Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Patent
1994-11-01
1999-11-16
Travers, Russell
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
A61K 3112
Patent
active
059859350
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to the use of a particular class of aromatic compounds, in particular bis-aromatic .alpha.,.beta.-unsaturated ketones, most of which are novel compounds, for the treatment or prophylaxis of a number of serious conditions caused by microorganisms or parasites, in particular protozoa such as Leishmania, Plasmodia, and Coccidia such as Eimeria, and intracellular bacteria, including Legionella and Mycobacteria. The invention also relates to the novel bis-aromatic .alpha.,.beta.-unsaturated ketones and methods of preparing them, as well as to pharmaceutical and antiparasitic compositions. Furthermore, the invention also relates to a method for treatment or prophylaxis of diseases caused by microorganisms or parasites.
Parasitic diseases, among these malaria and leishmaniasis, are, on a world basis, among the most important diseases. The most effective known drugs against the diseases have many side effects for which reason it is not possible to maintain the treatment or prophylaxis of specific diseases for years.
Recently, the development of resistance against the available drugs against particularly malaria and leishmania parasites has been reported.
Especially malaria and leishmaniasis remain serious diseases despite the efforts to control the diseases and reduce their prevalence by vector eradication and drug treatment.
More than 12 million people in the world are inflicted by leishmaniasis. There are more than 400,000 new cases and 100,000 deaths each year but as many as 350 million people are at risk of infection (WHO,1990). The annual incidence of clinical leishmaniasis is estimated to exceed 2,000,000 cases in some 80 countries. It is one of the 7 important tropical diseases included in the TDR program.
Leishmaniasis are characterized by a broad spectrum of clinical manifestations depending on the strain of the parasite and the host immune response. The parasites infect macrophages and multiply inside these cells. The first step in the Leishmania/macrophage interactions is the binding of the parasite to the macrophage followed by uptake of the parasite. Integrity and fluidity of the host cell membrane is essential for this interaction. Certain parasite surface antigens such as membrane glycoprotein (Gp63) and lipophosphoglycan (LPG) as well as a number of macrophage surface receptors are also important in binding and uptake of the parasite by macrophages.
Various species of the protozoan parasite Leishmania cause a broad spectrum of diseases ranlpg from the cutaneous healing skin lesions caused by L. major to a fatal visceral form of the disease called kala azar caused by L. donovani (Manson-Bahr, 1987). Leishmaniases are widespread in many parts of the world with highest prevalence in Africa, Asia, and Latin America (WHO, 1989). Recently an increasing number of AIDS patients are becoming infected with Leishmania (Brenguer, 1989; Flegg 1990).
Therapy of patients with leishmaaniasis still poses a serious problem. Most of the available antileishmanial drugs exhibit considerable toxicity and there are reports of large scale clinical resistance to the conventional antimonial drugs. No effective, safe, and nontoxic antileishmanial drug is available at present.
There are also reports of large scale clinical drug resistance in visceral leishmaniasis. (TDR News No. 34,1990)
Malaria, another parasitic disease, is also a serious health problem. Human malaria is caused by four species of the protozoan genus, Plasmodium. The species Plasmodium falciparum is the most dangerous, causing acute severe infections that are often fatal, especially in young children and immigrants entering endemic areas. The life cycle of P. falciparum includes different stages; in the first stage, the sporozoite stage, the parasite is brought into the blood stream by the Anopheles mosquito. The sporozoites are carried in the blood stream to the liver where they invade the hepatocytes and develop into merozoites in the course of 5-7 days. Merozoites released from infected cells start a new cycle by invading the
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Christensen S.o slashed.ren Br.o slashed.gger
Kharazmi Arsalan
Ming Chen
Theander Thor Grundtvig
Conlin David G.
Corless Peter F.
Statens Seruminstitut
Travers Russell
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