Benzofuran compounds for the treatment of hepatitis C virus infections

• US 9,682,999 B2
• Filed: 11/20/2014
• Issued: 06/20/2017
• Est. Priority Date: 08/19/2011
• Status: Expired due to Fees

• Current Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Original Assignee: Glaxo Group Limited (Glaxosmithkline Holdings Ltd.)
• Inventors: Chong, Pek Yoke, Miller, John F., Peat, Andrew James, Shotwell, John Brad
• Primary Examiner(s): CHONG, YONG SOO
• Application Number:
  US14/548,524
• Publication Number:
  US 20150080343A1
• Time in Patent Office: 943 Days
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07D 307/85 attached in position 2
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/027 Organoboranes and organoborohydrides
• CPC Class Codes: C07F 5/04 Esters of boric acids

Abstract

The present invention features compounds of formula (I):

and salts thereof, pharmaceutical compositions comprising said compounds, and uses of such compounds in treating or preventing viral infections, such as HCV infections, and diseases associated with such infections.

Claims

1. A compound of formula (I):

2. The compound of formula (I) according to claim 1 wherein R is halogen;

m is 1;

R¹ is —

C(O)NH R⁵ wherein R⁵ is C_1-6alkyl;

R² is C_3-6cycloalkyl;

R³ is —

S(O)₂R⁷ wherein R⁷ is C_1-6alkyl and wherein phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —

CN, —

C(H) F₂ and —

CF₃.

8. A pharmaceutically acceptable salt of a compound as claimed in claim 1.

9. A pharmaceutical composition comprising a compound according to claim 1 together with at least one pharmaceutically acceptable excipient.

10. A compound according to claim 1 for use in treating or preventing a viral infection or disease associated with such infection.

11. The compound according to claim 10 wherein the viral infection is HCV infection.

12. A compound of formula (I) or (I)′

as claimed in claim 1 in combination with one or more active anti-viral agents.

3. A compound of formula (I)′

4. The compound of formula (I)′

according to claim 3 wherein the phenyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, —

CN, —

C(H)F₂, and —

CF₃.

5. The compound of formula (I)′

according to claim 3, wherein the phenyl is optionally substituted one or more substituents independently selected from the group consisting of halogen, C_1-6alkoxy, —

C(H)F₂, —

CF₃, C_1-6alkyl, hydroxy, hydroxyalkyl and aminoalkyl.

6. The compound of formula (I)′

according to claim 3 wherein R⁷ is C_1-6alkyl.

7. A compound selected from the group consisting of:

(2-Chloro-4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)phenyl)boronic acid;

(2-Chloro-4-(N-(2-(4-chlorophenyl)-5-cyclopropyl-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)phenyl)boronic acid;

4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)phenylboronic acid;

3-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)phenylboronic acid;

4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-fluorophenylboronic acid;

4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-3-fluorophenylboronic acid;

4-(N-(2-(4-chlorophenyl)-5-cyclopropyl-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-fluorophenylboronic acid;

(4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-(difluoromethyl)phenyl)boronic acid;

(4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-(trifluoromethyl)phenyl)boronic acid;

(4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2,6-difluorophenyl)boronic acid;

(2-cyano-4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)phenyl)boronic acid;

(4-(N-(3-carbamoyl-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-6-yl)methylsulfonamido)-2-chlorophenyl)boronic acid;

(4-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-(methylsulfonyl)phenyl)boronic acid;

(4-(N-(2-(4-Chlorophenyl)-5-cyclopropyl-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)-2-cyanophenyl)boronic acid;

and pharmaceutically acceptable salts thereof.