Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-12
1999-03-16
Trinh, Ba K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
549548, 549552, 549553, A61K 31335, C07D30346
Patent
active
058831215
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP96/03603 dated Dec. 10, 1996.
TECHNICAL FIELD
The present invention relates to novel epoxysuccinamide derivatives or salts thereof, which exhibit inhibitory activity against cathepsin, and medicines comprising such a derivative or salt.
BACKGROUND ART
On the current trend toward the aging society, abnormal acceleration of bone resorption in a man advanced in years involves many of various senile diseases. In particular, senile osteoporosis is prominent and about to become a great social problem. When the present pharmacotherapy for this senile osteoporosis is viewed, it is conducted to administer (1) estrogen, (2) protein anabolic hormone, (3) calcitonin or (4) vitamin D. However, their effects are found only in improvement of subjective symptom, and hence there is no critical therapy under the circumstances.
On the other hand, it is considered that factors causing osteoporosis include two of calcification and decalcification, and abnormal decomposition of supporting tissue, collagen. However, the development of pharmaceutical agents by paying attention to the abnormal acceleration of collagen decomposition is only now under way. It is reported that this collagen decomposition is involved by a group of cathepsins which are certain kinds of cysteine proteases, and particularly cathepsin L among Vol. 269, No. 1, pp. 189-193 (1990), "Intracellular Proteolysis" (Tokyo Kagaku Dojin)!. It is also proposed to use a cysteine protease inhibitor as a substance, which inhibits decreases of calcium salts and collagen fibers at the same time, in treatment for absorptive osteopathy (Japanese Patent Application Laid-Open Nos. 284127/1988 and 218610/1990). As to compounds which inhibit cathepsin B and cathepsin L, epoxysuccinic acid derivatives are reported in, for example, European Patent Publication No. 655447A1. However, these compounds inhibit cathepsin L and cathepsin B at substantially the same inhibition coefficients, and does not selectively inhibit cathepsin L which is said to involve bone resorption.
It is therefore an object to provide a novel compound which inhibits cathepsin L and family enzymes thereof at a concentration lower than against other cathepsin groups and is useful as an agent for preventing and treating osteopathy such as osteoporosis or hypercalcemia.
DISCLOSURE OF THE INVENTION
In view of the foregoing circumstances, the present inventors have carried out an extensive investigation as to epoxysuccinamide derivatives which specifically inhibit cathepsin L and family enzymes thereof. As a result, the inventors have succeed in inventing compounds satisfying the desired object, thus leading to completion of the present invention.
Namely, the present invention provides an epoxysuccinamide derivative represented by the general formula (1) ##STR2## wherein R.sup.1 and R.sup.2 are the same or different from each other and independently represent a hydrogen atom or an aromatic hydrocarbon group or aralkyl group which may be substituted, or R.sup.1 and R.sup.2 may form a nitrogen-containing heterocyclic ring together with the adjacent nitrogen atoms, R.sup.3 is a hydrogen atom or an acyl group, R.sup.4 is a hydrogen atom or an aralkyl group, and R.sup.5 is an aromatic hydrocarbon group or aralkyl group which may be substituted, or R.sup.5 may form an amino acid residue, which may be protected, together with the adjacent nitrogen atom, or a salt thereof, and a preparation process thereof.
The present invention also provides a medicine comprising the above-described epoxysuccinamide derivative (1) or a salt thereof as an active ingredient.
The present invention further provides a medicinal composition comprising the above-described epoxysuccinamide derivative (1) or a salt thereof and a pharmaceutically acceptable carrier.
The present invention still further provides use of the above-described epoxysuccinamide derivative (1) or a salt thereof for a medicine.
The present invention yet still further provides a method of treating osteopathy, which comprises administ
REFERENCES:
patent: 5556853 (1996-09-01), Tsubotani et al.
Asao Tetsuji
Katunuma Nobuhiko
Suda Yoshimitsu
Tada Yukio
Yamashita Tomohiro
Taiho Pharmaceutical Co. Ltd.
Trinh Ba K.
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