Kyorin Pharmaceutical Co., Ltd.

Teijin Pharma Limited

Yoshikazu Asahina

Yasumichi Fukuda

Masanori Yamamoto

Koji Murakami

Masanori Takadoi

Tomohiro Ide

Masaya Takei

Kohei Ohata

Kazuya Yokota

Shinji Kobayashi

Fumiyoshi Kobayashi

Kanji Komatsu

Toshiyuki Matsui

Kenji Fujita

Ayako Nakamura

Yasuo Oomori

Futoshi Shiga

Hideyuki Fukuda

Hiroyuki Ebisu

Taro Sato

Satoru Katayama

Taku Shibue

Haruaki Kurasaki

A compound having a hypoglycemic effect is provided. The compound and a pharmaceutically acceptable salt thereof are useful for the treatment or prevention of diabetes, obesity, and the like. The compound is represented by the general formula (1): (wherein Rand Rare each independently a hydrogen atom, a halogen atom, an amino group, a hydroxyl group, a hydroxyamino group, a nitro group, a cyano group, a sulfamoyl group, a Cto Calkyl group, a Cto Calkoxy group, a Cto Calkylsulfanyl group, a Cto Calkylsulfinyl group, a Cto Calkylsulfonyl group, or a Cto Calkoxy-Cto Calkylsulfonyl group, and A is a substituted or unsubstituted heteroaryl group).

Cyclopentylacrylamide derivative

To provide a novel mutilin derivative having a substitution at the 14-position, which is a novel mutilin analogue exhibiting a potent and broad antimicrobial action against Gram-positive bacteria and Gram-negative bacteria including various drug-resistant bacteria, and which is expected to be useful as an agent for treating infectious diseases. A mutilin derivative represented by the following general formula (1): or a pharmaceutically acceptable addition salt thereof.

Mutilin derivative having heterocyclic aromatic ring carboxylic acid structure in substituent at 14-position

A compound represented by the following formula (1): (wherein the carbon atom denoted by * is in the R-configuration; Rand Rare each independently a hydrogen atom, a halogen atom, an amino group, a hydroxyl group, a hydroxyamino group, a nitro group, a cyano group, a sulfamoyl group, a C-Calkyl group, a C-Calkoxy group, a C-Calkylsulfanyl group, a C-Calkylsulfinyl group or a C-Calkylsulfonyl group; and A is a substituted or unsubstituted heteroaryl group), or a pharmaceutically acceptable salt thereof.

Glucokinase activator

Object To provide novel quinolinecarboxylic acid compounds serving as safe, strong antibacterial agents that are effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. Solving Means There are provided 7-(4-substituted-3-cyclopropylaminomethylpyrrolidinyl)quinolonecarboxylic acid derivatives (such as 1-cyclopropyl-7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid) that exhibit strong antibacterial activity against gram-positive bacteria, such as MRSA, PRSP and VRE, while being safe. The compounds are shown by the following general formula (I): 

7- (4-substituted-3-cyclopropylaminomethyl-1-pyrrolidinyl) quinolonecarboxylic acid derivative

Summary Novel bicycloester derivatives and pharmaceutically acceptable salts thereof have high DPP-IV inhibitory activity. Solving Means The novel bicycloester derivatives are represented by the general formula (1): Pharmaceutically acceptable salts thereof are also included (Example: (2S,4S)-1-[[(N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile)).

Bicycloester derivative

A compound, or a pharmaceutically acceptable salt thereof, represented by the formula (1), (wherein, the carbon atom marked with an * is in the R-configuration, Rrepresents a hydrogen atom, a halogen atom, an amino group, a hydroxyl group, a hydroxyamino group, a nitro group, a cyano group, a sulfamoyl group, a C-Calkyl group, or a C-Calkoxy group, Rrepresents a C-Ccycloalkylsulfanyl group, a C-Ccycloalkylsulfinyl group, or a C-Ccycloalkylsulfonyl group, and A represents a substituted or unsubstituted heteroaryl group).

Novel intermediates for the production of aminoacetyl pyrrolidine carbonitrile derivatives ensure the safe and efficient production of the compounds. Specifically, the present invention provides a sulfonyloxyacetyl pyrrolidine derivative, represented by the following formula: (Chemical Formula 1) (wherein R1 is a substituted or unsubstituted C-Calkyl group, a substituted or unsubstituted C-Ccycloalkyl group, a substituted or unsubstituted arylmethyl group, a substituted or unsubstituted aromatic hydrocarbon, a substituted or unsubstituted aromatic heterocyclic ring or a substituted or unsubstituted aliphatic heterocyclic ring; R2 is CONHor CN; and X is CH, CHF or CF.)

Process for producing aminoacetyl pyrrolidine carbonitrile derivative and intermediate for production thereof

Novel bicycloester derivatives and pharmaceutically acceptable salts thereof have high DPP-IV inhibitory activity. The novel bicycloester derivatives are represented by the general formula (1): Pharmaceutically acceptable salts thereof are also included (Example: (2S,4S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile)).

Novel bicycloamide derivatives (general formula (1)) and pharmaceutically acceptable salts thereof effectively inhibit DPP-IV. The bicycloamide derivatives are represented by the general formula (1): Pharmaceutically acceptable salts thereof are also included (Example: (2S,4S)-1-[[(4-carbamoylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile)).

Bicycloamide derivative

To provide novel quinolonecarboxylic acid compounds serving as safe, strong antibacterial agents that are effective against drug-resistant bacteria that are less susceptible to conventional antibacterial agents. There are provided 7-(4-substituted-3-cyclopropylaminomethylpyrrolidinyl)quinolonecarboxylic acid derivatives (such as 1-cyclopropyl-7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid) that exhibit strong antibacterial activity against gram-positive bacteria, such as MRSA, PRSP and VRE, while being safe. The compounds are shown by the following general formula (I): 

7-(4-Substituted-3-cyclopropylaminomethyl-1 pyrrolidinyl) quinolonecarboxylic acid derivative

A novel bicyclo derivative represented by the following general formula (1), or a pharmaceutically acceptable salt thereof, acts as an effective DPP-IV inhibitor:  One example is (2S,4S)-1-[[N-(4-methylbicyclo[2,2,2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile).

Bicyclo derivative

A compound as represented by the general formula (I) shown below exhibits high antibacterial activity against gram-positive bacteria, in particular, such drug-resistant bacteria as mRNA, PRSP and VRE: wherein R1 is a methyl group, a fluoromethyl group, a methoxymethyl group, an acetoxymethyl group, a hydroxymethyl group or a methylene; R2 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, or a pharmaceutically acceptable cation and an ester of a prodrug; R3 is a hydrogen atom or a halogen atom; R4 is a hydrogen atom, a lower alkyl group having 1 to 3 carbon atoms, a fluoromethyl group, a trifluoromethyl group or a fluorine atom; and R5 is a hydrogen atom or a fluorine atom, with exceptions where R1 is a methyl group, R4 and R5 are at the same time a hydrogen atom, and R3 is a fluorine atom.

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Tochigi, Japan

Yoshikazu Asahina