Diazaindole-dicarbonyl-piperazinyl antiviral agents

Abstract

The invention comprises substituted diazaindole-dicarbonyl-piperazinyl derivatives of general Formula I wherein: Q is selected from the group consisting of — may represent a bond; T is —C(O)— or —CH(CN)—; and —Y— is selected from the group consisting of compositions thereof and their use for treating HIV infection.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 525,624 filed Nov. 26, 2003.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with new diazaindole derivatives that possess unique antiviral activity. More particularly, the present invention relates to compounds useful for the treatment of HIV and AIDS. [0004] 2. Background Art [0005] HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with an estimated 42 million people infected worldwide at the end of 2002. The number of cases of HIV and AIDS (acquired immunodeficiency syndrome) has risen rapidly. In 2002, ˜5.0 million new infections were reported, and 3.1 million people died from AIDS. Currently available drugs for the treatment of HIV inc...

AI Technical Summary

Benefits of technology

[0244] Another embodiment of the present invention is a pharmaceutical composition comprising an antiviral effective amount of a compound of Formula I, including pharmaceutically acceptable salts thereof, and one or more pharmaceutically acceptable carriers, excipients, diluents and optionally in combination with an antiviral effective amount of an AIDS treatment agent selected from the group consisting of: (a) an AIDS antiviral agent; (b) an anti-infective agent; (c) an immunomodulator; and (d) HIV entry inhibitors.

Problems solved by technology

HIV-1 (human immunodeficiency virus-1) infection remains a major medical problem, with an estimated 42 million people infected worldwide at the end of 2002.

Each of these drugs can only transiently restrain viral replication if used alone.

However, when used in combination, these drugs have a profound effect on viremia and disease progression.

However, despite these impressive results, 30 to 50% of patients ultimately fail combination drug therapies.

Furthermore, the high replication rate and rapid turnover of HIV-1 combined with the frequent incorporation of mutations, leads to the appearance of drug-resistant variants and treatment failures when sub-optimal drug concentrations are present (Larder and Kemp; Gulick; Kuritzkes; Morris-Jones et al; Schinazi et al; Vacca and Condra; Flexner; Berkhout and Ren et al; (Ref. 6-14)).

However, the major drawback to the development and application of NNRTIs is the propensity for rapid emergence of drug resistant strains, both in tissue cell culture and in treated individuals, particularly those subject to monotherapy.

However, these structures differ from those claimed herein in that they are monoaza-indole mono-amide rather than oxoacetamide derivatives, and there is no mention of the use of these compounds for treating viral infections, particularly HIV.

However, these molecules differ from those claimed in that they do not contain the piperazine or piperidine moieties and there is no mention of the use of these molecules as antiviral agents, particularly against HIV.

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