ベクラブビル化学構造式

ベクラブビル

化学名:ベクラブビル

CAS番号.958002-33-0

英語名:Beclabuvir

CBNumberCB12717749

MFC36H45N5O5S

MW659.84

MOL File958002-33-0.mol

别名

ベクラブビル

(2S,4R)-N-(ジメチルスルファモイル)-18-メトキシ-4-[[(1R,5S)-3-メチル-3,8-ジアザビシクロ[3.2.1]オクタン-8-イル]カルボニル]-6-アザペンタシクロ[13.4.0.02,4.06,14.07,12]ノナデカン-1(19),7,9,11,13,15,17-ヘプタエン-9-カルボアミド

(8S,10R)-N-(ジメチルスルファモイル)-5-メトキシ-10-[(1R,5S)-3-メチル-3,8-ジアザビシクロ[3.2.1]オクタン-8-カルボニル]-12-アザペンタシクロ[10.7.0.02,7.08,10.013,18]ノナデカ-1(19),2,4,6,13,15,17-ヘプタエン-15-カルボキサミド

ベクラブビル物理性質

比重(密度)	1.45±0.1 g/cm3(Predicted)
貯蔵温度	Store at -20°C
溶解性	DMSO:30.0(Max Conc. mg/mL);45.46(Max Conc. mM)
外見	Solid
酸解離定数(Pka)	4.44±0.40(Predicted)
色	White to off-white

ベクラブビル化学特性,用途語,生産方法

効能
抗ウイルス薬, NS5Bポリメラーゼ阻害薬
説明
Beclabuvir is a non-nucleoside, nonstructural protein 5B (NS5B) polymerase inhibitor approved in Japan as part of a fixed-dose combination product for the treatment of hepatitis C virus (HCV). Upon administration and after intracellular uptake, the drug binds to the allosteric, noncatalytic “Thumb 1” site of NS5B resulting in a decreased rate of viral RNA synthesis and replication.4 Beclabuvir is combined with asunaprevir and declatasvir (both approved in 2014) and was discovered and developed by Bristol-Myers Squibb.
合成
The syntheses of asunaprevir and declatasvir were described in an earlier review article.Condensation of indole-6-carboxylic acid (1) with cyclohexanone under basic conditions gave acid 2 in quantitative yield. Hydrogenation of the double bond in 2 using Pearlman?ˉs catalyst was followed by esterification to give ester 3 in high yield. Bromination of the indole at the 2-position was accomplished with pyridinium tribromide, and this was followed by saponification to provide acid 4. Treatment of 4 with carbonyldiimidazole (CDI) followed by N,N- dimethylsulfamide and 1, 8 - diazabicyclo[5.4.0]undec-7-ene (DBU) gave compound 5 in 74% yield. Suzuki coupling of 5 with commercial boronic acid 6 provided intermediate 7, which converted to hemiaminal 8 upon continued heating in 61% yield. Compound 8 was then treated with methyl 2-(dimethoxyphosphoryl)acrylate (9) to affect a tandem conjugate addition and Horner?Wadsworth? Emmons (HWE) olefination to give ester 10. Alternatively, the Suzuki coupling reaction of 5 with 6 could be stopped at intermediate 7, which could be treated with 9 to promote the tandem conjugate addition/HWE to give 10. Corey?-Chaykovsky cyclopropanation of 10 using sodium hydride and trimethylsulfoxonium iodide followed by chiral separation provided cyclopropane 11 in good yield and >99% enantiomeric excess (ee). Saponification of the methyl ester of 11 followed by coupling with 3-methyl-3,8-diazabicyclo[3.2.1]- octane dihydrochloride (12) gave beclabuvir (I) in high yield.

ベクラブビル生産企業

Send Inquriy

ベクラブビル

ベクラブビル 化学特性,用途語,生産方法

ベクラブビル 生産企業

ベクラブビル化学特性,用途語,生産方法

ベクラブビル生産企業