Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
2003-01-03
2004-11-02
O'Sullivan, Peter (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C564S086000, C564S088000, C564S090000, C564S092000
Reexamination Certificate
active
06812252
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention relates to new acylsulfonamide derivatives, in particular, new acylsulfonamide derivatives having hypoglycemic effect.
Diabetes is a disease caused by various factors such as overeating, lack of exercise, stress and hereditary factors. The number of the patients suffering from diabetes is increasing as the life of the people is improved. At present, the number of diabetes cases is so large that this disease is called “a national disease” in Japan. Diabetes is classified into two types, i. e. insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM). In Japan, at least 90% of diabetes cases is NIDDM. Patients suffering from NIDDM scarcely have the subjective symptoms and when the patients are found to suffer from this disease, the disease has already progressed in many cases. In such a case, a suitable therapy is required for avoiding complications.
For the treatment of NIDDM, dietetic therapy or kinetotherapy is employed at first. By such a therapy, the effects such as reduction in obesity, increase in the insulin sensitivity and reduction of insulin requirement in peripheries and reduction of endogenous insulin requirement can be expected. As a result, the blood glucose level can be controlled. However, in many cases, a sufficient effect in reducing the blood glucose level cannot be obtained by the dietetic therapy or kinetotherapy. In such cases, the patients are treated with medicines.
Hypoglycemic agents known at present include insulin preparations, insulin secretion accelerators, &agr;-glucosidase inhibitors, biguanide and glitazone compounds. Depending on the pathological conditions of the patients, a medicine is given alone or in combination with other medicines having different action mechanisms.
In the background of NIDDM onset, it is considered to be important to solve the obesity caused by excess in vivo energy due to overeating and lack of exercise and also insulin resistance induced thereby. In the above-described medicines, glitazone compounds, capable of reducing the blood glucose level by releasing the insulin resistance, attract the greatest attention.
Glitazone compounds induce the differentiation of fat cells by activating PPAR &ggr; which is one of intranuclear receptors, and thus improve insulin resistance of peripheral tissues and exhibit the pharmaceutical effect. However, these compounds have strong side effects, and a serious hepatopathy including cases of death was reported. Further, because these compounds accelerate the differentiation of fat cells, the fat accumulation is accelerated to induce the obesity. Also in clinical cases, reduction or weakening of the pharmaceutical effect of them by the increase in the body weight or accumulation of fats was also reported.
DISCLOSURE OF THE INVENTION
The treatment with the above-described hypoglycemic agents is not yet satisfactory and, also the glitazone compounds which now attract the attention are also not yet perfect because of the above-described side effects. Under these circumstances, an object of the present invention is to develop a new compound having a hypoglycemic effect equal to or superior to the effects of the conventional medicines and free from the side effects unlike the glitazone compounds.
After intensive investigations, the inventors have found acylsulfonamide derivatives of general formula (I) given below. The present invention has been completed on the basis of this finding.
The present invention provides acylsulfonamide derivatives of the following general formula (I):
wherein Ar represents a phenyl group substituted with one or more fluorine atoms, trifluoromethyl groups or trifluoromethoxyl groups, R
1
represents a substituted or unsubstituted C
1
to C
20
alkyl group, a substituted or unsubstituted C
2
to C
20
alkenyl group, a substituted or unsubstituted C
2
to C
20
alkynyl group, a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group, a substituted amino group, a substituted or unsubstituted C
1
to C
20
alkoxyl group, a substituted or unsubstituted C
2
to C
20
alkenyloxyl group, a substituted or unsubstituted C
2
to C
20
alkynyloxyl group or a group of the formula: R
4
O— wherein R
4
represents a substituted or unsubstituted aromatic hydrocarbon group or a substituted or unsubstituted aromatic heterocyclic group, and ring A represents a substituted or unsubstituted aromatic hydrocarbon group, a substituted or unsubstituted aromatic heterocyclic group or a substituted or unsubstituted cycloalkyl group.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The detailed description will be made on the acylsulfonamide derivatives of the present invention. In this specification, the term “C
1
to C
20
alkyl groups” includes linear, branched and cyclic groups such as methyl, ethyl, n-propyl, 1-methylethyl, cyclopropyl, n-butyl, 2-methylpropyl, 1-methylproyl, 1,1-dimethylethyl, cyclobutyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, cyclopentyl, 2,2-dimethylpropyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 3,3-dimethylbutyl, cyclohexyl, n-heptyl, 1-methylhexyl, 2-methylhexyl, 5-methylhexyl, 4,4-dimethylpentyl, 1-propylbutyl, 2-ethylpentyl, cyclohexylmethyl, 1,1-diethylpropyl, cycloheptyl, n-octyl, 1-methylheptyl, 6-methylheptyl, 1-ethylhexyl, 2-ethylhexyl, 2-cyclohexylethyl, 5,5-dimethylhexyl, cyclooctyl, n-nonyl, 1-methyloctyl, 7-methyloctyl, 6,6-dimethylheptyl, n-decyl, 1-methylnonyl, 8-methylnonyl, 7,7-dimethyloctyl, n-undecyl, 1-methyldecyl, 9-methyldecyl, 8,8-dimethylnonyl, n-dodecyl, 1-methylundecyl, 10-methylundecyl, 5-methylundecyl, 9,9-dimethyldecyl, dodecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl and eicosyl groups. These alkyl groups may have various substituents. Examples of the substituents include halogen atoms such as chlorine, bromine, iodine and fluorine atoms, nitro group, amino group, cyano group, hydroxyl group, alkoxyl groups, thiol group, oxo group, trichloromethyl group, trifluoromethyl group, aromatic hydrocarbon groups such as phenyl and naphthyl groups, and aromatic heterocyclic groups such as thienyl, furyl and pyridyl groups. These aromatic hydrocarbon groups and aromatic heterocyclic groups may further have substituents such as halogen atoms, alkyl groups, alkoxyl groups, nitro group, amino group, cyano group, hydroxyl group and thiol group.
The “C
2
to C
20
alkenyl groups” may be linear or branched groups. They include, for example, 1-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, ethenyl, 1-methylethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 2-pentenyl, 1-pentenyl, 3-methylbutenyl, 1,3-butanedienyl, 1-hexenyl, 2-hexenyl, 3,3-dimethyl-l-butenyl, 4,4-dimethyl-1-pentenyl, 1,3-pentanedienyl, 1,3-hexanedienyl, 2-cyclohexylethenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tridecadienyl, tetradecenyl, tetradecadienyl, pentadecenyl, pentadecadienyl, pentadecatrienyl, hexadecenyl, hexadecadienyl, hexadecatrienyl, heptadecenyl, heptadecadienyl, heptadecatrienyl, octadecenyl, octadecadienyl, octadecatrienyl, nonadecenyl, nonadecadienyl, nonadecatrienyl, eicosenyl, eicosadienyl and eicosatrienyl groups. These alkenyl groups may further have various substituents. Examples of them may be the same as those listed above as the substituents of the C
1
to C
12
alkyl groups.
The “C
2
to C
20
alkynyl groups” may be linear or branched groups. They include, for example, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl, 1-ethyl-2-propynyl, ethynyl, 1-butynyl, 2-butynyl, 1,3-butadiynyl, 1-pentynyl, 2-pentynyl, 1,3-pentadiynyl, 1-hexynyl, 2-hexynyl, 1,3-hexadiynyl, tridecynyl, tridecadiynyl, tetradecynyl, tetradecadiynyl, pentadecynyl, pentadecadiynyl, pentadecatriynyl, hexadecynyl, hexadecadiynyl, hexadecatriynyl, heptadecynyl, heptadecadiynyl, heptadecatriynyl, octadecynyl, octadecadiynyl, octadecatriynyl, nonadecynyl, nonadecadiynyl, nonadecatriynyl, eicosynyl, eicosadiynyl and eicosatriynyl groups.
Ikawa Hiroshi
Kojima Kazuhiro
Kosono Hideki
Nakamura Takashi
Nishimura Masato
Ajinomoto Co. Inc.
O'Sullivan Peter
LandOfFree
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