6-amino acid heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis B virus infection

• US 9,447,086 B2
• Filed: 09/10/2013
• Issued: 09/20/2016
• Est. Priority Date: 09/10/2012
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Guo, Lei, Hu, Taishan, Hu, Yimin, Kocer, Buelent, Lin, Xianfeng, Liu, Haixia, Mayweg, Alexander V, Qiu, Zongxing, Shen, Hong, Tang, Guozhi, Wang, Lisha, Wu, Guolong, Yan, Shixiang, Zhang, Weixing, Zhou, Mingwei, Zhu, Wei
• Primary Examiner(s): RAO, DEEPAK R
• Application Number:
  US14/022,519
• Publication Number:
  US 20150031687A1
• Time in Patent Office: 1,106 Days
• Field of Search: 544/55, 544/60, 544/122, 544/333, 514/226.8, 514/227.8, 514/235.8, 514/256
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 31/541 Non-condensed thiazines containing further heterocyclic rings
• 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 31/20 for DNA viruses
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/14 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

Abstract

The invention provides novel compounds having the general formula:

wherein R¹, R², R³, R⁴ and A are as described herein, compositions including the compounds and methods of using the compounds.

Claims

1. A compound selected from

2. A pharmaceutical composition comprising a compound in accordance with claim 1 and a therapeutically inert carrier.

3. A method of inhibiting hepatitis B virus in a human, which method comprises administering an effective amount to said human of a compound as defined in claim 1.

4. A method for the treatment of hepatitis B virus infection in a human, which method comprises administering an effective amount to said human of a compound as defined in claim 1.

5. A method for the treatment of hepatitis B virus infection in a human, which method comprises administering an effective amount to said human of a compound as defined in claim 1 together with an agent selected from the group consisting of interferon, pegylated interferons, Lamivudine, Adefovir dipivoxil, Entecavir, Telbivudine, and Tenofovir disoproxil.