Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Reexamination Certificate
1998-12-10
2001-01-23
Padmanabhan, Sreeni (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
C514S690000, C568S335000, C568S337000, C568S377000
Reexamination Certificate
active
06177474
ABSTRACT:
TECHNICAL FIELD
This invention relates to novel polyhydroxyphenol derivatives, salts thereof, and medicinal compositions containing the same which have been developed for the purpose of being used for preventive and therapeutic osteolytic diseases such as, for example, malignant hypercalcemia, Paget's disease, and osteoporosis and diseases accompanying chondral degeneration and necrosis such as, for example, osteoarthritis apt to attack knees, shoulders, and hip joints, femoral head necrosis, and rheumatoid arthritis.
BACKGROUND ART
Japan has been plunging into such an aging society as has never existed to date and has come to encounter the spread of such osteolytic diseases as osteoporosity as a serious social issue. The term “osteolytic disease” means diseases of bones induced by abnormal aggravation of osteolysis such as, for example, malignant hypercalcemia causes by myeloma and lymphoma, Paget's disease caused by local osteolysis, and osteoporosis caused by various factors like aging and menopause. The growth in the number of aged persons laid up in bed on account of bone fractures which originate in such osteolytic diseases ultimately results in a huge addition to the national medical expenses. At present, vitamin D preparation, calcitonin preparation, and ipriflavone preparation are being used for the therapy of these diseases. The treatment with these medicines allows no radical cure but barely serves as a symptomatic measure. The osteoarthritis, femoral head necrosis, and rheumatoid arthritis form a group of diseases which occur when the articular cartilage and cartilaginified bone are aggravated until degeneration and necrosis by various factors such as, for example, mechanical stress, aging, and inflammation and ultimately suffered to induce defects of bones and cartilages. These chondral defects, by deforming joints and causing pains therein, have a conspicuous effect in the degradation of the quality of daily life of the affected persons. Though the diseases of this category are being treated with hyaluronic acid, anti-inflammatory agent, and analgesic agent, a medicine which is capable of effectively inhibiting or curing chondral defects has not yet been developed.
The object of this invention, therefore, is to improve the existing method of therapy and to provide a novel and more effective preventive and therapeutic medicine.
The present inventors formerly discovered that a substance exhibiting a powerful activity to repress osteolysis is contained in the hops and that the active principle of this substance is an &agr; acid and an iso &agr; acid represented by the following general formula (XIII) (JP-A-07-330594).
(wherein R
1
represents 2-methylpropyl group, 2-propyl group, or 2-butyl group).
It has been pointed out, however, that since the substance (XIII) effective in actively repressing the osteolysis mentioned above is a natural product, it tends to entail such problems as the dependency of the harvest of hops on weather conditions and the difficulty incurred in the procurement thereof. The inventors, with the expectation that the compounds approximating closely to this substance have the possibility of affording active substances as powerful as the aforementioned substance (XIII) capable of repressing osteolysis, have tried structural alterations of the active substance (XIII) mentioned above, synthesized many compounds, and tested them for activity. As a result, they have discovered powerful activity in the polyhydroxyphenol derivatives represented by the general formulas (I)-(XII) to be described herein below. The present invention has been perfected based
0
n this discovery.
DISCLOSURE OF THE INVENTION
This invention relates to a compound represented by the following general formula (I)
(wherein R
1
represents a branched or straight-chain alkyl group of 1-15 carbon atoms, a substituted or unsubstituted benzyl group, or a substituted or unsubstituted aryl group; R
2
represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group; R
3
represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, a substituted or unsubstituted benzyl group, a hydroxyl group, a branched or straight-chain alkoxy group of 1-15 carbon atoms, a branched or straight-chain alkenyloxy group of 2-15 carbon atoms, or a substituted or unsubstituted benzyloxy group; R
4
represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, a substituted or unsubstituted benzyl group, or a hydroxyl group; and R
5
and R
6
independently represent a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group; providing that the case in which R
2
and R
3
are each a hydrogen atom or a 3-methyl-2-butenyl group when R
4
is a hydroxyl group, R
3
and R
6
are each a hydrogen atom, and R
1
is a 2-propyl group or 2-butyl group and the case in which R
2
and R
3
are each a hydrogen atom, a 3-methyl-2-butenyl group, or a 3-methyl-n-butyl group when R
4
is a hydroxyl group, R
5
and R
6
are each a hydrogen atom, and R
1
is a 2-methylpropyl group are excluded) or an acylfluoroglucinol derivative thereof which is a salt thereof.
More specifically, this invention relates to a compound represented by the following general formula (II)
(wherein R
1
represents a 2-methylpropyl group or a 2,6-dimethylheptyl group; and R
2
and R
3
independently represent a hydrogen atom, a 3-methyl-2-butenyl group, a 3,7-dimethyl-2,6-octadienyl group, or a substituted or unsubstituted benzyl group; providing that the case in which R
1
is a 2-methylpropyl group and R
2
and R
3
independently are a hydrogen atom or a 3-methyl-2-butenyl group is excluded)
or an acylfluoroglucinol derivative thereof which is a salt thereof and a compound represented by the following general formula (III)
(wherein R
1
represents a branched or straight-chain alkyl group of 1-15 carbon atoms, a substituted or unsubstituted benzyl group, or a substituted or unsubstituted aryl group; R
2
and R
4
independently represent a hydrogen atom, a branched or straight-chain alkyl group or alkenyl group of 1-15 carbon atoms, or a substituted or unsubstituted benzyl group; and R
5
, R
6
, and R
7
independently represent a hydrogen atom, a branched or straight-chain alkyl group or alkenyl group of 1-15 carbon atoms, or a substituted or unsubstituted benzyl group) or an acylhydroxyhydroquinone derivative thereof which is a salt thereof.
This invention further relates to a compound represented by the following general formula (IV)
(wherein R
1
represents a branched or straight-chain alkyl group of 1-15 carbon atoms, a substituted or unsubstituted benzyl group, or a substituted or unsubstituted aryl group; R
2
represents a hydrogen atom, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group; R
3
represents a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group; and R
8
represents a hydroxyl group, a branched or straight-chain alkyl group of 1-15 carbon atoms, a branched or straight-chain alkenyl group of 2-15 carbon atoms, or a substituted or unsubstituted benzyl group; providing that the case in which R
2
and R
3
are each a 3-methyl-2-butenyl group when R
1
is a methyl group and R
8
is a hydroxyl group and the case in which at least two or three members of the class consisting of R
2
, R
3
, and R
8
are each a 3-methyl-2-butenyl group and the remaining member is a hydrogen atom or a hydroxyl group when R
1
is a 2-propyl group or 2-
Doi Kazuyuki
Kitamura Kazuyuki
Sakai Kunikazu
Satoh Yusuke
Bierman, Muserlian and Lucas
Hoechst Marion Roussel
Padmanabhan Sreeni
LandOfFree
Polyhydroxyphenol derivatives and preventive and therapeutic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polyhydroxyphenol derivatives and preventive and therapeutic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polyhydroxyphenol derivatives and preventive and therapeutic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2556751