公开(公告)号：US5541169A

公开(公告)日：1996-07-30

申请号：US232245

申请日：1994-05-10

申请人： Takeo Deushi ,  Yoshio Takahashi ,  Hiroyuki Ishiwata ,  Yukihiro Okuno ,  Toshiaki Oda ,  Masami Shiratsuchi ,  Katsuhiro Yamamoto

发明人： Takeo Deushi ,  Yoshio Takahashi ,  Hiroyuki Ishiwata ,  Yukihiro Okuno ,  Toshiaki Oda ,  Masami Shiratsuchi ,  Katsuhiro Yamamoto

IPC分类号： A01N51/00 ,  C07C291/08 ,  A61K31/655

CPC分类号： C07C291/08 ,  A01N51/00

摘要： An azoxy compound represented by the following general formula ##STR1## wherein R.sub.1 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkoxy group, a lower alkoxy-lower alkoxy group or a group of the formula X.sub.1 --C.tbd.C--CH.sub.2 O-- wherein X.sub.1 is a hydrogen atom or a halogen atom;R.sub.2 denotes a hydrogen atom or a lower alkyl group;R.sub.3 denotes a hydrogen atom or a lower alkyl group;R.sub.4 denotes a hydrogen atom or a group of the formula X.sub.2 --C.tbd.C--CH.sub.2 -- wherein X.sub.2 is a hydrogen atom or a halogen atom;R.sub.5 denotes a hydrogen atom or a lower alkyl group;andn is 0 or 1.This compound has an excellent antifungal activity against fungi infectious to warm-blooded animals and fungi infectious to agrohorticultural crops or fruit trees, and is useful as a medicine, a veterinary drug and an agrohorticultural antifungal agent.

摘要翻译： PCT No.PCT / JP93 / 01295 Sec。 371日期1994年5月10日 102（e）日期1994年5月10日PCT提交1993年9月10日PCT公布。 出版物WO94 / 05629 日期：1994年3月17日由以下通式表示的氧化偶氮化合物（Ⅰ）其中R1表示氢原子，卤原子，羟基，低级烷氧基，低级烷氧基 - 低级烷氧基或基团 式X1-C3Bic C-CH2O-，其中X1是氢原子或卤素原子; R2表示氢原子或低级烷基; R3表示氢原子或低级烷基; R4表示氢原子或式X2-C 3BOND C-CH2-的基团，其中X2是氢原子或卤素原子; R5表示氢原子或低级烷基; 并且n为0或1.该化合物对感染了农作物或果树的温血动物和真菌感染真菌具有优异的抗真菌活性，并且可用作药物，兽药和农业园艺抗真菌剂。

公开(公告)号：US5264559A

公开(公告)日：1993-11-23

申请号：US656829

申请日：1991-02-19

申请人： Masahito Nakayama ,  Takeo Deushi ,  Yoshio Takahashi ,  Hiroyuki Ishiwata ,  Yukihiro Okuno ,  Hisakatsu Itoh ,  Masami Shiratsuchi

发明人： Masahito Nakayama ,  Takeo Deushi ,  Yoshio Takahashi ,  Hiroyuki Ishiwata ,  Yukihiro Okuno ,  Hisakatsu Itoh ,  Masami Shiratsuchi

IPC分类号： A01N51/00 ,  C07C291/08

CPC分类号： C07C291/08 ,  A01N51/00 ,  C07C2101/16

摘要： A compound expressed by the formula: ##STR1## in which R.sub.11, R.sub.21 and R.sub.31 are identical with or different from each other and each denotes a hydrogen atom, a halogen atom, an alkyl group, an alkenyl group, a haloalkyl group, an alkoxy group, an alkylthio group, an aryl or an aralkyl group which aromatic ring is optionally substituted appropriately by one to three substituents or a heterocyclic group optionally substituted appropriately by one to three substituents, or R.sub.11 and R.sub.21 may together form an alkylene group, Y denotes O or NOH, with a proviso that where R.sub.21 (or R.sub.11) and R.sub.31 denote a hydrogen atom at the same time, R.sub.11 (or R.sub.21) cannot represent an n-butyl group. This compound is useful as an antifungal agent.

公开(公告)号：US06576642B2

公开(公告)日：2003-06-10

申请号：US09858592

申请日：2001-05-17

申请人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

发明人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

IPC分类号： A61K31165

CPC分类号： C07D213/40 ,  C07C235/34 ,  C07C235/36 ,  C07C235/38 ,  C07C235/44 ,  C07C235/56 ,  C07C237/34 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2602/10 ,  C07D207/09 ,  C07D207/14 ,  C07D213/75 ,  C07D213/82

摘要： Compounds having the formula (1): wherein A is a phenyl, naphthyl, dihydronaphthyindeny, pyridyl, indolyl,isoindolyl, quinolyl or isoquinolyl group which are optionally substituted; X is optionally substituted alicyclic, aromatic, imino or heterocyclic groups or —S— or —O—; Y is a single bond or an alkylene group; Z is an unsubstituted aliphatic group or divalent residue of benzene or pyridine, which is optionally substituted; anis hydrogen, lower alkyl, cycloalkyl, aryl or aralkyl; with certain provisos. These compounds exhibit an inhibitory effect on the production of IgE antibodies and are, hence, useful as antiallergic agents.

摘要翻译： 具有式（1）的化合物：其中A是任选取代的苯基，萘基，二氢萘并噻吩基，吡啶基，吲哚基，异吲哚基，喹啉基或异喹啉基; X是任选取代的脂环族，芳族，亚氨基或杂环基或-S-或-O-; Y是单键或亚烷基; Z是任选取代的未取代的脂族基团或苯或吡啶的二价残基; 芳烃氢，低级烷基，环烷基，芳基或芳烷基; 具有一定的条件。 这些化合物对IgE抗体的产生具有抑制作用，因此可用作抗过敏剂。

公开(公告)号：US06828316B2

公开(公告)日：2004-12-07

申请号：US09978102

申请日：2001-10-17

申请人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Hiromichi Shigyo ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

发明人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Hiromichi Shigyo ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

IPC分类号： A61K3155

CPC分类号： C07D213/69 ,  C07D213/56 ,  C07D213/70 ,  C07D213/82 ,  C07D215/12 ,  C07D231/12 ,  C07D233/56 ,  C07D241/04 ,  C07D241/42 ,  C07D243/08 ,  C07D249/08 ,  C07D295/185 ,  C07D471/04 ,  C07D487/04

摘要： The present invention relates to diamide derivatives represented by the following general formula (1): wherein A is a phenyl group or the like, which may be substituted, B is —CH═CH—, —C≡C—, —(CH═CH)2—, —C≡C—CH═CH—, —CH═CH—C≡C—, phenylene or the like, and W is and medicines comprising such a compound. These compounds have an excellent inhibitory effect on the production of an IgE antibody and are hence useful as antiallergic agents and the like.

摘要翻译： 本发明涉及由以下通式（1）表示的二酰胺衍生物：其中A是可被取代的苯基等，B是-CH = CH-，-C = C-， - （CH = CH）2 - ， - C = C-CH = CH - ， - CH = CH-C = C-，亚苯基等，W为包含这种化合物的药物。 这些化合物对IgE抗体的产生具有优异的抑制作用，因此可用作抗变应性剂等。

公开(公告)号：US06340682B1

公开(公告)日：2002-01-22

申请号：US09147711

申请日：1999-02-23

申请人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Hiromichi Shigyo ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

发明人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Hiromichi Shigyo ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

IPC分类号： A61K31495

CPC分类号： C07D213/69 ,  C07D213/56 ,  C07D213/70 ,  C07D213/82 ,  C07D215/12 ,  C07D231/12 ,  C07D233/56 ,  C07D241/04 ,  C07D241/42 ,  C07D243/08 ,  C07D249/08 ,  C07D295/185 ,  C07D471/04 ,  C07D487/04

摘要： The present invention provides diamide derivatives represented by the following general formula (1): wherein A is a phenyl group or the like, which may be substituted, B is —CH═CH—, —C═C—, —(CH═CH)2—, —C≡C—CH═CH—, —CH═CH—C≡C—, phenylene or the like, and W is or and medicines comprising such a compound. These compounds have an excellent inhibitory effect on the production of an IgE antibody and are hence useful as antiallergic agents and the like.

摘要翻译： 本发明提供由以下通式（1）表示的二酰胺衍生物：其中A是可以被取代的苯基等，B是-CH = CH-，-C = C-， - （CH = CH ）2-，-C = C-CH = CH-，-CH = CH-C = C-，亚苯基等，以及含有这种化合物的W异构体药物。 这些化合物对IgE抗体的产生具有优异的抑制作用，因此可用作抗变应性剂等。

公开(公告)号：US06297283B1

公开(公告)日：2001-10-02

申请号：US09269764

申请日：1999-04-09

申请人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

发明人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Masami Shiratsuchi ,  Yukio Hattori ,  Hiroshi Nakao ,  Takao Nagoya ,  Seiichi Sato ,  Soichi Oda ,  Makoto Suda ,  Manabu Shibasaki

IPC分类号： A61K31165

CPC分类号： C07D213/40 ,  C07C235/34 ,  C07C235/36 ,  C07C235/38 ,  C07C235/44 ,  C07C235/56 ,  C07C237/34 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2602/10 ,  C07D207/09 ,  C07D207/14 ,  C07D213/75 ,  C07D213/82

摘要： The present invention relates to compounds represented by the following general formula (1): wherein A is a phenyl, naphthyl, dihydronaphthyl, indenyl, pyridyl, indolyl, isoindolyl, quinolyl or isoquinolyl group which may be substituted; X is a lower alkylene group which may be substituted, or the like; Y is a single bond or an alkylene group; Z is a group of —CH═CH—, —C≡C—, —(CH═CH)2—, —C≡C—CH═CH— or —CH═CH—C≡C—, or the like; and R is a hydrogen atom, a lower alkyl group or the like, and medicines comprising such a compound. These compounds have an excellent inhibitory effect on the production of an IgE antibody and are hence useful as antiallergic agents and the like.

摘要翻译： 本发明涉及由以下通式（1）表示的化合物：其中A为可被取代的苯基，萘基，二氢萘基，茚基，吡啶基，吲哚基，异吲哚基，喹啉基或异喹啉基; X是可以被取代的低级亚烷基等; Y是单键或亚烷基; Z是-CH = CH-，-C = C - ， - （CH = CH）2 - ， - C = C-CH = CH-或-CH = CH-C = C - 等的基团; R为氢原子，低级烷基等，以及含有该化合物的药物。 这些化合物对IgE抗体的产生具有优异的抑制作用，因此可用作抗变应性剂等。

公开(公告)号：US08791090B2

公开(公告)日：2014-07-29

申请号：US13256549

申请日：2010-03-31

申请人： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

发明人： Masanori Ashikawa ,  Junya Tagashira ,  Akiyasu Koketsu ,  Toshiharu Morimoto ,  Takahiro Kitamura ,  Syunji Takemura ,  Gen Watanabe ,  Tatsuaki Nishiyama ,  Satoshi Goda ,  Masaki Yamabi ,  Takeshi Doi ,  Hiroyuki Ishiwata

IPC分类号： A01N57/00 ,  A61K31/385

CPC分类号： C07D215/42 ,  A61K31/47 ,  A61K31/4706 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/69 ,  C07D215/233 ,  C07D215/44 ,  C07D215/46 ,  C07D215/48 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/04 ,  C07D413/12 ,  C07D417/12

摘要： Disclosed is a compound which has a low molecular weight and has an activity of enhancing the production of EPO and/or an activity of enhancing the production of hemoglobin. Specifically disclosed is and EPO production enhancer and/or a hemoglobin production enhancer comprising a 1-acyl-4-(substituted oxy, substituted amino, or substituted thio)-1,2,3,4-tetrahydroquinoline derivative, more specifically a tetrahydroquinoline compound represented by general formula (1) [wherein R1, R2, R2′, R3 and R3′ independently represent a hydrogen atom, a C1-6 alkyl group, or the like; R4, R5, R6, R7, R8, R9 and R10 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or the like; A represents N—R11, a sulfur atom, or an oxygen atom; R11 represents a hydrogen atom, a C1-6 alkyl group, or the like; B represents a C6-14 aryl group, or a 5- to 10-membered heterocyclic group; and n represents an integer of 0 or 1], a salt of the tetrahydroquinoline compound, or a solvate of the tetrahydroquinoline compound or the salt.

摘要翻译： 公开了具有低分子量且具有增强EPO产生活性和/或提高血红蛋白生成活性的化合物。 具体公开的是EPO生产增强剂和/或包含1-酰基-4-（取代的氧基，取代的氨基或取代的硫代）-1,2,3,4-四氢喹啉衍生物，更具体地是四氢喹啉化合物的血红蛋白生成增强剂 由通式（1）表示[其中R1，R2，R2'，R3和R3'独立地表示氢原子，C1-6烷基等; R 4，R 5，R 6，R 7，R 8，R 9和R 10独立地表示氢原子，卤素原子，C 1-6烷基等; A表示N-R11，硫原子或氧原子; R 11表示氢原子，C 1-6烷基等; B表示C 6-14芳基或5至10元杂环基; n表示0或1的整数]，四氢喹啉化合物的盐或四氢喹啉化合物或其盐的溶剂合物。

公开(公告)号：US08133864B2

公开(公告)日：2012-03-13

申请号：US11909931

申请日：2006-03-29

申请人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Toru Kanke

发明人： Hiroyuki Ishiwata ,  Mototsugu Kabeya ,  Toru Kanke

IPC分类号： A61K38/08 ,  C07K5/083 ,  C07K5/087

CPC分类号： C07K5/0812 ,  A61K38/00 ,  C07K5/101 ,  C07K5/1016

摘要： The present invention relates to a pharmaceutical composition for preventing/treating conditions associated with PAR-2. The present invention also relates to a method for preventing/treating the condition using the pharmaceutical composition and use for manufacturing the pharmaceutical composition. The pharmaceutical composition comprises a compound represented by the following general formula (1), salt or solvate thereof and a pharmaceutically acceptable carrier: Ar—CO—AA1—AA2—AA3—AA4—NH—X—Y (1) wherein, Ar represents a phenyl group or an aromatic heterocyclic group optionally having substituent(s): AA1 represents a hydrophobic amino acid: AA2 represents an amino acid absent of substituent(s) having more than two carbon atoms: AA3 represents an amino acid absent of substituent(s) having more than two carbon atoms: AA4 represents a basic amino acid: X represents a straight chain or branched bivalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms: Y represents basic substituent(s); straight chain, branched, or cyclic bivalent saturated aliphatic hydrocarbon group having 1 to 6 carbon atoms; or an aromatic hydrocarbon group having 6 to 10 carbon atoms. The compound represented by the general formula (1) has dramatically improved PAR-2 activation potency compared to peptide comprised of 6 amino acids (Tethered receptor agonist peptide: TRAP) in spite of reduction of the number of amino acid.

摘要翻译： 本发明涉及用于预防/治疗与PAR-2相关的病症的药物组合物。 本发明还涉及使用药物组合物预防/治疗病症的方法以及用于制造药物组合物的方法。 药物组合物包含由以下通式（1）表示的化合物，其盐或溶剂合物和药学上可接受的载体：Ar-CO-AA1-AA2-AA3-AA4-NH-X-Y（1）其中Ar表示 任选具有取代基的苯基或芳族杂环基：AA1表示疏水性氨基酸：AA2表示不具有多于两个碳原子的取代基的氨基酸：AA3表示不存在取代基的氨基酸（s ）：AA4表示碱性氨基酸：X表示具有1〜6个碳原子的直链或支链二价饱和脂肪族烃基：Y表示碱性取代基; 具有1至6个碳原子的直链，支链或环状二价饱和脂族烃基; 或碳原子数为6〜10的芳香族烃基。 尽管氨基酸数量的减少，但由通式（1）表示的化合物与包含6个氨基酸的肽（束缚受体激动剂肽：TRAP）相比，显着提高了PAR-2的活化效力。

公开(公告)号：US20090012006A1

公开(公告)日：2009-01-08

申请号：US11576304

申请日：2005-09-30

申请人： Mototsugu Kabeya ,  Kyoko Yasuoka ,  Toru Kanke ,  Hiroyuki Ishiwata ,  Junya Tagashira

发明人： Mototsugu Kabeya ,  Kyoko Yasuoka ,  Toru Kanke ,  Hiroyuki Ishiwata ,  Junya Tagashira

IPC分类号： A61K38/06 ,  C07K5/083 ,  A61P35/00 ,  A61P11/06

CPC分类号： C07K5/0827 ,  A61K38/00 ,  C07D209/14 ,  C07K5/0806 ,  C07K5/0812

摘要： Compounds represented by the general formula (1) or salts thereof or solvates of both; PAR-2 antagonists containing the compounds; and preventive or therapeutic agents for PAR-2 related diseases containing the antagonists as the active ingredient: (1) wherein R1 is hydrogen, halogeno, or a group represented by the general formula (2): (wherein R11 is straight-chain or branched C1-6 alkylene or the like; and R12 and R13 together with the nitrogen atom adjacent to them form a 5- to 7-membered ring); R2 is straight-chain or branched C1-6 alkyl or the like; R3 and R4 are each independently hydrogen, one to three halogen atoms, or the like; and A1-A2-A3 is a tripeptide residue composed of α-amino acids each independently selected from the group consisting of glycine, alanine, cyclohexylalanine, and so on.

摘要翻译： 由通式（1）表示的化合物或其盐或两者的溶剂合物; 含有这些化合物的PAR-2拮抗剂; 以及含有拮抗剂作为活性成分的PAR-2相关疾病的预防或治疗剂：（1）其中R1是氢，卤素或由通式（2）表示的基团：（其中R11是直链或支链的 C 1-6亚烷基等; R 12和R 13与它们相邻的氮原子一起形成5-至7-元环）; R2是直链或支链C 1-6烷基等; R3和R4各自独立地为氢，一至三个卤素原子等; 并且A1-A2-A3是由各自独立地选自甘氨酸，丙氨酸，环己基丙氨酸等的α-氨基酸组成的三肽残基。

公开(公告)号：US06787653B2

公开(公告)日：2004-09-07

申请号：US10162602

申请日：2002-06-06

申请人： Hiroyuki Ishiwata ,  Seiichi Sato ,  Mototsugu Kabeya ,  Soichi Oda

发明人： Hiroyuki Ishiwata ,  Seiichi Sato ,  Mototsugu Kabeya ,  Soichi Oda

IPC分类号： C07D21126

CPC分类号： C07D295/192

摘要： A process for preparing a biphenylcarboxylic acid amide derivative represented by the following formula (1): wherein, R1, R2 and R3 each independently represents a hydrogen atom or a substituent, which comprises reacting, in the presence of a metal catalyst, a halogenobenzoic acid derivative represented by the following formula (2): wherein, X represents a halogen atom with a compound represented by the following formula (3): wherein, R1, R2 and R3 have the same meanings as described above, and Y represents an leaving group having an element selected from the group consisting of boron, silicon, zinc, tin and magnesium; or salt thereof. According to the present invention, biphenylcarboxylic acid amide derivatives of the formula (1) or salts thereof having excellent inhibitory activity against IgE antibody production can be prepared by the reduced number of steps, conveniently, at lower cost and in a high yield.

摘要翻译： 一种制备由下式（1）表示的联苯羧酸酰胺衍生物的方法：其中R 1，R 2和R 3各自独立地表示氢原子或取代基，其包括在 存在金属催化剂，由下式（2）表示的卤代苯甲酸衍生物：其中，X表示与下式（3）表示的化合物的卤素原子：其中，R 1，R 2和 R 3具有与上述相同的含义，Y表示具有选自硼，硅，锌，锡和镁的元素的离去基团; 或其盐。根据本发明，具有优异的抗IgE抗体产生抑制活性的式（1）的联苯基羧酸酰胺衍生物或其盐可以通过减少数量的步骤，以较低的成本和较高的成本 产量。