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1. 发明申请

WO2004039365A1 AGENT FOR PREVENTING OR TREATING NEUROPATHY 审中-公开
标题翻译：用于预防或治疗神经病的药剂
公开(公告)号：WO2004039365A1
公开(公告)日：2004-05-13
申请号：PCT/JP2003/013901
申请日：2003-10-30
申请人： TAKEDA CHEMICAL INDUSTRIES, LTD. , MOMOSE, Yu , SAKAI, Nozomu , MAEKAWA, Tsuyoshi , HAZAMA, Masatoshi , KAWAMURA, Toru , SERA, Misayo
发明人： MOMOSE, Yu , SAKAI, Nozomu , MAEKAWA, Tsuyoshi , HAZAMA, Masatoshi , KAWAMURA, Toru , SERA, Misayo
IPC分类号： A61K31/381
CPC分类号： C07D231/12 , A61K31/402 , A61K31/415 , A61K31/4155 , A61K31/416 , A61K31/4174 , A61K31/4178 , A61K31/4184 , A61K31/427 , A61K31/4439 , A61K31/66 , C07D401/12 , C07D403/12 , C07D413/12 , C07D417/12 , C07F9/4056 , C07F9/5537 , C07F9/65037 , C07F9/65067 , C07F9/65187 , C07F9/653 , C07F9/65395 , C07F9/65586 , C07F9/657181
摘要： The present invention provides an agent for preventing or treating neuropathy having superior action and low toxicity. This agent comprises a compound represented by the formula:wherein ring A is a 5-membered aromatic heterocycle containing 2 or more nitrogen atoms, which may further have substituent(s);B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group;X is a divalent acyclic hydrocarbon group;Z is -O-, -S-, -NR 2 -, -CONR 2 - or -NR 2 CO- (R 2 is a hydrogen atom or an optionally substituted alkyl group);Y is a bond or a divalent acyclic hydrocarbon group;R 1 is an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group, provided that when the 5-membered aromatic heterocycle represented by ring A is imidazole, then Z should not be -O-, or a salt thereof.
摘要翻译：本发明提供了用于预防或治疗具有优异作用和低毒性的神经病的药剂。该试剂包含由下式表示的化合物：其中环A为含有2个以上氮原子的5元芳族杂环，其还可具有取代基; B为任选取代的烃基或任选取代的杂环基; X是二价无环烃基; Z是-O - ， - S - ， - NR 2， - ， - CONR 2，其中R 2是氢原子或任选取代的烷基）; Y是键或二价无环烃基; R 1是任选取代的环状基团，任选取代的氨基基团或任选取代的酰基基团，条件是当所述5元芳族杂环代表环A是咪唑，那么Z不应该是-O-或其盐。

2. 发明公开

EP1486490A1 AZOLE COMPOUNDS 审中-公开
标题翻译： AZOLVERBINDUNGEN
公开(公告)号：EP1486490A1
公开(公告)日：2004-12-15
申请号：EP03742890.1
申请日：2003-02-27
申请人： Takeda Chemical Industries, Ltd.
发明人： SAKAI, Nozomu , MOMOSE, Yu , MURASE, Katsuhito , HAZAMA, Masatoshi
IPC分类号： C07D263/32
CPC分类号： C07D413/04 , C07D263/32 , C07D263/38 , C07D263/46 , C07D263/48 , C07D277/30 , C07D277/40 , C07D277/46 , C07D413/06 , C07D413/12 , C07D413/14 , C07D417/04 , C07D417/14 , C07F9/653 , C07F9/6539
摘要： The present invention provides a compound represented by the formula (I)
wherein R 1 is a hydrogen atom, a halogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group, an optionally substituted thiol group or an optionally substituted amino group,
A is an optionally substituted cyclic amino group or -NR 2 -W-D wherein R 2 is a hydrogen atom or an alkyl group, W is a bond or a divalent acyclic hydrocarbon group, and D is an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group,
B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group,
X is an oxygen atom, a sulfur atom or an optionally substituted nitrogen atom, and
Y is a bond or a divalent acyclic hydrocarbon group, or a salt thereof, which is useful for the prophylaxis or treatment of diabetic neuropathy and the like.
摘要翻译：本发明提供由式（I）表示的化合物，其中R 1是氢原子，卤素原子，任选取代的烃基，任选取代的杂环基，任选取代的羟基，任选地取代的硫醇基或任选取代的氨基，A是任选取代的环状氨基或-NR 2 -WD，其中R 2是氢原子或烷基，W是键或二价无环烃基，D为任意取代的环状基团，可以具有取代基的氨基或任意取代的酰基，B为任意取代的烃基或任意取代的杂环基，X为氧原子，硫原子或任意取代的氮原子，Y是可用于预防或治疗糖尿病性神经病变等的键或二价无环烃基或其盐。

3. 发明授权

EP0931074B1 CONDENSED 4,5,6,7-TETRAHYDROBENZO C]THIOPHENES AS ENHANCER FOR CELL DIFFERENTIATION INDUCTION FACTOR ACTION 失效
标题翻译： CONDENSED 4,5,6,7-四氢苯并C]噻吩AS加速器效应细胞分化诱导因子学报
公开(公告)号：EP0931074B1
公开(公告)日：2003-05-07
申请号：EP97939185.1
申请日：1997-09-05
申请人： Takeda Chemical Industries, Ltd.
发明人： YASUMA, Tsuneo , ODA, Tsuneo , HAZAMA, Masatoshi , TAKETOMI, Shigehisa
IPC分类号： C07D333/72 , C07D495/04 , C07D513/04 , C07D497/04 , C07F9/40 , A61K31/38
CPC分类号： C07D495/04 , C07D513/04 , C07F9/6561

4. 发明公开

EP0931074A1 CONDENSED 4,5,6,7-TETRAHYDROBENZO C]THIOPHENES AS ENHANCER FOR CELL DIFFERENTIATION INDUCTION FACTOR ACTION 失效
标题翻译： CONDENSED 4,5,6,7-四氢苯并C]噻吩AS加速器效应细胞分化诱导因子学报
公开(公告)号：EP0931074A1
公开(公告)日：1999-07-28
申请号：EP97939185.0
申请日：1997-09-05
申请人： Takeda Chemical Industries, Ltd.
发明人： YASUMA, Tsuneo , ODA, Tsuneo , HAZAMA, Masatoshi , TAKETOMI, Shigehisa
IPC分类号： C07D495 , C07D498 , C07D513 , C07F9
CPC分类号： C07D495/04 , C07D513/04 , C07F9/6561
摘要： A compound represented by formula (I') wherein X represents a sulfur atom or an oxygen atom; Y represents an optionally oxidized sulfur atom or an oxygen atom; Z represents a bond or a divalent hydrocarbon group; R1 represents an optionally substituted hydrocarbon group; R2 represents an optionally amidated or esterified carboxyl group; ring A represents an optionally substituted aromatic 5-membered heterocyclic ring; or a salt thereof. A compound of the above formula possesses cell differentiation inducing factor action-enhancing activity and anti-matrix metalloprotease activity and that is useful in the prevention and treatment of bone diseases such as osteoporosis, bone fractures, osteoarthritis and rheumatoid arthritis, arteriosclerosis, cancer metastasis, and diseases based on nerve degeneration.

5. 发明公开

EP1407770A1 TGF-BETA SUPERFAMILY PRODUCTION/SECRETION PROMOTER 有权
标题翻译： TGF-β超级蛋白酶制剂/ SEKRETIONS-PROMOTER
公开(公告)号：EP1407770A1
公开(公告)日：2004-04-14
申请号：EP02741288.1
申请日：2002-06-25
申请人： Takeda Chemical Industries, Ltd.
发明人： SUGIYAMA, Yasuo , HAZAMA, Masatoshi , SHINTANI, Asae
IPC分类号： A61K31/422 , A61K45/00 , A61P13/10 , A61P19/08 , A61P25/02 , A61P27/16 , A61P43/00
CPC分类号： A61K31/422
摘要： The present invention provides a TGF-β superfamily production/secretion promoter comprising a compound represented by the formula
wherein R 1 is a halogen atom, an optionally substituted heterocyclic group, an optionally substituted hydroxy group, an optionally substituted thiol group or an optionally substituted amino group; A is an optionally substituted acyl group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group or an optionally esterified or amidated carboxyl group; B is an optionally substituted aromatic group; X is an oxygen atom, a sulfur atom or an optionally substituted nitrogen atom; and Y is a divalent hydrocarbon group or heterocyclic group, or a salt thereof or a prodrug thereof, which is useful as an agent for the prophylaxis or treatment of dysautonomia, bladder dysfunction, hearing impairment, bone disease and the like.
摘要翻译：转化生长因子β（TGF-β）超家族分泌促进剂包含5元杂环衍生物（I）。 TGF-β超家族产生分泌促进剂包含式（I）的5元杂环衍生物或其盐或前药。 R 1卤代或任选取代的杂环基，羟基，硫醇或氨基; A：任选酯化或酰胺化的羧基或任选取代的酰基，杂环基或羟基; B'：任选取代的芳族基团; X：O，S或任选取代的亚氨基，Y：二价烃基或杂环基。活动：神经保护; Uropathic; 听觉; 骨科; 降血糖; 抗关节炎; 抗风湿; 内分泌; Nephrotropic; 止痛; 皮肤。机制：TGF-β激动剂。在SD大鼠的糖尿病神经病变模型中，给予10mg（4-氯苯基）-2-（2-甲基-1-咪唑基）-5- [3-（2-甲基苯氧基）丙基]恶唑（Ia） / kg /天口服4个月，增加/分化因子-15产量增加至135％的对照组。

6. 发明公开

EP1105140A2 BENZOTHIEPINE COMPOUNDS AS ENHANCER OF CELL DIFFERENTIATION INDUCTION FACTOR 审中-公开
标题翻译： Benzothiepines化合物作为加速器效应细胞分化诱导因子作者：
公开(公告)号：EP1105140A2
公开(公告)日：2001-06-13
申请号：EP99937019.0
申请日：1999-08-11
申请人： Takeda Chemical Industries, Ltd.
发明人： MAKINO, Haruhiko , FUJISAWA, Yukio , HAZAMA, Masatoshi , SOHDA, Takashi
IPC分类号： A61K31/67 , A61P19/08 , A61P19/10 , A61P25/00 , A61P25/28
CPC分类号： A61K31/67
摘要： This invention provides an enhancer of cell differentiation induction factor comprising a compound of formula (I), wherein ring A is an optionally substituted benzene ring; R is a hydrogen atom or an optionally substituted hydrocarbon group; B is an optionally esterified or amidated carboxyl group; X is -CH(OH)- or -CO-; k is 0 or 1; and k' is 0, 1 or 2, or its salt, which can be advantageously used as an enhancer of cell differentiation induction factor.

7. 发明公开

EP0975621A1 CELL DIFFERENTIATION INDUCING AMIDE DERIVATIVES, THEIR PRODUCTION AND USE 失效
标题翻译：细胞分化诱导酰胺衍生物，生产和使用
公开(公告)号：EP0975621A1
公开(公告)日：2000-02-02
申请号：EP98917647.4
申请日：1998-04-23
申请人： Takeda Chemical Industries, Ltd.
发明人： MARUI, Shogo , HAZAMA, Masatoshi , NOTOYA, Kohei , KATO, Koki
IPC分类号： C07D317/70 , A61K31/165 , C07D491/04 , C07D215/48 , C07D317/60 , C07C235/66 , C07D401/04
CPC分类号： C07D491/04 , A61K31/166 , A61K31/36 , A61K31/47 , A61K31/4709 , A61K31/4741 , A61K31/496 , A61K31/5377 , C07D215/48 , C07D317/70 , C07D401/04 , C07D405/04
摘要： The present invention provides a compound represented by formula (1) wherein R1 is an amino group which may be substituted; R2 is a hydrogen atom or a lower alkyl group which may be substituted; X is a methyne group which may be substituted or N(O)m (m is 0 or 1); a ring A is a homo- or hetero-cycle which is substituted by a halogen atom, lower alkyl, lower alkoxy or lower alkylenedioxy; and a ring B is a homo- or hetero-cycle which may be substituted; or a salt thereof, which exhibits excellent cell differentiation-inducing action and cell differentiation-inducing factor action-enhancing action, and is useful in the treatment and prevention of various nerve diseases of bone/joint diseases.

8. 发明公开

EP1491194A1 VDAC REGULATOR 有权
标题翻译： VDAC调节器
公开(公告)号：EP1491194A1
公开(公告)日：2004-12-29
申请号：EP03708595.8
申请日：2003-03-13
申请人： Takeda Chemical Industries, Ltd. , The Circle for the Promotion of Science and Engineering
发明人： SUGIYAMA, Yasuo , HAZAMA, Masatoshi , IWAKAMI, Norihisa
IPC分类号： A61K31/422
CPC分类号： A61K31/422 , C07D263/34 , C07D413/04 , C07D413/14 , G01N2500/04
摘要： The present invention provides a VDAC regulator comprising a compound represented by the formula (I):
wherein R 1 is a halogen atom, an optionally substituted heterocyclic group, an optionally substituted hydroxy group, an optionally substituted thiol group or an optionally substituted amino group; A is an optionally substituted acyl group, an optionally substituted heterocyclic group, an optionally substituted hydroxy group or an optionally esterified or amidated carboxyl group; B is an optionally substituted aromatic group; X is an oxygen atom, a sulfur atom or an optionally substituted nitrogen atom; and Y is a divalent hydrocarbon group or heterocyclic group, a salt thereof or a prodrug thereof, which is useful as an agent for the prophylaxis or treatment of Down's syndrome and the like, and the like.
摘要翻译：电压依赖性阴离子通道调节剂包含唑化合物（I）。电压依赖阴离子通道（VDAC）调节剂包含式（I）的唑化合物或其盐或前药。 R 1卤代，杂环基（任选取代的），羟基，硫醇或氨基; A：羧基（任选酰胺化或酯化）或酰基（任选取代的），杂环基或羟基; B：芳族（任选取代的）; X：O，S或N（任选取代的）; 和Y：二价烃或杂环基。还包括独立权利要求：（1）治疗或预防含有VDAC调节剂的唐氏综合征的药剂; （2）筛选用于治疗和预防包括VDAC调节剂的神经病变的化合物的方法; 和（3）凋亡抑制剂或包含（I）或其盐或前药的线粒体功能改进剂。活动：灵巧; 神经病理性; 降血糖; 杀病毒; 抗HIV; 嗜肝; CNS根; 反酗酒; 骨科; 抗关节炎; 听觉; 抗帕金森氏病; 镇惊; 抑制细胞生长; 脑保护; 抗抑郁药; 抗炎; 胃肠道根; 止痛; 安神; 厌食; 低血压; 降血脂; Cardiant; 抗动脉硬化; 肌肉根。作用机制：细胞凋亡抑制剂。在使用PC12细胞的测定中，在0.5％胎牛血清的存在下，加入4-（4-氯苯基）-2-（2-甲基-1-咪唑基）-5- [3-（2-甲基苯氧基）丙基] 恶唑（0.3μmol/ ml）将细胞色素C从19.4ng.ml（对照组）降至7.0ng / ml。

9. 发明公开

EP1277730A1 NEOVASCULARIZATION INHIBITORS 审中-公开
标题翻译： HEMMER DER NEOVASKULARISATION
公开(公告)号：EP1277730A1
公开(公告)日：2003-01-22
申请号：EP01917499.4
申请日：2001-03-27
申请人： Takeda Chemical Industries, Ltd.
发明人： HAZAMA, Masatoshi , MIYAZAKI, Takeshi , SUGIYAMA, Yasuo
IPC分类号： C07C251/54 , C07D263/32 , A61K31/195 , A61K31/421 , A61P29/00 , A61P35/00 , A61P9/10 , A61P27/14
CPC分类号： A61K31/195 , A61K31/421 , C07C251/24 , C07C251/54
摘要： An angiogenesis inhibitor containing a compound represented by the formula
wherein R 4 is an optionally substituted hydrocarbon group and the like; Xa is a bond and the like; k is an integer of 1 to 3; Ya is an oxygen atom and the like; ring Ea is a benzene ring optionally having additional substituent(s); p is an integer of 1 to 8; R 5 is a hydrogen atom and the like; q is an integer of 0 to 6; r is 0 or 1; R 8 is a hydroxy group and the like; and R 6 and R 7 are hydrogen atoms and the like, or a salt thereof is useful as an agent for the prophylaxis or treatment of tumor and the like.
摘要翻译：含有式CHEM的化合物的血管发生抑制剂，其中R 4为任选取代的烃基等; Xa是一个债券等; k为1〜3的整数， Ya是氧原子等; 环Ea是任选具有另外的取代基的苯环; p为1〜8的整数， R 5是氢原子等; q为0〜6的整数; r为0或1; R 8是羟基等; R 6和R 7为氢原子等，或其盐可用作预防或治疗肿瘤等的药剂。

10. 发明公开

EP0920416A1 NAPHTHOLACTAMS AND LACTONES AS BONE MORPHOGENETIC PROTEIN ACTIVE AGENTS 失效
标题翻译： NAPHTHOLACTAMS和LACONES作为骨形态发生蛋白活性剂
公开(公告)号：EP0920416A1
公开(公告)日：1999-06-09
申请号：EP97935809.0
申请日：1997-08-19
申请人： Takeda Chemical Industries, Ltd.
发明人： MARUI, Shogo , HAZAMA, Masatoshi , NOTOYA, Kohei , OGINO, Masaki
IPC分类号： A61K31 , C07D209 , C07D317 , C07D401 , C07D405 , C07D471 , C07D491
CPC分类号： C07D401/04 , A61K31/4035 , A61K31/4741 , A61K31/4745 , C07D209/64 , C07D209/66 , C07D317/70 , C07D405/04 , C07D471/04 , C07D491/04
摘要： A compound of formula (I) wherein Q is an optionally substituted carbon atom or N(O)p wherein p is 0 or 1; Y is an optionally substituted methylene group, S(O)q wherein q is an integer of 0 to 2, or an optionally substituted imino group; Z1 is a C¿1-3? alkylene group which may have an oxo group or a thioxo group and may contain etherified oxygen or sulfur within the carbon chain; Z?2¿ is an optionally substituted C¿1-3? alkylene group; Ar is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; one of R?1 and R2¿ is a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; the other is a halogen atom, a hydroxyl group, an optionally substituted lower alkyl group, or an optionally substituted lower alkoxy group; or R?1 and R2¿ taken together with adjacent -c=c- form a ring; and ring A is a benzene ring which may be substituted in addition to R?1 and R2¿; or a salt thereof.
摘要翻译：其中Q是任选取代的碳原子或N（O）p的式（I）化合物，其中p是0或1; Y是任选取代的亚甲基，S（O）q，其中q是0-2的整数，或任选取代的亚氨基; Z1是一个C1-3？亚烷基，其可以具有氧代基团或硫代基团并且可以在碳链内含有醚化的氧或硫; Z 2是任选取代的C 1-3 - 亚烷基; Ar是任选取代的碳环基团或任选取代的杂环基团; R 1和R 2中的一个是氢原子，卤素原子，羟基，任选取代的低级烷基或任选取代的低级烷氧基; 另一个是卤素原子，羟基，任选取代的低级烷基或任选取代的低级烷氧基; 或R 1和R 2'与相邻的-c = c-一起形成环; 环A是除R 1和R 2以外还可以被取代的苯环。或其盐。

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