Welcome to LookChem.com Sign In|Join Free

CAS

  • or

1535212-07-7

Post Buying Request

1535212-07-7 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

1535212-07-7 Usage

Appearance

off-white solid

Mechanism of Action

Voxilaprevir is an orally bioavailable inhibitor of the hepatitis C virus (HCV) non-structural protein 3/non-structural protein 4A (NS3/NS4A) serine protease, with antiviral activity. Upon administration, voxilaprevir binds to the HCV NS3/NS4A serine protease and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts both the processing of viral proteins and the formation of the viral replication complex, thereby preventing viral replication and function. NS3, a serine protease, is essential for the proteolytic cleavage of multiple sites within the HCV polyprotein and plays a key role during HCV ribonucleic acid (RNA) replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family; HCV infection is associated with the development of hepatocellular carcinoma (HCC).

Uses

Voxilaprevir(GS9857) is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor (by Gilead) that is used in combination with sofosbuvir and velpatasvir. The combination has the trade name Vosevi and received a positive opinion from the European Committee for Medicinal Products for Human Use in June 2017. On 18 July 2017, Vosevi was approved by the US Food and Drug Administration. Voxilaprevir is a new chemical entity recently approved in a fixed-dose combination with sofosbuvir1,2 and velpatasvir.3 Like glecaprevir and grazoprevir, voxilaprevir inhibits the NS3/4A protease involved in viral replication. Sofosbuvir is an NS5B nucleotide polymerase inhibitor and velpatasvir is an NS5A inhibitor.

Application

Voxilaprevir is a Direct-Acting Antiviral (DAA) medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients. Voxilaprevir exerts its antiviral action by reversibly binding and inhibiting the NS3/4A serine protease of Hepatitis C Virus (HCV). Following viral replication of HCV genetic material and translation into a single polypeptide, Nonstructural Protein 3 (NS3) and its activating cofactor Nonstructural Protein 4A (NS4A) are responsible for cleaving genetic material into the following structural and nonstructural proteins required for assembly into mature virus: NS3, NS4A, NS4B, NS5A, and NS5B. By inhibiting viral protease NS3/4A, voxilaprevir therefore prevents viral replication and function. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as voxilaprevir. Voxilaprevir has been available since July 2017 in a fixed dose combination product with [sofosbuvir] and [velpatasvir] as the commercially available product Vosevi. Vosevi is approved for the treatment of adult patients with chronic HCV infection with genotype 1, 2, 3, 4, 5, or 6 infection. Notably, Vosevi is approved for use in patients with genotypes 1-6 who have been previously treated with an NS5A inhibitor, or patients with genotypes 1a or 3 infection and have previously been treated with an HCV regimen containing sofosbuvir without an NS5A inhibitor. Prior to Vosevi, there were no approved retreatment options for patients who have previously received, and failed, a regimen containing an NS5A inhibitor for treatment of chronic HCV infection.

Check Digit Verification of cas no

The CAS Registry Mumber 1535212-07-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,5,3,5,2,1 and 2 respectively; the second part has 2 digits, 0 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 1535212-07:
(9*1)+(8*5)+(7*3)+(6*5)+(5*2)+(4*1)+(3*2)+(2*0)+(1*7)=127
127 % 10 = 7
So 1535212-07-7 is a valid CAS Registry Number.

1535212-07-7SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 12, 2017

Revision Date: Aug 12, 2017

1.Identification

1.1 GHS Product identifier

Product name Voxilaprevir

1.2 Other means of identification

Product number -
Other names (1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1 R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14- methoxy-3,6-dioxo-1,1a,3,4,5,6,9,1 0,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:1535212-07-7 SDS

1535212-07-7Synthetic route

methyl 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valinate
1026200-25-8

methyl 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valinate

(1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1 R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,1 0,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide
1535212-07-7

(1aR,5S,8S,9S,10R,22aR)-5-tert-butyl-N-[(1 R,2R)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-9-ethyl-18,18-difluoro-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,1 0,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxamide

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1.1: lithium hydroxide monohydrate / water; methanol / 4 h / 60 °C
2.1: sodium periodate; osmium(VIII) oxide / water; tetrahydrofuran / 72 h
3.1: sodium tetrahydroborate / methanol / 6 h / 0 - 20 °C
4.1: ortho-nitrophenyl selenocyanate; tributylphosphine / tetrahydrofuran / 0.42 h / 0 - 20 °C
4.2: 2 h / 0 - 60 °C
5.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 20 °C
6.1: 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene[2-(iso-propoxy)-5-(N,N-dimethylaminosulfonyl)phenyl]methylene ruthenium(II) dichloride / 1,2-dichloro-ethane / 1.33 h / 100 °C / Inert atmosphere
7.1: palladium 10% on activated carbon; hydrogen / ethanol / 2.5 h / 760.05 Torr
8.1: trifluoroacetic acid / dichloromethane / 3 h / 20 °C
9.1: N-ethyl-N,N-diisopropylamine; HATU; dmap / N,N-dimethyl-formamide / 0.67 h / 20 °C
View Scheme

1535212-07-7Downstream Products

1535212-07-7Relevant articles and documents

Discovery of the pan-genotypic hepatitis C virus NS3/4A protease inhibitor voxilaprevir (GS-9857): A component of Vosevi

Taylor, James G.,Zipfel, Sheila,Ramey, Kyla,Vivian,Schrier, Adam,Karki, Kapil K.,Katana, Ashley,Kato, Darryl,Kobayashi, Tetsuya,Martinez,Sangi, Michael,Siegel, Dustin,Tran, Chinh V.,Yang, Zheng-Yu,Zablocki, Jeff,Yang, Cheng Y.,Wang,Wang,Chan,Barauskas, Ona,Cheng, Guofeng,Jin, Debi,Schultz, Brian E.,Appleby, Todd,Villase?or, Armando G.,Link, John O.

, p. 2428 - 2436 (2019/05/29)

Treatment of hepatitis C virus (HCV) infection has been historically challenging due the high viral genetic complexity wherein there are eight distinct genotypes and at least 86 viral subtypes. While HCV NS3/4A protease inhibitors are an established treatment option for genotype 1 infection, limited coverage of genotypes 2 and/or 3 combined with serum alanine transaminase (ALT) elevations for some compounds has limited the broad utility of this therapeutic class. Our discovery efforts were focused on identifying an NS3/4A protease inhibitor with pan-genotypic antiviral activity, improved coverage of resistance associated substitutions, and a decreased risk of hepatotoxicity. Towards this goal, distinct interactions with the conserved catalytic triad of the NS3/4A protease were identified that improved genotype 3 antiviral activity. We further discovered that protein adduct formation strongly correlated with clinical ALT elevation for this therapeutic class. Improving metabolic stability and decreasing protein adduct formation through structural modifications ultimately resulted in voxilaprevir. Voxilaprevir, in combination with sofosbuvir and velpatasvir, has demonstrated pan-genotypic antiviral clinical activity. Furthermore, hepatotoxicity was not observed in Phase 3 clinical trials with voxilaprevir, consistent with our design strategy. Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) is now an approved pan-genotypic treatment option for the most difficult-to-cure individuals who have previously failed direct acting antiviral therapy.

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 1535212-07-7