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1. 发明授权

US06548695B2 Process for producing isocoumarins and intermediates for the same 失效
标题翻译：生产异香豆素及其中间体的方法
公开(公告)号：US06548695B2
公开(公告)日：2003-04-15
申请号：US10119734
申请日：2002-04-11
申请人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
发明人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
IPC分类号： C07C51493
CPC分类号： C07D311/76 , C07C67/31 , C07C67/343 , C07C67/46 , C07C69/92 , Y02P20/55 , C07C69/88
摘要： Provided is a process for producing an isocoumarin-3-yl-acetic acid derivative, characterized by reacting a homophthalic acid derivative represented by a formula: (wherein Rc, R2 and R are mainly protecting groups) with a malonic acid derivating represented by a formula: (wherein R is an organic group including a lower alkyl group; R3 is a protecting group for a carboxyl group; and X is a halogen atom or a —OM group (wherein M is alkaline metal or alkaline earth metal)). According to the above process, various isocoumarin-3-yl-acetic acid derivatives can efficiently be provided.
摘要翻译：提供了一种制备异香豆素-3-基 - 乙酸衍生物的方法，其特征在于使由式（其中Rc，R2和R主要是保护基团）表示的均苯二甲酸衍生物与由式（其中，R为低级烷基的有机基团，R3为羧基的保护基，X为卤原子或-OM基）（其中，M为碱金属或碱土金属）。根据上述方法，可以有效地提供各种异香豆素-3-基 - 乙酸衍生物。

2. 发明授权

US06361987B1 Gene encoding a protein having asymmetric hydrolase activity for 4-substituted 1,4-dihydropyridine derivatives and its expression product 失效
标题翻译：编码具有4-取代的1,4-二氢吡啶衍生物及其表达产物的不对称水解酶活性的蛋白质的基因
公开(公告)号：US06361987B1
公开(公告)日：2002-03-26
申请号：US09514340
申请日：2000-02-28
申请人： Akira Arisawa , Motoko Matsufuji , Takurou Tsuruta , Kazuyuki Dobashi , Takashi Nakashima , Kunio Isshiki , Takeo Yoshioka
发明人： Akira Arisawa , Motoko Matsufuji , Takurou Tsuruta , Kazuyuki Dobashi , Takashi Nakashima , Kunio Isshiki , Takeo Yoshioka
IPC分类号： C12N914
CPC分类号： C07D211/88 , C07D211/90 , C12N9/18 , C12N9/78 , C12P17/12 , C12P41/006
摘要： This invention provides DNA fragments for efficiently preparing a protein having asymmetric hydrolase activity for 4-substituted 1,4-dihydropyridine derivatives, transformants obtained by using such a DNA fragment, and a process for preparing the aforesaid enzyme. Specifically, an isolated gene derived from the chromosome of Streptomyces viridosporus and encoding a protein having asymmetric hydrolase activity for 4-substituted 1,4-dihydropyridine derivatives, plasmids having the aforesaid gene integrated thereinto, transformants obtained by using such a plasmid, and a process for preparing the aforesaid enzyme by using such a transformant are disclosed. A process for the enzymatic conversion of 4-substituted 1,4-dihydropyridine derivatives by using the aforesaid enzyme is also disclosed.
摘要翻译：本发明提供了用于有效制备对4-取代的1,4-二氢吡啶衍生物具有不对称水解酶活性的蛋白质的DNA片段，以及通过使用这样的DNA片段得到的转化体及其制备方法。具体来说，来源于链球菌链球菌的染色体的分离的基因，编码对4-取代的1,4-二氢吡啶衍生物具有不对称的水解酶活性的蛋白质，将上述基因整合到其中的质粒，使用这样的质粒获得的转化体，公开了通过使用这种转化体制备上述酶的方法。还公开了通过使用上述酶酶促转化4-取代的1,4-二氢吡啶衍生物的方法。

3. 发明授权

US5096924A Anticancer antibiotic MI43-37F11 substance 失效
标题翻译： ANTICANCER抗生素MI43-37F11物质
公开(公告)号：US5096924A
公开(公告)日：1992-03-17
申请号：US531109
申请日：1990-05-31
申请人： Masaaki Ishizuka , Hiroyuki Kumagai , Tsutomu Sawa , Hiroshi Naganawa , Hironobu Iinuma , Kunio Isshiki , Masa Hamada , Kenji Maeda , Tomio Takeuchi
发明人： Masaaki Ishizuka , Hiroyuki Kumagai , Tsutomu Sawa , Hiroshi Naganawa , Hironobu Iinuma , Kunio Isshiki , Masa Hamada , Kenji Maeda , Tomio Takeuchi
IPC分类号： A61K31/35 , A61K31/352 , A61P35/00 , C07D311/76 , C12N1/20 , C12P17/06 , C12R1/625
CPC分类号： C12P17/06 , C07D311/76
摘要： As a new antibiotic is provided a compound, now nominated as MI43-37F11 substance, which has formula ##STR1## This MI43-37F11 substance has an antitumor activity, an activity to enhance the production of interleukin-1 in vivo in a mammalian, and an activity to activate a macrophage in vivo in a mammalian. MI43-37F11 substance may be produced by cultivation of Streptoverticillium eurocidicum MI43-37F11 strain identified as FERM BP-2783.

4. 发明申请

US20050124050A1 Osteoclast differentiation inhibitors 失效
标题翻译：破骨细胞分化抑制剂
公开(公告)号：US20050124050A1
公开(公告)日：2005-06-09
申请号：US10506975
申请日：2003-03-06
申请人： Hiroyuki Kumagai , Tomohiro Sameshima , Motoko Matsufuji , Naoto Kawamura , Kunio Isshiki , Hiroyuki Inoue , Tetsuya Someno , Masaaki Sihizuka , Tomio Takeuchi
发明人： Hiroyuki Kumagai , Tomohiro Sameshima , Motoko Matsufuji , Naoto Kawamura , Kunio Isshiki , Hiroyuki Inoue , Tetsuya Someno , Masaaki Sihizuka , Tomio Takeuchi
IPC分类号： A61P19/02 , A61P19/10 , A61P29/00 , A61P35/00 , A61P35/04 , A61P43/00 , C07D265/38 , C07D498/04 , C12P17/14 , C12P17/18 , C12P17/16 , C07D498/02 , C12N1/21
CPC分类号： C07D265/38 , C12P17/14 , C12P17/188 , C12R1/645
摘要： A compound represented by formula (I); a process for producing a compound (substance F-1490) of formula (I), wherein X represents —O— and R represents a hydroxyl group, by using a microorganism belonging to the genus Cunninghamella; and a Cunninghamella sp. F-1490 strain (FERM BP-8287) capable of producing the substance F-1490; and an osteoclast differentiation inhibitory agent containing as an active ingredient the compound represented by formula (I): wherein X represents —O— or —CH2—, and R represents a hydroxyl group when X represents —O—, or a hydrogen atom when X represents —CH2—.
摘要翻译：由式（I）表示的化合物; 通过使用属于葫芦科属的微生物，制备式（I）化合物（F-1490物质）的方法，其中X表示-O-，R表示羟基; 和unning ella ella 能够生产物质F-1490的F-1490菌株（FERM BP-8287）; 和破骨细胞分化抑制剂，其含有作为活性成分的式（I）表示的化合物：其中X表示-O-或-CH 2 - ，当X表示-O时，R表示羟基 - 或当X代表-CH 2 - 2时为氢原子。

5. 发明授权

US06426420B1 Process for producing isocoumarines and intermediates for the same 失效
标题翻译：生产异香豆素及其中间体的方法
公开(公告)号：US06426420B1
公开(公告)日：2002-07-30
申请号：US09610362
申请日：2000-07-05
申请人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
发明人： Toshio Tsuchida , Hazuki Nagai , Takashi Nakashima , Masashi Yoshida , Kaname Konuki , Asako Kuroda , Kunio Isshiki , Tomio Takeuchi
IPC分类号： C07D31176
CPC分类号： C07D311/76 , C07C67/31 , C07C67/343 , C07C67/46 , C07C69/92 , Y02P20/55 , C07C69/88
摘要： Provided is a process for producing an isocoumarin-3-yl-acetic acid derivative, characterized by reacting a homophthalic acid derivative represented by a formula: (wherein Rc, R2 and R are mainly protecting groups) with a malonic acid derivating represented by a formula: (wherein R is an organic group including a lower alkyl group; R3 is a protecting group for a carboxyl group; and X is a halogen atom or a —OM group (wherein M is alkaline metal or alkaline earth metal)). According to the above process, various isocoumarin-3-yl-acetic acid derivatives can efficiently be provided.
摘要翻译：提供了一种制备异香豆素-3-基 - 乙酸衍生物的方法，其特征在于使由式（其中Rc，R2和R主要是保护基团）表示的均苯二甲酸衍生物与由式（其中，R为低级烷基的有机基团，R3为羧基的保护基，X为卤原子或-OM基）（其中，M为碱金属或碱土金属）。根据上述方法，可以有效地提供各种异香豆素-3-基 - 乙酸衍生物。

6. 发明授权

US5098935A Carcinostatic or antitumor antibiotic, conagenin, and production and uses thereof 失效
标题翻译：抗生素，抗生素，抗生素及其生产及其用途
公开(公告)号：US5098935A
公开(公告)日：1992-03-24
申请号：US524576
申请日：1990-05-17
申请人： Masaaki Ishizuka , Takashi Yamashita , Hiroshi Naganawa , Hironobu Iinuma , Kunio Isshiki , Masa Hamada , Kenji Maeda , Tomio Takeuchi
发明人： Masaaki Ishizuka , Takashi Yamashita , Hiroshi Naganawa , Hironobu Iinuma , Kunio Isshiki , Masa Hamada , Kenji Maeda , Tomio Takeuchi
IPC分类号： A61K31/195 , A61P35/00 , C07C235/12 , C12N1/20 , C12P13/02 , C12R1/465
CPC分类号： C12R1/465 , C07C235/12 , C12P13/02
摘要： A new antibiotic, named Conagenin, is provided which can exhibit useful carcinostatic or antitumor activities on carcinomas and tumors, particularly malignant tumors, of mammalian animals including man. Conagenin can be produced by fermentation of microorganisms of genus Streptomyces, typically Streptomyces roseosporus MI696-AF3 strain identified under the deposit number FERM BP-2738. Conagenin has formula (I) and is useful for medicinal purposes, particularly as carcinostatic agent or antitumor agent for inhibiting carcinomas and malignant tumors of mammalian animals, including man.

7. 发明授权

US06566394B1 Salicylamide derivatives 失效
标题翻译：水杨酰胺衍生物
公开(公告)号：US06566394B1
公开(公告)日：2003-05-20
申请号：US10049158
申请日：2002-05-30
申请人： Tomio Takeuchi , Kazuo Umezawa , Sakino To-E , Naoki Matsumoto , Tsutomu Sawa , Takeo Yoshioka , Naoki Agata , Shin-ichi Hirano , Kunio Isshiki
发明人： Tomio Takeuchi , Kazuo Umezawa , Sakino To-E , Naoki Matsumoto , Tsutomu Sawa , Takeo Yoshioka , Naoki Agata , Shin-ichi Hirano , Kunio Isshiki
IPC分类号： A61K31336
CPC分类号： C07D303/36 , C07C237/38 , C07C237/40
摘要： Salicylamide derivatives represented by formulae (1a) and (1b); intermediates in the production thereof; a process for producing the same; and drugs containing the same as the active ingredient. The salicylamide derivatives represented by formulae (1a) and (1b) are useful as anti-inflammatory agents and immunosuppressive agents which exert an effect of inhibiting the activation of NF-&kgr;B with little side effects.
摘要翻译：由式（1a）和（1b）表示的水杨酰胺衍生物; 中间体在其生产中; 其制造方法; 和含有与活性成分相同的药物。由式（1a）和（1b）表示的水杨酰胺衍生物可用作具有抑制NF-κB活化的副作用的抗炎剂和免疫抑制剂。

8. 发明授权

US06133443A Optically active 1,4-dihydropyridine derivatives and process for the preparation thereof 失效
标题翻译：光学活性的1,4-二氢吡啶衍生物及其制备方法
公开(公告)号：US06133443A
公开(公告)日：2000-10-17
申请号：US125608
申请日：1998-08-21
申请人： Takashi Nakashima , Kunio Isshiki , Noriaki Sakata , Naoki Agata , Takeo Yoshioka
发明人： Takashi Nakashima , Kunio Isshiki , Noriaki Sakata , Naoki Agata , Takeo Yoshioka
IPC分类号： C07D211/90 , C07D401/12 , C07D417/12 , C07D521/00 , C07D251/00 , C07D213/79 , C07D401/00 , C07D403/00 , C07D417/00
CPC分类号： C07D231/12 , C07D211/90 , C07D233/56 , C07D249/08 , C07D401/12 , C07D417/12
摘要： Optically active 1,4-dihydropyridine derivatives represented by general formula (I) and anion salts thereof and a production method therefor: ##STR1## (wherein R.sup.1 represents a C.sub.1-6 alkyl group, R.sup.2 represents a nitrogen-containing heterocyclic group forming a quaternary ammonium which may be substituted, and n is an integer of 1, 2 or 3). The optically active 1,4-dihydropyridine derivatives represented by general formula (I) have vasodilating activity and hypotensive activity and are excellent in water solubility so that they are useful as a drug for circulatory system such as a hypotensor or vasodilator.
摘要翻译： PCT No.PCT / JP96 / 03414 Sec。 371日期1998年8月21日 102（e）1998年8月21日PCT PCT 1996年11月21日PCT公布。公开号WO97 / 30987 日本8月28日，通式（I）表示的光学活性的1,4-二氢吡啶衍生物及其阴离子盐及其制造方法：其中，R1表示C1-6烷基，R2表示含氮杂环基，可以被取代的季铵，n是1,2或3的整数）。由通式（I）表示的光学活性的1,4-二氢吡啶衍生物具有血管扩张活性和降血压活性，并且水溶性优异，因此它们可用作循环系统如低血压或血管扩张剂的药物。

9. 发明授权

US5395941A Optically active 1,4-hydropyridine compounds 失效
标题翻译：光学活性的1,4-二氢吡啶化合物
公开(公告)号：US5395941A
公开(公告)日：1995-03-07
申请号：US216216
申请日：1994-03-22
申请人： Kunio Isshiki , Takashi Nakashima , Hiroshi Tanaka , Takeo Yoshioka
发明人： Kunio Isshiki , Takashi Nakashima , Hiroshi Tanaka , Takeo Yoshioka
IPC分类号： A61K31/455 , A61K31/443 , A61K31/4439 , A61K31/444 , A61P9/08 , A61P9/12 , A61P43/00 , C07B53/00 , C07D211/90 , C07D405/12 , C07D405/02
CPC分类号： C07D405/12 , C07D211/90 , Y02P20/55
摘要： Optically active 1,4-dihydropyridine derivatives represented by general formula (I), process for preparing compounds (Ic) (in general formula (I) , R.sup.1 is a lower alkyl group), process for preparing compounds represented by general formula (II) by hydrolyzing the compounds (Ic) under acidic conditions, process for preparing compounds represented by general formula (II) by solvolysis, under basic conditions, of compounds represented by general formula (III); ##STR1## wherein R.sup.1 is H, a lower alkyl group, a cyanoethyl group, a lower alkanoylaminoethyl group, or a lower dialkylaminoethyl group; R.sup.2 is a 2-tetrahydropyranyl group or a lower alkyloxymethyl group; R.sup.3 is a cyano group, a lower dialkylamino group or a lower alkanoylamino group; and R.sup.4 is a lower alkyl group. The compounds of general formula (I) and (II) are intermediate compounds for preparing optically active 1,4-dihydropyridine derivatives which are useful as medicines for circulatory organs. The compounds can be produced efficiently by the process of the present invention.
摘要翻译：通式（I）表示的光学活性的1,4-二氢吡啶衍生物，化合物（Ic）的制备方法（通式（I）中，R 1为低级烷基），由通式（II）表示的化合物的制备方法，通过在酸性条件下水解化合物（Ic），通过在碱性条件下通过通式（III）表示的化合物的溶剂分解来制备由通式（II）表示的化合物的方法; （II）其中R1是H，低级烷基，氰基乙基，低级烷酰基氨基乙基或低级二烷基氨基乙基; R2是2-四氢吡喃基或低级烷氧基甲基; R3是氰基，低级二烷基氨基或低级烷酰氨基; R4为低级烷基。通式（I）和（II）的化合物是制备用作循环器官药物的光学活性1,4-二氢吡啶衍生物的中间体化合物。可以通过本发明的方法有效地制备化合物。

10. 发明授权

US07022502B2 Process for the biological production of L-pipecolic acid 有权
标题翻译：生产L-哌啶酸的方法
公开(公告)号：US07022502B2
公开(公告)日：2006-04-04
申请号：US10169257
申请日：2000-12-22
申请人： Tadashi Fujii , Yasuhide Aritoku , Manabu Mukaihara , Takao Narita , Hitosi Agematu , Kunio Isshiki
发明人： Tadashi Fujii , Yasuhide Aritoku , Manabu Mukaihara , Takao Narita , Hitosi Agematu , Kunio Isshiki
IPC分类号： C12P17/00
CPC分类号： C12Y105/01002 , C12N9/0026 , C12N9/0028 , C12P17/12
摘要： A process for the production of L-pipecolic acid which comprises the step of reducing delta-1-piperideine-6-carboxylic acid by the use of pyrroline-5-carboxylate reductase. The delta-1-piperideine-6-carboxylic acid is obtained by the step of converting L-lysine by the use of lysine 6-aminotransferase encoded by a gene of Flavobacterium lutescens. The steps of reducing delta-1-piperideine-6-carboxylic acid and the converting of L-lysine into L-pipecolic acid by the use of lysine 6-aminotransferase are carried out by using a bacterium transformed with a gene encoding lysine 6-aminotransferase wherein such bacterium comprises pyrroline-5-carboxylate reductase encoded by a gene of Escherichia coli or a coryneform bacterium. A recombinant bacterium which can be used in this production process is also provided. Thus, the present invention can provide an efficient biological process for the production of L-pipecolic acid (or 2-piperidinecarboxylic acid).
摘要翻译：一种生产L-哌啶酸的方法，其包括通过使用吡咯啉-5-羧酸酯还原酶还原δ-1-哌啶-6-羧酸的步骤。通过使用由黄杆菌（Flavobacterium lutescens）基因编码的赖氨酸6-氨基转移酶转化L-赖氨酸的步骤获得δ-1-哌啶-6-羧酸。通过使用赖氨酸6-氨基转移酶减少δ-1-哌啶-6-羧酸和L-赖氨酸转化成L-哌啶酸的步骤是通过使用转染有编码赖氨酸6-氨基转移酶的基因的细菌其中这种细菌包括由大肠杆菌或棒杆菌型细菌的基因编码的吡咯啉-5-羧酸还原酶。还提供了可用于该生产方法的重组细菌。因此，本发明可以提供生产L-哌啶酸（或2-哌啶羧酸）的有效的生物学方法。

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