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1. 发明授权

US07229985B2 Amorphous substance of tricyclic triazolobenzazepine derivative 失效
标题翻译：三环三氮苯并氮杂衍生物的无定形物质
公开(公告)号：US07229985B2
公开(公告)日：2007-06-12
申请号：US10500071
申请日：2002-12-25
申请人： Toyoaki Ishikura , Takayuki Ishizawa , Kenji Suemune , Mayumi Ishiwata , Chikako Udagawa
发明人： Toyoaki Ishikura , Takayuki Ishizawa , Kenji Suemune , Mayumi Ishiwata , Chikako Udagawa
IPC分类号： C07D487/04 , A61K31/55 , A61K9/14 , A61K47/38
CPC分类号： C07D487/04
摘要： Disclosed are 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine, which has been rendered amorphous and possesses improved absorption and dissoluvability, and a pharmaceutical composition comprising the same. Also disclosed are processes for producing 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine, which has been rendered amorphous, and a pharmaceutical composition comprising the same.
摘要翻译：公开了2-（1-异丙氧基羰基氧基-2-甲基丙基）-7,8-二甲氧基-4（H），10-二氧代-2H-YY =“S” 已经变成无定形且具有改善的吸收和溶解性的2,3-三唑并[4,5-c] [1]苯并氮杂，以及包含该组合物的药物组合物。还公开了制备2-（1-异丙氧基羰基氧基-2-甲基丙基）-7,8-二甲氧基-4（5-UYYY =“S”）的方法，10-二氧代-2

2. 发明申请

US20050130955A1 Amorphous substance of tricyclic triazolobenzazepine derivative 失效
标题翻译：三环三氮苯并氮杂衍生物的无定形物质
公开(公告)号：US20050130955A1
公开(公告)日：2005-06-16
申请号：US10500071
申请日：2002-12-25
申请人： Toyoaki Ishikura , Takayuki Ishizawa , Kenji Suemune , Mayumi Ishiwata , Chikako Udagawa
发明人： Toyoaki Ishikura , Takayuki Ishizawa , Kenji Suemune , Mayumi Ishiwata , Chikako Udagawa
IPC分类号： A61P29/00 , A61P37/08 , C07D487/04 , A61K31/55
CPC分类号： C07D487/04
摘要： Disclosed are 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine, which has been rendered amorphous and possesses improved absorption and dissoluvability, and a pharmaceutical composition comprising the same. Also disclosed are processes for producing 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dioxo-2H-1,2, 3-triazolo[4,5-c][1]benzazepine, which has been rendered amorphous, and a pharmaceutical composition comprising the same.
摘要翻译：公开了2-（1-异丙氧基羰基氧基-2-甲基丙基）-7,8-二甲氧基-4（H），10-二氧代-2H-YY =“S” 已经变成无定形且具有改善的吸收和溶解性的2,3-三唑并[4,5-c] [1]苯并氮杂，以及包含该组合物的药物组合物。还公开了制备2-（1-异丙氧基羰基氧基-2-甲基丙基）-7,8-二甲氧基-4（5-UYYY =“S”）的方法，10-二氧代-2

3. 发明申请

US20070167402A1 Product of coprecipitation of sparingly soluble substance and water-soluble polymer and process for producing the same 审中-公开
标题翻译：微溶性物质和水溶性聚合物的共沉淀物及其制造方法
公开(公告)号：US20070167402A1
公开(公告)日：2007-07-19
申请号：US10561212
申请日：2004-06-21
申请人： Toyoaki Ishikura , Chikako Udagawa , Masato Misaka , Kenji Suemune , Shinichi Kitahara , Kiyoko Ono , Akihiro Koyanagi
发明人： Toyoaki Ishikura , Chikako Udagawa , Masato Misaka , Kenji Suemune , Shinichi Kitahara , Kiyoko Ono , Akihiro Koyanagi
IPC分类号： A61K31/717 , A61K31/551
CPC分类号： C07D487/04 , A61K9/146 , A61K31/5517 , C08L1/28
摘要： The present invention provides a coprecipitate of 2-(1-isopropoxycarbonyloxy-2-methylpropyl)-7,8-dimethoxy-4(5H), 10-dio xo-2H-1,2,3-triazolo[4,5-c][1]benzazepine and a water-soluble polymer, excellent in solubility and absorbability.
摘要翻译：本发明提供2-（1-异丙氧基羰基氧基-2-甲基丙基）-7,8-二甲氧基-4（5H），10-二氧代-2H- 1,2-1,2,3-三唑并[4,5-c ] [1]苯并氮杂和溶解性和吸收性优异的水溶性聚合物。

4. 发明授权

US5580904A Formamido and carboxyamido compounds which can be retained in brain 失效
标题翻译：可以保留在脑中的甲酰氨基和羧酰氨基化合物
公开(公告)号：US5580904A
公开(公告)日：1996-12-03
申请号：US211304
申请日：1994-06-24
申请人： Toyoaki Ishikura , Teruomi Ito , Takashi Kato , Kazutoshi Horie , Hiroshi Ishihara , Takashi Senou
发明人： Toyoaki Ishikura , Teruomi Ito , Takashi Kato , Kazutoshi Horie , Hiroshi Ishihara , Takashi Senou
IPC分类号： A61K47/20 , A61K47/22 , A61K47/48 , C07C323/41 , C07C327/30 , C07D207/16 , C07D239/42 , C07D295/12 , C07D295/13 , C07D405/12 , A61K31/16 , C07C233/01
CPC分类号： C07D239/42 , A61K47/48023 , A61K47/48061 , A61K47/48215 , C07C323/41 , C07C327/30 , C07D207/16 , C07D295/13 , C07D405/12 , C07C2101/14
摘要： According to the present invention, a novel compound group which can pass through blood-brain barrier (BBB) with carrying a drug thereon and stay within brain to release the drug and a well-known compound group having the properties described above are provided.The compound represented by the general formula ##STR1## wherein, R.sup.1 represents C.sub.1-6 alkyl which may be substituted by a group selected from hydroxyl, carboxyl, amino group which may be substituted by C.sub.1-6 alkyl, and a five- to seven-membered saturated heterocyclic ring,R.sup.2 represents hydrogen or C.sub.1-6 alkyl,R.sup.3 represents hydrogen or C.sub.1-6 alkyl which may be substituted by hydroxyl,R.sup.4 represents hydrogen or C.sub.1-6 alkyl,R.sup.5 represents an amino acid residue, or --S--R.sup.6 or --CO--R.sup.6 wherein R.sup.6 represents C.sub.1-14 alkyl which may be substituted by a five- to seven-membered saturated ring; C.sub.2-6 alkenyl; aryl; or a five- to seven-membered saturated ring; or the group represented by the general formula (IVa): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the same meanings as defined above, and.multidot..multidot..multidot..multidot..multidot..multidot..multidot..multidot..multidot. represents a single bond or a double bondprovided that at least one of R.sup.1, R.sup.3 and R.sup.5 contains hydroxyl, carboxyl or amino, and a salt thereof.
摘要翻译： PCT No.PCT / JP93 / 01075 Sec。 371日期：1994年6月24日 102（e）1994年6月24日PCT 1993年7月30日PCT公布。公开号WO94 / 03424 日本1994年2月17日根据本发明，可以通过血脑屏障（BBB）携带药物并保持在脑内以释放药物的新型化合物组和具有所述性质的公知化合物组提供以上。由通式（Ia）表示的化合物，其中，R 1表示可被选自羟基，羧基，可被C 1-6烷基取代的氨基的基团取代的C 1-6烷基，至7元饱和杂环，R 2表示氢或C 1-6烷基，R 3表示氢或可被羟基取代的C 1-6烷基，R 4表示氢或C 1-6烷基，R 5表示氨基酸残基，或 - S-R6或-CO-R6，其中R6表示可被5至7元饱和环取代的C 1-14烷基; C 2-6烯基; 芳基; 或五至七元饱和环; 或由通式（IVa）表示的基团：其中R 1，R 2，R 3和R 4具有与上述相同的含义，并且+ E，uns xxxxxxxxx + EE表示单键或双键条件是R 1，R 3和R 5中的至少一个含有羟基，羧基或氨基，及其盐。

5. 发明申请

US20060074074A1 Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents 失效
标题翻译：三环三氮代氮杂吖庚因衍生物，其制备方法和抗过敏剂
公开(公告)号：US20060074074A1
公开(公告)日：2006-04-06
申请号：US11269828
申请日：2005-11-09
申请人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
发明人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
IPC分类号： A61K31/55 , C07D487/02 , C07D249/16
CPC分类号： C07D487/04 , C07C59/76 , C07C69/738 , C07D249/04 , C07D401/12 , C07F9/6561
摘要： Tricyclic triazolobenzazepine derivatives in the form or a prodrug are provided. The compounds according to the present invention are those represented by formula (I) and pharmacologically acceptable salts and solvates thereon. The compounds are useful as antiallergic agents and exhibit excellent bioavailability. wherein R1 represents hydrogen, OH, alkyl or phenyl alkyl, R2, R3, R4, and R5 represent hydrogen, halogen, optionally protected hydroxyl, formyl, optionally substituted alkyl, alkenyl, alkoxy or the like, and Q represents a group selected from the following groups (i) to (iv), halogen, or alkoxy:
摘要翻译：提供了形式或前体药物的三环三唑并苯并吖嗪衍生物。根据本发明的化合物是由式（I）表示的化合物及其上的药理学上可接受的盐和溶剂合物。这些化合物可用作抗过敏剂并且表现出优异的生物利用度。其中R 1表示氢，OH，烷基或苯基烷基，R 2，R 3，R 4，和R 5表示氢，卤素，任意保护的羟基，甲酰基，任选取代的烷基，烯基，烷氧基等，Q表示选自以下组（i）至（iv）中的基团，卤素或烷氧基：

6. 发明授权

US07022860B2 Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents 失效
标题翻译：三环三氮代氮杂吖庚因衍生物，其制备方法和抗过敏剂
公开(公告)号：US07022860B2
公开(公告)日：2006-04-04
申请号：US10073326
申请日：2002-02-13
申请人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
发明人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
IPC分类号： C07D249/04
CPC分类号： C07D487/04 , C07C59/76 , C07C69/738 , C07D249/04 , C07D401/12 , C07F9/6561
摘要： A process for preparing a compound represented by formula (IIa′) wherein Q represents group (i) as defined in the specification and R2 to R5, R31, R32, and R52 are as defined in the specification, by (1) reacting a compound represented by formula (V) wherein R2 to R5 and R52 are as defined in the specification. with a compound represented by R31R32C═O wherein R31 and R32 are as defined in the specification; (2) reacting the compound prepared in (1) with a compound represented by R71—C(═O)—R72 wherein R71 and R72 each independently represent a chlorine atom, 4-nitrophenyl, or 1-imidazolyl; and (3) reacting the compound prepared in (2) with a compound represented by R33OH wherein R33 is as defined in the specification.
摘要翻译：制备由式（IIa'）表示的化合物的方法，其中Q表示如说明书中定义的基团（i），R 2，R 5，R 5，通式（1）使由式（Ⅴ）表示的化合物（其中R 32的化合物按照本说明书中所定义的化合物，其中R 31，R 32， ; （2）使（1）中制备的化合物与由R 71表示的化合物-C（-O）-R 72，其中R 71 = O >和R“72各自独立地表示氯原子，4-硝基苯基或1-咪唑基; 和（3）使（2）中制备的化合物与由R 33 OH表示的化合物反应，其中R 33是如说明书中所定义的。

7. 发明授权

US4938964A External dermatological composition 失效
标题翻译：外用皮肤组成
公开(公告)号：US4938964A
公开(公告)日：1990-07-03
申请号：US281356
申请日：1988-12-08
申请人： Yasuyuki Sakai , Toyoaki Ishikura , Kazuo Kanbayashi , Tadashi Kato , Koichi Abe
发明人： Yasuyuki Sakai , Toyoaki Ishikura , Kazuo Kanbayashi , Tadashi Kato , Koichi Abe
IPC分类号： A61K9/00 , A61K9/70 , A61K31/19 , A61K47/32
CPC分类号： A61K9/7053 , A61K31/19 , A61K47/32 , A61K9/0014 , A61K9/7061
摘要： An external dermatological composition containing a drug supply layer carried on a support and containing 5% to 35% by weight of ketoprofen in an acrylic or methacrylic copolymer, which copolymer is composed of (i) 0.5% to 11.0% by weight of an .alpha.,.beta.-unsaturated carboxylic acid or its anhydride, (ii) 0.1% to 28.0% by weight of a vinyl monomer, (iii) 1.0% to 5.5% by weight of a hydroxy C.sub.2 -C.sub.4 alkyl ester of acrylic or methacrylic acid, and (iv) a balance of a C.sub.4 -C.sub.18 alkyl ester of acrylic or methacrylic acid, and has a glass transition point of -15.degree. C. to -70.degree.C.

8. 发明授权

US07238812B2 Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic agents 失效
标题翻译：三环三氮代氮杂吖庚因衍生物，其制备方法和抗过敏剂
公开(公告)号：US07238812B2
公开(公告)日：2007-07-03
申请号：US11269828
申请日：2005-11-09
申请人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
发明人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
IPC分类号： C07D249/04
CPC分类号： C07D487/04 , C07C59/76 , C07C69/738 , C07D249/04 , C07D401/12 , C07F9/6561
摘要： Tricyclic triazolobenzazepine derivatives in the form or a prodrug are provided. The compounds according to the present invention are those represented by formula (I) and pharmacologically acceptable salts and solvates thereon. The compounds are useful as antiallergic agents and exhibit excellent bioavailability. wherein R1 represents hydrogen, OH, alkyl or phenyl alkyl, R2, R3, R4, and R5 represent hydrogen, halogen, optionally protected hydroxyl, formyl, optionally substituted alkyl, alkenyl, alkoxy or the like, and Q represents a group selected from the following groups (i) to (iv), halogen, or alkoxy:
摘要翻译：提供了形式或前体药物的三环三唑并苯并吖嗪衍生物。根据本发明的化合物是由式（I）表示的化合物及其上的药理学上可接受的盐和溶剂合物。这些化合物可用作抗过敏剂并且表现出优异的生物利用度。其中R 1表示氢，OH，烷基或苯基烷基，R 2，R 3，R 4，和R 5表示氢，卤素，任意保护的羟基，甲酰基，任选取代的烷基，烯基，烷氧基等，Q表示选自以下组（i）至（iv）中的基团，卤素或烷氧基：

9. 发明授权

US06372735B1 Tricyclic triazolobenzazepine derivatives, process for producing the same, and antiallergic 有权
标题翻译：三环三氮苯并氮杂衍生物，其制备方法和抗过敏剂
公开(公告)号：US06372735B1
公开(公告)日：2002-04-16
申请号：US09509494
申请日：2000-03-29
申请人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
发明人： Yasuo Ohtsuka , Toshio Nishizuka , Sohjiro Shiokawa , Seiji Tsutsumi , Mami Kawaguchi , Hideo Kitagawa , Hiromi Takata , Takashi Shishikura , Toyoaki Ishikura , Kenichi Fushihara , Yumiko Okada , Sachiko Miyamoto , Maki Shiobara
IPC分类号： A61K3155
CPC分类号： C07D487/04 , C07C59/76 , C07C69/738 , C07D249/04 , C07D401/12 , C07F9/6561
摘要： Tricyclic triazolobenzazepine derivatives in the form or a prodrug are provided. The compounds according to the present invention are those represented by formula (I) and pharmacologically acceptable salts and solvates thereof. The compounds are useful as antiallergic agents and exhibit excellent bioavailability. wherein R1 represents hydrogen, OH, alkyl or phenyl alkyl, R2, R3, R4, and R5 represent hydrogen, halogen, optionally protected hydroxyl, formyl, optionally substituted alkyl, alkenyl, alkoxy or the like, and Q represents a group selected from the following groups (i) to (iv), halogen, or alkoxy:
摘要翻译：提供了形式或前体药物的三环三唑并苯并吖嗪衍生物。根据本发明的化合物是由式（I）表示的化合物及其药理学上可接受的盐和溶剂化物。该化合物可用作抗过敏药物并且表现出优异的生物利用度。其中R1代表氢，OH，烷基或苯基烷基，R2，R3，R4和R5代表氢，卤素，任选保护的羟基，甲酰基，任选取代的烷基，烯基，烷氧基和Q表示选自以下组（i）至（iv）中的基团，卤素或烷氧基：

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