Inhibitors of viral replication, their process of preparation and their therapeutical uses

• US 9,994,509 B2
• Filed: 07/07/2014
• Issued: 06/12/2018
• Est. Priority Date: 07/05/2013
• Status: Expired due to Fees

• Current Assignee: HIVIH
• Original Assignee: HIVIH
• Inventors: Ledoussal, Benoit, Le Strat, Frdric, Chasset, Sophie, Barbion, Julien, Brias, Julie, Caravano, Audrey, Faivre, Fabien, Vomscheid, Sophie
• Primary Examiner(s): Heyer, Dennis
• Application Number:
  US14/902,955
• Publication Number:
  US 20160152543A1
• Time in Patent Office: 1,436 Days
• Field of Search: None
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4741 condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 59/13 containing rings
• CPC Class Codes: C07D 311/04 Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
• CPC Class Codes: C07D 311/58 other than with oxygen or sulphur atoms in position 2 or 4
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 409/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 491/052 the oxygen-containing ring being six-membered

Abstract

The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.

Claims

1. A compound according to formula (I):

2. A compound according to claim 1 that is of formula (A) or (D):

3. A compound according to claim 1 that is of formula (D):

4. A compound according to claim 1 that is of formula (DA):

5. A compound according to claim 1 that is of formula (AB), (AC), (AD), (BD), or (CD):

6. A compound according to claim 1 that is of formula (ABC), (ABD), or (BCD):

7. A compound according to claim 1 that is of formula (ABCD):

8. A compound according to claim 1 that is of formula (A), (D), (AB), (AC), (AD), (BD), (CD), (DA), (ABC), (ABD), (BCD) or (ABCD):

9. A compound according to claim 1 wherein

R⁴ represents a tert-butyl;

and

R¹ and R⁶ represent a hydrogen atom.

10. A compound according to claim 1 wherein:

R⁴ represents a cyclopropyl.

11. A compound according to claim 1 that is selected from the group consisting of:

2-(tert-butoxy)-2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]acetic acid;

2-(tert-butoxy)-2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-(trifluoromethyl)phenyl]acetic acid;

2-(tert-butoxy)-2-(6-cyclopropyl-4′

-methoxy-3-methyl-biphenyl-2-yl]acetic acid;

(S)-2-(tert-butoxy)-2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]acetic acid;

2-(tert-butoxy)-2-(6-cyclopropyl-3,4′

-dimethyl-biphenyl-2-yl)-acetic acid;

2-(tert-butoxy)-2-(6-cyclopropyl-4′

-fluoro-3-methyl-biphenyl-2-yl)-acetic acid;

2-(tert-butoxy)-2-[3-cyclopropyl-6-methyl-2-(5-methyl-chroman-6-yl)-phenyl]acetic acid;

(trans-3-bicyclopropyl-2-yl-2-chroman-6-yl-6-methyl-phenyl)-tert-butoxy-acetic acid;

2-(tert-butoxy)-2-[3-cyclopropyl-2-(4,4-dimethyl-cyclohex-1-enyl)-6-methyl-phenyl]acetic acid;

2-(tert-butoxy)-2-(4′

-chloro-6-cyclopropyl-3-methyl-biphenyl-2-yl)acetic acid;

tert-butoxy-[3-cyclopropyl-2-(8-fluoro-5-methyl-chroman-6-yl)-6-methyl-phenyl]-acetic acid;

tert-butoxy-[2-chroman-6-yl-6-methyl-3-(1-methyl-cyclopropyl)-phenyl]-acetic acid;

tert-Butoxy-[2-chroman-6-yl-6-methyl-3-(cis-2-methyl-cyclopropyl)-phenyl]-acetic acid;

(S)-tert-butoxy-[3-cyclopropyl-6-methyl-2-(5-methyl-chroman-6-yl)-phenyl]-acetic acid;

(S)-tert-butoxy-[3-cyclopropyl-2-(8-fluoro-5-methyl-chroman-6-yl)-6-methyl-phenyl]-acetic acid;

2-(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-2-ethoxy-acetic acid;

2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]-2-cyclopropoxyacetic acid;

(S)-2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]-2-cyclopropoxyacetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-propoxy-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-cyclopropyl methoxy-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-(2,2,2-trifluoro-ethoxy)-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-cyclobutoxy-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-(2,2-difluoro-ethoxy)-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-(2-fluoro-ethoxy)-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-isopropoxy-acetic acid;

cyclopropoxy-[3-cyclopropyl-2-(8-fluoro-5-methyl-chroman-6-yl)-6-methyl-phenyl]-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-(1-methyl-cyclopropoxy)-acetic acid;

(S)-cyclopropoxy-[3-cyclopropyl-6-methyl-2-(5-methyl-chroman-6-yl)-phenyl]-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-trifluoromethyl-phenyl)-cyclopropoxy-acetic acid;

cyclopropoxy-[3-cyclopropyl-6-methyl-2-(5-methyl-chroman-6-yl)-phenyl]-acetic acid;

(S)-cyclopropoxy-[3-cyclopropyl-2-(8-fluoro-5-methyl-chroman-6-yl)-6-methyl-phenyl]-acetic acid;

(2-chroman-6-yl-3-cyclopropyl-6-methyl-phenyl)-(2,2-difluoro-cyclopropoxy)-acetic acid;

3-cyclopropyl-2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]propanoic acid;

2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]-4-methylpentanoic acid; and

2-[3-cyclopropyl-2-(3,4-dihydro-2H-1-benzopyran-6-yl)-6-methylphenyl]pent-4-enoic acid.

12. A pharmaceutical composition comprising a compound according to claim 1 as an active ingredient and at least one pharmaceutically acceptable carrier.

13. A pharmaceutical composition according to claim 12 comprising at least one further antiviral agent.

14. A pharmaceutical composition comprising a compound according to claim 8 as an active ingredient and at least one pharmaceutically acceptable carrier.

15. The pharmaceutical composition according to claim 14 and at least one antiviral agent.

16. A method for treating a HIV infection comprising administering to a person in need thereof a therapeutically effective amount of a compound according to claim 1.

17. A method for treating a HIV infection comprising administering to a person in need thereof a therapeutically effective amount of a compound according to claim 8.