The present invention relates to derivatives of aminoquinolone, and uses therefor.
AIDS (Acquired Immuno-deficiency Syndrome) is now generally accepted as being caused by the Human Immunodeficiency Virus (HIV).
The aetiology of AIDS is not yet precisely known, but it is known that HIV mainly infects CD.sub.4 lymphocytes, generally of the class of helper/inducer cells. Lymphocyte numbers gradually decrease, and this eventually leads to severe cellular immunodeficiency.
Very considerable research has been put into finding a cure for AIDS, but the development of a vaccine has proven extremely difficult. Accordingly, other avenues have also been pursued. One such avenue is the development of antiviral agents.
An antiviral agent currently on the market for the treatment of AIDS is AZT (Azidothymidine). The method of action of AZT is to inhibit the inherent reverse transcriptase of HIV, thus retarding or stopping reproduction of the virus. However, such a treatment can, at the best, only prolong life expectancy, and cannot cure AIDS completely. Other antiviral agents which have been developed act in a similar fashion.
Such inhibitory agents are also associated with side effects, such as disorders of the bone marrow and digestive system, and it has also been found that tolerance, or even total resistance, can be induced in the virus with a high frequency. Such resistant viruses can be generated even in patients receiving long-term therapy.
In order to overcome the above problems, it would be highly desirable to develop new antiviral agents which could be used either alone, or in combination therapy with known agents.
Anti-HIV activity has recently been reported for the compound DR-3355, which is an optical isomer (S-isomer) of Ofloxacin, a synthetic anti-bacterial agent. Ofloxacin has a quinolone skeleton [J. Nozaki, Renard et l., AIDS (1990), 4, p. 1283]. Attempts by the present inventors to reproduce the antiviral activity of DR-3355, using the method of R. Pauwel, et al., (infra), have failed.
WO-A-90-13542 discloses the anti-HIV activity of Norfloxacin, Enoxacin, Ciprofloxacin, Lomefloxacin, Difloxacin and Tosufloxacin but, again, these compounds demonstrate little or no anti-HIV activity when tested by the Pauwel method. These compounds also possess a quinolone skeleton.
USPTO Backgrounds
USPTO Backgrounds