Asunaprevir

Base Information

• Chemical Name: Asunaprevir
• CAS No.: 630420-16-5
• Deprecated CAS: 1214735-08-6
• Molecular Formula: C35H46ClN5O9S
• Molecular Weight: 748.297
• European Community (EC) Number: 681-328-7
• UNII: S9X0KRJ00S
• ChEMBL ID: CHEMBL2105735
• DSSTox Substance ID: DTXSID201026065
• Metabolomics Workbench ID: 144562
• NCI Thesaurus Code: C114982
• Nikkaji Number: J2.846.989F
• Wikidata: Q4811881
• Wikipedia: Asunaprevir
• Mol file: 630420-16-5.mol

Synonyms:asunaprevir;BMS 650032;BMS-650032

Chemical Property of Asunaprevir

Chemical Property:

• PKA: 4.49±0.40(Predicted)
• PSA: 201.18000
• Density: 1.37
• LogP: 6.75750
• Storage Temp.: -20°C Freezer, Under inert atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated)
• XLogP3: 4.9
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 14
• Exact Mass: 747.2704769
• Heavy Atom Count: 51
• Complexity: 1470

Purity/Quality:

99%, ^*data from raw suppliers

Asunaprevir ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(C)(C)C(C(=O)N1CC(CC1C(=O)NC2(CC2C=C)C(=O)NS(=O)(=O)C3CC3)OC4=NC=C(C5=C4C=C(C=C5)Cl)OC)NC(=O)OC(C)(C)C
• Isomeric SMILES: CC(C)(C)[C@@H](C(=O)N1C[C@@H](C[C@H]1C(=O)N[C@@]2(C[C@H]2C=C)C(=O)NS(=O)(=O)C3CC3)OC4=NC=C(C5=C4C=C(C=C5)Cl)OC)NC(=O)OC(C)(C)C
• Recent ClinicalTrials: Phase III China GT 1b Interferon (IFN) Intolerant Prev Exclude Dual
• Recent EU Clinical Trials: Effect of ASV and DCV therapy on the quality of immune status in chronic HCV patients
• Recent NIPH Clinical Trials: Post-marketing, prospective and non-randomized trial regarding to daclatasvir and asunaprevir combination therapy for chronic liver disease with genotype 1 hepatitis C virus
• Description: Sold under the trade name Sunvepra?, asunaprevir received approval in Japan as part of a combination treatment for the hepatitis C virus (HCV). Working in concert with daclatasvir (IX) (vide infra), asunaprevir is a unique treatment for HCV, as it is free from both interferon and ribavirin and is administered orally. This direct-acting anti-viral, which was developed by Bristol–Myers Squibb (BMS), works as an NS3/4A protease inhibitor, representing a valuable treatment option for patient populations who are unable to receive, or do not respond to, the standard course of treatment—peginterferon/ribavirin. Asunaprevir is an inhibitor of the hepatitis C non-structural 3/4A serine protease, which is required for viral replication. It is a direct-acting inhibitor of hepatitis C virus (HCV). It is commonly used in combination with daclatasvir and beclabuvir, which are also direct-acting HCV inhibitors.
• Uses: Asunaprevir is an inhibitor of the viral enzyme serine protease HCV NS3. Also functions as a second generation NS3/4A protease inhibitor used in the treatment of hepatitis C.

Technology Process of Asunaprevir

There total 18 articles about Asunaprevir which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 94.0%

(2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide dihydrochloride + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → tert-butyl ((S)-1-((2S,4R)-4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)carbamate (630420-16-5)

Guidance literature:

With O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20 ℃;

Reference yield: 94.0%

N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) + (2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide hydrochloride → tert-butyl ((S)-1-((2S,4R)-4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)carbamate (630420-16-5)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 0 - 20 ℃; for 16h;

Reference yield: 94.0%

(2S,4R)-tert-butyl 4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-2-(((1R,2S)-1-((cyclopropylsulfonyl)-carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidine-1-carboxylate (1028252-17-6) + N-tert-butyloxycarbonyl-L-tert-leucine (62965-35-9) → tert-butyl ((S)-1-((2S,4R)-4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)carbamate (630420-16-5)

Guidance literature:

With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 20 ℃; for 16h; Inert atmosphere;

DOI:10.1021/jm500297k

upstream raw materials:

(2S,4R)-4-((7-chloro-4-methoxyisoquinolin-1-yl)oxy)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide hydrochloride

N-tert-butyloxycarbonyl-L-tert-leucine

(2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yloxy)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)pyrrolidine-2-carboxamide

diphenyl phosphoryl azide

Refernces

• 1、 -. "TRIPEPTIDES INCORPORATING DEUTERIUM AS INHIBITORS OF HEPATITIS C VIRUS". . . Retrieved 2013/02/27.
• 2、 -. "CRYSTALLINE FORMS OF N-(TERT-BUTOXYCARBONYL)-3-METHYL-L-VALYL-(4R)-4-((7-CHLORO-4-METHOXY-1-ISOQUINOLINYL)OXY)-N-((1R,2S)-1-((CYCLOPROPYLSULFONYL)CARBAMOYL)-2-VINYLCYCLOPROPYL)-L-PROLINAMIDE". Page/Page column 25; 26-27. . Retrieved 2009/08/14.