Kissei Pharmaceutical Co., Ltd.

Kazuo Shimizu

Masato Iizuka

Masayuki Isaji

Masahiro Hiratochi

Yasushi Takigawa

Hideki Fujikura

Nobuhiko Fushimi

Norihiko Kikuchi

Shigeru Yonekubo

Hirotaka Teranishi

Takashi Miyagi

Kohsuke Ohno

Yasunori Ueno

Fumiaki Ito

Hikaru Suzuki

Masaki Tomae

Yusuke Onda

Toshihide Shibazaki

Hideyuki Muranaka

Kazuya Tatani

Hiroaki Shiohara

Yoshinori Nonaka

Yu Kuramochi

Masato Lizuka

The present invention provides a new compound which has NKreceptor antagonist activity, whose CYP3A4 inhibitory activity is reduced compared to aprepitant, and which are useful for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting. That is, the present invention relates to carboxymethyl piperidine derivatives represented by the following formula (I) or a pharmaceutically acceptable salt thereof. Wherein, ring A is a benzene ring or the like; ring B is a pyridine ring or the like; Ris Calkyl or Calkoxy; Rand Rare a hydrogen atom or methyl; and n is an integral number from 0 to 5. 

Carboxymethyl piperidine derivative

A problem of the present invention is to provide a new compound which has NKreceptor antagonist activity, whose CYP3A4 inhibitory activity is reduced compared to aprepitant, and which are useful for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting. That is, the present invention relates to cyclohexyl pyridine derivatives represented by the following formula (I) or a pharmaceutically acceptable salt thereof, wherein, ring A is 4-fluoro-2-methylphenyl or the like; X is a hydrogen atom or the like; Ris carboxymethyl or the like; Ris alkyl or the like; Y is 0-2 or the like; U is &#x2014;N(CH)COC(CH)-3,5-bistrifluoromethylphenyl or the like. 

Cyclohexyl pyridine derivative

A problem of the present invention is to provide a new compound which has NKreceptor antagonist activity, whose CYP3A4 inhibitory activity is reduced compared to aprepitant, and which are useful for the prevention or treatment of cancer-chemotherapy-induced nausea and vomiting. That is, the present invention relates to cyclohexyl pyridine derivatives represented by the following formula (I) or a pharmaceutically acceptable salt thereof. wherein, ring A is 4-fluoro-2-methylphenyl or the like; X is a hydrogen atom or the like; Ris carboxymethyl or the like; Ris alkyl or the like; Y is 0-2 or the like; U is &#x2014;N(CH)COC(CH)-3,5-bistrifluoromethylphenyl or the like. 

(Aza)indolizine derivatives represented by Formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, salts thereof or the like. In Formula (I), 0 to 2 of X, X, Xand Xare a nitrogen atom and the others are CR; one of Tand Trepresents cyano and the other represents a group represented by Formula (A), with the proviso that when Tis cyano, at least one of Xto Xis a nitrogen atom; Rindependently represents a hydrogen atom, a halogen atom, a hydroxy group, Calkyl, Calkoxy or the like; ring U represents a benzene ring or the like; m represents integral number from 0 to 2; Rindependently represents a fluorine atom, a hydroxy group or the like. 

(aza)indolizine derivative and pharmaceutical use thereof

Compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level and the like. Fused heterocyclic derivatives represented by the following formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, or prodrugs thereof, or pharmaceutically acceptable salts thereof. In the formula (I), ring U represents Caryl or the like; Rindependently represents a hydrogen atom, a hydroxy group, Calkyl or the like; m represents an integral number from 1 to 2; ring Q represents 5-membered heteroaryl; n represents an integral number from 1 to 3; Rindependently represents a hydrogen atom, a halogen atom, Calkyl or the like. 

Fused heterocyclic derivative and pharmaceutical use thereof

5-membered heterocyclic derivatives represented by general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro, cyano and the like; ring J represents aryl or heteroaryl; Q represents carboxy, 5-tetazolyl and the like; Y represents H, OH, NH, halogen, haloalkyl and the like; Xand Xindependently represent CRor N; Rrepresents H, alkyl and the like; Rrepresents halogen, cyano, haloalkyl, A-D-E-G-L-M, &#x2014;N(-D-L-M)and the like, A represents a single bond, O, S and the like; D, G and M independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E and L independently represent a single bond, O, S, COO, SOand the like. 

5-membered nitrogen containing heterocyclic derivatives and pharmaceutical compositions comprising the same

The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level which has a uricosuric activity or the like. The present invention relates to (aza)indole derivatives represented by the following general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro or cyano and the like; ring J represents aryl or heteroaryl and the like; Q represents carboxy or 5-tetazolyl and the like; Y represents H, OH, NH, halogen, nitro, alkyl, alkoxy and the like; X, Xand Xindependently represent CRor N; Rand Rindependently represent halogen, cyano, haloalkyl, A-D-E-G, &#x2014;N(-D-E-G)and the like, in the formula, A represents a single bond, O, S and the like; D and G independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E represents a single bond, O, S, COO, SOand the like. 

(aza)indole derivative and use thereof for medical purposes

The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level and the like. That is, the present invention relates to indolizine derivatives represented by the following formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, salts thereof or the like. In the formula, ring U represents aryl or heteroaryl; Rrepresents halogen, a hydroxy group or the like; Rrepresents halogen, a hydroxy group, alkyl, alkoxy, alkyl substituted by fluorine, alkoxy substituted by fluorine or the like; m represents a number from 0 to 2; n represents a number from 0 to 3; and Rrepresents hydrogen, fluorine or the like. 

Indolizine derivative and use thereof for medical purposes

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 compounds useful as agents for the prevention or treatment of a disease associated with abnormal plasma uric acid level and the like. The present invention relates to fused ring derivatives represented by the following formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of plasma uric acid level, prodrugs thereof, salts thereof or the like. In the formula (I), Xand Xrepresent CH or N; ring U represents aryl or heteroaryl; m represents integral number from 0 to 2; n represents integral number from 0 to 3; Rrepresents a hydroxy group, amino or Calkyl; Rrepresents Calkyl, Calkoxy Calkyl or the like. 

Fused-ring derivative and medical application of same

The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level which has a uricosuric activity or the like. The present invention relates to 5-membered heterocyclic derivatives represented by the following general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro, cyano and the like; ring J represents aryl or heteroaryl; Q represents carboxy, 5-tetazolyl and the like; Y represents H, OH, NH, halogen, haloalkyl and the like; Xand Xindependently represent CRor N; Rrepresents H, alkyl and the like; Rrepresents halogen, cyano, haloalkyl, A-D-E-G-L-M, -N(-D-L-M)and the like, in the formula, A represents a single bond, O, S and the like; D, G and M independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E and L independently represent a single bond, O, S, COO, SOand the like. 

The present invention provides compounds useful as agents for the prevention or treatment of a disease associated with abnormal serum uric acid level which has a uricosuric activity or the like. The present invention relates to (aza)indole derivatives represented by the following general formula (I) having xanthine oxidase inhibitory activities and useful as agents for the prevention or treatment of a disease associated with abnormality of serum uric acid level, prodrugs thereof, or salts thereof. In the formula (I), T represents nitro or cyano and the like; ring J represents aryl or heteroaryl and the like; Q represents carboxy or 5-tetrazolyl and the like; Y represents H, OH, NH, halogen, nitro, alkyl, alkoxy and the like; X, Xand Xindependently represent CRor N; Rand Rindependently represent halogen, cyano, haloalkyl, A-D-E-G, &#x2014;N(-D-E-G)and the like, in the formula, A represents a single bond, O, S and the like; D and G independently represent optionally substituted alkylene, cycloalkylene, heterocycloalkylene, arylene, heteroarylene and the like; E represents a single bond, O, S, COO, SOand the like. 

(Aza)indole derivative and use thereof for medical purposes

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. 

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Azumino, Japan

Kazuo Shimizu