Antiviral compounds

• US 8,809,267 B2
• Filed: 07/01/2013
• Issued: 08/19/2014
• Est. Priority Date: 06/29/2007
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Cottell, Jeromy J., Link, John O., Schroeder, Scott D., Taylor, James, Tse, Winston C., Vivian, Randall W., Yang, Zheng-Yu
• Primary Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US13/932,945
• Publication Number:
  US 20140051626A1
• Time in Patent Office: 414 Days
• Field of Search: None
• US Class Current: 514/4.3
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 207/16 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07K 5/0804 and aliphatic
• CPC Class Codes: C07K 5/0808 the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
• CPC Class Codes: C07K 5/0812 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/0821 with the first amino acid being heterocyclic, e.g. His, Pro, Trp

Abstract

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Claims

1. A method of treating hepatitis C in a human patient, said method comprising administering to the patient a pharmaceutical composition comprising an excipient and a compound of formula (V) or a pharmaceutically acceptable salt thereof:

2. The method of claim 1 wherein:

X is a bond; and

Y⁴ is pyrrol-1-yl, morpholino, or (C2-10)alkyl.

3. The method of claim 1 wherein:

X is O; and

Y⁴ is tert-butyl, cyclopentyl, 1,1-dimethylethyl, cyclopropyl, tetrahydrofuranyl, isopropyl, 2,2-dimethylpropyl, cyclobutyl or

4. The method of claim 1 wherein:

X is NH; and

Y⁴ is (C2-10)alkyl that is optionally substituted with one or more halo.

5. The method of claim 1 wherein:

R^f is alkyl, aryl, or cycloalkyl, optionally substituted with one or more R_g independently selected from the group consisting of alkyl, halo, —

C(═

O)OR_d, and trifluoromethyl, wherein each alkyl of R_g is optionally substituted with one or more halo, alkoxy, or cyano.

6. The method of claim 1 wherein:

R^f is phenyl, cyclopropyl, 2-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl, 2,6-dimethylphenyl, 2-methylphenyl, 2,2-dimethylpropyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 1-methylcyclopropyl, 1-isopropylcyclopropyl, 1-propylcyclopropyl, 2,2,2-trifluoro-1,1-dimethylethyl, 1-(methoxycarbonyl)cyclopropyl, 1-ethylcyclopropyl, 1-trifluoromethylcyclobutyl, 1-(methoxymethyl)cyclopropyl, 1-(2-cyanoethyl)cyclopropyl, or 1-(2,2,2-trifluoroethyl)cyclopropyl.

7. The method of claim 1 wherein:

Q¹ is hydrogen, methyl, ethyl, vinyl, cyanomethyl, propyl, 2-fluoroethyl, 2,2-difluoroethyl, 2-cyanoethyl, 2-methoxyethyl, 2-methylsulfonylethyl, or cyclopropyl.

8. A method of treating hepatitis C in a human patient, said method comprising administering to the patient a pharmaceutical composition comprising an excipient and a compound of formula (V) or a pharmaceutically acceptable salt thereof, wherein the compound of formula (V) is: