Ono Pharmaceutical Co., Ltd.

Ono Pharmaceuticals Co., Ltd.

Satoshi Itadani

Jun Takeuchi

Masato Higashino

Masahiro Ikura

Tetsuya Yasuhiro

Takeshi Nagaura

Kazuya Hashimura

Manabu Fujita

Yoshisuke Nakayama

Shinya Takahashi

Tadashi Tatsumi

Shizuka Ono

Kazuyuki Ohmoto

Takahiro Nekado

Hideomi Kijima

Junya Ueda

The present invention provides a drug containing a compound having Trk-inhibiting activity as an active ingredient in prophylaxis and/or therapy for Trk-related diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. A compound represented by the general formula (I), wherein all symbols represent the same meanings as described in the specification, a salt thereof, an N-oxide thereof, a solvate thereof or a prodrug thereof is useful as a drug component having Trk-inhibiting activity in prophylaxis and/or therapy of diseases such as pain, pruritus, lower urinary tract dysfunction, asthma, allergic rhinitis, inflammatory bowel disease or Chagas disease. 

Trk-inhibiting compound

In order to provide a prophylactic and/or therapeutic agent for Trk-related diseases, the present invention provides a compound which has a selective Trk-inhibiting activity and persistently inhibits NGF vascular hyper permeability and does not have a drug interaction and in addition thereto, is excellent in solubility and absorbability against free bases. The compound of the present invention has a selective Trk-inhibiting activity and persistently inhibits NGF vascular hyper permeability and does not have a drug interaction and is excellent in solubility and absorbability against free bases, and is therefore useful as a prophylactic and/or therapeutic agent for Trk-related diseases.

Acid-addition salt of Trk-inhibiting compound

The present invention provides type C crystal of compound I, type B crystal of compound II, or type C crystal of compound III set forth in this specification.

Crystalline forms of 4, 4'-[4-fluoro-7-({4-[4-(3-fluoro-2-methylphenyl) butoxy] phenyl} ethynyl)-2-methyl-1H-indole-1,3-diyl] dibutanoic acid, 4,4&#x2032;-[2-methyl-7-({4-[4-(pentafluorophenyl) butoxy] phenyl} ethynyl)-1H-indole-1, 3-diyl] dibutanoic acid, and 4,4&#x2032;-[4-fluoro-2-methyl-7-({4-[4-(2, 3, 4, 6-tetrafluorophenyl) butoxy] phenyl} ethynyl)-1H-indole-1, 3-diyl] dibutanoic acid

The present invention relates to a compound of formula (I) (wherein all symbols have the same meanings as described hereinbefore). The compound antagonizes cysLTand therefore, it is useful as an agent for the prevention and/or treatment of respiratory diseases such as bronchial asthma, bronchial asthma, chronic obstructive pulmonary disease, pneumonectasia, chronic bronchitis, pneumonia (e.g. interstitial pneumonitis etc.), severe acute respiratory syndrome (SARS), acute respiratory distress syndrome (ARDS), allergic rhinitis, sinusitis (e.g. acute sinusitis, chronic sinusitis, etc.), and the like, or as an expectorant or antitussives.

Substituted indole derivatives for the treatment of respiratory diseases

As a compound having a potent oral activity and a long-lasting cysLT/cysLTreceptor antagonistic activity, the compound of the formula (I): which exhibits potent antagonistic activity against the cysLT/cysLTreceptor, and have long-lasting effects even in case of oral administration, and therefore is useful as an oral agent for preventing and/or treating a variety of diseases, for example, respiratory disease (for example, asthma (bronchial asthma, etc.), chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, pneumonia (interstitial pneumonia, etc.), severe acute respiratory syndrome (SARS), acute respiratory distress syndrome (ARDS), apnea syndrome, allergic rhinitis, sinusitis (acute sinusitis, chronic sinusitis, etc.), pulmonary fibrosis, coughing (chronic coughing, etc.), and the like) was developed.

Ethynylindole compounds

Carboxylic acid derived benzoxazines as agents for the treatment of respiratory diseases

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Osaka, Japan

Satoshi Itadani