Kyowa Hakko Kogyo Co., Ltd.

Kyowa Hakko Kirin Co., Limited

University of Pittsburgh

Roussel Uclaf

Akira Karasawa

Kazuhiro Kubo

Akio Ishii

Ichiro Miki

Hiroyuki Obase

Hiromi Nonaka

Etsuo Oshima

Hiroshi Kase

Tetsuji Ohno

Junichi Shimada

Fumio Suzuki

Haruki Takai

Shigeki Fujiwara

Kenji Ohmori

Kozo Yao

Hideaki Kusaka

Shiro Shirakura

Daisuke Machii

Katsuichi Shuto

Yoshihisa Kuwana

Mitsuru Takahashi

Masaji Kasai

Kunikatsu Shirahata

Isao Kawamoto

Yutaka Ohsawa

Tsuyoshi Yamagata

Kaoru Atsuki

Michiyo Kawakage

Hidee Ishii

Akihisa Mori

Koji Suzuki

Shigeru Aono

Yutaka Waki

Yuko Okamura

Makoto Yoshida

Ryo Okachi

Shizuo Shiozaki

Takeshi Kuroda

Haruhiko Manabe

Nobuhiro Nakamizo

Toshiaki Kumazawa

Kiyoshi Nakayama

Masayuki Teranishi

Tokuyuki Kuroda

Kenji Muto

Naoki Yoshimura

Ken Nagashima

William C De Groat

Hisayo Nomoto

Shin-ichi Sasaki

Takahiro Moriyama

Obase Hiroyuki

Kubo Shizuoka

Adrian Sculptoreanu

Kazuihiro Kubo

Hideaki Mizumoto

Chikako Katagiri

Toru Noji

Takashi Seishi

Takashi Deguchi

Masayuki Yamato

The present invention is directed to methods of treating movement disorders by administering an effective amount of one or more adenosine Areceptor antagonists to a patient in need thereof. The present invention also provides methods of decreasing the adverse effects of L-DOPA in patients receiving L-DOPA therapy in the treatment of Parkinson's disease. The present invention further provides methods and compositions for treating Parkinson's disease patients with sub-clinically effective doses of L-DOPA by combining L-DOPA treatment with an effective amount of one or more adenosine Areceptor antagonists (i.e., L-DOPA sparing effect). The present invention further provides methods of effective treatment of Parkinson's disease by co-administering at least one adenosine Areceptor antagonist, L-DOPA and a dopamine agonist and/or a COMT inhibitor and/or a MAO inhibitor. The present invention further provides methods of prolonging effective treatment of Parkinson's disease by administering an adenosine Areceptor antagonist singly or together with a dopamine agonist, and/or a COMT inhibitor, and/or a MAO inhibitor without prior or subsequent administration of L-DOPA, delaying or removing on-set of L-DOPA motor complication.

Methods of treating patients suffering from movement disorders

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The present invention provides a therapeutic agent for bladder irritative symptoms associated with benign prostatic hyperplasia comprising, as an active ingredient, a tricyclic compound represented by formula (I): [wherein Rrepresents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy or halogen;X-X-Xrepresents CR&#x2550;CR&#x2014;CR&#x2550;CR, N(O)&#x2550;CR&#x2014;CR&#x2550;CR, CR&#x2550;CR&#x2014;N(O)&#x2550;CR, CR&#x2550;CR&#x2014;CR&#x2550;N(O), CR&#x2550;CR&#x2014;O, CR&#x2550;CR&#x2014;S, O&#x2014;CR&#x2550;CR, S&#x2014;CR&#x2550;CRor O&#x2014;CR&#x2550;N;Y represents 13 CHS&#x2014;, &#x2014;CHSO&#x2014;, &#x2014;CHSO&#x2014;, &#x2014;CHO&#x2014;, &#x2014;CH&#x2550;CH&#x2014;, &#x2014;(CH)&#x2014;, &#x2014;SCH&#x2014;, &#x2014;SOCH&#x2014;, &#x2014;SOCH&#x2014; or &#x2014;OCH&#x2014;; andRrepresents a hydrogen atom, substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted lower alkoxy, amino, mono(substituted or unsubstituted lower alkyl)-substituted amino, di(substituted or unsubstituted lower alkyl)-substituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkylamino, substituted or unsubstituted arylamino or a substituted or unsubstituted heteroalicyclic group] or a pharmaceutically acceptable salt thereof.

Therapeutic agent for bladder irritative symptoms associated with benign prostatic hyperplasia

The present invention provides a therapeutic agent for overactive bladder comprising, as an active ingredient, a tricyclic compound represented by formula (I): [wherein Rrepresents a hydrogen atom, substituted or unsubstituted lower alkyl, and the like;

Remedies for vesical hyperactivity

The present invention provides an agent for the treatment of bladder irritative symptoms accompanied by benign prostatic hyperplasia, comprising, as an active ingredient, a compound having a slowly-inactivating A-type Kchannel opening activity or a pharmaceutically acceptable salt thereof, and a method for screening agents for the treatment of bladder irritative symptoms accompanied by benign prostatic hyperplasia, comprising measuring a slowly-inactivating A-type Kchannel opening activity as an index.

Agent for the treatment of bladder irritative symptoms accompanied by benign prostatic hyperplasia

The present invention provides tricyclic compounds which are useful for the treatment of pollakiuria and urinary incontinence and which are represented by general formula (I):

Tricyclic compounds

Disclosed are quinazoline derivatives represented by formula (I): wherein R.sup.1 represents hydrogen, lower alkyl, alkenyl, or aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 represent hydrogen, lower alkyl, lower alkoxy, lower alkanoyl, or the like; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 represent hydrogen, lower alkyl, lower alkoxy, aralkyloxy, or the like, or any adjoining two of them are combined to form methylenedioxy or the like; R.sup.10 represents hydrogen, lower alkyl, or the like; R.sup.11 and R.sup.12 represent hydrogen, lower alkyl, cycloalkyl, phenyl, or aralkyl, or R.sup.11 and R.sup.12 are combined together with N to form a heterocyclic group; and n represents 0, 1 or 2, and pharmaceutically acceptable salts thereof. These compounds have adenosine uptake inhibitory activity and are useful for the protection of myocardium and for the prevention or treatment of renal diseases such as nephritis and diabetic nephropathy.

Quinazoline derivatives

The present invention relates to a prophylactic agent or a therapeutic agent of pancreatitis, containing an adenosine uptake inhibitor or a pharmaceutically acceptable salt thereof.

Pancreatitis remedy

The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema, comprising a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR1## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C--R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen), or a pharmaceutically acceptable salt thereof as an active ingredient.

Isoquinolines having adenosine uptake inhibitor activity

The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema, comprising a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR1## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C--R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen),

Quinazolines and phthalazines having adenosine uptake inhibitor activity

Piperidinyl-dioxoquinazolines as adenosine reuptake inhibitors

The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema, comprising a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR1## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C-R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen), or a pharmaceutically acceptable salt thereof as an active ingredient.

Benzotriazines having adenosine uptake inhibitor activity

Novel xanthine compounds represented by the following formula: ##STR1## wherein each of R.sup.1, R.sup.2 and R.sup.3 independently represents hydrogen or lower alkyl;

Xanthine compounds

A xanthine derivative of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and are substituted or unsubstituted alicyclic alkyl; m1 and m2 are the same or different and represent an integer of 0 to 2; and Q represents ##STR2## (in which R.sup.3 and R.sup.4 are the same or different and are substituted or unsubstituted alicyclic alkyl) or ##STR3## (in which n is 0 or 1, and Y is a single bond or alkylene); or a pharmaceutically acceptable salt thereof is disclosed. This derivative has diuretic activity and renal protecting activity.

Xanthine derivatives

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Shizuoka, Japan

Akira Karasawa