Diarylsulfone non-nucleoside reverse transcriptase inhibitors of human immunodeficiency virus

• US 6,303,630 B1
• Filed: 04/11/2000
• Issued: 10/16/2001
• Est. Priority Date: 07/29/1997
• Status: Expired due to Fees

• Current Assignee: University Of The Sciences In Philadelphia (The)
• Original Assignee: University Of The Sciences In Philadelphia (The)
• Inventors: Zanger, Murray
• Primary Examiner(s): Huang, Evelyn Mei
• Application Number:
  US09/547,820
• Time in Patent Office: 553 Days
• Field of Search: 546/153, 546/166, 564/87, 568/30, 568/33, 568/34, 514/311, 514/312, 514/603, 514/709
• US Class Current: 514/311
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07C 311/21 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: C07C 311/29 having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 215/36 Sulfur atoms C07D215/24 takes precedence
• CPC Class Codes: C07D 215/58 with hetero atoms directly attached to the ring nitrogen atom

Abstract

In accordance with the present invention, there is now provided novel anti-HIV compounds of the formulae selected from the group consisting of:

wherein R₁ is hydrogen or C₁-C₄ alkyl; R₂ is hydrogen, C₁-C₄ alkyl, C₁-C₄ alkoxy or halogen; R₃ is hydrogen, hydroxy, C₁-C₄ alkyl, C₁-C₄ alkoxy or halogen; R₄ is hydrogen or halogen, R₅ is hydrogen; C₁-C₄ alkoxy, nitro, halogen or haloalkyl; R₆ is hydrogen or nitro; R₇ is hydrogen or C₁-C₄ alkyl, C₁-C₄ alkoxy, nitro or halogen; R₈ is hydrogen, hydroxy, C₁-C₄ alkyl, C₁-C₄ alkoxy or halogen; R₉ is hydrogen or nitro; R₁₀ is hydrogen or halogen; R₁₁ is hydrogen, C₁-C₄ amine; R₁₂ is hydrogen, C₁-C₄ alkyl or halogen; R₁₃ is hydrogen, C₁-C₄ amine; R₁₄ is hydrogen or halogen; R₁₅ is hydrogen, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, nitro, or halogen; R₁₆ is hydrogen or nitro; R₁₇ is hydrogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, nitro or halogen; R₁₈ is hydrogen, C₁-C₄ alkoxy, hydroxy, or halogen; R₁₉ is hydrogen or nitro; and R₂₀ is hydrogen or halogen, or a pharmaceutically acceptable salt thereof.

Claims

1. A method of treating human immunodeficiency virus infection which comprises administering to a human in need thereof an effective amount of a compound of the formula selected from the group consisting of

wherein R₁₁ is hydrogen, C₁-C₄ amine, with the proviso that when R₁₁ is H, R₁₃ is C₁-C₄ amine;

R₁₂ is hydrogen, C₁-C₄ alkyl or halogen;

R₁₃ is hydrogen, C₁-C₄ amine, with the proviso that when R₁₃ is H, R₁₁ is C₁-C₄ amine;

R₁₄ is hydrogen or halogen;

R₁₅ is nitro;

R₁₆ is hydrogen or nitro;

R₁₇ is hydrogen, C₁-C₄ alkyl, C₁-C₄ alkoxy, nitro or halogen;

R₁₈ is hydrogen, C₁-C₄ alkoxy, hydroxy, or halogen;

R₁₉ is nitro;

R₂₀ is hydrogen or halogen; and

R₂₁ is NO₂; and

pharmaceutically acceptable salts thereof.

2. The method of claim 1 wherein said compound has an octanol/water partition coefficient (LogP) of from about 2.5 to about 4.

3. The method of claim 2 wherein said compound is administered in a pharmaceutical formulation which comprises said compound or a pharmaceutically acceptable salt thereof associated with one or more pharmaceutically acceptable carriers, excipients or diluents therefor.