Kissei Pharmaceutical Co., Ltd.

Masayuki Isaji

Hideki Fujikura

Nobuhiko Fushimi

Toshihiro Nishimura

Kenji Katsuno

Kazuo Shimizu

Shigeru Yonekubo

Hirotaka Teranishi

Kazuya Tatani

Norihiko Kikuchi

Takeshi Nakabayashi

Masahiro Hiratochi

Akira Iyobe

Fumiaki Ito

Minoru Fujioka

Hiroshi Miyata

Yukiyoshi Ajisawa

Shigeki Tazawa

Tokuhisa Yamato

Hiroaki Shiohara

Hidetoshi Isawa

Yukihiko Hotei

Masaki Tomae

Itaru Miyashita

Masaaki Takemura

Toshihide Shibazaki

Yoshimitsu Komatsu

Takashi Miyagi

Hideyuki Muranaka

Yoshinori Nonaka

Yu Kuramochi

Yoshiki Tokutake

Yoshikazu Fujimori

The present invention provides pyrazole derivatives, uses thereof for medical purposes and so on. More particularly, the present invention relates to pharmaceuticals useful for the prevention or treatment of constipation, which comprise as an active ingredient 3-(3-{4-[3-(&#x3b2;-D-glucopyranosyloxy)-5-isopropyl-1H-pyrazol-4-ylmethyl]-3-methylphenoxy}propylamino)-2,2-dimethylpropionamide, or a pharmaceutically acceptable salt thereof. The pharmaceuticals of the present invention exert an effect of increasing the frequency of bowel movement or the like, and are useful for the prevention or treatment of constipation.

Pyrazole derivative and use thereof for medical purposes

The present invention provides pharmaceutical compositions useful as agents for the inhibition of progression of diseases associated with abnormal accumulation of liver lipids. In particular, the pharmaceutical compositions of the present invention which comprise as an active ingredient a sodium/glucose co-transporter 2 inhibitor are highly suitable as an agent for the inhibition of progression of not only common fatty liver but also non-alcoholic fatty liver disease (NAFL), non-alcoholic steatohepatitis (NASH), hypernutritive fatty liver, diabetic fatty liver, alcoholic fatty liver disease toxic fatty liver or the like.

Progression inhibitor for disease attributed to abnormal accumulation of liver fat

The present invention provides pyrazole derivatives represented by the general formula: wherein Rrepresents H, an optionally substituted Calkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted Calkyl group etc.; Rrepresents H, a halogen atom, OH, an optionally substituted Calkyl group etc.; X represents a single bond, O or S; Y represents an optionally substituted Calkylene group etc.; Z represents &#x2014;R, &#x2014;CORetc. in which Rrepresents an optionally substituted Calkyl group etc.; and Rrepresents an optionally substituted Calkyl group etc.; Rrepresents H, an optionally substituted Calkyl group etc.; and R, Rand Rrepresent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, impaired glucose tolerance, impaired fasting glycemia, diabetic complications or obesity, and a disease associated with the increase of blood galactose level such as galactosemia, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

Pyrazole derivatives, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof

The present invention provides fused heterocyclic derivatives represented by the following general formula (I) or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, in the formula Rto Rrepresent H, OH, an amino group, etc.; Rand Rrepresent H, OH, a halogen atom, an option ally substituted alkyl group, etc.; Q represents alkylene, alkenylene, etc.; ring A represents an aryl group or a heteroaryl group; the following ring (R1) represents a group represented by the following ring (R2); G represents a group represented by the following general formula (G-1) or (G-2) (Erepresents H, F or OH; and E represents H, F, a methyl group, etc.), and pharmaceutical compositions comprising the same, and pharmaceutical uses thereof. 

Fused heterocycle derivative, medicinal composition containing the same, and medicinal use thereof

The present invention provides nitrogen-containing fused-ring derivatives represented by the following general formula, or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, in the formula Rrepresent H, an optionally substituted alkyl group, an alkenyl group, etc.; Rrepresent H, a halogen atom or an alkyl group; Rand Rrepresent H, OH, a halogen atom, an optionally substituted alkyl group, etc.; Y represents CH or N; Q represents alkylene, alkenylene, etc.; ring A represents an aryl group or a heteroaryl group; G represents a group represented by the following general formula (G-1) or (G-2) (in which Erepresents H, F or OH; and Erepresents H, F, a methyl group, etc.), and pharmaceutical compositions comprising the same, and pharmaceutical uses thereof. 

Nitrogenous fused-ring derivatives, medicinal compositions containing the derivatives, and use thereof as drugs

The present invention provides glucopyranosyloxypyrazole derivatives represented by the general formula: wherein R represents a hydrogen atom, a lower alkyl group or a group forming a prodrug; one of Q and T represents a group represented by the general formula: (wherein P represents a hydrogen atom or a group forming a prodrug), while the other represents a lower alkyl group or a halo(lower alkyl) group; Rrepresents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a lower alkylthio group, a halo(lower alkyl) group or a halogen atom; and with the proviso that P does not represent a hydrogen atom when R represents a hydrogen atom or a lower alkyl group, or pharmaceutically acceptable salts thereof, which exert an inhibitory activity in human SGLT2 and have an improved oral absorption, and therefore are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutically acceptable salts thereof, and pharmaceutical uses thereof.

Glucopyranosyloxypyrazole derivatives and use thereof in medicines

Pyrazole derivatives represented by the general formula: wherein Rrepresents H, an optionally substituted Calkyl group etc.; one of Q and T represents a group selected from the following groups: and the other represents &#x2014;(CH)&#x2014;Ar wherein Ar represents a substituted Caryl group, etc., and n represents 0 to 2, R represents an optionally substituted Ccycloalkyl group, etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human 1,5-anhydroglucitol/fructose/mannose transporter and are useful as agents for the prevention, inhibition of progression or treatment of a disease associated with the excess uptake of at least a kind of carbohydrates from glucose, fructose and mannose or a disease associated with hyperglycemia and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

Pyrazole derivative, medicinal composition containing the same, medicinal use thereof and intermediate in producing the same

The present invention provides nitrogen-containing fused cyclic derivatives represented by the following general formula or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, in the formula one of Rand Rrepresents a group represented by the following general formula (S) (in which Rand Rrepresent H, OH, a halogen atom, etc.; Q represents an alkylene group etc.; and ring A represents an aryl group etc.), and the other represents H, OH, an amino group, etc.; Rand Rrepresent H, OH, an amino group, a halogen atom, and an optionally substituted alkyl group, etc.; Arepresents O, S, etc.; Arepresents CH or N; G represents a group represented by the following general formula (G-1) or (G-2) (Erepresents H, F or OH; and Erepresents H, F, a methyl group, etc.), and pharmaceutical compositions comprising the same, and pharmaceutical uses thereof. 

The present invention provides nitrogen-containing heterocyclic derivatives represented by the general formula: wherein Xrepresents N or CR; Xrepresents N or CR; Xrepresents N or CR; Xrepresents N or CR; and with the proviso that one or two of Xto Xrepresent N; R represents optionally substituted Ccycloalkyl, optionally substituted Caryl, etc.; Rto Rrepresent H, a halogen atom, etc.) or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exert an excellent inhibitory activity in human SGLT2 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications, obesity or the like, pharmaceutical compositions comprising the same, and medicinal uses thereof.

Nitrogen-containing heterocyclic derivatives, medicinal compositions containing the same and medicinal use thereof

The present invention provides pyrazole derivatives represented by the general formula: wherein Rrepresents H, an optionally substituted Calkyl group etc.; one of Q and T represents a group represented by the general formula: or a group represented by the general formula: while the other represents an optionally substituted Calkyl group etc.; Rrepresents H, a halogen atom, OH, an optionally substituted Calkyl group etc.; X represents a single bond, O or S; Y represents a single bond, a Calkylene group etc.; Z represents CO or SO; Rand Rrepresent H, an optionally substituted Calkyl group etc.; and R, Rand Rrepresent H, a halogen atom etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT1 and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, diabetic complications or obesity, and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

Pyrazole derivative, medicinal composition containing the same, medicinal use thereof, and intermediate for production thereof

The present invention provides pyrazole derivatives represented by the general formula: wherein Rrepresents H, an optionally substituted Calkyl, etc.; one of Q and T represents a group selected from the following: and the other represents -Z-Ar wherein Z represents &#x2014;O&#x2014;, &#x2014;S&#x2014;, etc.; Ar represents an optionally substituted Caryl, etc.;R represents an optionally substituted Ccycloalkyl, an optionally substituted Caryl, etc., pharmaceutically acceptable salts thereof, and prodrugs thereof, which exhibit an excellent inhibitory activity in human sodium/glucose cotransporter (SGLT) and are useful as agents for the prevention, inhibition of progression or treatment of a disease associated with the excess uptake of at least a kind of carbohydrates selected from glucose, fructose and mannose (diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications, etc.), and pharmaceutical compositions containing the same, medicinal uses thereof and intermediates for production therefor.

Pyrazole derivative, drug composition containing the same and production intermediate therefor

The present invention provides pyrazole derivatives represented by the general formula: wherein Rrepresents H, an optionally substituted Calkyl group etc.; one of Q and T represents a group selected from the following groups: and the other represents &#x2014;(CH)&#x2014;Ar wherein Ar represents an optionally substituted Caryl group or an optionally substituted Cheteroaryl group; and n represents an integral number from 0 to 2, an optionally substituted Calkoxyl group, an optionally substituted amino group, an optionally substituted Cheterocycloalkyl group or an optionally substituted heterocycle-fused phenyl group; R represents an optionally substituted Ccycloalkyl group, an optionally substituted Caryl group etc., pharmaceutically acceptable salts thereof or prodrugs thereof, which exhibit an excellent inhibitory activity in human 1,5-anhydroglucitol/fructose/mannose transporter and are useful as agents for the prevention, inhibition of progression or treatment of a disease associated with the excess uptake of at least a kind of carbohydrates selected from glucose, fructose and mannose or a disease associated with hyperglycemia (e.g., diabetic complications, diabetes, etc.), and pharmaceutical compositions comprising the same, pharmaceutical uses thereof, and intermediates for production thereof.

The present invention provides fused heterocyclic derivatives represented by the general formula: wherein Rrepresents H, halogen, OH, etc.; Rrepresents H, halogen or an alkyl group; Rand Rrepresent H, OH, halogen, etc.; Q represents alkylene, etc.; ring A represents aryl or heteroaryl; and G represents or pharmaceutically acceptable salts thereof, or prodrugs thereof, which exhibit an excellent inhibitory activity in human SGLT and are useful as agents for the prevention or treatment of a disease associated with hyperglycemia such as diabetes, postprandial hyperglycemia, impaired glucose tolerance, diabetic complications or obesity, pharmaceutical compositions comprising the same, and pharmaceutical uses thereof.

Growing community of inventors

Nagano, Japan

Masayuki Isaji