公开(公告)号：US20090076280A1

公开(公告)日：2009-03-19

申请号：US11912811

申请日：2006-05-30

申请人： Yukiyoshi Yamazaki ,  Takaaki Araki ,  Minoru Koura ,  Kimiyuki Shibuya

发明人： Yukiyoshi Yamazaki ,  Takaaki Araki ,  Minoru Koura ,  Kimiyuki Shibuya

IPC分类号： C07D263/58

CPC分类号： C07D413/12 ,  C07D263/58

摘要： The invention provides a process for producing an optically active butyric acid compound and a production intermediate therefor at high yield and high purity.The present invention provides a process for producing Compound (6), including reacting Compound (1) with optically active 2-trifluoromethanesulfonyloxybutyrolactone (2a) in the presence of a base or reacting optically active 2-hydroxybutyrolactone (2b) under Mitsunobu reaction conditions, to thereby form Compound (3); reacting Compound (3) with an alcohol and a halogenating agent, to thereby form Compound (4); dehalogenating Compound (4), to thereby form Compound (5); and de-esterifying Compound (5).

摘要翻译： 本发明提供一种以高产率和高纯度生产光学活性丁酸化合物及其制备中间体的方法。 本发明提供化合物（6）的制造方法，其包括使光学活性2-三氟甲磺酰氧基丁内酯（2a）在光学活性2-羟基丁内酯（2b）的存在下，在Mitsunobu反应条件下，使化合物（1）与光活性2-三氟甲磺酰氧基丁内酯 从而形成化合物（3）; 使化合物（3）与醇和卤化剂反应，从而形成化合物（4）; 脱卤化合物（4），从而形成化合物（5）; 并使化合物（5）脱酯化。

公开(公告)号：US20080194833A1

公开(公告)日：2008-08-14

申请号：US11816472

申请日：2006-02-23

申请人： Yukiyoshi Yamazaki ,  Takaaki Araki ,  Minoru Koura ,  Kimiyuki Shibuya

发明人： Yukiyoshi Yamazaki ,  Takaaki Araki ,  Minoru Koura ,  Kimiyuki Shibuya

IPC分类号： C07D263/58

CPC分类号： C07D263/58

摘要： A process for obtaining a compound (1) and an intermediate thereof in high yield and high optical yield is provided.A process for producing a compound (4), the process including reacting a compound (2) with a compound (3) in the presence of a base; and a process for producing a compound (1), the process including reacting a compound (2) with a compound (3) in the presence of a base to yield a compound (4) and then deesterifying the compound (4). wherein R represents an alkyl group having 1 to 6 carbon atoms or an aralkyl group having 7 to 8 carbon atoms.

摘要翻译： 提供了以高产率和高光学收率获得化合物（1）及其中间体的方法。 一种制备化合物（4）的方法，该方法包括在碱的存在下使化合物（2）与化合物（3）反应; 和化合物（1）的制造方法，其特征在于，在碱的存在下使化合物（2）与化合物（3）反应，得到化合物（4），然后使化合物（4）脱酯化。 其中R表示碳原子数1〜6的烷基或碳原子数7〜8的芳烷基。

公开(公告)号：US07301033B2

公开(公告)日：2007-11-27

申请号：US11335669

申请日：2006-01-20

申请人： Yukiyoshi Yamazaki ,  Tsutomu Toma ,  Masahiro Nishikawa ,  Hajime Yamada ,  Hidefumi Ozawa ,  Ayumu Okuda ,  Kazutoyo Abe

发明人： Yukiyoshi Yamazaki ,  Tsutomu Toma ,  Masahiro Nishikawa ,  Hajime Yamada ,  Hidefumi Ozawa ,  Ayumu Okuda ,  Kazutoyo Abe

IPC分类号： C07D263/58 ,  A61K31/423

CPC分类号： C07D263/58

摘要： The present invention provides a compound selectively activating PPARα, which is useful as a medicament. The present invention is specifically directed to a benzoic acid derivative represented by the following general formula (1): wherein A represents an oxygen atom, a nitrogen atom, or a sulfur atom; R represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkyl-alkyl group, an aryl group, an aryl-alkyl group an aryl-oxy-alkyl group, a pyridyl-alkyl group, an alkoxycarbonyl-alkyl group, or a carboxy-alkyl group; X represents an oxygen atom, an NH group, or an S(O)n group (wherein n represents an integer of 0, 1, or 2); and m represents an integer from 2 to 8; or a salt thereof. The present invention also provides a medicament comprising the benzoic acid derivative or the salt thereof as an active ingredient.

摘要翻译： 本发明提供选择性活化PPARα的化合物，其可用作药物。 本发明具体涉及由以下通式（1）表示的苯甲酸衍生物：其中A表示氧原子，氮原子或硫原子; R表示氢原子，烷基，烯基，炔基，环烷基，环烷基 - 烷基，芳基，芳基 - 烷基，芳氧基 - 烷基，吡啶基 - 烷基 ，烷氧基羰基 - 烷基或羧基 - 烷基; X表示氧原子，NH基或S（O）n N（其中n表示0,1或2的整数）; m表示2〜8的整数， 或其盐。 本发明还提供了包含苯甲酸衍生物或其盐作为活性成分的药物。

公开(公告)号：US20050065155A1

公开(公告)日：2005-03-24

申请号：US10986350

申请日：2004-11-12

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

发明人： 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分类号： A61K31/50 ,  A61K31/501 ,  A61P19/02 ,  A61P19/10 ,  A61P29/00 ,  A61P37/00 ,  C07D213/00 ,  C07D237/00 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/04 ,  C07D401/06 ,  C07D43/02

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： 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 (subsituted) 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.

摘要翻译： 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-位被低级烷氧基或低级烷硫基取代的苯基 R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代的）含氮杂环残基，（取代的） ）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 - 位是单键或双键，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：US06509329B1

公开(公告)日：2003-01-21

申请号：US09893697

申请日：2001-06-29

申请人： Tatsuhiko Kodama ,  Masahiro Tamura ,  Toshiaki Oda ,  Yukiyoshi Yamazaki ,  Masahiro Nishikawa ,  Takeshi Doi ,  Yoshinori Kyotani

发明人： Tatsuhiko Kodama ,  Masahiro Tamura ,  Toshiaki Oda ,  Yukiyoshi Yamazaki ,  Masahiro Nishikawa ,  Takeshi Doi ,  Yoshinori Kyotani

IPC分类号： C07D25112

CPC分类号： C07D295/096 ,  A61K31/495 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551 ,  C07D213/38

摘要： A cyclic diamine compound of formula (1): wherein A is a single bond or C≡C; X and Y are individually CH or a nitrogen atom; m is 1 or 2; and n is a number of 1 to 5; an acid-addition salt thereof, or a hydrate thereof. The compound has excellent inhibitory effects on both cell adhesion and cell infiltration and is useful as a medicine for prevention or treatment of diseases such as allergy, asthma, rheumatism, arteriosclerosis and inflammation.

摘要翻译： 式（1）的环状二胺化合物：其中A是单键或C = C; X和Y分别是CH或氮原子; m为1或2; n为1〜5的数; 其酸加成盐或其水合物。 该化合物对细胞粘附和细胞浸润具有优异的抑制作用，可用作预防或治疗诸如过敏，哮喘，风湿病，动脉硬化和炎症等疾病的药物。

公开(公告)号：US07714141B2

公开(公告)日：2010-05-11

申请号：US11912811

申请日：2006-05-30

申请人： Yukiyoshi Yamazaki ,  Takaaki Araki ,  Minoru Koura ,  Kimiyuki Shibuya

发明人： Yukiyoshi Yamazaki ,  Takaaki Araki ,  Minoru Koura ,  Kimiyuki Shibuya

IPC分类号： C07D263/58 ,  C07D277/82 ,  C07D235/30

CPC分类号： C07D413/12 ,  C07D263/58

摘要： The invention provides a process for producing an optically active butyric acid compound and a production intermediate therefore at high yield and high purity.The present invention provides a process for producing Compound (6), including reacting Compound (1) with optically active 2-trifluoromethanesulfonyloxybutyrolactone (2a) in the presence of a base or reacting optically active 2-hydroxybutyrolactone (2b) under Mitsunobu reaction conditions, to thereby form Compound (3); reacting Compound (3) with an alcohol and a halogenating agent, to thereby form Compound (4); dehalogenating Compound (4), to thereby form Compound (5); and de-esterifying Compound (5).

摘要翻译： 本发明提供了一种以高产率和高纯度生产光学活性丁酸化合物和生产中间体的方法。 本发明提供化合物（6）的制造方法，其包括使光学活性2-三氟甲磺酰氧基丁内酯（2a）在光学活性2-羟基丁内酯（2b）的存在下，在Mitsunobu反应条件下，使化合物（1）与光活性2-三氟甲磺酰氧基丁内酯 从而形成化合物（3）; 使化合物（3）与醇和卤化剂反应，从而形成化合物（4）; 脱卤化合物（4），从而形成化合物（5）; 并使化合物（5）脱酯化。

公开(公告)号：US20070208025A1

公开(公告)日：2007-09-06

申请号：US11741947

申请日：2007-04-30

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

发明人： 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分类号： A61K31/50

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： 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.

摘要翻译： 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：US20060167058A1

公开(公告)日：2006-07-27

申请号：US11335669

申请日：2006-01-20

申请人： Yukiyoshi Yamazaki ,  Tsutomu Toma ,  Masahiro Nishikawa ,  Hajime Yamada ,  Hidefumi Ozawa ,  Ayumu Okuda ,  Kazutoyo Abe

发明人： Yukiyoshi Yamazaki ,  Tsutomu Toma ,  Masahiro Nishikawa ,  Hajime Yamada ,  Hidefumi Ozawa ,  Ayumu Okuda ,  Kazutoyo Abe

IPC分类号： A61K31/4439 ,  A61K31/428 ,  A61K31/423 ,  A61K31/4184

CPC分类号： C07D263/58

摘要： The present invention provides a compound selectively activating PPARα, which is useful as a medicament. The present invention is specifically directed to a benzoic acid derivative represented by the following general formula (1): wherein A represents an oxygen atom, a nitrogen atom, or a sulfur atom; R represents a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkyl-alkyl group, an aryl group, an aryl-alkyl group an aryl-oxy-alkyl group, a pyridyl-alkyl group, an alkoxycarbonyl-alkyl group, or a carboxy-alkyl group; X represents an oxygen atom, an NH group, or an S(O)n group (wherein n represents an integer of 0, 1, or 2); and m represents an integer from 2 to 8; or a salt thereof. The present invention also provides a medicament comprising the benzoic acid derivative or the salt thereof as an active ingredient.

摘要翻译： 本发明提供选择性活化PPARα的化合物，其可用作药物。 本发明具体涉及由以下通式（1）表示的苯甲酸衍生物：其中A表示氧原子，氮原子或硫原子; R表示氢原子，烷基，烯基，炔基，环烷基，环烷基 - 烷基，芳基，芳基 - 烷基，芳氧基 - 烷基，吡啶基 - 烷基 ，烷氧基羰基 - 烷基或羧基 - 烷基; X表示氧原子，NH基或S（O）n N（其中n表示0,1或2的整数）; m表示2〜8的整数， 或其盐。 本发明还提供了包含苯甲酸衍生物或其盐作为活性成分的药物。

公开(公告)号：US20050267113A1

公开(公告)日：2005-12-01

申请号：US11203174

申请日：2005-08-15

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

发明人： 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分类号： A61K31/50 ,  A61K31/501 ,  A61P19/02 ,  A61P19/10 ,  A61P29/00 ,  A61P37/00 ,  C07D213/00 ,  C07D237/00 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/04 ,  C07D401/06 ,  C07D43/02

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： 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 (subsituted) 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 immmune system diseases, inflammatory diseases, ischemic diseases and the like.

摘要翻译： 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，（取代的）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生成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药物和治疗剂。

公开(公告)号：US06552188B2

公开(公告)日：2003-04-22

申请号：US09893699

申请日：2001-06-29

申请人： Tatsuhiko Kodama ,  Masahiro Tamura ,  Toshiaki Oda ,  Yukiyoshi Yamazaki ,  Masahiro Nishikawa ,  Shunji Takemura ,  Takeshi Doi ,  Yoshinori Kyotani

发明人： Tatsuhiko Kodama ,  Masahiro Tamura ,  Toshiaki Oda ,  Yukiyoshi Yamazaki ,  Masahiro Nishikawa ,  Shunji Takemura ,  Takeshi Doi ,  Yoshinori Kyotani

IPC分类号： A61K31496

CPC分类号： C07D213/81 ,  C07D213/36 ,  C07D213/82 ,  C07D401/12

摘要： Cyclic diamine compounds of formula (1) are disclosed: wherein A is (CH2)n, (CH2)n—CH═CH, CO—(CH2)n or CO—(CH2)n—CH═CH, in which n is a number of 0 to 3; Z represents a formula (2) or (3): in which R1, R2, R4, R5 and R6 are individually a hydrogen atom, alkyl group, alkoxy group, halogen atom or nitro group; R3is a hydrogen atom, alkyl group, alkoxy group, halogen atom, nitro group, naphthyl group, or phenyl group which may be substituted by 1 to 3 substituents selected from the group consisting of alkyl groups, alkoxy groups, halogen atoms, a nitro group and a phenyl group; and X and Y are individually CH or a nitrogen atom; and m is 1 or 2; an acid-addition salt thereof, or a hydrate thereof, and a medicine containing such a compound.

摘要翻译： 公开了式（1）的环二胺化合物：其中A是（CH 2）n，（CH 2）n -CH = CH，CO-（CH 2）n或CO-（CH 2）n -CH = CH，其中n是 数字0到3; Z表示式（2）或（3）：其中R1，R2，R4，R5和R6分别为氢原子，烷基，烷氧基，卤素原子或硝基; R3是氢原子，烷基，烷氧基，卤素原子，硝基，萘基或可以被1〜3个选自烷基，烷氧基，卤原子，硝基的取代基取代的苯基 和苯基; X和Y分别是CH或氮原子; m为1或2;其酸加成盐或其水合物，以及含有这种化合物的药物。