Daiichi Sankyo Company, Limited

Suntory Limited

Asubio Pharma Co. Ltd.

Ausbio Pharma Co., Ltd.

Hidekazu Inoue

Yasuhiro Hayashi

Hidenobu Murafuji

Tetsuo Shimamoto

Masaji Ishiguro

Takashi Nakatsuka

Hitoshi Ohki

Yasuyuki Takeda

Masahiro Ota

Rie Tanaka

Kazuto Sekiuchi

Junya Kawai

Masahiro Imoto

Yoshito Kawamoto

Kenichi Hiramatsu

Minako Tomino

Katsuhide Kamei

Tadashi Toki

Rie Inaba

Bitoku Takahashi

Satoshi Muneoka

Toshiharu Noji

Yamato Suzuki

Cystic fibrosis is developed through mutation of Cystic Fibrosis Transmembrane conductance Regulator (CFTR), which is one type of chloride channel. An object of the present invention is to provide compounds effective in the treatment of cystic fibrosis that open a chloride channel different from CFTR, which is the cause of the disease, and do not depend on CFTR. Compounds of the present invention are compounds or pharmaceutically acceptable salts thereof that open calcium dependent chloride channels (CaCCs) via G-protein coupled receptor 39 (GPR39) agonism to have strong chloride ion-secretory action, and are represented by the following general formula (I): General formula (I): wherein,

Pyrimidine derivative

Provided is a novel compound or a salt thereof inhibiting MTHFD2 and useful for treating a disease caused by overexpression of MTHFD2, a disease involved in overexpression of MTHFD2 and/or a disease associated with overexpression of MTHFD2. Solution Provided is a sulfonamide derivative having a coumarin skeleton represented by the following formula (I) and having various substituents: wherein R, R, R, R, R, Rand Rare the same as defined in the specification,and a salt thereof.

Sulfonamide derivative having coumarin skeleton

Compounds having PDE10A inhibitory activity and having general formula (I), or an isotope thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same as an active ingredient.

Benzothiophene derivative

To provide thienopyrazole derivatives inhibiting PDE 7 selectively, and therefore, enhance cellular cAMP level. Consequently, the compound is useful for treating various kinds of disease such as allergic diseases, inflammatory diseases or immunologic diseases. The compound is thienopyrazole compound represented by the following formula (I): [wherein, especially, Ris a cyclohexyl, a cycloheptyl group or a tetrahydropyranyl group; Ris methyl; Ris a hydrogen atom; and Ris a group: &#x2014;CONRR(in which any one of Rand Ris a hydrogen atom)].

Thienopyrazole derivative having PDE7 inhibitory activity

To provide the compounds inhibiting PDE 7 selectively, and therefore, enhance cellular cAMP level. Consequently, the compound is useful for treating various kinds of disease such as allergic disease, inflammatory disease or immunologic disease. The compound is pyridinylpyrazolo-pyrimidinone compound represented by the following formula (IA) or (IB): especially, Ris cyclohexyl or cycloheptyl group, Ris methyl; Ris a group: &#x2014;NRRor &#x2014;S(O)R;hydrogen atom; nitro group; cyano group; a halogen atom; heteroaryl group; and Ris methoxy or ethoxy group.

Pyridinylpyrazolopyrimidinone derivatives as PDE 7 inhibitors

The present invention provides the compounds inhibiting PDE 7 selectively, and therefore, enhances cellular cAMP level. Consequently, the compound is useful for treating various kinds of disease such as allergic disease, inflammatory disease or immunologic disease. The compound is imidazotriazinone compound represented by the following formula (IA) or (IB): especially, R1 is cyclohexyl group, R2 is methyl group; R3 is a hydrogen atom; nitro group; cyano group; a halogen atom; heteroaryl group; substituted or unsubstituted C1-C6 alkyl group; substituted or unsubstituted C2-C6 alkenyl group; saturated or unsaturated heterocycloalkyl group which is substituted or unsubstituted; a group: &#x2014;NR5R6, &#x2014;C(O)R7, &#x2014;SO2R7, &#x2014;OR8, &#x2014;NR8COR7, &#x2014;NR8S02R7; A is CR4; and B is CH. 

Imidazotriazinone derivatives as PDE 7 (phosphodiesterase 7) inhibitors

Pyrazolopyrimidinone derivatives expressed by the following general formula (IA) or (IB): where the symbols are as disclosed in the specification, are provided as desired compounds. These compounds selectively inhibiting PDE7, thereby increasing the intracellular cAMP level and inhibiting the activation of T cells. Thus, these compounds are useful for prevention and treatment of various allergic diseases and inflammatory or immunological diseases.

1,3,5-trisubstituted-5-phenyl and 5-pyridyl pyrazolopyrimidinone derivatives having PDE7 inhibiting action

1-aryl-1,8-naphthylidin-4-one derivative as type IV phosphodiesterase inhibitor

A 1-cycloalkyl-1,8-naphthylidin-4-one derivative having the formula (I):

1-cycloalkyl-1,8-naphthyridin-4-one derivative as type IV phosphodiesterase inhibitor

A 1-aryl-1,8-naphthylidin-4-one derivative having the formula (I):

A carbapenem derivative represented by the following formula (I), ##STR1## wherein R.sub.1 represents a hydrogen atom, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, R.sub.2 indicates a hydrogen atom or a protective group for a carboxyl group, and R.sub.3 is a methyl group or an ethyl group; or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising this carbapenem derivative or a salt thereof as an active ingredient. The carbapenem derivative exhibits a wide and strong antimicrobial activity, particularly a strong antimicrobial activity against MRSA. An intermediate compound for preparing the carbapenem derivative is also disclosed.

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Osaka, Japan

Hidekazu Inoue