445305-87-3

Upstream product

• 746657-36-3 (1R,2S)-ethyl 1-amino-2-vinylcyclopropanecarboxylate 
• 259214-37-4 (2S,4R)-1-(tert-butoxycarbonyl)-4-(7-methoxy-2-phenylquinolin-4-yloxy)pyrrolidine-2-carboxylic acid 
• 20430-72-2 7-methoxy-2-phenylquinolin-4-ol 
• 536-90-3 m-Anisidine 
• 94-02-0 ethyl 3-oxo-3-phenylpropionate 
• 74844-91-0 1-tert-butyl 2-methyl (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate 
• 259214-70-5 (2S,4R)-4-(7-Methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester 
• 681807-60-3 (1R,2S)-ethyl 1-amino-2-vinylcyclopropanecarboxylate hydrochloride 
• 259214-54-5 (trans)-ethyl 1-amino-2-vinylcyclopropanecarboxylate hydrochloride 
• 259214-54-5 ethyl (1R,2S)-1-amino-2-vinylcyclopropanecarboxylate hydrochloride 

Downstream Products

• 793661-43-5 1-{[4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid ethyl ester 
• 445306-14-9 1-[[[(2S,4R)-1-[(1,1-dimethylethoxy)carbonyl]-4-[(7-methoxy-2-phenyl-4-quinolinyl)oxy]-2-pyrrolidinyl]carbonyl]amino]-2-ethenyl-(1R,2S)-cyclopropanecarboxylic acid 

Relevant academic research and scientific papers

Hepatitis C Virus Inhibitors

Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.

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.

Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors

A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (Ki = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 μM) inhibitor, displaying an excellent PK profile in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration.

MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS

Inhibitors of HCV replication of formula (I), the N-oxides, salts, and stereochemically isomeric forms thereof, wherein each dashed line (represented by -------) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted on any carbon or nitrogen ring atom with one, two, three, or four substituents; L is a direct bond, -O-. -O-C1-4alkanediyl-, -O-C(=O)-, -O-C(=O)-NR4a- or -O-C(=O)-NR4aC1-4alkanediyl-; R2 is hydrogen, -OR5, -C(O)OR5, -C(=O)R6, -C(=O)NR4aR4b, -C(=O)NHR4c,-NR4aR4b, -NHR4c, -NR4aSOpNR4aR4b, -NR4aSOpR7, or B(OR5)2; R3 is hydrogen, and where X is C or CH, R3 may also be C1-6alkyl; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be 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 each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be 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.

Hepatitis C virus inhibitors

The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which inhibit the function of the NS3 protease (also referred to herein as “serine protease”) encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS3 protease.

Substituted cycloalkyl P1' hepatitis C virus inhibitors

The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.

Potent inhibitors of the hepatitis C virus NS3 protease: Design and synthesis of macrocyclic substrate-based β-strand mimics

The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring β-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.

Hepatitis C virus inhibitors

The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.