923604-56-2

Usage

Uses

Used in Pharmaceutical Industry:
(1R,2S)-2-Ethenyl-1-[[[(1R,2R,4R)-2-[(5-hexen-1-ylmethylamino)carbonyl]-4-[[7-methoxy-8-methyl-2-[4-Isopropyl-thiazol-2-yl]-quinolin-4-yl]oxy]cyclopentyl]carbonyl]amino]cyclopropane-carboxylic acid ethyl ester is used as a pharmaceutical compound for its potential biological activity due to its complex structure and the presence of various functional groups and heterocyclic compounds.
Used in Research and Development:
(1R,2S)-2-Ethenyl-1-[[[(1R,2R,4R)-2-[(5-hexen-1-ylmethylamino)carbonyl]-4-[[7-methoxy-8-methyl-2-[4-Isopropyl-thiazol-2-yl]-quinolin-4-yl]oxy]cyclopentyl]carbonyl]amino]cyclopropane-carboxylic acid ethyl este is also used in research and development for studying its chemical properties, potential interactions with biological systems, and possible applications in drug discovery and design. Its unique structure makes it an interesting candidate for exploring new therapeutic approaches and understanding its mechanism of action.

Upstream product

• 922727-93-3 (1R,2S)-1-{[(1R,2R,4S)-2-(hex-5-enyl-methyl-carbamoyl)-4-hydroxy-cyclopentanecarbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester 
• 923289-21-8 8-methyl-2-[4-(1-methylethyl)-1,3-thiazol-2-yl]-7-(methyloxy)-4-quinolinol 
• 862259-02-7 trans-(3R,4R)-3,4-bis(methoxycarbonyl)cyclopentanol 
• 55863-02-0 N-methylhex-5-en-1-amine 
• 1333964-94-5 (1R,2R,4R)-2-[[(1R,2S)-1-(ethoxycarbonyl)-2-vinyl-cyclopropyl]carbamoyl]-4-[[2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4-quinolinyl]oxy]cyclopentanecarboxylic acid 
• 1703-61-3 racemic trans-cyclopentanone-3,4-dicarboxylic acid 
• 35079-19-7 trans-(1R,2R)-1,2-Bis(methoxycarbonyl)-4-oxocyclopentane 
• 1333964-81-0 benzyl methyl (1R,2R,4R)-4-hydroxy-1,2-cyclopentanedicarboxylate 
• 1333964-84-3 benzyl methyl (1R,2R,4S)-4-([2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4-quinolinyl]oxy)-1,2-cyclopentanedicarboxylate 
• 1333964-85-4 (1R,2R,4R)-4-[[2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4-quinolinyl]oxy]-2-(methoxycarbonyl)cyclopentanecarboxylic acid 
• 1333964-92-3 methyl (1R,2R,4R)-2-[[(1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropyl]carbamoyl]-4-[[2-(4-isopropyl-1,3-thiazol-2-yl)-7-methoxy-8-methyl-4-quinolinyl]oxy]cyclopentanecarboxylate 
• 862174-60-5 (1R,4R,5R)-3-oxo-2-oxabicyclo[2.2.1]heptane-5-carboxylic acid 
• 1703-61-3 rac-4-oxocyclopentane-1,2-dicarboxylic acid 
• 1042695-84-0 methyl (1R,2R,4R)-2-[5-hexen-1-yl-(methyl)carbamoyl]-4-hydroxycyclopentanecarboxylate 

Downstream Products

• 923604-58-4 (2R,3aR,10Z,11aS,12aR,14aR)-2-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-5-methyl-4,14-dioxo-2,3,3a,4,5,6,7,8,9,11a,12,13,14,14a-tetradecahydrocyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)-carboxylic acid 
• 923604-59-5 simeprevir 
• 923604-57-3 2,3,3a,4,5,6,7,8,9,11a,12,13,14,14a-tetradecahydro-2-[[7-methoxy-8-methyl-2-[4-10(1-methylethyl)-2-thiazolyl]-4-quinolinyl]oxy]-5-methyl-4,14-dioxo-(2R,3aR,10Z,11aS,2aR,14aR)-cyclopenta[c]cyclopropa[g][1,6]diazacyclotetradecine-12a(1H)-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

Ring-Closing Metathesis on Commercial Scale: Synthesis of HCV Protease Inhibitor Simeprevir

The key macrocyclization step in the synthesis of simeprevir, a hepatitis C virus (HCV) antiviral drug, was studied. N-Boc substitution on the diene precursor changes the site of insertion of the metathesis catalyst and, consequently, the kinetic model of the ring closing metathesis (RCM), enabling a further increase in the macrocyclization efficiency under simulated high dilution (SHD) conditions. NMR of the inserted species of both first and second generation RCM catalysts are reported and discussed.

PROCESSES AND INTERMEDIATES FOR PREPARING A MACROCYCLIC PROTEASE INHIBITOR OF HCV

A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-(-)- ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-(-)-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-(-)-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis- (1R,2S)-(-)-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-(-)-ephedrine from the precipitated salt obtained in step (b).

PROCESSES AND INTERMEDIATES FOR PREPARING A MACROCYCLIC PROTEASE INHIBITOR OF HCV

The present invention relates to synthesis procedures and intermediates of a compound offormula: (XVII) and the salts thereof.

HCV INHIBITING MACROCYCLIC PHOSPHONATES AND AMIDOPHOSPHATES

Inhibitors of HCV replication of Formula (I) the /V-oxides, salts, and stcreochcmically isomeric forms thereof; pharmaceutical compositions containing compounds (1) and processes for preparin compounds (I). The side chain R2 is an amidophosphate or a phosphonate group and X, R1, R3, E and n are as defined in the application.

Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350

SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]- 13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamid e (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics.

MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS

Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is -OR7, -NH-SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents ; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.