Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-09-01
2002-10-01
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S220000, C514S003100, C514S369000, C514S866000
Reexamination Certificate
active
06458782
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a medicament useful for preventive and/or therapeutic treatment of diabetes and complications thereof and to a method for preventive and/or therapeutic treatment of diabetes and complications thereof.
2. Discussion of Background Information
As medicaments for treatment of diabetes that can be orally administered, sulfonylurea-type drugs or biguanide-type drugs have conventionally been used. However, sulfonylurea-type drugs are known to cause critical and prolonged hypoglycemia, and biguanide-type drugs cause critical lactic acidosis or hypoglycemia. Therefore, administration of these drugs requires sufficient precautions with respect to doses, methods of administration and so forth.
It has been reported that thiazoline derivatives have hypoglycemic activity (Japanese Patent Unexamined Publication [Kokai] Nos. 61-85372/1986, 60-51189/1985 and the like), and they have been clinically used as medicament for treatment of diabetes having overcome the aforementioned drawbacks. However, because of the diversity of origins of diabetes, thiazoline derivatives cannot always exhibit sufficient curative effects for all patients with diabetes (Diabetes Care, 19, 151). Therefore, it has been desired to develop medicament for treatment of diabetes with still higher effectiveness.
Benzodiazepine derivatives such as 4-[5H-2,3-(2,5-dimethyl-2,5-hexano)-5-methyldibenzo[b,e][1,4]diazepin-11-yl]benzoic acid and 4-[1,3-dihydro-7,8-(2,5-dimethyl-2,5-hexano)-2-oxo-2H-1,4-benzodiazepin-5-yl]benzoic acid have been known (PCT/JP96/2709, International Publication WO97/11061). These compounds have activity for markedly enhancing the action of retinoids such as retinoic acid, while the compounds, per se, have no retinoid action or their retinoid actions are very weak, and they are suggested to be useful for therapeutic and preventive treatment of vitamin A deficiency disease, hyperkeratosis of epithelial tissue, rheumatism, delayed allergy, bone disease, leukemia and certain types of cancer. However, the aforementioned publications neither teach nor suggest that the aforementioned compounds are useful for therapeutic or preventive treatment of diabetes.
SUMMARY OF THE INVENTION
The present invention provides a medicament useful for therapeutic and/or preventive treatment of diabetes. The present invention also provides a medicament useful for therapeutic and/or preventive treatment of complications of diabetes such as hyperlipidemia. The present invention further provides a medicament having such characteristics as mentioned above, which can achieve the therapeutic and/or preventive effects by oral administration, and have reduced or no side effects such as hypoglycemic shock.
Various studies were conducted, and as a result, it was discovered that the benzodiazepine derivatives disclosed in International Publication WO 97/11061 (PCT/JP96/2709) had an excellent action for enhancing differentiation of precursor adipocytes and excellent hypoglycemic action. It was also discovered that those compounds were useful for therapeutic and/or preventive treatment of diabetes, and that when they were used in combination with thiazoline compounds or insulin-like compounds, agents conventionally used for treatment of diabetes, the aforementioned therapeutic and preventive effects were synergistically enhanced.
The present invention thus provides agents for therapeutic and/or preventive treatment of diabetes, which comprise, as an active ingredient, a substance selected from compounds represented by the following general formula (I):
or compounds represented by the following general formula (II):
wherein, R
1
represents hydrogen atom or a C
1-6
alkyl group; R
2
, and R
3
independently represent hydrogen atom or a C
1-6
alkyl group, or R
2
and R
3
may combine together with carbon atoms of the phenyl ring to which R
2
and R
3
bind to represent a 5- or 6-membered ring which may optionally be substituted with one or more C
1-4
alkyl groups; R
4
represents hydrogen atom, a C
1-6
alkyl group, a C
1-6
alkoxyl group, hydroxyl group, nitro group, or a halogen atom; R
5
represents hydrogen atom, a C
1-6
alkyl group, or an aryl-substituted C
1-6
alkyl group; R
6
represents hydrogen atom or a C
1-6
alkyl group; X represents —NR
7
—, —NO—, —O—, —CHR
7
—, —S—, —SO— or —SO
2
— in which R
7
represents hydrogen atom, a C
1-6
alkyl group, or an aryl-substituted C
1-6
alkyl group; and Y represents a phenylene group or a pyridinediyl group, physiologically acceptable salts thereof, and hydrates thereof and solvates thereof
According to another aspect of the present invention, there are provided medicaments for therapeutic and/or preventive treatment of complications of diabetes (for example, hyperlipidemia), which comprise the aforementioned substance as an active ingredient. There are further provided the aforementioned therapeutic and/or preventive medicament, which are used in combination with an agent for therapeutic and/or preventive treatment of diabetes selected from the group consisting of thiazoline compounds and substances having insulin-like action; medicaments for therapeutic and/or preventive treatment of diabetes, which are in the form of a pharmaceutical composition comprising the aforementioned substance and an agent for therapeutic and/or preventive treatment of diabetes which is selected from the group consisting of thiazoline compounds and substances having insulin-like action; medicaments for therapeutic and/or preventive treatment of complications of diabetes, which are in the form of a pharmaceutical composition comprising the aforementioned substance and an agent for therapeutic and/or preventive treatment of diabetes selected from the group consisting of thiazoline compounds and substances having insulin-like action; and the aforementioned therapeutic and/or preventive medicaments, which are used as an agent to enhance the action of an agent for therapeutic and/or preventive treatment of diabetes selected from the group consisting of thiazoline compounds and substances having insulin like action.
According to further aspects of the present invention, there are provided use of the aforementioned substance for the manufacture of the aforementioned therapeutic and/or preventive medicaments; and methods for therapeutic and/or preventive treatment of diabetes or complications thereof, which comprises the step of administering an effective amount of the aforementioned substance to a mammal including human.
DETAILED DESCRIPTION OF THE PRESENT INVENTION
The present invention concerns a medicament which comprises a compound represented by the aforementioned formula (I) or (II) as an active ingredient, and is used for therapeutic and/or preventive treatment of diabetes or therapeutic and/or preventive treatment of complications of diabetes.
In the above general formulae, R
1
represents hydrogen atom or a linear or branched C
1-6
(i.e., having 1 to 6 carbon atoms) alkyl group. Examples of the alkyl group include, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, and tert-butyl group, and methyl group is preferably used. R
2
and R
3
independently represent hydrogen atom or a linear or branched C
1-6
alkyl group. As for the alkyl group, those mentioned above may be used, and ethyl group, isopropyl group, tert-butyl group or the like may preferably be used. The substituting positions of R
2
and R
3
are not particularly limited, and each of them may independently substitute at any position. It is preferred that R
2
and R
3
are in para-position and meta-position with reference to X, respectively, or R
2
and R
3
are in meta-position and ortho-position with reference to X. It is particularly preferred that R
2
and R
3
are in para-position and meta-position with reference to X, respectively.
R
2
and R
3
may combine to form a 5- or 6-membered ring together with two carbon atoms on the phenyl ring to which each
Ekimoto Hisao
Fujii Hideji
Hashimoto Yuichi
Kagechika Hiroyuki
Yonekawa Yoshiaki
Institute of Medicinal Molecular Design Inc.
Weddington Kevin E.
LandOfFree
Remedies for diabetes does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Remedies for diabetes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Remedies for diabetes will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3000302