed by a series of reduction and coupling reactions. It has no detectable activity for β1and β2-AR (EC50>10,000 nM). Mirabegron is a white to off-white solid and is marketed under the brand name Betanis.
Uses
Mirabegron is used as a potent bladder relaxant compound for the treatment of overactive bladder syndrome. It increases bladder capacity without influencing the frequency of bladder contraction, providing relief from urgency, urinary frequency, and urinary urge urinary incontinence.
Used in Pharmaceutical Industry:
Mirabegron is used as an internal standard for the quantification of Mirabegron by GCor LC-mass spectrometry, aiding in the accurate measurement and analysis of the compound in various applications.
Used in Overactive Bladder Treatment:
Mirabegron is used as a selective β3-adrenoceptor agonist for the treatment of overactive bladder (OAB), helping to manage symptoms such as urgency, urinary frequency, and urinary urge urinary incontinence.
Originator
Astellas Pharma Inc. (Japan)
Clinical Use
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.
Synthesis
The synthesis of mirabegron began with a condensation
reaction between (R)-styrene oxide (182) and 4-nitrophenylethylamine
(183) in refluxing isopropanol to yield corresponding
aminoalcohol 184 in 22% yield. Aminoalcohol 184
was protected as its N-Boc derivative with t-butyl dicarbonate
in THF in 96% yield, and this was followed by nitro group
hydrogenative reduction with 10% Pd/C to give free amine 185
in 96% yield. Aniline 185 was coupled with 2-amino-4-thiazolyl
acetic acid 186 in the presence of EDCI and HOBt to give amide
187 in 85% yield. Removal of the Boc group was affected with
4 N HCl solution in a 2:1 volume ratio in ethyl acetate to obtain
mirabegron HCl in 52% yield. The HCl salt was neutralized with
1 N NaOH to deliver mirabegron (XVII).
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
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.
Check Digit Verification of cas no
The CAS Registry Mumber 223673-61-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,2,3,6,7 and 3 respectively; the second part has 2 digits, 6 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 223673-61:
(8*2)+(7*2)+(6*3)+(5*6)+(4*7)+(3*3)+(2*6)+(1*1)=128
128 % 10 = 8
So 223673-61-8 is a valid CAS Registry Number.
InChI:InChI=1/C21H24N4O2S/c22-21-25-18(14-28-21)12-20(27)24-17-8-6-15(7-9-17)10-11-23-13-19(26)16-4-2-1-3-5-16/h1-9,14,19,23,26H,10-13H2,(H2,22,25)(H,24,27)
223673-61-8Relevant articles and documents
Preparation method of mirabegron key intermediate
-
, (2022/01/12)
The invention provides a preparation method of a mirabegron key intermediate, namely, a compound as shown in a formula (III). The method is simple, convenient and safe to operate, free of harsh reaction conditions, high in reaction purity and yield and low in process cost which is about 40% of that of a process using a metal catalyst such as palladium carbon, is suitable for large-scale production and conforms to the green chemistry principle. A finished product of mirabegron continues to be prepared by using the intermediate compound as shown in the formula (III) prepared by the method so as to meet the existing requirements.
Preparation method of mirabegron (by machine translation)
-
, (2020/08/02)
The method is convenient to operate, controllable in reaction process, high in 2 - final product purity,4 - high in yield and suitable for industrial production, so that a more valuable synthesis route is provided for preparing mirabead, good social benefits and economic benefits can be brought, and the economic value potential is great. (by machine translation)
Preparation method of mirabegron
-
, (2019/04/30)
The invention discloses a preparation method of mirabegron, and the method comprises: S1, carrying out reduction reaction on p-nitrophenylacetonitrile to obtain p-nitrophenylacetaldehyde; S2, carryingout condensation reduction on the p-nitrophenylacetaldehyde and (R) 2-amino-1-phenethyl alcohol to obtain (R) 2-(4-nitrophenethyl) amino)-1-phenyl ethyl alcohol; S3, carrying out reduction on the (R)2-amino-1-phenethyl alcohol to obtain (R) 2-(4-nitrophenethyl) amino)-1-phenyl ethyl alcohol to obtain an intermediate (R) 2-((4-aminophenyl ethyl) amino)-1-phenyl ethyl alcohol; and S4, carrying outcondensation on the (R) 2-((4-aminophenyl ethyl) amino)-1-phenyl ethyl alcohol and aminothiazole acetic acid to obtain the mirabegron. According to the method, the starting raw materials are cheap and easy to obtain, the reaction conditions are controllable, the synthetic route steps are few, the yield is high, the cost is low, and the prepared mirabegron is high in purity.