# US 9,434,738 B2 · Macrocyclic benzofuran and azabenzofuran compounds for the treatment of hepatitis C

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,434,738 B2
- Document ID: US9434738B2
- Status: Granted
- Kind: B2
- Application number: 14/759,684
- Filed: 2014-01-08
- Published: 2015-12-03
- Granted: 2016-09-06
- Earliest claimed: 2013-01-10
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Tao Wang; Zhongxing Zhang; John F. Kadow
- Web page: https://patentgrep.com/patent/US9434738B2

## CPC

- C07D 491/06: Peri-condensed systems
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 31/14: for RNA viruses
- C07D 307/84: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 491/04: Ortho-condensed systems
- C07D 498/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

Compounds of formula I, including their salts, as well as compositions and methods of using the compounds are set forth. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.

## Claims

### Claim 1

A compound of formula I, including pharmaceutically acceptable salts thereof:
wherein
n, m are independently 0 or 1;
R1 is methyl;
R2 is phenyl that is independently substituted with 0-2 halo or methoxy or is para substituted with W—Ar1;
W is —O— or —NH—;
Ar1 is phenyl or para-halophenyl;
R3 is hydrogen, halo, or alkyl;
R4, R5, R6 are independently selected from hydrogen, halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkoxy, hydroxyalkyloxy, alkoxyalkyloxy, COOR11 and CON(R12)(R13);
R11 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R12, R13 are each independently hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy; or
R12 and R13 can form a ring by joining two atoms, one from each of R12 and R13;
R14 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, hydroxyl, alkoxy, and haloalkoxy;
R7 is hydrogen, alkyl, halo, N(R21)(R22), or alkylsulfonyl;
R21 and R22 are independently hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, alkylsulfonyl, or alkylsulfonylalkyl;
or N(R21)(R22) taken together is azetidinyl, pyrrolidinyl, piperidinyl, or piperazinyl, and is substituted with 0-2 substituents selected from alkyl, hydroxyalkyl, and hydroxy;
X, Y are independently selected from CR31R32, CO, O, NR33, NCN, S, SO, and S(O)2;
R31, R32 are each independently alkyl or cycloalkyl, further substituted with 0-3 substituents; or
R31 and R32 can form a ring by joining two atoms, one from each of R31 and R32;
R33 is hydrogen, alkyl, cycloalkyl, or S(O)2R11 with 0-3 substituents selected from halo, haloalkoxy, OR11, NR12R13, COOR11, CONR12R13, S(O)2R11, S(O)2NR12R13, and NR14CONR12R13;
Z is an alkylene or alkenylene chain containing 0-12 groups selected from the group consisting of O, NR41, S, S(O), S(O)2, C(O), C(O)O, C(O)NR41, C(S)NR41, O—C(O)NR41, NR41C(O)NR42, and Ar2, provided that any O or S atom does not directly bond to another O or S atom, such that ring A is 11-24 membered; and further wherein the alkylene or alkenylene chain is substituted with 0-6 substituents selected from alkyl, cycloalkyl, halo, alkoxy, haloalkyl, OH, OR11, haloalkoxy, NH2, NR12R13, COOR11, CONR12R13, S(O)2R11, S(O)2NR12R13, NR14CONR12R13, and Ar3;
R41, R42 is hydrogen, alkyl or cycloalkyl with 0-3 substituents selected from halo, haloalkoxy, OR11, NR12R13, COOR11, CONR12R13, S(O)2R11, S(O)2NR12R13, and NR14CONR12R13;
Ar2 is phenyl, 5-membered heteroaryl or 6-membered heteroaryl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, cycloalkyl, haloalkyl, OH, OR11, haloalkoxy, NH2, NR12R13, COOR11, CONR12R13, S(O)2R11, S(O)2NR12R13, and NR14CONR12R13;
Ar3 is phenyl, 5-membered heteroaryl or 6-membered heteroaryl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, cycloalkyl, haloalkyl, OH, OR11, haloalkoxy, NH2, NR12R13, COOR11CONR12R13, S(O)2R11, S(O)2NR12R13, and NR14CONR12R13.

### Claim 2 (depends on 1)

A compound of claim 1 wherein n and m are each 1.

### Claim 3 (depends on 2)

A compound of claim 2 wherein R2 is phenyl substituted with halo.

### Claim 4 (depends on 3)

A compound of claim 3 wherein halo is fluoro.

### Claim 5 (depends on 1)

A compound of claim 1 wherein R3, R4, R6 and R7 are each hydrogen.

### Claim 6 (depends on 1)

A compound of claim 1 wherein X and Y are each NR33.

### Claim 7 (depends on 6)

A compound of claim 6 wherein R33 is hydrogen or S(O)2CH3.

### Claim 8 (depends on 1)

A compound of claim 1 wherein A is at least a 12-member ring.

### Claim 9 (depends on 8)

A compound of claim 8 wherein A is at least a 15-member ring.

### Claim 10 (depends on 9)

A compound of claim 9 wherein A is at least a 17-member ring.

### Claim 11 (depends on 10)

A compound of claim 10 wherein A is at least a 19-member ring.

### Claim 12

A compound, including pharmaceutically acceptable salts thereof, which is selected from the group of:

### Claim 13 (depends on 1)

A composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

### Claim 14 (depends on 12)

A composition comprising a compound of claim 12 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

### Claim 15 (depends on 1)

A method of treating hepatitis C infection comprising administering a therapeutically effective amount of a compound of claim 1 to a patient.