# US 7,608,592 B2 · HCV inhibitors

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- Number: US 7,608,592 B2
- Document ID: US7608592B2
- Status: Granted
- Kind: B2
- Application number: 11/478,337
- Filed: 2006-06-28
- Published: 2007-03-08
- Granted: 2009-10-27
- Earliest claimed: 2005-06-30
- Assignees: ViroBay, Inc.
- Inventors: Michael Graupe; John O. Link; Chandrasekar Venkataramani
- Web page: https://patentgrep.com/patent/US7608592B2

## CPC

- A61K 38/05: Dipeptides
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/14: for RNA viruses
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 5/06034: {the side chain containing 2 to 4 carbon atoms}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention is directed to compounds that are antiviral agents. Specifically the compounds of the present invention inhibit replication of HCV and are therefore useful in treating hepatitis C infections. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

## Claims

### Claim 1

A compound of Formula (I):
wherein
E is —COCONR5R6, —COCF2CONR5R6, —COCF2C(O)OR5, —COCOR7, —COCF2R8, —COR9, or —B(OR13)2 where R5, R6, R7, R9, and each R13 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl and R8 is halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in E are optionally substituted with one, two, or three Ra independently selected from hydroxy, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkenylaminocarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic or alicyclic ring in Ra is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl;
R1 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R1 are optionally substituted with one or two Rb independently selected from hydroxy, alkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic ring in Rb is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, carboxy, or carboxyalkyl;
X is —O—, —NH—, —S—, —SO—, or —SO2—;
R3 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R3 are optionally substituted with one or two Rc independently selected from hydroxy, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic ring in Rc is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl;
Y is —C(O)NH—, —OC(O)NH—, —NR14—C(O)NH—, or —NR14C(O)O— where each R14 is selected from hydrogen, alkyl optionally substituted with halo, hydroxy, alkoxy, amino, monosubstituted amino, disubstituted amino, aryl, heteroaryl or heterocyclyl;
R2 is a group of formula (a):
where
Rd1 is hydrogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkoxy or alkylsulfonyl;
Rd and Rd2 are independently hydrogen, alkyl, halo, alkoxy, alkvlthio, or alkylsulfonyl; or
Rd1 and Rd or Rd1 and Rd2 together with the carbon atoms to which they are attached form a 4, 5, or 6- atom heterocyclyl ring wherein one or two ring atoms are replaced by oxygen or —N— where the heterocyclyl ring is optionally substituted with one or two alkyl;
Rd3 is aryl, heteroaryl, or heterocyclyl optionally substituted with halo, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkoxy, nitro, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkycarbonylamino, alkyloxycarbonylamino, amino, alkylamino, dialkylamino, or —NHCONRR′ where R is hydrogen or alkyl and R′ is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl wherein cycloalkyl and cycloalkylalkyl are optionally substituted with one, two or three alkyl; and
R4 is selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, and heterocyclylalkyl; provided that:
(i) when R4 is alkyl and when Y is —C(O)NH —, then Rd3 is a heteroaryl ring; and
(ii) when R4 is cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl, then Rd3 is a heteroaryl ring;
wherein the aromatic or alicyclic ring in R4 is optionally substituted with one, two, or three Rf independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, carboxyalkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, alkylsulfonyl, alkylcarbonyl, aryl, aralkyl, arylsulfonyl, arylcarbonyl, aryloxycarbonyl, aminosulfonyl, aminocarbonyl, heteroaryl, heteroaralkyl, heteroarylsulfonyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heterocyclyl, heterocyclylalkyl heterocyclylsulfonyl, heterocyclylcarbonyl, heterocyclyloxycarbonyl monosubstituted amino, or disubstituted amino wherein the aromatic ring in Rf is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, carboxy, alkoxycarbonyl, monosubstituted amino, disubstituted amino, or acylamino; or
a pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

The compound of claim 1 wherein:
Rd1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
Rd and Rd2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and Rd3 is a group of formula:
optionally substituted with halo, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkoxy, nitro, amkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkyloxycarbonylaminol amino, alkylamino, dialkylamino, or —NHCONRR′ where R is hydrogen or alkyl and R′ is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl wherein cycloalkyl and cycloalkylalkyl are optionally substituted with one, two or three alkyl.

### Claim 3 (depends on 1)

The compound of claim 1 wherein:
Rd1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
Rd and Rd2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and Rd3 is a group of formula:
optionally substituted with halo, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkoxy, nitro, amkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkyloxycarbonylamino, amino, alkylamino, dialkylamino, or —NHCONRR′ where R is hydrogen or alkyl and R′ is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl wherein cycloalkyl and cycloalkylalkyl are optionally substituted with one, two or three alkyl.

### Claim 4 (depends on 1)

The compound of claim 1 wherein:
Rd1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino;
Rd and Rd2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and Rd3 is a group of formula:
optionally substituted with halo, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkoxy, nitro, amkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkyloxycarbonylamino, amino, alkylamino, dialkylamino, or —NHCONRR′ where R is hydrogen or alkyl and R′ is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl wherein cycloalkyl and cycloalkylalkyl are optionally substituted with one, two or three alkyl.

### Claim 5 (depends on 1, 2, 3)

The compound of any of the claims 1, 2, 3, or 4 wherein Rd3 is optionally substituted with methyl, ethyl, n-propyl, i-propyl, n-butyl, 1-methylpropyl, 2-methylpropyl, tert-butyl, 2,2,-dimethylpropyl, 1,2-dimethylpropyl, 1,2,2-trimethylpropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl.

### Claim 6 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4 wherein Rd3 is optionally substituted with amino, methylamino, ethylamino, propylamino, 1-methylethylamino, 1,1-dimethylethylamino, 2-methylpropylamino, 1-methylpropylamino, 2,2-dimethyipropylamino, 1,2-dimethylpropylamino, 1,1-dimethylpropylamino, methylcarbonylamino, ethylcarbonylamino, propylcarbonylamino, 1-methylethylcarbonylamino, 1,1-dimethylethylcarbonylamino, 2-methyipropylcarbonylamino, 1-methylpropylcarbonylamino, 2,2-dimethylpropylcarbonylamino, 1,2-dimethylpropylcarbonylamino, 1,1-dimethylpropylcarbonylamino, cyclopropylcarbonylamino, cyclobutylcarbonylamino, cyclopentylcarbonylamino, cyclohexylcarbonylamino, cyclopropylmethylcarbonylamino, cyclobutylmethylcarbonylamino, cyclopentylmethylcarbonylamino, cyclohexylmethylcarbonylamino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, 1-methylethoxycarbonylamino, 1,1-dimethyl-ethoxycarbonylamino, 2-methyipropoxycarbonylamino, 1-methyipropoxycarbonylamino, 2,2-dimethyipropoxycarbonylamino, 1,2-dimethylpropoxycarbonylamino, or 1,1-dimethyipropoxy-carbonylamino.

### Claim 7

A compound of Formula (I):
wherein
E is —COCONR5R6, —COCF2CONR5R6, —COCF2C(O)OR5, —COCOR7, —COCF2R8, —COR9, or —B(OR13)2 where R5, R6, R7, R9, and each R13 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl and R8 is halo, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl, or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in E are optionally substituted with one, two, or three Ra independently selected from hydroxy, alkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkenylaminocarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic ring in Ra is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl;
R1 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R1 are optionally substituted with one or two Rb independently selected from hydroxy, alkoxy, aryloxy. heteroaryloxy, alkylthio. arylthio, heteroarvlthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic ring in Rb is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl;
X is —O—, —NH—, —S—, —SO—, or —SO2—;
R3 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R3 are optionally substituted with one or two Rc independently selected from hydroxy, alkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic ring in Rc is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl;
Y is —OC(O)NH—, —NR14—C(O)NH—, or NR14C(O)O—where each R14 selected from hydrogen, alkyl optionally substituted with hydroxy, alkoxy, amino, monosubstituted amino, disubstituted amino, aryl, heteroaryl or heterocyclyl;
R2 is a group of formula (b):
where:
Rd1 is hydrogen, hydroxy, alkoxy, amino, alkylamino, dialkylamino, haloalkoxy or alkylsulfonyl;
Rd and Rd2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; or
Rd1 and Rd or Rd1 and Rd2 together with the carbon atoms to which they are attached form 4, 5, or 6-atom heterocyclyl ring wherein one or two ring atoms are replaced by oxygen or —N— where the heterocyclyl ring is optionally substituted with one or two alkyl;
Rd3 is hydrogen, alkyl, cycloalkyl or cycloalkylalkyl; wherein at least one of Rd, Rd1, Rd2 and R d3 is other than hydrogen; and
R 4 is alkyl;
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The compound of claim 7 wherein Rd1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino; Rd and Rd2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and Rd3 is a hydrogen, alkyl or cycloalkyl.

### Claim 9 (depends on 7)

The compound of claim 7 wherein Rd1 is hydrogen, hydroxy, methoxy, ethoxy, n-propoxy, iso-propoxy, methylamino, ethylamino, n-propylamino, isopropylamino, dimethylamino, methylethylamino, methyl(n-propyl)amino or methyl(isopropyl)amino; and Rd and Rd2 are independently, fluoro, chloro, methyl, methoxy, ethoxy, thiomethyl or methylsulfonyl.

### Claim 10 (depends on 7)

The compound of claim 7 wherein Rd1 is hydrogen, hydroxy, methoxy, or ethoxy; and Rd and Rd2 are independently, hydrogen, fluoro, chloro or methyl.

### Claim 11 (depends on 7)

The compound of claim 7 wherein Rd1 is methoxy or ethoxy; and Rd, Rd2 and Rd3 are each hydrogen.

### Claim 12 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4, wherein X is —O—; R1 is alkyl or cycloalkylalkyl; and R3 is 1-methylethyl, 1 -methylpropyl, tert-butyl, cyclopropyl, phenyl, or cyclohexyl.

### Claim 13 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4 wherein X is —O—; R1 is cyclobutylmethyl, ethyl, or n-propyl; and R3 is tert-butyl or cyclohexyl.

### Claim 14 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4, wherein E is —COCONHR6 where R6 is hydrogen, alkyl, cycloalkyl, aralkyl, or heteroaralkyl wherein the aromatic ring is optionally substituted with one or two halo.

### Claim 15 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4, wherein E is —COCONHR6 where R6 is cyclopropyl.

### Claim 16 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4, wherein Y is —NHC(O)NH— and R4 is alkyl.

### Claim 17 (depends on 1, 2, 3, 4)

The compound of any of the claims 1, 2, 3 or 4, wherein Y is —OC(O)NH— and R4 alkyl.

### Claim 18 (depends on 1, 2, 3)

The compound of any of the claims 1, 2, 3 4, wherein Y is —C(O)NH— and R4 is alkyl.

### Claim 19

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 20

A compound having the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 21

A diastereomeric mixture of compounds represented by the structure:
or a pharmaceutically acceptable salt thereof.

### Claim 22

A compound selected from the group consisting of:
1-[2S-(3-tert-butylureido)-3,3-dimethylbutyryl]-4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-2S-carboxylic acid (1S-cyclopropylaminooxalylbutyl)amide;
1-[2S-(3-tert-butylureido)-3,3-dimethylbutyryl]-4R-(7-methoxy-2-pyrazol-1-yl quinolin-4-yloxy)-pyrrolidine-2-carboxylic acid (1S-cyclobutylmethyl-2-cyclopropylcarbamoyl-2-oxoethyl)amide;
1-[2S-(3-tert-butylureido)-3,3-dimethylbutyryl]-4R-(5-chloropyridin-2-yloxy)-pyrrolidine-2S-carboxylic acid (1S-cyclobutylmethyl-2-cyclopropylcarbamoyl-2-oxoethyl)-amide;
{1S[2S-(1S-cyclopropylaminooxalylbutylcarbamoyl)-4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-1-carbonyl]- 2,2-dimethyipropyl }-carbamic acid tert-butyl ester;
{1S-[2S-( 1 S-cyclopropylaminooxalylbutylcarbamoyl)-4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-1-carbonyl]- 2,2-dimethylpropyl }-carbamic acid tert-butyl ester;
{1S-[4R-(5-chloropyridin-2-yloxy)-2S-(1S-cyclopropylaminooxalylbutyl-carbamoyl)-pyrrolidine-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester;
{1S-[4R-(5-chloropyridin-2-yloxy)-2S-(1S-cyclobutylmethyl-2-cyclopropylcarbamoyl-2-oxo-ethylcarbamoyl)-pyrrolidine-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester; and
1-[2-(3-tert-butylureido)-3,3-dimethyl-butyryl]-4-(5-chloro-pyridin-2-yloxy)-pyrrolidine-2-carboxylic acid (1-cyclopropylaminooxalyl-butyl)-amide.

### Claim 23 (depends on 1, 2, 3, 4)

A pharmaceutical composition comprising a compound of any of the claims 1, 2, 3 or 4, and one or more pharmaceutically acceptable excipients.

### Claim 24 (depends on 1, 2, 3)

A method of treating hepatitis C infections in a patient comprising administering to the patient a pharmaceutical composition comprising a compound of any of the claims 1, 2, 3- or 4, and one or more pharmaceutically acceptable excipients.

### Claim 25 (depends on 1)

The compound of claim 1 which is 1-[2S-(3-tert-butylureido)-3,3-dimethylbutyryl]-4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-2S-carboxylic acid (1S-cyclopropylaminooxalylbutyl)amide; or a pharmaceutically acceptable salt thereof.

### Claim 26

The compound which is 1-[2S-(3-tert-butylureido)-3,3-dimethylbutyryl]-4R-(7-methoxy-2-pyrazol-1-yl-quinolin-4-yloxy)-pyrrolidine-2S-carboxylic acid (1R-cyclopropylaminooxalylbutyl)amide; or the sulfate or methylsulfonate salt thereof.

### Claim 27 (depends on 14)

A pharmaceutical composition comprising a compound of claim 14 and one or more pharmaceutically acceptable excipients.

### Claim 28 (depends on 19)

A pharmaceutical composition comprising a compound of claim 19 and one or more pharmaceutically acceptable excipients.

### Claim 29 (depends on 15)

A method of treating hepatitis C infections in a patient comprising administering to the patient a pharmaceutical composition comprising a compound of claim 15, and one or more pharmaceutically acceptable excipients.

### Claim 30 (depends on 15)

A method of treating hepatitis C infections in a patient comprising administering to the patient a pharmaceutical composition comprising a compound of claim 15, and one or more pharmaceutically acceptable excipients.

### Claim 31

A compound selected from the group consisting of:
1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid(1S-cyclopropylaminooxalyl-butyl)-amide;
1-[2S-(3tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid(2-cyclopropylcarbamoyl-1S-cyclopropylmethyl -2-oxo-ethyl)-amide;
1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-ethoxy-isoquinolin- 1-yloxy)-pyrrolidine-2-carboxylic acid(2-cyclopropylcarbamoyl-1S-cyclopropylmethyl-2S-oxo-ethyl)-amide;
1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-ethoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid(1S-cyclopropylaminooxalyl-butyl)-amide;
1-[2S-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4R-(6-methoxy-isoquinolin-1-yloxy)-pyrrolidine-2S-carboxylic acid(1S-cyclopropylaminooxalyl-pentyl)-amide;
(S)-1-[2-(3-tert-Butylureido)-3,3-dimethylbutyryl]-4-trans-(3-cyclopropyl-6-methoxyisoquinolin-1-yloxy)pyrrolidine- 2-(S)-carboxylic acid (1-cyclopropylaminooxalyl-butyl)amide Hydrochloride; and
1-[2-(3-tert-Butyl-ureido)-3,3-dimethyl-butyryl]-4-(3-methyl-6-methoxyisoquinolin-1-yloxy)-pyrrolidine-2-carboxylic acid(1-cyclopropylaminooxalylbutyl)-amide.