Azole compounds used as tuberculostatic and leishmanicide agents

Abstract

This invention refers to new 1,2,3-triazole and imidazole compounds included in the families of compounds represented by general formula VIII.where: X is an atom of “C” or “N;” where X is “N” the radicals do triazole ring are represented by: R1=COR2, CSR3, CN(R4)R5 or CF2R6; R2=H, NHNH2, alkyl, aryl substituted or not, OH, NR7R8 or OR9; R3=alkyl or aryl substituted or not; R4=H, OH, alkyl or aryl substituted or not; R5=R6=R7=R8=R9=R10=H, alkyl or aryl substituted or not; where X is “C” the radicals do imidazolic ring are represented by: R1=COR2; R2=NHNH2, OH, OR3, or NR4R5; R3=alkyl or aryl substituted or not; =R5H, alkyl or aryl substituted or not; R10=NHR6 or NR6R7; R6=R7=COR8; R8=aryl substituted or not; while radical Rn can be located in any one or in more than one of the carbon atoms of the aromatic ring, and these radicals can be equal or different, represented by hydrogen, alkylic groups with 1 or more carbon atoms in a linear or branched chain alkenes or alkynes, hydroxyl, hydroxyalkyl or oxygenated functions in acyclic or cyclic systems forming an heterocyclic ring, free or substituted amines, thioalkyl, donators and / or removing groupings of electrons or halogens, thus “n” can vary from 1 to 5. This invention also refers to a pharmaceutical composition comprising, as active principle, at least one of the azole compounds represented by the general formula VIII, to the use of such compositions and to method of treatment or inhibition de tuberculosis and leishmaniasis.

Description

[0001]This invention refers to azole compounds pertaining to the 1,2,3-triazole and imidazole classes that can be used to treat tuberculosis and leishmaniasis, with the advantage of having high activity against microorganisms, more specifically against Mycobacterium tuberculosis and protozoa of Leishmania gender, agents that cause these diseases, as well as their salts, its stereoisomeric forms, racemic mixtures, pro-drugs, their metabolites; as well as pharmacological compositions containing at least one of these compounds or their salt as an active principle and to the use of such compositions as drugs to treat or inhibit diseases.[0002]Besides that, this invention also includes a treatment method or inhibition of tuberculosis and leishmaniasis, with the advantage of presenting a high activity against microorganisms, more specifically against Mycobacterium tuberculosis and protozoa of the Leishmania gender, comprising the administration of a pharmacologically effective quantity of...

AI Technical Summary

Problems solved by technology

Inadequate or even non-existing treatments to infectious and parasitic diseases are victimizing an elevated number or persons, especially in countries in development.

Thousands of lives are lost or severely damaged due to these diseases that impact the social well-being and exclude an important parcel of individuals from their social and productivity activities.

Neglected diseases is the classification attributed to diseases that do not present a satisfactory treatment, do not create interest in pharmaceutical industries and, besides that, government funding is insufficient to fight these kinds of diseases.

The lack of investment from pharmaceutical industries in the development of new drugs for certain diseases is directly connected to the low capacity of purchase of populations of countries in development.

Since HIV progressively destroys the immune system, there is a greater chance that virus infected persons develop tuberculosis.

The presence of multi-resistant lineages reflects deficiencies in the control of TB, thus hindering treatment and prevention of the disease, causing its propagation (Rossetti, M. L. R.; Valim, A. R. M.; Silva, M. S. N.; Rodrigues, V. S.; “Tuberculosis resistente: revisão molecular”; Rev.

However, SM administered in higher doses can affect the central and peripheral nervous systems.

However, in cases with monotherapy, inadequate prescription, incorrect use of the primary plan by the patient or even intolerance to first line drugs can lead to failure in therapy and development of the M. tuberculosis strains resistant to one or more drugs.

Its use as a leishmanicide agent is restricted due to its high toxicity that can cause adverse effects such as nausea, vomiting, headache, hypoglycemia and sudden death.

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