Ono Pharmaceutical Co., Ltd.

Ono Pharmaceuticalco.,ltd.

Kensuke Kusumi

Atsushi Naganawa

Hiroshi Yamamoto

Tetsuya Sekiguchi

Kazuhiro Otsuki

Koji Shinozaki

Akito Kakuuchi

Shigeyuki Nonaka

Takaki Komiya

Haruto Kurata

Toshihide Watanabe

Hiromu Habashita

Shinji Nakade

Hiroshi Hagiya

Takeji Ono

Masashi Minami

Satomi Imaide

Hirotaka Mizuno

Toshimitsu Endo

Hiroshi Saga

Kazuhiro Ohtsuki

Naomi Tsuburaya

Yuichi Inagaki

Shiro Shibayama

Masaya Kokubo

Joseph Raker

Hiroshi Ochiai

Mark Allan Wolf

Yasuko Yamamoto

Yasuyo Kodera

Hiroya Takizawa

A compound represented by the general formula (V) wherein all the symbols are as defined in the specification, has an improved balance of the agonist activity against the S1Preceptor relative to the S1Preceptor, and can thus serve as a therapeutic agent for S1P-mediated diseases such as schizophrenia and Binswanger's disease and other neurodegenerative diseases.

Compounds having S1P5 receptor agonistic activity

A compound represented by general formula (I) wherein all the symbols are as defined in the specification has a selective S1P5 receptor agonist activity due to having a linker from a phenyl group to a cyclic substituent in a dihydronaphthalene skeleton; i.e., due to having a short linker of one atom or less as L in general formula (I), and can therefore serve as an agent for treating S1P5-mediated disease, e. g., neurodegenerative disease such as schizophrenia. 

Dihydronaphthalene derivative

The compound of the formula (I-1): wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1Pantagonistic activity. The compound may therefore be used as a therapeutic agent for S1P-mediated diseases such as diseases resulting from vascular constriction, fibrosis, and respiratory diseases.

Phenyl derivative

Tetrahydronaphthalene derivative

An object of the present invention is to provide a compound having strong human S1Pantagonistic activity in order to develop a useful medicament for therapy of a S1P-mediated disease such as a disease resulting from vascular constriction, fibrosis and respiratory disease. The compound represented by the general formula (I), wherein all the symbols have the same meanings as described in the specification, has a halogen atom or a haloalkyl group and a phenoxy group at certain substitution sites, and thus has strong human S1Pantagonistic activity. Therefore, the compound can be a therapeutic agent for a S1P-mediated disease, such as a disease resulting from vascular constriction, fibrosis and respiratory disease. 

The compound represented by the formula (I-1): wherein all the symbols have the same meanings as described in the specification, has two cyclic groups, particularly phenoxy groups at specific substitution positions and thus has high human S1Pantagonistic activity. The compound may therefore be used as a therapeutic agent for S1P-mediated diseases such as diseases resulting from vascular constriction, fibrosis and respiratory diseases.

A compound having an ability to bind to an SIP receptor and represented by formula (I), a salt thereof, a solvate thereof or a prodrug thereof is useful for prevention and/or treatment of rejection of transplantation, graft-versus-host disease, autoimmune disease, allergic disease and the like: 

Compound capable of binding S1P receptor and pharmaceutical use thereof

A compound represented by general formula (I): a salt thereof, a solvate thereof, or a prodrug thereof wherein all symbols are as defined in the specification. The compound of the present invention has antagonistic activity against CXCR4 and is therefore useful as a preventive and/or therapeutic agent for CXCR4-mediated diseases, for example, inflammatory and immune diseases (for example, rheumatoid arthritis, arthritis, systemic erythematosus, retinopathy, macular degeneration, pulmonary fibrosis, transplanted organ rejection, etc.), allergic diseases, infections (for example, human immunodeficiency virus infection, acquired immunodeficiency syndrome, etc.), psychoneurotic diseases, cerebral diseases, cardiovascular disease, metabolic diseases, cancerous diseases (for example, cancer, cancer metastasis, etc.), or an agent for regeneration therapy.

Compound having acidic group which may be protected, and use thereof

A compound having an ability to bind to an S1P receptor (particularly EDG-6, preferably EDG-1 and EDG-6), for example, the compound represented by formula (I) of the present invention, a salt thereof, a solvate thereof or a prodrug thereof is useful for prevention and/or treatment of rejection of transplantation, graft-versus-host disease, autoimmune disease, allergic disease and the like. wherein ring A is a cyclic group; ring B is a cyclic group which may have substituent(s); X is a spacer having 1 to 8 atoms in its main chain, etc.; Y is a spacer having 1 to 10 atoms in its main chain, etc.; n is 0 or 1, wherein when n is 0, m is 1 and Ris a hydrogen atom or a substituent, and wherein when n is 1, m is 0 or an integer of 1 to 7 and Ris a substituent, and wherein m is 2 or more, Rs are the same or different.

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Osaka, Japan

Kensuke Kusumi