公开(公告)号：US06391905B1

公开(公告)日：2002-05-21

申请号：US09847416

申请日：2001-05-03

申请人： Tsuneo Yasuma ,  Tsuneo Oda ,  Masatoshi Hazama ,  Shigehisa Taketomi

发明人： Tsuneo Yasuma ,  Tsuneo Oda ,  Masatoshi Hazama ,  Shigehisa Taketomi

IPC分类号： A61K314162

CPC分类号： C07D495/04 ,  C07D513/04 ,  C07F9/6561

摘要： A compound represented by the formula: 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.

摘要翻译： 由下式表示的化合物：其中X表示硫原子或氧原子; Y表示任选氧化的硫原子或氧原子; Z表示键或二价烃基; R1表示任选取代的烃基; R 2表示任选的酰胺化或酯化的羧基; 环A表示任选取代的芳族5元杂环; 或其盐。上述化合物具有细胞分化诱导因子作用增强活性和抗基质金属蛋白酶活性，并且其可用于预防和治疗骨疾病如骨质疏松症，骨折，骨关节炎和类风湿性关节炎， 动脉硬化，癌转移以及基于神经变性的疾病。

公开(公告)号：US6066658A

公开(公告)日：2000-05-23

申请号：US252913

申请日：1999-02-19

申请人： Tsuneo Yasuma ,  Tsuneo Oda ,  Masatoshi Hazama ,  Shigehisa Taketomi

发明人： Tsuneo Yasuma ,  Tsuneo Oda ,  Masatoshi Hazama ,  Shigehisa Taketomi

IPC分类号： C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07F9/6561 ,  A61K31/4439 ,  A61K31/429

CPC分类号： C07D495/04 ,  C07D513/04 ,  C07F9/6561

摘要： A compound represented by the formula: ##STR1## 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; R.sup.1 represents an optionally substituted hydrocarbon group; R.sup.2 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.

摘要翻译： 由下式表示的化合物：其中X表示硫原子或氧原子; Y表示任选氧化的硫原子或氧原子; Z表示键或二价烃基; R1表示任选取代的烃基; R 2表示任选的酰胺化或酯化的羧基; 环A表示任选取代的芳族5元杂环; 或其盐。 上述化合物具有细胞分化诱导因子作用增强活性和抗基质金属蛋白酶活性，可用于预防和治疗骨质疏松症，骨折，骨关节炎和类风湿性关节炎，动脉硬化，癌症转移等骨疾病， 和基于神经变性的疾病。

公开(公告)号：US20080131370A1

公开(公告)日：2008-06-05

申请号：US11579104

申请日：2005-04-26

申请人： Masatoshi Hazama ,  Yasushi Fujitani ,  Hidenori Ichijo

发明人： Masatoshi Hazama ,  Yasushi Fujitani ,  Hidenori Ichijo

IPC分类号： A61K39/395 ,  G01N33/00 ,  A61P3/10 ,  A61K31/70 ,  C07H21/00 ,  A61K38/45 ,  G01N33/53 ,  A61K49/00 ,  C12Q1/68 ,  A61K38/00 ,  C07K16/18 ,  A61P11/00 ,  C12Q1/02

CPC分类号： C12Q1/485 ,  A61K38/16 ,  G01N2500/00 ,  G01N2510/00

摘要： The present invention provides a method for screening for a prophylactic or therapeutic drug for apoptosis or an inflammation-associated disease, diabetes and complications thereof or a chronic obstructive pulmonary disease (COPD), namely, a method for screening for a prophylactic or therapeutic drug for apoptosis or an inflammation-associated disease, diabetes and complications thereof or COPD, which includes (1) comparing the activities of a protein having an amino acid sequence the same as or substantially the same as the amino acid sequence shown by SEQ ID NO: 2 or a partial peptide thereof or a salt thereof, between in the presence of a test substance and in the absence of the test substance, or (2) comparing the expressions of a protein having an amino acid sequence the same as or substantially the same as the amino acid sequence shown by SEQ ID NO: 2, a partial peptide thereof and a salt thereof in the cells having the ability to produce the protein, the partial peptide thereof and the salt thereof, between in the presence of a test substance and in the absence of the test substance.

摘要翻译： 本发明提供了用于筛选用于凋亡或炎症相关疾病，糖尿病及其并发症或慢性阻塞性肺病（COPD）的预防或治疗药物的方法，即用于预防或治疗药物的预防或治疗药物的筛选方法 凋亡或炎症相关疾病，糖尿病及其并发症或COPD，其包括（1）比较具有与SEQ ID NO：2所示氨基酸序列相同或基本相同的氨基酸序列的蛋白质的活性 或其部分肽或其盐，在测试物质的存在下和不存在测试物质之间，或（2）比较具有与或不相同的氨基酸序列的蛋白质的表达 在具有产生蛋白质的能力的细胞中SEQ ID NO：2所示的氨基酸序列，其部分肽及其盐，其部分肽 在测试物质的存在下和不存在测试物质之间。

公开(公告)号：US20050234116A1

公开(公告)日：2005-10-20

申请号：US10507731

申请日：2003-03-13

申请人： Yasuo Sugiyama ,  Masatoshi Hazama ,  Norihisa Iwakami

发明人： Yasuo Sugiyama ,  Masatoshi Hazama ,  Norihisa Iwakami

IPC分类号： A61K31/422 ,  A61P1/00 ,  A61P1/16 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P7/06 ,  A61P9/00 ,  A61P9/10 ,  A61P9/12 ,  A61P19/02 ,  A61P21/00 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P27/02 ,  A61P31/18 ,  A61P31/20 ,  A61P43/00 ,  C07D263/34 ,  C07D413/04 ,  C07D413/14 ,  A61K31/4178 ,  A61K31/427

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 R1 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： 本发明提供一种VDAC调节剂，其包含由式（I）表示的化合物：其中R 1是卤素原子，任选取代的杂环基，任选取代的羟基，任选取代的硫醇基 或任选取代的氨基; A是任选取代的酰基，任选取代的杂环基，任选取代的羟基或任选酯化或酰胺化的羧基; B是任选取代的芳基; X是氧原子，硫原子或任选取代的氮原子; Y是可用作预防或治疗唐氏综合征等的二价烃基或杂环基，其盐或前体药物等。

公开(公告)号：US20050090534A1

公开(公告)日：2005-04-28

申请号：US10505742

申请日：2003-02-27

申请人： Nozomu Sakai ,  Yu Momose ,  Katsuhito Murase ,  Masatoshi Hazama

发明人： Nozomu Sakai ,  Yu Momose ,  Katsuhito Murase ,  Masatoshi Hazama

IPC分类号： A61P3/10 ,  A61P25/00 ,  A61P25/24 ,  A61P43/00 ,  C07D263/32 ,  C07D263/38 ,  C07D263/46 ,  C07D263/48 ,  C07D277/28 ,  C07D277/30 ,  C07D277/40 ,  C07D277/46 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  C07F9/653 ,  C07F9/6539 ,  C07D417/02 ,  A61K31/4178 ,  A61K31/422 ,  A61K31/427 ,  C07D413/02 ,  C07D43/02

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 R1 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 —NR2—W-D wherein R2 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为氢原子，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， 任选取代的硫醇基或任选取代的氨基，A是任选取代的环氨基或-NR 2 -WD，其中R 2是氢原子或烷基 基团，W是键或二价无环烃基，D是任选取代的环状基团，任选取代的氨基或任选取代的酰基，B是任选取代的烃基或任选取代的杂环基，X是 氧原子，硫原子或任选取代的氮原子，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。

公开(公告)号：US06489351B1

公开(公告)日：2002-12-03

申请号：US10105333

申请日：2002-03-26

申请人： Tsuneo Yasuma ,  Tsuneo Oda ,  Masatoshi Hazama ,  Shigehisa Taketomi

发明人： Tsuneo Yasuma ,  Tsuneo Oda ,  Masatoshi Hazama ,  Shigehisa Taketomi

IPC分类号： A61K311424

CPC分类号： C07D495/04 ,  C07D513/04 ,  C07F9/6561

摘要： A compound represented by the formula: 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.

摘要翻译： 由下式表示的化合物：其中X表示硫原子或氧原子; Y表示任选氧化的硫原子或氧原子; Z表示键或二价烃基; R1表示任选取代的烃基; R 2表示任选的酰胺化或酯化的羧基; 环A表示任选取代的芳族五元杂环; 或其盐。上述化合物具有细胞分化诱导因子作用增强活性和抗基质金属蛋白酶活性，并且其可用于预防和治疗骨疾病如骨质疏松症，骨折，骨关节炎和类风湿性关节炎， 动脉硬化，癌转移以及基于神经变性的疾病。

公开(公告)号：US20100029724A1

公开(公告)日：2010-02-04

申请号：US12309348

申请日：2007-07-18

申请人： Masatoshi Hazama ,  Norihisa Iwakami ,  Hiroaki Yashiro

发明人： Masatoshi Hazama ,  Norihisa Iwakami ,  Hiroaki Yashiro

IPC分类号： A61K31/41 ,  C12Q1/48 ,  A61P3/10 ,  A61P25/00 ,  A61P7/06

CPC分类号： G01N33/6896 ,  A61K31/4245 ,  A61K31/662 ,  C12Q1/527 ,  G01N33/6893 ,  G01N2500/04 ,  G01N2800/042 ,  G01N2800/28

摘要： The present invention provides a method of screening for a therapeutic drug for diabetes or a nerve system disease, including using ferrochelatase, and a ferrochelatase activator containing a compound represented by the formula: wherein ring A is a 5-membered aromatic heterocycle containing two or more nitrogen atoms and optionally further having substituent(s); B is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; X is a divalent noncyclic hydrocarbon group; Z is —O—, —S—, —NR2—, —CONR2— or —NR2CO— wherein R2 is a hydrogen atom or an optionally substituted alkyl group; Y is a bond or a divalent noncyclic hydrocarbon group; and R1 is an optionally substituted cyclic group, an optionally substituted amino group or an optionally substituted acyl group, or a salt thereof.

摘要翻译： 本发明提供一种筛选糖尿病治疗药物或神经系统疾病的方法，包括使用铁螯合酶，以及含有由下式表示的化合物的铁螯合酶激活剂：其中环A为含有两个或更多个的5-元芳族杂环 氮原子和任选地还具有取代基; B是任选取代的烃基或任选取代的杂环基; X是二价非环状烃基; Z是-O - ， - S - ， - NR 2 - ， - CONR 2 - 或-NR 2 CO-，其中R 2是氢原子或任选取代的烷基; Y是键或二价非环状烃基; 和R 1是任选取代的环状基团，任选取代的氨基或任选取代的酰基，或其盐。

公开(公告)号：US20080287438A1

公开(公告)日：2008-11-20

申请号：US12219073

申请日：2008-07-15

申请人： Yu Momose ,  Nozomu Sakai ,  Tsuyoshi Maekawa ,  Masatoshi Hazama ,  Toru Kawamura ,  Misayo Sera

发明人： Yu Momose ,  Nozomu Sakai ,  Tsuyoshi Maekawa ,  Masatoshi Hazama ,  Toru Kawamura ,  Misayo Sera

IPC分类号： A61K31/5377 ,  A61K31/4196 ,  A61K31/4164 ,  A61K31/4152 ,  C07D403/02 ,  A61K31/4439 ,  A61P25/00 ,  C07D401/02 ,  C07D249/12 ,  C07D233/00 ,  C07D413/02

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 ,  C07F9/65031 ,  C07F9/6506 ,  C07F9/6518 ,  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—, —NR2—, —CONR2— or —NR2CO— (R2 is a hydrogen atom or an optionally substituted alkyl group); Y is a bond or a divalent acyclic hydrocarbon group; R1 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.

公开(公告)号：US07423159B2

公开(公告)日：2008-09-09

申请号：US10532667

申请日：2003-10-30

申请人： Yu Momose ,  Nozomu Sakai ,  Tsuyoshi Maekawa ,  Masatoshi Hazama ,  Toru Kawamura

发明人： Yu Momose ,  Nozomu Sakai ,  Tsuyoshi Maekawa ,  Masatoshi Hazama ,  Toru Kawamura

IPC分类号： C07D213/10

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 ,  C07F9/65031 ,  C07F9/6506 ,  C07F9/6518 ,  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—, —NR2—, —CONR2— or —NR2CO— (R2 is a hydrogen atom or an optionally substituted alkyl group); Y is a bond or a divalent acyclic hydrocarbon group; R1 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。 该试剂包括由下式表示的化合物：其中环A是含有2个或更多个氮原子的5元芳族杂环，其可进一步具有取代基; B是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 - 或-NR 2 CO-（R SUB > 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，任选取代的氨基或任选取代的酰基，条件是当由环A表示的5元芳族杂环是咪唑时，则Z不应该是 - O-或其盐。

公开(公告)号：US20060004069A1

公开(公告)日：2006-01-05

申请号：US10532667

申请日：2003-10-30

申请人： Yu Momose ,  Nozomu Sakai ,  Tsuyoshi Maekawa ,  Masatoshi Hazama ,  Toru Kawamura ,  Misayo Sera

发明人： Yu Momose ,  Nozomu Sakai ,  Tsuyoshi Maekawa ,  Masatoshi Hazama ,  Toru Kawamura ,  Misayo Sera

IPC分类号： A61K31/4196 ,  A61K31/4164 ,  A61K31/4152 ,  C07D43/02

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 ,  C07F9/65031 ,  C07F9/6506 ,  C07F9/6518 ,  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—, —NR2—, —CONR2— or —NR2CO— (R2 is a hydrogen atom or an optionally substituted alkyl group); Y is a bond or a divalent acyclic hydrocarbon group; R1 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。 该试剂包括由下式表示的化合物：其中环A是含有2个或更多个氮原子的5元芳族杂环，其可进一步具有取代基; B是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 - 或-NR 2 CO-（R SUB > 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，任选取代的氨基或任选取代的酰基，条件是当由环A表示的5元芳族杂环是咪唑时，则Z不应该是 - O-或其盐。