Use of all allylamine derivatives such as terbinafine, in the ma

Details Use of all allylamine derivatives such as terbinafine, in the ma Use of all allylamine derivatives such as terbinafine, in the ma

1998-01-06

1999-08-10

Weddington, Kevin E.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

N-c doai

514249, 514650, 514655, 514925, 514926, 514927, A61K 3127, A61K 31495, A61K 31135

Patent

active

059359986

DESCRIPTION:

BRIEF SUMMARY
This is a 371 of PCT/EP96/02970, filed Jul. 5, 1996.
The invention relates to a new therapeutic use of certain allylamine compounds.
Allylamines are known for being squalene epoxidase inhibitors and exhibit antimycotic activity. Surprisingly it was now found that some compounds of this class are also active against Helicobacter pylori (Campylobacter pylordis).
Members of the genus Helicobacter are gram-negative spiral bacteria that are usually found in the mucus layer of the stomach of humans and animals. They are microaerophilic, possess flagella, and produce numerous extracellular products, including urease, proteases, and other compounds that enable them to survive in the hostile environment of the stomach. Worldwide, approximately half of the human population are H.pylori-positive. Without eradication therapy, established Helicobacter pylori infection seems to persist for life. H.pylori infection regularly results in chronic active gastris (type-B gastritis), but rarely becomes clinically evident. Recently, a causal relationship between H.pylori infection and peptic ulcer disease has been proven.
Furthermore, on the basis of previous epidemiological evidence, H.pylori has been classified as a category 1 (definite) human carcinogen by the WHO (World Health Organization). The difficulties faced in assessing the risk of gastric cancer in different susceptible populations have been addressed and new data presented to support a model of chronic gastritis leading to atrophy, followed by intestinal metaplasia and gastric cancer.
It has now been found that some compounds of the allylamine class of antimycotics exhibit excellent inhibitory activity against IH.pylori. They are therefore useful in the therapy in the above mentioned diseases.
The, invention concerns the use of a compound of formula I ##STR1## wherein
either R is attached at the 1 or 2 position of the naphthyl ring and is ##STR2## or R is attached at the I position and is ##STR3## pharmaceutically acceptable salt form, in the therapy of Helicobacter pylori infection and associated diseases such as gastritis, peptic ulcer, duodenal ulcer, gastric atrophy, intestinal metaplasia, non-ulcerative dyspepsia, MALT lymphoma (lymphoma of gastric mucosa--associated lymphatic tissue), non-Hodgkin's lymphoma and gastric cancer, hereinafter briefly named "the use of the invention".
It also concerns the use of a compound of formula I as defined above in fee base form or in pharmaceutically acceptable salt form for the manufacture of a medicament for use in the therapy of Helicobacter pylori infection and associated diseases as defined above, optionally in combination with one or more other, preferably orally active agents.
It further concerns a method of treatment of Helicobacter pylori infection and associated diseases as defined above, comprising administration of a therapeutically effective amount of a compound of formula I as defined above in free base form or in pharmaceutically acceptable salt form to a subject in need of such treatment. Administration may optionally be effected in combination with one or more other, preferably orally active agent.
It further concerns an agent for use in the therapy of Helicobacter pylori infection and associated diseases as defined above, comprising a compound of formula I in free base form or in pharmaceutically acceptable salt form together with at least one pharmaceutically acceptable carrier or diluent, optionally in combination with one or more other, preferably orally active agents.
The invention further concerns a process for the preparation of a medicament for use as defined above, which comprises mixing a compound of formula I in free base form or in pharmaceutically acceptable salt form optionally in combination with one or more other, preferably orally active agents together with at least one pharmaceutically acceptable carrier or diluent.
It also concerns a pharmaceutical composition adapted for use as defined above, which comprises a compound of formula I in free base form or in pharmaceutically acceptable sa

REFERENCES:
patent: 4282251 (1981-08-01), Berney
patent: 4755534 (1988-07-01), Stuetz et al.
patent: 4894375 (1990-01-01), Gadebusch et al.
patent: 5132459 (1992-07-01), Stuetz et al.
patent: 5348746 (1994-09-01), Dong et al.
Derwent Abstract 95:000525/01 corresponding to DE 43 17 449.
King D. et al., "In Vitro Activities of Econazole Nitrate and Terbinafine Against Fungal and Bacterial Pathogens Commonly Encountered in Podiatric Practice", Advances in Therapy, vol. 11, No. 3, 1994, pp. 120-131.
Nolting S., "Clinical Relevance of the Antibacterial Activity of Terbinafine: A Contralateral Comparison Between 1% Terbinafine Cream and 0.1% Gentamicin Sulphate Cream in Pyoderma", British Journal of Dermatology, vol. 126, 1992, pp. 56-60.
Weil M. et al., "Topical Econazole Versus Terbinafine in the Treatment of Toe Web Space Infections: A Comparison", Advances in Therapy, vol. 13, 1996, pp. 355-364.
"Activity of the antimycotic ketoconazole against Helicobacter pylori", J. Antimicrob, Chemother., vol. 30, 1992, pp. 238-240.
Am. J. Gastroenterol., vol. 89, 1994, pp. 1603-1604.
Eur. J. Clin. Microbiol. Infect. Dis., vol. 11, 1992, pp. 273-274.
J. Micologie Medicale (France), vol. 5, 1995, Suppl. 1., pp. 17-20.
Stutz et al., "Synthesis and Structure-Activity Correlations within Allylamine Antimycotics", Ann. N.Y. Acad. Sci., vol. 544, 1988, pp. 46-62.
von Recklinghausen et al., "Activity of Antibiotics and Azole Antimycotics Against Helicobacter pylori", Int. J. Med., Micr., vol. 280, 1993, pp. 279-285.
Y. Glupczynski, "In vitro Susceptibility Testing of Helicobacter pylori to Antimicrobial Agents: Basis for Treatment or Microbiologists' Obession?", Int. J. Med. Micr., vol. 280, 1993, pp. 227-238.
Jensen, J.C., "Pharmacokinetics of Lamisil in Humans," J. Derm. Treatment, vol. 1, No. Suppl. 2, (1990), pp. 15-8.

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