Inhibitors of influenza viruses replication

• US 9,808,459 B2
• Filed: 10/21/2016
• Issued: 11/07/2017
• Est. Priority Date: 06/17/2009
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Charifson, Paul S., Clark, Michael P., Bandarage, Upul K., Bethiel, Randy S., Court, John J., Deng, Hongbo, Davies, Ioana, Duffy, John P., Farmer, Luc J., Gao, Huai, Gu, Wenxin, Jacobs, Dylan H., Kennedy, Joseph M., Ledeboer, Mark W., Ledford, Brian, Maltais, Francois, Perola, Emanuele, Wang, Tiansheng, Wannamaker, M. Woods, Byrn, Randal, Zhou, Yi, Lin, Chao, Jiang, Min, Jones, Steven, Germann, Ursula A., Salituro, Francesco G., Kwong, Ann Dak-Yee
• Primary Examiner(s): Wang, Shengjun
• Application Number:
  US15/299,757
• Publication Number:
  US 20170100400A1
• Time in Patent Office: 382 Days
• Field of Search: 514256
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 239/30 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I):

or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A compound is represented by Structural Formula (IA) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

Claims

1. A method of inhibiting the replication of influenza viruses in a biological sample or in a patient comprising administering to said biological sample or patient an effective amount of a compound having the formula

5. The method of any one of claims 1-4, wherein the influenza viruses are influenza A viruses.

2. A method of inhibiting the replication of influenza viruses in a biological sample or in a patient comprising administering to said biological sample or patient an effective amount of a pharmaceutically composition comprising compound having the formula

3. A method of reducing the amount of influenza viruses in a biological sample inhibiting the replication of influenza viruses in a biological sample or in a patient comprising administering to said biological sample or patient an effective amount of a compound having the formula

4. A method of reducing the amount of influenza viruses in a biological sample or in a patient comprising administering to said biological sample or patient an effective amount of a pharmaceutically composition comprising compound having the formula

6. A method of treating influenza infection in a patient, comprising administering to said patient an effective amount of a compound having the formula

8. The method of either of claim 6 or 7, wherein the influenza infection is an influenza A infection.

7. A method of treating influenza infection in a patient, comprising administering to said patient an effective amount of a pharmaceutical composition comprising a compound having the formula