862119-82-2

Usage

Uses

Used in Pharmaceutical Industry:
(2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate is used as a potential drug candidate for the treatment of various diseases and medical conditions due to its structural features and functional groups. Its specific stereochemistry and arrangement of constituent groups make it a valuable molecule for further research and development in the pharmaceutical field.

Upstream product

• 259214-54-5 (trans)-ethyl 1-amino-2-vinylcyclopropanecarboxylate hydrochloride 
• 13726-69-7 (2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid 
• 259214-54-5 ethyl (1R,2S)-1-amino-2-vinylcyclopropanecarboxylate hydrochloride 
• 746657-36-3 (1R,2S)-ethyl 1-amino-2-vinylcyclopropanecarboxylate 
• 1159609-95-6 (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid ethyl ester tosylate salt 
• 787548-29-2 (1R,2S)/(1S,2R) 1-amino-2-vinylcyclopropane carboxylic acid ethyl ester 
• 40350-82-1 1-(t-butoxycarbonyl)-4-hydroxyproline 
• 213316-32-6 rac-(1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid ethyl ester 
• 213316-49-5 (1RS,2SR)-ethyl 2-vinyl-1-(tert-butoxycarbonylamino)cyclopropanecarboxylate 
• 681807-59-0 (1R,2S)-ethyl 1-(tert-butoxycarbonylamino)-2-vinylcyclopropanecarboxylate 
• 1393095-18-5 (E)-ethyl 1-(benzylideneamino)-2-vinylcyclopropanecarboxylate 
• 1023795-84-7 C₂₁H₂₁NO₂ 
• 259217-95-3 N-Boc-(1R,2S)-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester 
• 1072833-34-1 4-fluoro-1,3-dihydro-isoindole-2-carboxylic acid (3R,5S)-1-((S)-2-tert-butoxy-carbonylamino-non-8-enoyl)-5-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidin-3-yl ester 

Downstream Products

• 922732-11-4 (2S,4R)-2-((1R,2S)-1-ethoxycarbonyl-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 922727-89-7 (2S,4S)-2-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-4-(4-nitro-benzoyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 862119-83-3 (1R,2S)-1-[(2S,4R)-(4-hydroxy-pyrrolidine-2-carbonyl)-amino]-2-vinyl-cyclopropanecarboxylic acid ethyl ester 
• 924305-02-2 (1R,2S)-ethyl 1-((2S,4R)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate hydrochloride 
• 1352302-75-0 (2S,4R)-2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)pyrrolidinium chloride 
• 1352302-76-1 (3R,5S)-1-((S)-2-(tert-butoxycarbonylamino)non-8-enoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-nitrobenzoate 
• 1352302-78-3 (2R,6S,14aR,16aS,Z)-15-tert-butyl 14a-ethyl 6-(tert-butoxycarbonylamino)-2-(4-nitrobenzoyloxy)-5,16-dioxo-2,3,5,6,7,8,9,10,11,13a,14,14a,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a,15(1H)-dicarboxylate 
• 1352302-80-7 (2R,6S,13aS,14aR,16aS,Z)-14a-(ethoxycarbonyl)-2-(4-nitrobenzoyloxy)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-aminium 4-methylbenzenesulfonate 
• 1352302-81-8 (2R,6S,13aS,14aR,16aS,Z)-ethyl 6-(5-methylisoxazole-3-carboxamido)-2-(4-nitrobenzoyloxy)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate 
• 552335-44-1 (1R,2S)-ethyl 1-((2S,4R)-1-((S)-2-(((tert-butoxy)carbonyl)amino)non-8-enoyl)-4-hydroxypyrrolidine-2-carboxamido)-2-vinylcyclopropanecarboxylate 
• 922726-51-0 4-nitro-benzoic acid (3S,5S)-5-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidin-3-yl ester 
• 922726-52-1 4-nitro-benzoic acid (3S,5S)-5-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-1-(hex-5-enyl-methyl-carbamoyl)-pyrrolidin-3-yl ester 
• 923274-86-6 18-hydroxy-14-(4-methoxy-benzyl)-2,15-dioxo-3,14,16-triaza-tricyclo-[14.3.0.0*4,6*]nonadec-7-ene-4-carboxyric acid ethyl ester 
• 923274-85-5 4-nitro-benzoic acid (3S,5S)-5-((1R,2S)-1-ethoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-1-[hept-6-enyl-(4-methoxy-benzyl)-carbamoyl]-pyrrolidin-3-yl ester 

Relevant academic research and scientific papers

Discovery of danoprevir (ITMN-191/R7227), a highly selective and potent inhibitor of hepatitis C virus (HCV) NS3/4A protease

HCV serine protease NS3 represents an attractive drug target because it is not only essential for viral replication but also implicated in the viral evasion of the host immune response pathway through direct cleavage of key proteins in the human innate im

MACROCYCLIC INHIBITORS OF HEPATITIS C PROTEASE

The invention provides macrocyclic compounds inhibitory to the Hepatitis C viral protease, compositions and combinations including the compounds, methods of treatment of conditions wherein inhibition of the Hepatitis C viral protease is medically indicated, and methods of treatment of a Hepatitis C viral infection in a human patient.

Macrocylic Inhibitors of Hepatitis C Virus

Compounds of the formula I: and N-oxides, salts, and stereoisomers thereof wherein A is OR1, NHS(═O)pR2; wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl;R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl;p is independently 1 or 2;n is 3, 4, 5 or 6; — denotes an optional double bond;L is N or CRz; Rz is H or forms a double bond with the asterisked carbon;Rq is H or when L is CRz, Rq can also be C1-C6alkyl;Rr is quinazolinyl, optionally substituted with one two or three substituents each independently selected from C1-C6 alkyl, C1-C6alkoxy, hydroxyl, halo, haloC1-C6alkyl, amino, mono- or dialkylamino, mono- or dialkylaminocarbonyl, C1-C6alkyl-carbonylamino, C0-C3alkylenecarbocyclyl and C0-C3 alkyleneheterocyclyl;R5 is hydrogen, C1-C6alkyl, C1-C6alkoxyC1-C6alkyl or C3-C7cycloalkyl;R6 is hydrogen, C1-C6alkyl, C1-C6alkoxy, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl, hydroxy, bromo, chloro or fluoro have utility in the treatment or prophylaxis of flaviviral infections such as HCV

Macrocyclic Inhibitors of Hepatitis C Virus

Compounds of the formula (I): and N-oxides, salts and stereoisomers thereof wherein A is OR1, NHS(═O)pR2, NHR3, NRaRb, C(═O)NHR3 or C(═O)NRaRb wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl; R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl or NRaRb; R3 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl, —OC1-C6alkyl, —OC0-C3alkylenecarbocyclyl, —OC0-C3alkyleneheterocyclyl; wherein any alkyl, carbocyclyl or heterocycylyl in R1, R2 or R3 are optionally substituted p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; Rq is H or when L is CRz, Rq can also be C1-C6alkyl; Ry and Ry′ are independently C1-C6alkyl; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; W is —CH2—, —O—, —OC(═O)NH—, —OC(═O)—, —S—, —NH—, —NRa, —NHS(═O)2—, —NHC(=0)NH— or —NHC(═O)—, —NHC(═S)NH— or a bond; R8 is an optionally substituted ring system containing 1 or 2 saturated, partially saturated or unsaturated carbo or heterocyclic rings have utility in the inhibition of NS-3 serine proteases, such as flavivirus infections.

Process for the preparation of a macrocycle

The present invention relates to a new process for the preparation of macrocyclic HCV protease inhibitor compounds of the formula wherein R1 is an amino protecting group and X is halogen by way of a ring closing metathesis approach.

Inhibitors of Hepatitis C Virus

Macrocyclic peptides are disclosed having the general formula: wherein R3, R3′, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

Inhibitors of Hepatitis C Virus

Macrocyclic peptides are disclosed having the general formula: wherein R3, R′3, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS

Macrocyclic peptides having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

Process for the preparation of macrocyclic compounds

The present invention relates to a new process for the preparation of diene compounds of the formula I wherein R1 is an amino protecting group and X is a halogen atom which may serve as intermediates for the manufacture of macrocyclic HCV protease inhibitors.

Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors

Starting from the previously reported HCV NS3/4A protease inhibitor BILN 2061 (1), we have used a fast-follower approach to identify a novel series of HCV NS3/4A protease inhibitors in which (i) the P3 amino moiety and its capping group have been truncated, (ii) a sulfonamide is introduced in the P1 cyclopropyl amino acid, (iii) the position 8 of the quinoline is substituted with a methyl or halo group, and (iv) the ring size of the macrocycle has been reduced to 14 atoms. SAR analysis performed with a limited set of compounds led to the identification of N-{17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin-4-yloxy]-2,14-dioxo-3,15-diazatricyclo [13.3.0.0 [Bartenschlager, R.; Lohmann, V. J. Gen. Virol. 2000, 81, 1631; Vincent Soriano, Antonio Madejon, Eugenia Vispo, Pablo Labarga, Javier Garcia-Samaniego, Luz Martin-Carbonero, Julie Sheldon, Marcelle Bottecchia, Paula Tuma, Pablo Barreiro Expert Opin. Emerg. Drugs, 2008, 13, 1-19]]octadec-7-ene-4-carbonyl}(1-methylcyclopropyl)(1-methylcyclopropyl)sulfonamide 19l an extremely potent (Ki = 0.20 nM, EC50 = 3.7 nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor, which has features attractive for further preclinical development.