公开(公告)号：US20090156582A1

公开(公告)日：2009-06-18

申请号：US11884054

申请日：2006-02-09

申请人： Tetsuya Tsukamoto ,  Takeshi Yamamoto ,  Ryosuke Tokunoh ,  Tomohiro Kawamoto ,  Masahiro Okura ,  Masakumi Kori ,  Katsuhito Murase

发明人： Tetsuya Tsukamoto ,  Takeshi Yamamoto ,  Ryosuke Tokunoh ,  Tomohiro Kawamoto ,  Masahiro Okura ,  Masakumi Kori ,  Katsuhito Murase

IPC分类号： A61K31/55 ,  A61K31/454 ,  A61K31/4162 ,  C07D403/02

CPC分类号： C07D231/38 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14

摘要： The present invention provides a pyrazole compound represented by the formula (I): wherein ring A0 is a pyrazole ring optionally further having 1 or 2 substituents; Ra is a substituted carbamoyl group; and Rb is an optionally substituted acylamino group, or a salt thereof or a prodrug thereof, which is useful as an agent for the prophylaxis or treatment of GSK-3β related pathology or disease, and a GSK-3β inhibitor including same.

摘要翻译： 本发明提供由式（I）表示的吡唑化合物：其中环A0是任选还含有1或2个取代基的吡唑环; Ra是取代的氨基甲酰基; 和Rb是可用作预防或治疗GSK-3β相关病理学或疾病的药剂的任选取代的酰基氨基或其盐或其前药，以及包含GSK-3β抑制剂的GSK-3β抑制剂。

公开(公告)号：US07101867B2

公开(公告)日：2006-09-05

申请号：US10120102

申请日：2002-04-11

申请人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

发明人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

IPC分类号： A61K31/33 ,  A61K31/40 ,  C07D405/00 ,  C07D411/00 ,  C07D209/00

CPC分类号： C07D307/79 ,  C07D405/04 ,  C07D407/06 ,  C07D407/12 ,  C07D409/06

摘要： Compounds represented by the formula: wherein R1 and R2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates (i) a group represented by the formula: wherein ring B indicates a 5- to 7-membered ring, or (ii) a group represented by the formula: wherein R4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R5 is hydrogen atom, a C1-6 alkyl, or an acyl group, provided that, when W is Wa, R3 is hydrogen atom, a hydrocarbon group or a heterocyclic group, when W is Wb, R3 indicates a C6-14 aryl group, or salts thereof or prodrugs thereof have an excellent action to inhibit neurodegeneration and the like as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as prophylactic or therapeutic drugs for nerve degenerative diseases and the like.

摘要翻译： 由下式表示的化合物：其中R 1和R 2是氢原子，烃基或杂环基，或R 1和R 2 可以与相邻的碳原子一起形成3-至8-元的杂环或杂环，W表示（i）由下式表示的基团：其中环B表示5-至 或（ii）由下式表示的基团：其中R 4表示（1）可被芳基取代的脂族烃基，或（2）酰基 含有芳基的基团R 5是氢原子，C 1-6烷基或酰基，条件是当W是Wa时，R“ 当W为Wb时，R 3为氢原子，烃基或杂环基，R 3为C 6-14芳基，或其盐 或其前药具有抑制神经变性等优异的作用以及优异的脑渗透性，并且l 因此可用作神经变性疾病等的预防或治疗药物。

公开(公告)号：US07008950B1

公开(公告)日：2006-03-07

申请号：US09445193

申请日：1998-06-04

申请人： Shigenori Ohkawa ,  Masaki Setoh ,  Mitsuru Kakihana ,  Masahiro Okura

发明人： Shigenori Ohkawa ,  Masaki Setoh ,  Mitsuru Kakihana ,  Masahiro Okura

IPC分类号： A61K31/44 ,  A61K31/34 ,  C07D421/00 ,  C07D307/78

CPC分类号： C07D307/79 ,  C07D307/81 ,  C07D405/12 ,  C07D491/10

摘要： A compound of the formula: wherein R1 and R2 each is H or a hydrocarbon group which may be substituted, or R1 and R2 form a 3- to 8-membered carbo or heterocyclic ring which may be substituted; R3 is H, a lower alkyl which may be substituted or an aromatic group which may be substituted; R4 is (1) an aromatic group which may be substituted, (2) an aliphatic hydrocarbon group substituted by an aromatic group which may be substituted, which hydrocarbon group may be further substituted or (3) an acyl; X and Y each is oxygen or sulfur which may be oxidized; and ring A is a benzene ring which may be further substituted, or a salt thereof, is useful for an agent for suppressing neurodegeneration.

摘要翻译： 下式化合物：其中R 1和R 2各自为H或可被取代的烃基，或R 1和R 2 形成可被取代的3-至8-元碳环或杂环; R 3是H，可被取代的低级烷基或可被取代的芳基; R 4是（1）可以被取代的芳族基团，（2）被可被取代的芳族基团取代的脂肪族烃基，该烃基可以进一步被取代，或者（3） 酰基; X和Y各自为可被氧化的氧或硫; 环A是可以被进一步取代的苯环，或其盐可用于抑制神经变性的药剂。

公开(公告)号：US06479536B1

公开(公告)日：2002-11-12

申请号：US09857293

申请日：2001-06-01

申请人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

发明人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

IPC分类号： A61K3140

CPC分类号： C07D307/79 ,  C07D405/04 ,  C07D407/06 ,  C07D407/12 ,  C07D409/06

摘要： Compounds represented by the formula: wherein R1 and R2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates (i) a group represented by the formula:  wherein ring B indicates a 5- to 7-membered ring, or (ii) a group represented by the formula:  wherein R4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R5 is hydrogen atom, a C1-6 alkyl, or an acyl group, provided that, when W is Wa, R3 is hydrogen atom, a hydrocarbon group or a heterocyclic group, when W is Wb, R3 indicates a C6-14 aryl group, or salts thereof or prodrugs thereof have an excellent action to inhibit neurodegeneration and the like as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as prophylactic or therapeutic drugs for nerve degenerative diseases and the like.

摘要翻译： 由下式表示的化合物：其中R 1和R 2是氢原子，烃基或杂环基，或者R 1和R 2可以与相邻的碳原子一起形成3至8元的杂环或杂环，W表示 （i）由下式表示的基团：其中环B表示5-至7-元环，或（ii）由下式表示的基团：其中R4表示（1）脂族烃基，其可以被 芳香基，或（2）含芳基的酰基，R5为氢原子，C1-6烷基或酰基，条件是当W为Wa时，R3为氢原子，烃基或 杂环基，当W为Wb时，R 3表示C 6-14芳基，或其盐或其前药具有抑制神经变性等优异的作用以及优异的脑渗透性，毒性低，因此有用 作为神经退行性疾病的预防或治疗药物 类似。

公开(公告)号：US20090012081A1

公开(公告)日：2009-01-08

申请号：US12002273

申请日：2007-12-14

申请人： Shigenori Okawa ,  Masaomi Miyamoto ,  Masahiro Okura

发明人： Shigenori Okawa ,  Masaomi Miyamoto ,  Masahiro Okura

IPC分类号： A61K31/5377 ,  A61K31/343 ,  A61K31/438 ,  A61P25/00

CPC分类号： C07D307/79 ,  A61K31/343 ,  A61K31/36 ,  A61K31/381 ,  A61K31/4035 ,  A61K31/407 ,  A61K31/438 ,  A61K31/443 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/5377 ,  C07D405/04 ,  C07D407/04 ,  C07D409/04 ,  C07D491/04 ,  C07D491/10

摘要： An agent for promoting the proliferation or differentiation of a stem cell and/or neural progenitor cell, comprising a compound represented by Formula: wherein each of R1 and R2 is H, a hydrocarbon group or a heterocyclic group, or taken together with the adjacent carbon atom to form a ring, R3 is H, a hydrocarbon group or a heterocyclic group, W is a group represented by Formula: wherein Ring A is an optionally substituted benzene ring, Ring B is an optionally substituted 5- to 7-membered nitrogen-containing heterocyclic ring, R4 is an acyl group having an aliphatic hydrocarbon group, which is substituted by an aromatic group and may have a further substitutent, or aromatic group, R5 is H, C1-6 alkyl or acyl, R4c is an aromatic group, an aliphatic hydrocarbon group or acyl, and X is O or S; Y is O, S or NH, Ring C is an optionally substituted benzene ring, or a salt or prodrug thereof is provided.

摘要翻译： 用于促进干细胞和/或神经祖细胞的增殖或分化的试剂，其包含由下式表示的化合物：其中R 1和R 2各自为H，烃基或杂环基，或与相邻碳一起 原子形成环，R 3为H，烃基或杂环基，W为由下式表示的基团：其中环A为任选取代的苯环，环B为任选取代的5-至7-元氮 - R4是具有脂肪族烃基的酰基，被芳基取代，可以具有其它的取代基或芳基，R5是H，C1-6烷基或酰基，R4c是芳基， 脂族烃基或酰基，X是O或S; Y是O，S或NH，环C是任选取代的苯环，或其盐或前药。

公开(公告)号：US07456162B2

公开(公告)日：2008-11-25

申请号：US11081615

申请日：2005-03-17

申请人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

发明人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

IPC分类号： A61K31/33 ,  C07D405/00 ,  C07D411/00 ,  C07D209/00

CPC分类号： C07D307/79 ,  C07D405/04 ,  C07D407/06 ,  C07D407/12 ,  C07D409/06

摘要： Compounds represented by the formula: wherein R1 and R2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates a group represented by the formula: wherein R4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R5 is hydrogen atom, a C1-6 alkyl, or an acyl group, R3 indicates a C6-14 aryl group, or salts thereof. The compounds have an excellent action to inhibit neurodegeneration as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as drugs for nerve degenerative diseases.

摘要翻译： 由下式表示的化合物：其中R 1和R 2是氢原子，烃基或杂环基，或R 1和R 2 可以与相邻的碳原子一起形成3-至8-元的杂环或杂环，W表示由下式表示的基团：其中R 4表示 （1）可以被芳族基团取代的脂族烃基，或（2）含有芳基的酰基，R 5是氢原子，C 1-6 烷基或酰基，R 3表示C 6-14芳基或其盐。 该化合物具有抑制神经变性以及优异的脑渗透性的优异作用，毒性低，因此可用作神经退行性疾病的药物。

公开(公告)号：US07208495B2

公开(公告)日：2007-04-24

申请号：US10481367

申请日：2002-07-04

申请人： Shigenori Ohkawa ,  Masaomi Miyamoto ,  Masahiro Okura ,  Tetsuya Tsukamoto

发明人： Shigenori Ohkawa ,  Masaomi Miyamoto ,  Masahiro Okura ,  Tetsuya Tsukamoto

IPC分类号： A61K31/497 ,  A61K31/445 ,  C07D405/00 ,  C07D401/00

CPC分类号： A61K31/4525 ,  A61K31/496 ,  C07D307/79 ,  C07D307/80 ,  C07D307/81 ,  C07D307/82 ,  C07D307/83 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/04 ,  C07D409/04 ,  C07D409/14

摘要： A compound represented by the formula: (wherein, R1 and R2 are the same or different and each represents a hydrogen atom, hydrocarbon group or heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3–8 membered iso- or heterocyclic group, R3 represents a cyclic group, a hydroxy group, a mercapto group that may have oxo, or an amino group, R4 represents a hydrogen atom, a hydrocarbon group, a hydroxy group, a mercapto group which may have oxo, or an amino group, or R2 and R4 may link together to form a double bond, X represents a bond or a linear hydrocarbon group, W represents an oxygen atom or a sulfur atom, ring B represents a 5–8 membered nitrogen-containing heterocyclic group, ring C represents a benzene ring, and— represents a single bond or a double bond), or a salt or a prodrug thereof that has excellent neurodegenerative inhibitory activity and brain penetrability, and is useful as an agent for preventing/treating neurodegenerative diseases.

摘要翻译： 由下式表示的化合物（其中，R 1和R 2相同或不同，各自表示氢原子，烃基或杂环基， 可以与相邻的碳原子一起形成3-8元的异或杂环基，R 3表示环状 基团，羟基，可具有氧代基的巯基或氨基，R 4表示氢原子，烃基，羟基，可具有氧代基的巯基，或 氨基或R 2和R 4可以连接在一起形成双键，X表示键或直链烃基，W表示氧原子或 硫原子，环B表示5-8元含氮杂环基，环C表示苯环，代表单键或双键）或其盐或前药具有优异的神经变性抑制活性， 脑穿透性 并且可用作预防/治疗神经变性疾病的药剂。

公开(公告)号：US20070149558A1

公开(公告)日：2007-06-28

申请号：US11679257

申请日：2007-02-27

申请人： Shigenori Ohkawa ,  Masaomi Miyamoto ,  Masahiro Okura ,  Tetsuya Tsukamoto

发明人： Shigenori Ohkawa ,  Masaomi Miyamoto ,  Masahiro Okura ,  Tetsuya Tsukamoto

IPC分类号： A61K31/4747 ,  A61K31/407

CPC分类号： A61K31/4525 ,  A61K31/496 ,  C07D307/79 ,  C07D307/80 ,  C07D307/81 ,  C07D307/82 ,  C07D307/83 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/04 ,  C07D409/04 ,  C07D409/14

摘要： A compound represented by the formula: (wherein, R1 and R2 are the same or different and each represents a hydrogen atom, hydrocarbon group or heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3-8 membered iso- or heterocyclic group, R3 represents a cyclic group, a hydroxy group, a mercapto group that may have oxo, or an amino group, R4 represents a hydrogen atom, a hydrocarbon group, a hydroxy group, a mercapto group which may have oxo, or an amino group, or R2 and R4 may link together to form a double bond, X represents a bond or a linear hydrocarbon group, W represents an oxygen atom or a sulfur atom, ring B represents a 5-8 membered nitrogen-containing heterocyclic group, ring C represents a benzene ring, and represents a single bond or a double bond), or a salt or a prodrug thereof that has excellent neurodegenerative inhibitory activity and brain penetrability, and is useful as an agent for preventing/treating neurodegenerative diseases.

摘要翻译： 由下式表示的化合物（其中，R 1和R 2相同或不同，各自表示氢原子，烃基或杂环基， 可以与相邻的碳原子一起形成3-8元的异或杂环基，R 3表示环状 基团，羟基，可具有氧代基的巯基或氨基，R 4表示氢原子，烃基，羟基，可具有氧代基的巯基，或 氨基或R 2和R 4可以连接在一起形成双键，X表示键或直链烃基，W表示氧原子或 硫原子，环B表示5-8元含氮杂环基，环C表示苯环，并且表示单键或双键）或其具有优异的神经变性抑制活性和脑渗透性的盐或其前药，并且可用作预防/治疗神经变性疾病的药剂。

公开(公告)号：US20050187238A1

公开(公告)日：2005-08-25

申请号：US11081615

申请日：2005-03-17

申请人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

发明人： Shigenori Ohkawa ,  Yasuyoshi Arikawa ,  Kouki Kato ,  Masahiro Okura ,  Masaki Setoh

IPC分类号： A61P25/28 ,  C07D307/79 ,  C07D405/04 ,  C07D407/06 ,  C07D407/12 ,  C07D409/06 ,  C07D491/056 ,  C07D491/107 ,  A61K31/4747 ,  C07D493/04

CPC分类号： C07D307/79 ,  C07D405/04 ,  C07D407/06 ,  C07D407/12 ,  C07D409/06

摘要： Compounds represented by the formula: wherein R1 and R2 are hydrogen atom, a hydrocarbon group or a heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3- to 8-membered homocyclic or heterocyclic ring, W indicates (i) a group represented by the formula: wherein ring B indicates a 5- to 7-membered ring, or (ii) a group represented by the formula: wherein R4 indicates (1) an aliphatic hydrocarbon group, which may be substituted with an aromatic group, or (2) an acyl group containing an aromatic group, R5 is hydrogen atom, a C1-6 alkyl, or an acyl group, provided that, when W is Wa, R3 is hydrogen atom, a hydrocarbon group or a heterocyclic group, when W is Wb, R3 indicates a C6-14 aryl group, or salts thereof or prodrugs thereof have an excellent action to inhibit neurodegeneration and the like as well as an excellent brain penetrability and are low in the toxicity, thereby being useful as prophylactic or therapeutic drugs for nerve degenerative diseases and the like.

摘要翻译： 由下式表示的化合物：其中R 1和R 2是氢原子，烃基或杂环基，或R 1和R 2 可以与相邻的碳原子一起形成3-至8-元的杂环或杂环，W表示（i）由下式表示的基团：其中环B表示5-至 或（ii）由下式表示的基团：其中R 4表示（1）可被芳基取代的脂族烃基，或（2）酰基 含有芳基的基团R 5是氢原子，C 1-6烷基或酰基，条件是当W是Wa时，R“ 当W为Wb时，R 3为氢原子，烃基或杂环基，R 3为C 6-14芳基，或其盐 或其前药具有抑制神经变性等优异的作用以及优异的脑渗透性，并且l 因此可用作神经变性疾病等的预防或治疗药物。