公开(公告)号：US20090270399A1

公开(公告)日：2009-10-29

申请号：US12497797

申请日：2009-07-06

Applicant: Masao OHKUCHI ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

Inventor： Masao OHKUCHI ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

IPC: A61K31/50 ,  C07D237/14

CPC classification number: C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl, group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.

Abstract translation: 本发明涉及由式（1）表示的哒嗪衍生物：其中R1表示（取代）芳基，R2表示在4-位被低级烷氧基，低级烷硫基或低级烷硫基取代的苯基，R3表示低级 烷氧基，卤代低级烷基，低级环烷基，（取代）芳基，（取代）芳氧基，（取代）含氮杂环残基，（取代）氨基羰基或低级烷基羰基 A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5-位之间的碳 - 碳键为单键或 双键或其盐; 以及含有它们作为有效成分的药物。 这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。

公开(公告)号：US06861428B2

公开(公告)日：2005-03-01

申请号：US10396726

申请日：2003-03-26

Applicant: Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

Inventor： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC: A61K31/50 ,  A61K31/501 ,  C07D237/14 ,  C07D237/24 ,  A61K31/51 ,  C07D237/04 ,  C07D403/06

CPC classification number: A61K31/50 ,  A61K31/501 ,  C07D237/14 ,  C07D237/24

Abstract: Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represents a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represents a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to pharmaceutical compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

Abstract translation: 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子或烷基，羟基烷基，二羟基烷基或炔基，或R 2 >和R 3可以与相邻的氮原子一起形成取代或未取代的含氮饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子或 n，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。

公开(公告)号：US06828316B2

公开(公告)日：2004-12-07

申请号：US09978102

申请日：2001-10-17

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

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

IPC: A61K3155

CPC classification number: 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

Abstract: 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.

Abstract translation: 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

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

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

IPC: A61K31495

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US4394382A

公开(公告)日：1983-07-19

申请号：US271927

申请日：1981-06-09

Applicant: Masami Shiratsuchi ,  Noboru Shimizu ,  Hiromichi Shigyo ,  Yoshinori Kyotani ,  Hisashi Kunieda ,  Kiyoshi Kawamura ,  Seiichi Sato ,  Toshihiro Akashi ,  Masahiko Nagakura ,  Naotoshi Sawada ,  Yasumi Uchida

Inventor： Masami Shiratsuchi ,  Noboru Shimizu ,  Hiromichi Shigyo ,  Yoshinori Kyotani ,  Hisashi Kunieda ,  Kiyoshi Kawamura ,  Seiichi Sato ,  Toshihiro Akashi ,  Masahiko Nagakura ,  Naotoshi Sawada ,  Yasumi Uchida

IPC: C07D311/04 ,  A61K31/353 ,  A61P9/02 ,  A61P9/04 ,  A61P21/02 ,  C07D311/22 ,  C07D311/58 ,  C07D311/64 ,  C07D311/66 ,  A61K31/35

CPC classification number: C07D311/22 ,  C07D311/58 ,  C07D311/64 ,  C07D311/66 ,  Y10S514/821

Abstract: A benzopyran compound represented by the following ##STR1## wherein A represents a direct bond or the bond --CH.sub.2 --O--,R.sub.1 represents a member selected from the group consisting of a C.sub.3 -C.sub.5 alkyl group, a hydroxy-(C.sub.3 -C.sub.5 alkyl) group, a lower alkylamino-lower alkyl group, a nitrato-(C.sub.3 -C.sub.5 alkyl) group and a phenyl-(C.sub.1 -C.sub.5) alkyl group, provided that the phenyl may be substituted by a lower alkoxy group, R.sub.2 represents a member selected from the group consisting of hydrogen, halogen, OH, NO.sub.2, a carbamoyl group, a lower alkyl group, a lower alkoxy group, a lower alkyleneoxy group and acetyl group,R.sub.3 represents hydrogen or NO.sub.2,B represents a direct bond, a C.sub.1 -C.sub.7 alkylene group, a --O-lower alkylene group or a --CONH-lower alkylene group, andn represents 1 or 2;and an acid addition salt thereof and a pharmaceutical composition comprising aforesaid compound.

Abstract translation: 由下式（I）表示的苯并吡喃化合物，其中A表示直接键或键-CH2-O-，R1表示选自C3-C5烷基，羟基 - （C3 -C 5烷基）基，低级烷基氨基 - 低级烷基，硝基 - （C 3 -C 5烷基）基和苯基 - （C 1 -C 5）烷基，条件是苯基可以被低级烷氧基取代，R 2 表示选自氢，卤素，OH，NO 2，氨基甲酰基，低级烷基，低级烷氧基，低级亚烷基氧基和乙酰基的成员，R 3表示氢或NO 2，B表示直接键 ，C 1 -C 7亚烷基，-O-低级亚烷基或-CONH-低级亚烷基，n表示1或2; 及其酸加成盐和包含上述化合物的药物组合物。

公开(公告)号：US20080119474A1

公开(公告)日：2008-05-22

申请号：US12013691

申请日：2008-01-14

Applicant: Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

Inventor： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

IPC: A61K31/50 ,  C07D237/02 ,  A61P19/00 ,  A61P9/00 ,  A61P37/00

CPC classification number: C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

Abstract: This invention relates to pyridazine derivatives represented by the formula (1): wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (substituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1β production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.

Abstract translation: 本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4位被取代的苯基 通过低级烷氧基或低级烷硫基，R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代）芳基，取代的芳氧基 ，（取代）的含氮杂环残基，（取代）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线 表示4-位和5-位之间的碳 - 碳键是单键或双键，或其盐; 以及含有它们作为有效成分的药物。 这些化合物对白细胞介素-1β产生具有优异的抑制活性，并且可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防和治疗。

公开(公告)号：US20050085480A1

公开(公告)日：2005-04-21

申请号：US10960993

申请日：2004-10-12

Applicant: Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

Inventor： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC: C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  A61P1/04 ,  A61P9/00 ,  A61P19/02 ,  A61P19/10 ,  A61P29/00 ,  A61P31/04 ,  A61P37/02 ,  A61P43/00 ,  C07D237/24 ,  C07D43/02

CPC classification number: C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  C07D237/24

Abstract: Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represent a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represent a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to medicinal compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

Abstract translation: 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子 或烷基，羟基烷基，二羟基烷基或炔基或R 2和R 3可以与相邻的氮原子一起形成取代或未取代的含氮的 饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子等，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。

公开(公告)号：US06664256B1

公开(公告)日：2003-12-16

申请号：US09612953

申请日：2000-07-10

Applicant: Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Natsuyo Kumai ,  Kyoko Kotaki

Inventor： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Natsuyo Kumai ,  Kyoko Kotaki

IPC: A61K3150

CPC classification number: C07D401/12 ,  A61K31/50 ,  C07D237/08 ,  C07D237/12 ,  C07D237/14 ,  C07D237/18 ,  C07D237/20 ,  C07D237/24 ,  C07D405/04 ,  C07D417/04

Abstract: Phenylpyridazine compounds represented by the following formula (I): are provided, wherein R1, R2, R3, R4, and n are as defined herein having excellent inhibitory activity against interleukin-1&bgr; production, and useful in the treatment of prevention of diseases caused by stimulation of interleukin-1&bgr; production, such as immune system diseases, inflammatory diseases, and ischemic diseases.

Abstract translation: 提供由下式（I）表示的苯基哒嗪化合物：其中R 1，R 2，R 3，R 4和n如本文所定义，对白细胞介素-1β生产具有优异的抑制活性 可用于治疗由免疫系统疾病，炎症性疾病和缺血性疾病等白细胞介素-1β产生刺激引起的疾病的预防。

公开(公告)号：US07087606B2

公开(公告)日：2006-08-08

申请号：US10960993

申请日：2004-10-12

Applicant: Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

Inventor： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC: A01N43/58 ,  A61K31/50

CPC classification number: C07D237/14 ,  A61K31/50 ,  A61K31/501 ,  C07D237/24

Abstract: Compounds having the formula (1): wherein R1 represents an alkyl or alkenyl group, R2 and R3 each independently represent a hydrogen atom or an alkyl, hydroxyalkyl, dihydroxyalkyl or alkynyl group, or R2 and R3 may be fused together with the adjacent nitrogen atom to form a substituted or unsubstituted, nitrogen-containing, saturated heterocyclic group, X, Y and Z each independently represent a hydrogen atom, an alkyl group, a halogen atom or the like, and n stands for an integer of from 1 to 5; and also to medicinal compositions containing them. These compounds have inhibitory activity against IL-1β production, high water solubility and good oral absorbability.

Abstract translation: 具有式（1）的化合物：其中R 1表示烷基或烯基，R 2和R 3各自独立地表示氢原子 或烷基，羟基烷基，二羟基烷基或炔基或R 2和R 3可以与相邻的氮原子一起形成取代或未取代的含氮的 饱和杂环基，X，Y和Z各自独立地表示氢原子，烷基，卤素原子等，n表示1〜5的整数， 以及含有它们的药物组合物。 这些化合物对IL-1β生产具有抑制活性，水溶性高，口服吸收性好。

公开(公告)号：US20060142292A1

公开(公告)日：2006-06-29

申请号：US10544881

申请日：2004-03-16

Applicant: Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

Inventor： Yoshinori Kyotani ,  Tomoyuki Koshi ,  Hiromichi Shigyo ,  Hideo Yoshizaki ,  Takahiro Kitamura ,  Shunji Takemura ,  Kyoko Yasuoka ,  Junko Totsuka ,  Seiichi Sato

IPC: A61K31/501 ,  C07D403/02 ,  A61K31/50

CPC classification number: A61K31/501 ,  A61K31/50 ,  C07D237/14

Abstract: A phenylpyridazine derivative represented by the formula (1): Wherein, R1, R2, R3, X, Y, Z and n have the same meaning as defined in the specification; or a salt thereof, or a medicine containing the compound. The present invention provides water-soluble phenylpyridazine derivatives and medicines containing them, which have excellent inhibitory activity against interleukin-β production, high water solubility and high oral absorbability.

Abstract translation: 由式（1）表示的苯基哒嗪衍生物：其中R1，R2，R3，X，Y，Z和n与说明书中定义相同; 或其盐，或含有该化合物的药物。 本发明提供水溶性苯基哒嗪衍生物和含有它们的药物，其对白细胞介素-β产生具有优异的抑制活性，高水溶性和高口服吸收性。