Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-07-10
1997-05-13
Evans, Joseph E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514720, 514733, 549499, 549500, 549501, 549502, 549562, A61K 3134, A61K 3105, A61K 31075
Patent
active
056293402
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP93/01893 Dec. 27, 1993.
TECHNICAL FIELD
The present invention relates to an angiogenesis inhibitor and a novel compound for use therein.
PRIOR ART
While angiogenesis(vascularization) is known to occur in normal physiological states of human beings or animals, such as germinal occurrence and ovulocycle and placentationa in female estrus cycle, and to occur in healthy and normal physiological states such as wound healing and restration processes of inflammations and the like, it is known to occur in a wide variety of pathological states accompanying a rapid increase or expansion of blood capillaries which will cause serious damage to tissues. For example, as described in N. English. J. Med. 285: 1182, 1971, that tumor growth is dependent on the increase in the angiogenesis of the tumor tissue. Mastubara et al. also report, in Inflammation, Vol. 10, No. 4, July 1990, p 241-245, that there is a correlation between the neogenesis of small blood vessels, such as capillaries and postcapillary venules, and the cellular infiltration of monocytes and lymphocytes in inflammatory processes, and that the neogenesis of the small blood vessels serving as a nutrition-supply blood vessel is indispensable for growth of proud flesh.
Other examples of the disorders associated with abnormal acceleration of angiogenesis, ophthalmological diseases such as diabetic retinitis, retrolental fibroplasia, angiogenesis associated with corneal implantation, glaucoma, eye tumor, and trachoma; pediatric diseases such as angioma and fibrous angioma; surgical disorders such as hypertrophic scar and proud flesh; diseases of internal medicine such as rheumatoid arthritis and edematous sclerosis; and a heart disease such as atherosclerosis; and various types of tumors.
Recently, attention has been paid to angiogenesis inhibitor, which may be used in pharmaceuticals for treating the various types of disorders mentioned above. A drug having an anti-angiogenic activity is useful for the treatment of various diseases, during whose pathological processes, it is known that the neogenesis of small blood vessels occurs. These diseases contain, for example, a cancer, a chronic inflammation such as chronic articular rheumatism, diabetic retinitis, prematurity retinitis, various thrombotic disorders in a retina, arteriosclerosis, angioma, fibrous angioma and psoriasis.
As one of drugs having an anti-angiogenic activity, tetrahydrocortizol is disclosed in Inflammation (Vol. 10, No. 4, July 1990, p 241-245) described above. It is also disclosed that some of the anti-rheumatoid agents used in chronic articular rheumatism treatment have the anti-angiogenic activity. Examples of the antirheumatoid agents include SH compounds such as aurothiomaleate sodium, auranofin and D-penicillamine.
However, the drugs having the anti-angiogenic activity have various clinical problems. For example, to express the anti-angiogenic activity, tetrahydrocortizol must be applied together with heparin having an angiogenesis accelerating activity.
On the other hand, Most of the aforementioned anti-rheumatoid agents having the anti-angiogenic activity have serious side effects. They can hardly be applied in view of control of drug administration.
The present invention was made on the basis of the aforementioned circumstances and provides an angiogenesis inhibitor having a remarkable antiangiogenic activity and useful for treatment and protection of various diseases accompanying abnormal acceleration of angiogenesis, and provides a novel compound having the anti-angiogenic activity.
DISCLOSURE OF THE INVENTION
The present inventors made intensive studies with a view toward solving the above-mentioned problems. As a result, they found a remarkable anti-angiogenic activity in lignans which they have previously described in Jpn. Pat. Appln. KOKAI Publication No. 2-180846, provided by the present applicant, and will be described later. They investigated further into the compounds having an anti-angiogenic activity. As a result, they newly foun
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Kusano Mika
Kuwano Michihiko
Ono Mayumi
Takeda Masakazu
Watanabe Junko
Evans Joseph E.
Tsumura & Co.
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