801282-60-0

Upstream product

• 98-58-8 4-bromobenzenesulfonyl chloride 
• 572922-89-5 (2S,4R)-4-hydroxy-2-[(1R,2S)-1-methoxycarbonyl-2-vinylcyclopropylcarbamoyl]pyrrolidine-1-carboxylic acid tert-butyl ester 
• 572922-91-9 (2S,4S)-4-Hydroxy-2-((1R,2S)-1-methoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 367258-59-1 4-(4-bromobenzenesulfonyloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 
• 681260-04-8 (1R,2S)-1-amino-2-vinyl-cyclopropyl carboxylic acid methyl ester 
• 138-36-3 p-bromobenzene sulfonic acid 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 438452-29-0 1-tert-butyl 2-methyl (2S,4S)-4-{[(4-bromo-phenyl)sulfonyl]oxy}-pyrrolidine-1,2-dicarboxylate 

Downstream Products

• 1309889-22-2 C₃₃H₄₁BrN₆O₉S₂ 
• 1098199-68-8 C₁₈H₂₁BrN₂O₆S*ClH 
• 1309888-72-9 C₃₂H₄₄BrN₃O₉S 
• 861397-55-9 C₃₀H₄₀BrN₃O₉S 
• 1309888-79-6 C₂₉H₃₈BrN₃O₉S 
• 1309888-80-9 C₂₉H₃₆BrN₃O₈S 
• 1309888-81-0 C₃₃H₄₅BrN₄O₁₀S₂ 
• 1309889-23-3 C₂₈H₃₇BrN₄O₈S₂*ClH 
• 769167-58-0 (1S,2R)-1-{[(2S,4S)-4-(4-bromo-benzenesulfonyloxy)-1-((S)-2-cyclopentyloxycarbonylamino-oct-7-enoyl)pyrrolidine-2-carbonyl]-amino}-2-vinylcyclopropanecarboxylic acid methyl ester 
• 879623-40-2 18-(4-bromobenzenesulfonyloxy)-14-cyclopentyloxycarbonylamino-2,15-dioxo-3,16-diaza-tricyclo-[14.3.0.0(4,6)]nonadec-7-ene-4-carboxylic acid methyl ester 
• 1007205-38-0 ciluprevir 
• 874124-85-3 C₂₅H₃₂BrN₃O₉S₂ 

Relevant academic research and scientific papers

Peptide backbone replacement of hepatitis C virus NS3 serine protease C-terminal cleavage product analogs: Discovery of potent succinamide inhibitors

A number of potent peptidic inhibitors of the NS3 protease have been described in the literature based on a substrate-based approach. In an on-going effort to reduce the peptidic character of this class of inhibitors, two novel series of analogs have been

Novel, sulfonamide linked inhibitors of the hepatitis C virus NS3 protease

A sulfonamide replacement of the P2-P3 amide bond in the context of macrocyclic HCV NS3 protease inhibitors was investigated. These analogs displayed good inhibitory potency in the absence of any P3 capping group. The synthesis and preliminary SAR are des

Discovery of hepatitis C Virus NS3-4A protease inhibitors with improved barrier to resistance and favorable liver distribution

Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly improved potency against the key resistant variants and with increased liver partitioning.

A concise synthesis of the HCV protease inhibitor BILN 2061 and its P3 modified analogs

A concise synthesis of BILN 2061 was achieved through more efficient installation of P2 4-quinoline moiety via SN2 displacement of the β-OBs group located on the 4-hydroxyl proline intermediate, which was prepared from 4-α-hydroxyl proline analog via Mitsunobu reaction with inversion of stereochemistry. In addition, a short and practical synthesis for P3 unit is also described herein. Final assembly of four fragments for BILN 2061 was achieved with an overall yield of 58% in 4 steps from P1 to 15a. Furthermore several analogs of BILN 2061 (WX-1-WX-5) containing modifications on P3 unit were synthesized successfully using the same synthetic route as described for the parent inhibitor BILN 2061. Copyright

Hepatitis C inhibitor peptide analogs

Compounds of formula (I): wherein R1, R2, R3, R4, R5, Y, n and m are as defined herein. The compounds are useful as inhibitors of HCV NS3 protease.

HEPATITIS C INHIBITOR DIPEPTIDE ANALOGS

The present invention relates to compounds of formula (I): wherein R1, R2, R4, n and m are as defined herein and R3 is selected from: (i) -C(O)OR31 wherein R31 is (C1-6)alkyl or aryl, wherein the (C1-6)alkyl is optionally substituted with one to three halogen substituents; (ii) -C(O)NR32R33, wherein R32 and R33 are each independently selected form H, (C1-6)alkyl, and Het; (iii) -SOvR34, wherein v is 1 or 2 and R34 is selected from: (C1-6)alkyl, aryl, Het, and NR32R33 wherein R32 and R33 are as defined above; and (iv) -CO(O)-R35, wherein R35 is selected from (C1-8)alkyl, (C3-7)cycloalkyl-(C1-4)alkyl, aryl, aryl-(C1-6)alkyl, Het and Het-(C1-6)alkyl, each of which are optionally substituted with one or more substituents each independently selected from halo, (C1-6)alkyl, (C3-7)cycloalkyl, aryl, Het, hydroxyl, -O-(C1-6)alkyl, -S-(C1-6)alkyl, -SO-(C1-6)alkyl, -SO2-(C1-6)alkyl, -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl, wherein the aryl portion of the -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl are each optionally substituted with one to five halo substituents. The present invention further relates to pharmaceutical compositions containing the compounds of formula (I) and methods for using these analogs in the treatment of HCV infection.