Otsuka Pharmaceutical Company, Limited

Kazumi Kondo

Hidenori Ogawa

Hiroshi Yamashita

Michiaki Tominaga

Yoichi Yabuuchi

Kenji Nakaya

Hisashi Miyamoto

Hajime Komatsu

Michinori Tanaka

Shin Miyamura

Muneaki Kurimura

Keizo Kan

Takafumi Fujioka

Tomoichi Shinohara

Shuji Teramoto

Shigeharu Tamada

Kazuyoshi Kitano

Yoshihisa Tanada

Yusuke Kato

Takakuni Matsuda

Takeshi Kuroda

Yasuhiro Menjo

Satoshi Shimizu

Takayuki Matsuzaki

Takahiro Tomoyasu

Yuso Tomohira

Haruka Takahashi

Tae Fukushima

Keigo Yamada

Shinya Kora

Geraldine C Harriman

Masaki Suzuki

Akira Takahashi

Amy M Elder

Kevin J Hodgetts

Jason S Newcom

Indranath Ghosh

Krishna Reddy Valluru

Abhishek Dogra

Kazuyuki Nakagawa

Seiji Sato

Nobuaki Ito

Masahiro Murakami

Tatsuyoshi Tanaka

Satoshi Hayakawa

Hitoshi Tone

Kunio Oshima

Minoru Uchida

Hideaki Kuroda

Yohji Sakurai

Youichi Taniguchi

Shinichi Taira

Jun Matsubara

Toyoki Mori

Yoshihiko Ito

Yoshimasa Nakano

Motohiro Itotani

Shinji Nishitani

Katsumi Tamura

Seiji Morita

Hideaki Sato

Tomoyuki Kawaguchi

Yasumitsu Tamura

Atsushi Abiko

Yasuyuki Kita

Shuji Akai

Hiromichi Fujioka

Katsuhide Matoba

Toshinori Kaneyasu

Takafumi Fujiioka

Amy Elder

Methods of treating disorders using compounds that modulate striatal-enriched tyrosine phosphatase (STEP), such as those of formula (III), and composition thereof are described herein. Exemplary disorders include schizophrenia and cognitive deficit. 

Therapeutic compounds and related methods of use

The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) wherein Rrepresents a &#x2014;CO&#x2014;(CH)&#x2014;CORgroup (wherein n is an integer of 1 to 4, and Ris (2-1) a hydroxy group; (2-2) a lower alkoxy group optionally substituted with a hydroxy group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkoxycarbonyloxy group, a cycloalkyloxycarbonyloxy group, or 5 -methyl-2-oxo-1,3-dioxol-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.

Benzazepine derivatives useful as vasopressin antagonists

Compounds, pharmaceutical compositions containing the compounds, and methods of using the compounds to treat a disorder, e.g., schizophrenia and cognitive deficit, in a subject are described herein. The compounds disclosed herein include quinoline and quinazoline-containing compounds that modulate striatal-enriched tyrosine phosphatase (STEP) activity.

The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) wherein Rrepresents a &#x2014;CO&#x2014;(CH)&#x2014;CORgroup (wherein n is an integer of 1 to 4, and Ris (2-1) a hydroxy group; (2-2) a lower alkoxy group optionally substituted with a hydroxy group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkoxycarbonyloxy group, a cycloalkyloxycarbonyloxy group, or 5-methyl-2-oxo-1,3-dioxol-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.

The present invention provides a benzazepine compound that can maintain for a long period of time the blood level of tolvaptan enabling to provide the desired pharmaceutical effects. The benzazepine compound of the present invention is represented by general formula (1) wherein Rrepresents a &#x2014;CO&#x2014;(CH)&#x2014;CORgroup (wherein n is an integer of 1 to 4, and Ris (2-1) a hydroxy group; (2-2) a lower alkoxy group optionally substituted with a hydroxy group, a lower alkanoyl group, a lower alkanoyloxy group, a lower alkoxycarbonyloxy group, a cycloalkyloxycarbonyloxy group, or 5-methyl-2-oxo-1,3-dioxo-4-yl; or (2-3) an amino group optionally substituted with a hydroxy-lower alkyl group), or the like.

A heterocyclic compound or a salt thereof represented by the formula (1): where Rrepresents a hydrogen atom or a lower alkyl group; A represents a lower alkylene group or lower alkenylene group; and Rrepresents an aromatic group or a heterocyclic group. The compound of the present invention has a wide treatment spectrum for mental disorders including central nervous system disorders, no side effects and high safety. 

Derivatives of 4-piperazin-1-yl-4-benzo[B]thiophene suitable for the treatment of CNS disorders

Benzoheterocyclic derivatives

Benzazepine derivatives with vasopressin agonistic activity

Novel benzoheterocyclic compounds of the formula: ##STR1## wherein R.sup.1 is H, halogen, alkyl, optionally substituted amino, alkoxy; R.sup.2 is H, halogen, alkoxy, phenylalkoxy, OH, alkyl, optionally substituted amino, carbamoyl-alkoxy, optionally substituted amino-alkoxy, optionally substituted benzoyloxy; R.sup.3 is a group: --NR.sup.4 R.sup.5 or --CO--NR.sup.11 R.sup.12 ; R.sup.4 is H, optionally substitued benzoyl, alkyl; R.sup.5 is a group: ##STR2## [R.sup.16 is halogen, optionally substituted alkyl, OH, alkoxy, alkanoyloxy, alkylthio, alkanoyl, carboxy, alkoxycarbonyl, CN, NO.sub.2, optionally substituted amino, phenyl, cycloalkyl, etc., or a group: --O--A--NR.sup.6 R.sup.7 ; m is 0 to 3], phenyl-alkoxycarbonyl, alkanoyl, phenylalkanoyl, etc.; R.sup.11 is H or alkyl; R.sup.12 is cycloalkyl or optionally substituted phenyl; and W is a group: --(CH.sub.2).sub.p (p is 3 to 5) or --CH.dbd.CH--(CH.sub.2).sub.q (q is 1 to 3), the carbon atom of these groups beign optionally replaced by O, S, SO, SO.sub.2 or a group: --N(R.sup.13)-- and further these groups having optionally 1 to 3 substituents of alkyl, alkoxycarbonyl, carboxy, OH, O, alkanoyloxy, etc., which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

Benzoheterocyclic compounds

Novel benzoheterocyclic compounds of the formula: ##STR1## which have excellent vasopressin antagonistic activities and are useful as vasodilator, hypotensive agent, water diuretics, platelet agglutination inhibitor, and a vasopressin antagonistic composition containing the compound as the active ingredient.

An object of the present invention is to provide a vasopressin antagonist and oxytocin antagonist. The vasopressing antagonist and oxytocin antagonist according to the present invention contain, as the active ingredient, a benzoheterocyclic compound represented by the general formula (1): ##STR1## (wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and the carbon-carbon bond between 4- and 5-positions in the benzoazepine skeleton are the same as defined in claims 1, 2 and 3.) or salt thereof.

Vasopressin antagonist and oxytocin antagonist

Novel benzoheterocyclic compound of the formula (1): ##STR1## and pharmaceutically acceptable salts thereof, which show excellent anti-vasopressin activity and oxytocin antagonistic activity, and are useful as a vasopressin antagonist or oxytocin antagonist.

Novel carbostyril derivatives of the formula: ##STR1## wherein R.sup.1 is H, NO.sub.2, alkoxy, alkoxycarbonyl, alkyl, halogen, optionally substituted amino, OH, CN, COOH, alkanoyloxy, hydrazinocarbonyl; q is 1 to 3, and R is a group of the formula: ##STR2## [wherein R.sup.2 is H, alkoxycarbonyl, optionally substituted phenoxycarbonyl, phenylalkenyl-CO--, optionally substituted phenylalkanoyl, alkanoyl, alkenyl-CO--, optionally substituted phenyl-SO.sub.2 --, --CONR.sup.8 R.sup.9, optionally substituted heterocyclic group-CO--, naphthyl-CO--, thienylalkanoyl, tricyclo[3.3.1.1]alkanoyl, ##STR3## (R.sup.13 is OH, optionally substituted alkoxy, --NR.sup.32 R.sup.33, --O--A--(E).sub.l --NR.sup.4 R.sup.5, --(B).sub.l --NR.sup.6 R.sup.7, etc.),

Carbostyril derivatives

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Osaka, Japan

Kazumi Kondo