ミラベグロン 化学特性,用途語,生産方法
用途
ミラベグロンの効能?効果は「過活動膀胱における尿意切迫感、頻尿および切迫性尿失禁」であり、膀胱の排尿筋に存在するアドレナリンβ3受容体に作用し、膀胱平滑筋を弛緩させて膀胱容積を増加させる。
ミラベグロンは近年、褐色脂肪細胞の活性化と代謝増進作用を有することが発見された。
効能
過活動膀胱用薬, β3アドレナリン受容体作動薬
商品名
ベタニス (アステラス製薬)
説明
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 EC
50 of 22 nM (intrinsic activity=0.8) for β3-AR with no detectable activity for β1- andβ2-AR (EC
50>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.
化学的特性
White to Off-White Solid
使用
Potent bladder relaxant and reagent for diabetes remedy.;Labeled Mirabegron, intended for use as an internal standard for the quantification of Mirabegron by GC- or LC-mass spectrometry.
定義
ChEBI: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 2-amino-1,3-thiazol-4-ylacetic acid with the anilino group of (1R)-2-{[2-(4-aminophenyl)ethyl]amino}-1-phenylethanol. Used for the treatment of overactive
ladder syndrome.
臨床応用
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.
ミラベグロン 上流と下流の製品情報
原材料
準備製品