Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1986-09-03
1990-02-20
Gerstl, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514461, 514530, 514532, 514583, A61K 3134, A61K 31557, A61K 31175
Patent
active
049027174
DESCRIPTION:
BRIEF SUMMARY
This invention relates to the treatment of neoplastic and in particular of hormone-dependent neoplasias.
Certain neoplasias, for example prostatic, mammary and endometrial carcinomas, are hormone-dependent and such neoplasias may be treated not only with cytotoxic agents but also by altering the hormonal status of the patient. However, although such endocrine therapy can produce worthwhile results, there is the same urgent need in this area as exists with other types of neoplastic disease for improvement in the existing methods of treatment.
We have now found that compounds possessing thromboxane antagonist activity have a previously quite unexpected use in the treatment of hormone-dependent neoplastic disease, this being an area quite unconnected with the existing pharmaceutical uses for such compounds. One group of compounds described as having activity at thromboxane receptor sites which is of particular interest in the context of the present invention comprises those compounds developed by Jones and Wilson and described in UK patent Nos. (a) 2039909, (b) 2039480; (c) 2081258 and (d) 2113678 and their equivalents [(a) European Pat. No. 0013607, Japanese Pat. application No. 80/500131 and U.S. Pat. No. 4,430,345; (b) European Pat. 0013,608, Japanese Pat. application No. 80/500132 and U.S. Pat. No. 4,438,136; (c) European Pat. application No. 81303000.4, Japanese Pat. application No. 81/502230 and U.S. patent application No. 349,084; and (d) European Pat. application 82306605.5, Japanese Pat. application 83/500327 and U.S. patent application 531,899].
In addition to the description of the medical uses of these compounds to be found these patent specifications, reports upon certain of the compounds have appeared in the scientific literature concerning investigations of a more academic character into the detailed nature of their activity, but without identifying any further uses for the compounds beyond those described in the patent specifications. The present invention is based upon an appreciation that one facet of the activity of these and other compounds having thromboxane antagonist activity provides a further valuable medical use for them.
Accordingly the present invention comprises a compound having thromboxane antagonist activity for use in the manufacture of a medicament for use in the treatment hormone-dependent neoplasias.
The present invention is based upon an appreciation that it is possible to utilise the newly discovered additional properties possessed by compounds having thromboxane antagonist activity of inhibition of the growth of hormone-dependent, particularly oestrogen-dependent, tissue and stimulation of blood flow to such tissue in the treatment of neoplastic disease. Thus the compounds may be applied to the treatment of neoplastic disease in hormone-dependent tissue either alone or in conjunction with hormonal therapy agents and/or with cytotoxic agents when the effect produced by these agents can be enhanced. The use of the compound alone to produce an inhibitory effect on the growth of the neoplastic tissue is clearly of value per se and by using the compound together with a hormonal therapy agent the effect upon growth produced by the compound augments that produced by the agent. When the compound is used in conjunction with a cytotoxic agent the effect of the compound will be to selectively improve the blood flow through the neoplastic tissue and thereby increase the selectivity of the cytotoxic agent.
Thromboxane antagonist compounds of use in the present invention may be of various types. The compounds of particular interest are those which are inhibitors acting at the thromboxane A.sub.2 (TXA.sub.2) receptor site. These may take a wide variety of forms, extending to thromboxane antagonists described by other workers as well as those described in the four UK patents referred to hereinbefore. The antagonists include non-prostanoid compounds such as 4-[2-benzenesulphonamido-ethyl]-phenoxyactic acid, and N,N'-bis-[7-(3-chlorobenzeneaminosulphonyl)-1,2,3,4-tetrahydroisoquinolyl] -d
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Senior Judith
Troughton Kay M.
Gerstl Robert
National Research Development Corporation
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