Yamanouchi Pharmaceutical Company Ltd.

Astellas Pharma Gmbh

Tacurion

Hymo Corporation

Astella Pharma Inc.

Hiroyuki Koshio

Souichirou Kawazoe

Fukushi Hirayama

Yuzo Matsumoto

Tsukasa Ishihara

Akihiro Tanaka

Norio Seki

Yuji Koga

Keizo Sugasawa

Ryota Shiraki

Akira Matsuhisa

Issei Tsukamoto

Takeyuki Yatsu

Shunichiro Hachiya

Akio Kakefuda

Kazuyoshi Obitsu

Chikashi Saitoh

Nobuaki Taniguchi

Takeshi Shigenaga

Seijiro Akamatsu

Takahiro Akiba

Kiichi Sato

Akio Miyafuji

Junji Itoh

Ken-ichiro Sakamoto

Shun Hirasawa

Hiroyuki Ito

Mitsuaki Ohta

Keiji Miyata

Takafumi Shimizu

Atsuki Yamazaki

Norio Asai

Taisuke Takahashi

Tomihisa Kawasaki

Kiyoshi Iwaoka

Yasuhito Nagai

Keiko Kawabata

Karl Bruce Thor

Takeshi Suzuki

Isao Yanagisawa

Ippei Sato

Ryutaro Wakayama

Masashi Funatsu

Isamu Kubota

Masanao Sanagi

Hirotsune Itahana

Takahiro Kuramochi

Seiji Kaku

Hideki Anan

Kenichi Kazuta

Naoki Imanishi

The present invention provides a method for producing a 4,4,7-trifluoro-1,2,3,4-tetrahydro-5H-1-benzazepine compound which has an superior agonistic activity to an arginine vasopressin V2 receptor and is useful as an active ingredient for a pharmaceutical composition for preventing and/or treating urinary frequency, urinary incontinence, enuresis, central diabetes insipidus, nocturia, nocturnal enuresis, or the like; and useful intermediates for use in the methods. The production method of the present invention is suitable for the industrial production of a medicament, because of a smaller number of steps, a higher yield, and a lower cost, as compared with the methods in the related art.

Method for producing 4,4,7-trifluoro-1,2,3,4-tetrahydro-5H-1-benzazepine compound and intermediate used in the method

Provided is a compound which is useful as an agent for treating or preventing 5-HTreceptor-related diseases, particularly incontinence such as stress urinary incontinence, urge urinary incontinence, mixed urinary incontinence, and the like, sexual dysfunction such as erectile dysfunction syndrome and the like, obesity, and the like. The present inventors have investigated compounds having a 5-HTreceptor agonist activity and have found that the benzazepine compounds of the present invention have an excellent 5-HTreceptor agonist activity, thereby completing the present invention. That is, the benzazepine compounds of the present invention have a 5-HTreceptor agonist activity and can be used as an agent for treating or preventing 5-HTreceptor-related diseases, particularly incontinence such as stress urinary incontinence, urge urinary incontinence, mixed urinary incontinence, and the like, sexual dysfunction such as erectile dysfunction syndrome and the like, obesity, and the like.

Benzazepine compound

To provide a compound which has an anticoagulation action based upon inhibition of activated blood coagulation factor X and is useful as an anticoagulant or an agent for prevention and treatment of diseases caused by thrombus or embolus. A diazepan derivative such as 4-[(3-carbamimidoylphenylamino)methyl]-3-[4-(4-methyl-1,4-diazepan-1-yl)benzoylamino]benzoic acid and 3-hydroxy-4'-methoxy-2-{[4-(4-methyl-1,4-diazepan-1-yl)benzoyl]amino}benzanilide or a salt thereof is an effective ingredient.

Diazepan derivatives or salts thereof

A novel 4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivative or a pharmaceutically acceptable salt thereof, which is useful as an agent for treating or preventing nocturia and/or diabetes insipidus, is provided.

4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivative or salt thereof

The invention relates to an amphoteric water-soluble polymer dispersion containing polymer particles with particle diameters of 100 &#x3bc;m or smaller and produced by dispersion-copolymerization of a monomer mixture comprising a methacrylate monomer containing a quaternary ammonium salt group, an acrylate monomer containing a quaternary ammonium salt group, an anionic monomer, and a (meth)acrylamide in respectively ratios specified in an aqueous salt solution in the presence of a polymer dispersant soluble in the aqueous salt solution and the invention also relates to a dewatering agent for organic sludge, a pretreatment agent or yield improver for paper making raw materials, and/or a drainage properties-enhancing agent using the amphoteric water-soluble polymer.

Amphoteric water-soluble polymer dispersion and use thereof

4,4-difluoro-1,2,3,4-tetrahydro-5h-1-benzazepine derivative or salt thereof

4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivatives, which have excellent arginine vasopressin Vactivity and are useful for a drug for the treatment of central diabetes insipidus and/or nocturia.

4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine derivatives or salts thereof

To provide a compound having a superior arginine vasopressin antagonism. A novel 1,4,5,6-tetrahydroimidazo[4,5-d]benzazepine derivative or a pharmaceutically acceptable salt thereof.

1,4,5.6-tetrahydroimidazo[4,5-d]diazepine derivatives or salts thereof

To provide a compound which has an anticoagulation action based upon inhibition of activated blood coagulation factor X and is useful as an anticoagulant or an agent for prevention and treatment of diseases caused by thrombus or embolus. A diazepan derivative such as 4-&lsqb;(3-carbamimidoylphenylamino)methyl&rsqb;-3-&lsqb;4-(4-METHYL-1,4-diazepan-1-yl)benzoylamino&rsqb;benzoic acid and 3-hydroxy-4&prime;-methoxy-2-&lcub;&lsqb;4-(4-methyl-1,4-diazepan-1-yl)benzoyl&rsqb;amino&rcub;benzanilide or a salt thereof is an effective ingredient.

Hexahydro-1,4-diazepine derivatives represented by general formula (I); pharmaceutically acceptable salts thereof; and drugs containing the same as the active ingredient, such as activated blood coagulation factor X inhibitor, wherein A: phenylene, pyridylene, or the like; B: a 5- or 6-membered aryl or heteroaryl ring; X: &mdash;CO&mdash;, &mdash;CONH&mdash;, &mdash;CSNH&mdash;, &mdash;SO,&mdash;, &mdash;SO,NH&mdash;, or the like; Y: a bond or alkylene; R,: hydrogen, alkyl, &mdash;Y&mdash;(hetero) aryl, or the like; R,: hydrogen, alkoxy, &mdash;COOH, or the like; R,: amidino or a group capable of being converted into amidino; and R,, R,: each independently hydrogen or lower alkyl.

Hexahydro-1,4-diazepine derivatives or salts thereof

Amidinonaphthyl derivative or salt thereof

Growing community of inventors

Tokyo, Japan

Hiroyuki Koshio