Kyowa Hakko Kogyo Co., Ltd.

Kyowa Hakko Kirin Co., Limited

University of Pittsburgh

Shiro Shirakura

Akira Karasawa

Koji Yamada

Tetsuji Ohno

Toshiaki Kumazawa

Tsuyoshi Yamagata

Kaoru Atsuki

Masashi Yanase

Kazuhiro Kubo

Hiroyuki Obase

Shoji Oda

Hiroyuki Harakawa

Hiroshi Kase

Katsutoshi Sasaki

Akio Ishii

Ichiro Miki

Koji Suzuki

Naoki Yoshimura

William C De Groat

Makoto Takayama

Megumi Takeuchi

Adrian Sculptoreanu

Obase Hiroyuki

Kubo Shizuoka

Katsumi Shinoda

Yozo Kojima

Shunji Kunori

Jun Ouchi

Eiko Oishi

Provided are: an agent for suppressing an undesirable effect of an opioid-type analgesic (opioid), which comprises a compound having adenosine Areceptor antagonistic activity or a pharmaceutically acceptable salt thereof as an active ingredient; the agent for suppressing an undesirable effect of an opioid-type analgesic (opioid), wherein the undesirable effect of the opioid-type analgesic (opioid) is analgesic tolerance or constipation; the agent for suppressing an undesirable effect of an opioid-type analgesic (opioid), wherein the undesirable effect of the opioid-type analgesic (opioid) is analgesic tolerance; and the like.

Inhibitor of analgesic tolerance

A method for treating migraine comprising administering, as an active ingredient, a xanthine derivative represented by the following formula or a pharmaceutically acceptable salt thereof. 

Agents for treating migraine

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

Disclosed is a tricyclic compound represented by formula (I): ##STR1## where X.sup.1 -X.sup.2 represents CH.dbd.CH--CH.dbd.CH, CH.dbd.CH--CH.dbd.N or S--CH.dbd.CH;

Tricyclic compounds having ACAT inhibiting activity

Disclosed is a tricyclic compound represented by the formula (I): ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represents hydrogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, amino, C1-6 alkylamino, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, halogen, nitro, cyano, carboxy, C1-6 alkoxycarbonyl, hydroxymethyl, CR.sup.9 R.sup.10 CO.sub.2 R.sup.11 (wherein each of R.sup.9, R.sup.10 and R.sup.11 independently represents hydrogen or C1-6 alkyl) or CONR.sup.12 R.sup.13 (wherein each of R.sup.12 and R.sup.13 independently represents hydrogen or C1-6-alkyl); R.sup.5 represents hydrogen or C1-6 alkyl; each of R.sup.6, R.sup.7 and R.sup.8 independently represents hydrogen, C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkanoyloxy, C1-6 alkylthio, thiocyanato or halogen; X represents CH or N; Y.sup.1 -Y.sup.2 represents CH.sub.2 -O, CH.sub.2 -S(O).sub.n, (wherein n represents 0, 1, or 2), CH.sub.2 CH.sub.2, CH.dbd.CH or CON(R.sup.14) (wherein R.sup.14 represents hydrogen or C1-6 alkyl) and Z represents oxygen or sulfur, or a pharmaceutically acceptable salt thereof. The compound possesses an acyl coenzyme A: cholesterol acyltransferase-inhibiting activity, and thus are expected to have preventive and therapeutic effects on hyperlipemia and arteriosclerosis.

Tricyclic compounds and intermediates thereof

Disclosed is a tricyclic compound represented by the formula (I): ##STR1## wherein each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represents hydrogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, amino, C1-6 alkylamino, halogenated C1-6 alkyl, halogenated C1-6 alkoxy, halogen, nitro, cyano, carboxy, C1-6 alkoxycarbonyl, hydroxymethyl, CR.sup.9 R.sup.10 CO.sub.2 R.sup.11 (wherein each of R.sup.9, R.sup.10 and R.sup.11 independently represents hydrogen or C1-6 alkyl) or CONR.sup.12 R.sup.13 (wherein each of R.sup.12 and R.sup.13 independently represents hydrogen or C1-6 alkyl); R.sup.5 represents hydrogen or C1-6 alkyl; each of R.sup.6, R.sup.7 and R.sup.8 independently represents hydrogen, C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkanoyloxy, C1-6 alkylthio, thiocyanato or halogen; X represents CH or N; Y.sup.1 -Y.sup.2 represents CH.sub.2 --O, CH.sub.2 --(O).sub.n, (wherein n represents 0, 1, or 2), CH.sub.2 CH.sub.2, CH.dbd.CH or CON(R.sup.14) (wherein R.sup.14 represents hydrogen or C1-6 alkyl) and Z represents oxygen or sulfur, or a pharmaceutically acceptable salt thereof. The compound possesses an acyl coenzyme A: cholesterol acyltransferase-inhibiting activity, and thus are expected to have preventive and therapeutic effects on hyperlipemia and arteriosclerosis.

A pyridine derivative represented by formula (I): ##STR1## wherein the symbols are as defined in the specification, which exhibits selective, potential, and long-lasting inhibitory activity on biosynthesis of thromboxane A.sub.2 and is useful in the treatment and prevention of a broad range of diseases.

Pyridine derivatives

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Mishima, Japan

Shiro Shirakura