1361028-94-5

Basic information

• Product Name: L-Proline, 4-[(3-chloro-7-Methoxy-2-quinoxalinyl)oxy]-, Methyl ester, (hydrochloride)(1:1),(4R)-
• Synonyms: L-Proline, 4-[(3-chloro-7-Methoxy-2-quinoxalinyl)oxy]-, Methyl ester, (hydrochloride)(1:1),(4R)-;methyl(2S,4R)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-2-carboxylate;EOS-62310;Methyl (2S)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-2-carboxylate hydrochloride
• CAS NO: 1361028-94-5
• Molecular Formula: C₁₅H₁₆ClN₃O₄*ClH
• Molecular Weight: 374.21918
• Mol File: 1361028-94-5.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: L-Proline, 4-[(3-chloro-7-Methoxy-2-quinoxalinyl)oxy]-, Methyl ester, (hydrochloride)(1:1),(4R)-(CAS DataBase Reference)
• NIST Chemistry Reference: L-Proline, 4-[(3-chloro-7-Methoxy-2-quinoxalinyl)oxy]-, Methyl ester, (hydrochloride)(1:1),(4R)-(1361028-94-5)
• EPA Substance Registry System: L-Proline, 4-[(3-chloro-7-Methoxy-2-quinoxalinyl)oxy]-, Methyl ester, (hydrochloride)(1:1),(4R)-(1361028-94-5)

Safety Data

• Hazardous Substances Data: 1361028-94-5(Hazardous Substances Data)

Upstream product

• 31910-18-6 2,3-dioxo-6-methoxy-1,2,3,4-tetrahydroquinoxaline 
• 1263814-66-9 3-chloro-7-methoxyquinoxalin-2(1H)-one 
• 39267-04-4 2,3-dichloro-6-methoxyquinoxaline 
• 96-96-8 4-methoxy-2-nitroaniline 
• 102-51-2 4-methoxy-1,2-phenylenediamine 
• 31910-18-6 2,3-dihydroxy-6-methoxyquinoxaline 
• 59548-39-9 4-methoxyphenylene-1,2-diamine dihydrochloride 
• 1206524-79-9 1-(tert-butyl) 2-methyl (2S,4R)-4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)pyrrolidine-1,2-dicarboxylate 

Downstream Products

• 1350514-68-9 grazoprevir 
• 1206524-84-6 methyl (1aR,5S,8S,10R,22aR)-5-tert-butyl-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxa-diazacyclononadecino[11,12-b]quinoxaline-8-carboxylate 
• 1206524-85-7 (1aR,5S,8S,10R,22aR)-5-tert-butyl-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradeca-hydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxylic acid hydrate 
• 1206524-83-5 methyl (1aR,5S,8S,10R,18E,22aR)-5-tert-butyl-14-methoxy-3,6-dioxo-1,1a,3,4,5,6,9,10,20,21,22,22a-dodecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxylate 
• 1425038-23-8 methyl (1aR,5S,8S,10R,22aR)-5-tert-butyl-14-methoxy-3,6-dioxo-18,19-didehydro-1,1a,3,4,5,6,9,10,20,21,22,22a-dodecahydro-8H-7,10-methanocyclopropa[18,19][1,10,3, 6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxylate 
• 1206524-81-3 (2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate 

Relevant articles and documents

Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants

A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite. In contrast, inhibitors with larger groups at this position were highly susceptible to mutations at Arg155, Ala156, and Asp168. Excitingly, several inhibitors exhibited exceptional potency profiles with EC50 values ≤5 nM against major drug resistant HCV variants. These findings support that inhibitors designed to interact with evolutionarily constrained regions of the protease, while avoiding interactions with residues not essential for substrate recognition, are less likely to be susceptible to drug resistance.

METHODS AND INTERMEDIATES FOR THE PREPARATION OF MACROLACTAMS

The present invention relates to synthetic processes useful in the preparation of macrolactams that inhibit hepatitis C virus (HCV), specifically macrolactam compounds that inhibit the HCV NS3 protease activity and have application in the treatment of conditions caused by HCV. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

MACROCYCLIC AND BICYCLIC INHIBITORS OF HEPATITIS C VIRUS

Compounds of formula (I):or pharmaceutically acceptable salts thereof, wherein the various substituents are defined herein, methods of using said compounds, and pharmaceutical compositions containing said compounds.

Discovery of MK-5172, a macrocyclic hepatitis C virus NS3/4a protease inhibitor

A new class of HCV NS3/4a protease inhibitors containing a P2 to P4 macrocyclic constraint was designed using a molecular modeling-derived strategy. Building on the profile of previous clinical compounds and exploring the P2 and linker regions of the series allowed for optimization of broad genotype and mutant enzyme potency, cellular activity, and rat liver exposure following oral dosing. These studies led to the identification of clinical candidate 15 (MK-5172), which is active against genotype 1-3 NS3/4a and clinically relevant mutant enzymes and has good plasma exposure and excellent liver exposure in multiple species.

Macrocyclic Quinoxaline Compounds as HCV NS3 Protease Inhibitors

The present invention relates to macrocyclic a compound of formula (I) and its use as inhibitors of the hepatitis C virus (HCV) NS3 protease, and in treating or preventing HCV infections.