Antiviral compounds and uses thereof

• US 9,637,478 B2
• Filed: 04/28/2016
• Issued: 05/02/2017
• Est. Priority Date: 03/25/2009
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Incorporated
• Inventors: Betebenner, David A., Pratt, John K., DeGoey, David A., Donner, Pamela L., Flentge, Charles A., Hutchinson, Douglas K., Kati, Warren M., Krueger, Allan C., Longenecker, Kenton L., Maring, Clarence J., Randolph, John T., Rockway, Todd W., Tufano, Michael D., Wagner, Rolf, Liu, Dachun
• Primary Examiner(s): Pagano, Alexander R
• Application Number:
  US15/141,556
• Publication Number:
  US 20160368905A1
• Time in Patent Office: 369 Days
• CPC Class Codes: A61K 31/18 Sulfonamides compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/402 1-aryl substituted, e.g. piretanide
• CPC Class Codes: A61K 31/4166 having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
• CPC Class Codes: A61K 31/421 1,3-Oxazoles, e.g. pemoline, trimethadione
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 31/503 spiro-condensed
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• 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 31/14 for RNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 311/08 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 207/27 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 213/64 attached in position 2 or 6
• CPC Class Codes: C07D 233/32 One oxygen atom
• CPC Class Codes: C07D 233/72 Two oxygen atoms, e.g. hydantoin
• CPC Class Codes: C07D 239/10 Oxygen or sulfur atoms
• CPC Class Codes: C07D 239/54 as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• CPC Class Codes: C07D 263/22 : with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
• CPC Class Codes: C07D 263/24 : with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
• CPC Class Codes: C07D 275/02 : not condensed with other rings
• CPC Class Codes: C07D 403/10 : linked by a carbon chain containing aromatic rings
• 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: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

Claims

1. A compound or salt thereof, wherein:

the compound corresponds in structure to formula (I-L0);

2. The compound or salt of claim 1, wherein R¹ is

3. The compound or salt of claim 2, wherein n is 1.

4. The compound or salt of claim 2, wherein n is 2.

5. The compound or salt of claim 2, wherein R¹⁵ is amino.

6. The compound or salt of claim 2, wherein R¹⁵ is tert-butoxycarbonylamino.

7. The compound or salt of claim 1, wherein R¹ is

8. The compound or salt of claim 7, wherein m is 0.

9. The compound or salt of claim 7, wherein m is 2.

10. The compound or salt of claim 7, wherein R¹⁶ is hydrogen.

11. The compound or salt of claim 7, wherein R¹⁶ is phenyl.

12. The compound or salt of claim 7, wherein R¹⁶ is C₁-C₃-alkyl.

13. The compound or salt of claim 7, wherein R¹⁶ is C₁-C₃-alkyloxycarbonyl.

14. The compound or salt of claim 1, wherein R¹ is benzoyl.

15. The compound or salt of claim 1, wherein R² is selected from the group consisting of tert-butyl, perfluoroethyl, and trifluoromethyl.

16. The compound or salt of claim 1, wherein R² is selected from the group consisting of furanyl, pyrazolyl, and thiophenyl, wherein each such substituent optionally is substituted with methyl.

17. The compound or salt of claim 1, wherein R³ is selected from the group consisting of C₂-C₃-alkenyl, C₁-C₃-alkyl, alkyloxy, amino, and halo.

18. The compound or salt of claim 1, wherein R³ is methoxy.

19. The compound or salt of claim 1, wherein R⁴ is selected from the group consisting of naphthalenyl, dihydronaphthalenyl, tetrahydronaphthalenyl, hexahydronaphthalenyl, octahydronaphthalenyl, decahydronaphthalenyl, indenyl, dihydroindenyl, hexahydroindenyl, octahydroindenyl, pentalenyl, octahydropentalenyl, and hexahydropentalenyl.

20. The compound or salt of claim 1, wherein:

R⁴ is a fused 2-ring carbocyclyl selected from the group consisting of naphthalenyl, indenyl, and dihydroindenyl, wherein each such substituent is substituted with a substituent selected from the group consisting of R^F and R^J;

R^F is alkylsulfonylaminoalkyl; and

R^J is alkylsulfonylamino.

22. A pharmaceutical composition comprising one or more compounds and/or salts recited in claim 1 and one or more excipients.

23. The pharmaceutical composition of claim 22, wherein the pharmaceutical composition further comprises one or more additional therapeutic agents.

24. A method for inhibiting replication of a hepatitis C virus, wherein the method comprises exposing the virus to one or more compounds and/or salts recited in claim 1.

25. A method for treating hepatitis C in a human in need of such treatment, wherein the method comprises administering to the human one or more compounds and/or salts recited in claim 1.

26. The method of claim 25, wherein the method further comprises administering to the human one or more additional therapeutic agents selected from the group consisting of an interferon agent, ribavirin, an HCV inhibitor, and an HIV inhibitor.

21. A compound or salt thereof, wherein the compound is selected from the group consisting of

N-(6-(3-tert-butyl-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-methoxyphenyl)naphthalen-2-yl)methanesulfonamide;

N-(6-(3-tert-butyl-2-methoxy-5-ureidophenyl)naphthalen-2-yl)methanesulfonamide;

N-(6-(3-tert-butyl-2-methoxy-5-(3-phenylureido)phenyl) naphthalen-2-yl)methanesulfonamide;

N-(6-(3-tert-butyl-5-(3-isopropylureido)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide;

tert-butyl 2-(3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen-2-yl)phenylamino)-2-oxoethylcarbamate;

2-amino-N-(3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen-2-yl)phenyl)acetamide;

ethyl 3-(3-(3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen-2-yl)phenyl)ureido)propanoate;

N-(6-(3-tert-butyl-5-(3-ethylureido)-2-methoxyphenyl) naphthalen-2-yl)methanesulfonamide;

tert-butyl 3-(3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen-2-yl)phenylamino)-3-oxopropylcarbamate;

3-amino-N-(3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen-2-yl)phenyl)propanamide;

N-(6-(5-benzoyl-3-tert-butyl-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide;

(E)-N-(4-(5-benzoyl-3-tert-butyl-2-methoxystyryl)phenyl) methanesulfonamide;

(E)-N′

-((3′

-tert-butyl-5′

-(2-(1,1-dioxidoisothiazolidin-2-yl))-2′

methoxybiphenyl-4-yl)methylene)methanesulfonylhydrazide;

N-(3-tert-butyl-4-methoxy-5-(6-(methylsulfonamido) naphthalen-2-yl)phenyl)acetamide; and

(E)-N-(4-(5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-2-methoxy-3-(trifluoromethyl)styryl)phenyl)methanesulfonamide.