Astellas Pharma Gmbh

Yamanouchi Pharmaceutical Company Ltd.

Tacurion

Souichirou Kawazoe

Makoto Takeuchi

Hiroyuki Koshio

Keizo Sugasawa

Akira Toyoshima

Yasuhiro Yonetoku

Hirokazu Kubota

Masashi Funatsu

Jun Ishikawa

Norio Seki

Fukushi Hirayama

Yuzo Matsumoto

Takayuki Suzuki

Yuji Koga

Tsukasa Ishihara

Kenichi Onda

Ryota Shiraki

Yoshinori Okamoto

Shunichiro Hachiya

Kazuyoshi Obitsu

Takeshi Shigenaga

Takahiro Akiba

Kiichi Sato

Junji Itoh

Shun Hirasawa

Akio Miyafuji

Tatsuya Maruyama

Atsushi Ichikawa

Toshiyuki Takasu

Hiroyuki Hisamichi

Kazuhito Tanabe

Kenichirou Sakamoto

Yuji Awamura

Akiko Orita

Ryo Naito

Eiichi Nakai

Keizou Sugasawa

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

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

To provide novel crystals useful as an ingredient for the production of a diabetes remedy. The invention is concerned with &#x3b1;-form crystal and &#x3b2;-form crystal of (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]acetanilide. The &#x3b1;-form crystal does not exhibit hygroscopicity and has stability such that it can be used as a medicine, and is useful for mass synthesis in the industrial production. The &#x3b2;-form crystal does not relatively exhibit hygroscopicity and is also useful as a production intermediate of the &#x3b1;-form crystal.

&#x3b1;-form or &#x3b2;-form crystal of acetanilide derivative

To provide novel crystals useful as an ingredient for the production of a diabetes remedy. The invention is concerned with &#x3b1;-form crystal and &#x3b2;-form crystal of (R)-2-(2-aminothiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenyleth-yl)amino]ethyl]acetanilide. The &#x3b1;-form crystal does not exhibit hygroscopicity and has stability such that it can be used as a medicine, and is useful for mass synthesis in the industrial production. The &#x3b2;-form crystal does not relatively exhibit hygroscopicity and is also useful as a production intermediate of the &#x3b1;-form crystal.

Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-activated calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-activated calcium channel inhibitors containing the above compounds as the active ingredient, (in the formula, each symbol has the following meaning:D: pyrazolyl which may have 1 to 3 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, -halogeno-lower alkyl, -Alk-cycloalkyl, -Alk-O-Alk, -cycloalkyl, &#x2014;O-Alk, &#x2014;COOH, &#x2014;COO-Alk and -Hal,n: 0 or 1,B: phenylene, a nitrogen-containing, divalent, saturated ring group, or a monocyclic, divalent heteroaromatic ring group which may be substituted with Alk,X: &#x2014;NR&#x2014;CRR&#x2014;, &#x2014;CRR&#x2014;NR&#x2014;, &#x2014;NR&#x2014;SO&#x2014;, &#x2014;SO&#x2014;NR&#x2014; or &#x2014;CR&#x2550;CR&#x2014;, andA: benzene ring which may have one or more substituents; mono-, di- or tricyclic fused heteroaryl which may have one or more substituents; cycloalkyl which may have one or more substituents; a nitrogen-containing, saturated ring group which may have one or more substituents; lower alkenyl which may have one or more substituents; lower alkynyl which may have one or more substituents; or Alk which may have one or more substituents).

Pyrazole derivative

Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-dependent calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-dependent calcium channel inhibitors containing the above compounds as the active ingredient, (in the formula, each symbol has the following meaning:

The present invention is directed to drugs, in particular, pyrazole derivatives represented by the following general formula (I)which have a calcium release-activated calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-activated calcium channel inhibitors containing the above compounds as the active ingredient, wherein each substituent is defined in the specification. The present invention also relates to a pharmaceutical composition containing an effective amount of the compound of formula (I) and a pharmaceutically effective carrier. The present invention further relates to methods of treatment of diseases associated with calcium release-activated calcium channels, diseases associated with IL-2 production, and methods of treatment of allergic, inflammatory or auto-immune diseases.

A nitrogen-containing six-membered heterocyclic compound having substituents &mdash;X&mdash;A&mdash;R , &mdash;N(R )-(Ph substituted by R ), and &mdash;CONH , a salt thereof, a prodrug thereof, and a Syk inhibitor containing the same as an active ingredient. (In the formula, A: a (substituted) lower alkylene, a (substituted) arylene, or the like; X: NR , CONR , NR CO, O, or S; R , R : H, a lower alkyl, &mdash;CO-lower alkyl, or &mdash;SO -lower alkyl; R : H, a (substituted) lower alkyl, &mdash;O-lower alkyl, &mdash;S-lower alkyl, &mdash;O-aryl, nitro, cyano, or the like; R : &mdash;CO H, &mdash;CO -lower alkyl, -lower alkylene-CO H, &mdash;NH , -alkylene-NH or the like.

Heterocyclecarboxamide derivative

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.

Pyrimidine-5-carboxamide derivatives

Pharmaceutical compound comprising a pyrazole derivative and methods of using the same for the treatment of calcium release-activated calcium channel associated diseases

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Ibaraki, Japan

Souichirou Kawazoe