Methods of treating opportunistic infections with azaspiranes

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514278, 514212, A61K 3140, A61K 3144, A61K 3155

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active

057863768

DESCRIPTION:

BRIEF SUMMARY
METHODS

This invention relates to a method of treating opportunistic infections in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a substituted azaspirane.


BACKGROUND OF THE INVENTION

Opportunistic infections are an increasing problem in medicine. Opportunistic infections can be caused by a wide variety of bacteria, viruses, fungi and protozoa, as described in Microbiology 16th edition. Appleton Crofts, N.Y., 1976, p 405. Of particular interest are e.g. Candida sp., Pseudomonas sp., Listeria sp., Pneumocystis carinii, Pneumococci, Neisseria sp., Salmonella sp., Mycobacteria sp., Cryptococcus sp., Aspergillis sp., Cryptosporidium sp., Herpes simplex, Herpes zoster, Cytomegalovirus and Toxoplasma sp. These organisms, which are often part of the normal flora, are rarely a cause for concern in normal hosts but, under certain circumstances, can cause serious disease. These circumstances include but are not limited to: prolonged high dose antibiotic therapy, cancer chemotherapy, transplantation and acquired immunodeficiency syndrome (AIDS). In the first two examples cited, a Biologic Response Modifier, (i.e., compounds with immunostimulatory activity, e.g. muramylpeptides) would be the adjunct treatment of choice for an opportunistic infection (Walsh TH et al. Curr Opin Oncol 4:647-655, 1992). In the latter two examples, however, immunostimulation may be contraindicated. In the case of transplantation, a Biologic Response Modifier would be expected to exacerbate graft rejection of graft versus host disease. In AIDS, simple immunostimulation may accelerate disease progression.
Immunomodulatory agents are, in general, not known for their ability to treat opportunistic infections. Further, there is presently no acceptable means for predicting whether a particular class of immunomodulatory agents will have utility in treating opportunistic infections.
Badger, et al., U.S. Pat. No. 4,963,557 (Badger I) discloses compounds of the formula I: ##STR1## wherein: n is 3-7; m is 1 or 2; R.sup.1 and R.sup.2 are the same or different and are selected from hydrogen or straight or branched chain alkyl, provided that the total number of carbon atoms contained by R.sup.1 and R.sup.2 when taken together is 5-10; or R.sup.1 and R.sup.2 together form a cyclic alkyl group having 3-7 carbon atoms; R.sup.3 and R.sup.4 are the same or different and are selected from hydrogen or straight chain alkyl having 1-3 carbon atoms; or R.sup.3 and R.sup.4 are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof.
Badger I discloses compounds of Formula I as a class of novel compounds which induce an immunomodulatory effect which is characterized by the stimulation of suppressor cell activity.
Badger I does not disclose the compounds of Formula I as agents for treating opportunistic infections.


SUMMARY OF THE INVENTION

This invention relates to a method of treating opportunistic infections in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a compound of the formula ##STR2## wherein: n is 3-7; hydrogen or straight or branched chain alkyl, provided that the total number of carbon atoms contained by R.sup.1 and R.sup.2 when taken together is 5-10; or R.sup.1 and R.sup.2 together form a cyclic alkyl group having 3-7 carbon atoms; hydrogen or straight chain alkyl having 1-3 carbon atoms; or R.sup.3 and R.sup.4 are joined together with the nitrogen atom to form a heterocyclic group having 5-8 atoms; or a pharmaceutically acceptable salt or hydrate or solvate thereof.


DETAILED DESCRIPTION OF THE INVENTION

The preparation of all compounds of Formula (I) and pharmaceutically acceptable salts, hydrates and solvates and formulations thereof is disclosed in U.S. Pat. No. 4,963,557, the entire disclosure of which is hereby incorporated by reference.
A preferred compound used in the novel method is the dihydrochloride salt o

REFERENCES:
patent: 4963557 (1990-10-01), Badger et al.

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