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1. 发明授权

US07256204B2 Amine compounds, their production and use 失效
标题翻译：胺化合物，其生产和使用
公开(公告)号：US07256204B2
公开(公告)日：2007-08-14
申请号：US10645934
申请日：2003-08-21
申请人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
发明人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
IPC分类号： A61K31/38 , A61K31/36 , A61K31/18 , A61K31/16 , A61K31/135
CPC分类号： C07D213/30 , C07B2200/07 , C07C217/74 , C07C255/54 , C07C2602/10 , C07D215/14 , C07D215/20 , C07D215/58 , C07D271/06 , C07D277/64 , C07D295/096 , C07D307/80 , C07D317/54 , C07D333/16
摘要： A compound of the formula: wherein Ar is an aromatic ring assembly group which may be substituted or a fused aromatic group which may be substituted; X is (i) a bond, (ii) —S—, —SO— or —SO2—, (iii) C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene, etc., (iv) —CO—O— or (v) —(CH2)p-X1—, —(CH2)p-X1—CH2)q-, —(CH2)r-CO—X1—, —SO2—NR8— or —(CH2)r-SO2—NR8— wherein X1 is O or NR8, R8 is H, a hydrocarbon group which may be substituted or an acyl, p is 0 to 5, q is 1 to 5, p+q is 1 to 5, and r is 1 to 4; Y is a divalent C1-6 aliphatic hydrocarbon group optionally containing O or S, which may be substituted; R1 and R2 each is H or a lower alkyl which may be substituted, or R1 and R2 form a N-containing heterocyclic ring which may be substituted; Ring A is a benzene ring which may be further substituted; and Ring B is a 4- to 8-membered ring which may be further substituted, or a salt thereof has the effect of inhibiting amyloid-β protein production and/or secretion and is useful as a pharmaceutical composition for preventing and/or treating the neurodegenerative disease, etc.
摘要翻译：下式的化合物：其中Ar是可被取代的芳环组合基团或可被取代的稠合芳基; X是（i）键，（ii）-S-，-SO-或-SO 2 - ，（iii）C 1-6亚烷基，C _{（2-6）亚烯基或C 2-6亚炔基等，（iv）-CO-O-或（v） - （CH 2） q - ， - （CH 2）n - ， - （CH 2 CH 2） R 2 CO-X 1 - ， - SO 2 -NR 8 - 或 - （CH _{，R 8是H，可以被取代的烃基或酰基，p是0-5，q是1至5，p + q是1至5，并且r是1至 4; Y是任选地含有可被取代的O或S的二价C 1-6烷基脂族烃基; R 1和R 2各自为H或可以被取代的低级烷基，或R 1和R 2 2 >形成可以被取代的含氮杂环; 环A是可以被进一步取代的苯环; 环B为可进一步取代的4-至8-元环，或其盐具有抑制淀粉样蛋白β蛋白产生和/或分泌的作用，并且可用作预防和/或治疗神经变性疾病等}}

2. 发明授权

US07008950B1 Benzofurans as suppressors of neurodegeneration 失效
标题翻译：苯并呋喃作为神经退行性抑制因子
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。

3. 发明授权

US06613805B2 Amine compounds, their production and use 有权
标题翻译：胺化合物，其生产和使用
公开(公告)号：US06613805B2
公开(公告)日：2003-09-02
申请号：US09931140
申请日：2001-08-16
申请人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
发明人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
IPC分类号： A61K31137
CPC分类号： C07D213/30 , C07B2200/07 , C07C217/74 , C07C255/54 , C07C2602/10 , C07D215/14 , C07D215/20 , C07D215/58 , C07D271/06 , C07D277/64 , C07D295/096 , C07D307/80 , C07D317/54 , C07D333/16
摘要： A compound of the formula: wherein Ar is an aromatic ring assembly group which may be substituted or a fused aromatic group which may be substituted; X is (i) a bond, (ii) —S—, —SO— or —SO2—, (iii) C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene, etc., (iv) —CO—O— or (v) —(CH2)p-X1—, —(CH2)p-X1-(CH2)q-, —(CH2)r-CO-X1-, —SO2—NR8— or —(CH2)r-SO2—NR8— wherein X1 is O or NR8, R8 is H, a hydrocarbon group which may be substituted or an acyl, p is 0 to 5, q is 1 to 5, p+q is 1 to 5, and r is 1 to 4; Y is a divalent C1-6 aliphatic hydrocarbon group optionally containing O or S, which may be substituted; R1 and R2 each is H or a lower alkyl which may be substituted, or R1 and R2 form a N-containing heterocyclic ring which may be substituted; Ring A is a benzene ring which may be further substituted; and Ring B is a 4- to 8-membered ring which may be further substituted, or a salt thereof has the effect of inhibiting amyloid-&bgr; protein production and/or secretion and is useful as a pharmaceutical composition for preventing and/or treating the neurodegenerative disease, etc.
摘要翻译：下式的化合物：其中Ar是可被取代的芳环组合基团或可被取代的稠合芳基; X是（i）键，（ii）-S-，-SO-或-SO 2 - ，（iii）C 1-6亚烷基，C 2-6亚烯基或C 2-6亚炔基等，（iv）-CO- O-或（V） - （CH 2）p -X 1 - ， - （CH 2）p -X 1 - （CH 2）q - ， - （CH 2）r -CO-X 1 - ，-SO 2 -NR 8 - 或 - （CH 2） r-SO 2 -NR 8 - ，其中X 1为O或NR 8，R 8为H，可被取代的烃基或酰基，p为0至5，q为1至5，p + q为1至5，r 是1到4; Y是任选地含有O或S的二价C 1-6脂族烃基，其可被取代; R 1和R 2各自为H或可被取代的低级烷基，或R 1和R 2形成可被取代的含氮杂环; 环A是可以被进一步取代的苯环; 环B为可进一步取代的4-至8-元环，或其盐具有抑制淀粉样蛋白β蛋白产生和/或分泌的作用，并且可用作预防和/或治疗神经变性疾病等

4. 发明授权

US06586475B1 &bgr;-amyloid protein production/secretion inhibitors 失效
标题翻译： β-淀粉样蛋白生成/分泌抑制剂
公开(公告)号：US06586475B1
公开(公告)日：2003-07-01
申请号：US09856317
申请日：2001-06-05
申请人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
发明人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
IPC分类号： A61K31165
CPC分类号： C07D213/82 , C07C217/60 , C07C235/34 , C07C235/50 , C07C237/22 , C07C237/42 , C07C237/44 , C07C311/21 , C07D295/088 , C07D295/13
摘要： A compound of the formula: wherein Ar is an aromatic group; X and Y are a bivalent group selected from —O—, —S—, —CO—, —SO2—, —NR8—, —CONR8—, SO2NR8 and —COO— (wherein R8 is H, a hydrocarbon group or acyl), or a bivalent C1-6 aliphatic hydrocarbon group which may contain one or two above bivalent groups; R1 and R2 are H or C1-6 alkyl, or R1 and R2 may form, together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic ring; and ring A is a monocyclic aromatic ring, or a salt thereof or a prodrug thereof exhibits an excellent inhibitory activity of the production and/or the secretion of amyloid-&bgr; protein.
摘要翻译：下式的化合物：其中Ar是芳族基团; X和Y是选自-O - ， - S - ， - CO - ， - SO 2 - ， - NR 8 - ， - CONR 8 - ，SO 2 NR 8和-COO-（其中R 8是H，烃基或酰基），或可以含有一个或两个上述二价基团的二价C 1-6脂族烃基; R1和R2是H或C1-6烷基，或R1和R2可以与相邻的氮原子一起形成含氮杂环; 环A是单环芳环，或其盐或其前药对淀粉样蛋白-β蛋白的产生和/或分泌具有优异的抑制活性。

5. 发明授权

US06310107B1 Amine compounds, their production and use as amyloid-&bgr; production inhibitors 有权
标题翻译：胺化合物，其生产和用作淀粉样蛋白-β生产抑制剂
公开(公告)号：US06310107B1
公开(公告)日：2001-10-30
申请号：US09331460
申请日：1999-06-21
申请人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
发明人： Kaneyoshi Kato , Jun Terauchi , Hiroaki Fukumoto , Mitsuru Kakihana
IPC分类号： A61K31137
CPC分类号： C07D213/30 , C07B2200/07 , C07C217/74 , C07C255/54 , C07C2602/10 , C07D215/14 , C07D215/20 , C07D215/58 , C07D271/06 , C07D277/64 , C07D295/096 , C07D307/80 , C07D317/54 , C07D333/16
摘要： A compound of the formula: wherein Ar is an aromatic ring assembly group which may be substituted or a fused aromatic group which may be substituted; X is (i) a bond, (ii) —S—, —SO— or —SO2—, (iii) C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene, etc., (iv) —CO—O— or (v) —(CH2)p-X1—, —(CH2)p-X1— (CH2)q-, —(CH2)r-CO—X1—, —SO2—NR8— or —(CH2)r-SO2—NR8— wherein X1 is O or NR8, R8 is H, a hydrocarbon group which may be substituted or an acyl, p is 0 to 5, q is 1 to 5, p+q is 1 to 5, and r is 1 to 4; Y is a divalent C1-6 aliphatic hydrocarbon group optionally containing O or S, which may be substituted; R1 and R2 each is H or a lower alkyl which may be substituted, or R1 and R2 form a N-containing heterocyclic ring which may be substituted; Ring A is a benzene ring which may be further substituted; and Ring B is a 4- to 8-membered ring which may be further substituted, or a salt thereof has the effect of inhibiting amyloid-&bgr; protein production and/or secretion and is useful as a pharmaceutical composition for preventing and/or treating the neurodegenerative disease, etc.
摘要翻译：下式的化合物：其中Ar是可被取代的芳环组合基团或可被取代的稠合芳基; X是（i）键，（ii）-S-，-SO-或-SO 2 - ，（iii）C 1-6亚烷基，C 2-6亚烯基或C 2-6亚炔基等，（iv）-CO- O-或（V） - （CH 2）p -X 1 - ， - （CH 2）p -X 1 - （CH 2）q - ， - （CH 2）r -CO-X 1 - ，-SO 2 -NR 8 - 或 - （CH 2） r-SO 2 -NR 8 - ，其中X 1为O或NR 8，R 8为H，可被取代的烃基或酰基，p为0至5，q为1至5，p + q为1至5，r 是1到4; Y是任选地含有O或S的二价C 1-6脂族烃基，其可被取代; R 1和R 2各自为H或可被取代的低级烷基，或R 1和R 2形成可被取代的含氮杂环; 环A是可以被进一步取代的苯环; 环B为可进一步取代的4-至8-元环，或其盐具有抑制淀粉样蛋白β蛋白产生和/或分泌的作用，并且可用作预防和/或治疗神经变性疾病等

6. 发明授权

US5965568A Composition for inhibiting production or secretion of amyloid .beta. protein to treat Down's syndrome 失效
标题翻译：用于抑制淀粉样蛋白β蛋白的产生或分泌以治疗唐氏综合征的组合物
公开(公告)号：US5965568A
公开(公告)日：1999-10-12
申请号：US646354
申请日：1996-05-10
申请人： Mitsuru Kakihana , Takuo Kosaka , Akinobu Nagaoka , Giichi Goto
发明人： Mitsuru Kakihana , Takuo Kosaka , Akinobu Nagaoka , Giichi Goto
IPC分类号： A61K31/475 , A61K31/44
CPC分类号： A61K31/475
摘要： A pharmaceutical composition for inhibiting production or secretion of amyloid .beta. protein, which comprises a compound of the formula (I): ##STR1## wherein ring A is an optionally substituted benzene ring, R represents OR.sup.1, ##STR2## or SR.sup.1, wherein R.sup.1, R.sup.2 and R.sup.3 are the same or different and each is selected from a hydrogen atom, an optionally substituted hydrocarbon group or R.sup.2 and R.sup.3, taken together with the adjacent nitrogen atom, form an optionally substituted nitrogen-containing heterocyclic group, and Y is an optionally substituted alkyl group, or a pharmaceutically acceptable salt thereof, if necessary, with a pharmaceutically acceptable excipient, carrier or diluent.
摘要翻译： PCT No.PCT / JP96 / 00265 Sec。 371日期：1996年5月10日 102（e）日期1996年5月10日PCT提交1996年2月8日PCT公布。 WO96 / 25161 PCT出版物日本1996年8月22日用于抑制淀粉样β蛋白的产生或分泌的药物组合物，其包含式（I）的化合物：其中环A是任选取代的苯环，R表示OR 1或SR 1，其中R 1，R 2 和R3相同或不同，各自选自氢原子，任选取代的烃基或与相邻的氮原子一起形成的R 2和R 3，形成任选取代的含氮杂环基，Y是任选取代的烷基或其药学上可接受的盐，如果需要，与药学上可接受的赋形剂，载体或稀释剂。

7. 发明授权

US06930104B2 Heterocyclic derivatives 失效
标题翻译：杂环衍生物
公开(公告)号：US06930104B2
公开(公告)日：2005-08-16
申请号：US10474963
申请日：2002-04-25
申请人： Mitsuru Kakihana , Kaneyoshi Kato , Masaaki Mori , Toshiro Yamashita
发明人： Mitsuru Kakihana , Kaneyoshi Kato , Masaaki Mori , Toshiro Yamashita
IPC分类号： A61K31/4709 , A61K31/4725 , A61K31/473 , A61K31/496 , A61K31/498 , A61K31/538 , A61K31/5415 , A61K31/55 , A61P25/00 , A61P25/16 , A61P25/28 , A61P43/00 , C07D215/22 , C07D215/233 , C07D215/42 , C07D401/04 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D417/04 , C07D471/10 , C07D401/02 , A61K31/47
CPC分类号： C07D215/233 , A61K31/4709 , A61K31/4725 , A61K31/473 , A61K31/496 , A61K31/498 , A61K31/538 , A61K31/5415 , A61K31/55 , C07D215/42 , C07D401/04 , C07D401/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D417/04 , C07D471/10
摘要： The object of the present invention is to provide soluble β-amyloid precursor protein secretory stimulators, which are effective in treating neurodegenerative diseases as well as cerebrovascular disorder-induced neuronopathy. More specifically, the present invention provides a novel compound of the following Formula (I) or a salt or prodrug thereof: [wherein R1 and R2 each represent a hydrogen atom or a lower alkyl group, etc., Ar1 and the ring B each represent an optionally substituted aromatic group, the ring A represents an optionally substituted benzene ring, the ring C represents an optionally substituted 4- to 8-membered ring which may further be condensed with an optionally substituted ring, X represents CH or N, and Y represents CH or N].
摘要翻译：本发明的目的是提供可溶性β-淀粉样蛋白前体蛋白分泌刺激剂，其可有效治疗神经变性疾病以及脑血管障碍诱导的神经元病变。更具体地说，本发明提供下式（I）的新化合物或其盐或前药：其中R 1和R 2各自表示氢原子或低级烷基等，Ar 1和B各自表示任选取代的芳族基团，环A表示任选取代的苯环，环C表示任选取代的4-至可以进一步与任选取代的环稠合的8-元环，X表示CH或N，Y表示CH或N。

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