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公开(公告)号：EP0788501B1
公开(公告)日：2002-06-05
申请号：EP95937391.1
申请日：1995-10-04
发明人： LEWIS, Michael, E. , KAUER, James, C. , NEFF, Nicola , GLICKSMAN, Marcie , ROBERTS-LEWIS, Jill , MURAKATA, Chikara , SAITO, Hiromitsu , MATSUDA, Yuzuru , KANAI, Fumihiko , KANEKO, Masami
IPC分类号： C07D498/22 , A61K31/55 , C07D487/14 , A61K31/40
CPC分类号： C07D487/14 , A61K31/407 , A61K31/5377 , A61K31/553 , A61K31/7056 , A61K2300/00
摘要： The invention features novel derivatives of K-252a e.g. (II-4) as well as novel bis-N-substituted derivatives of staurosporine of Formula (I). The invention also features a method for treating diseased neuronal cells involving the administration of either the novel staurosporine derivatives or specified functional derivatives of K-252a. In the formula (I): [Stau] -N(CH3)-W-N(CH3)-[Stau], [Stau] represents a residue of formula (a) and W represents a radical of the formula: -C(=Y)-NH-W'-NH-C(=Y)- where W' is a hydrocarbylene radical of 2-20 carbon atoms and Y is O or S. In formula (II-4) R?1, R2, Z1, and Z2¿ are each H; X is CH¿2?OH; and R is OCH3.
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公开(公告)号：EP0651754B1
公开(公告)日：1997-04-23
申请号：EP93917337.3
申请日：1993-07-26
发明人： LEWIS, Michael, E. , NEFF, Nicola , ROBERTS-LEWIS, Jill , MURAKATA, Chikara 2-11-2-702, Bessho , SAITO, Hiromitsu , MATSUDA, Yuzuru 1-22-7, Nukuiminami-cho , KAUER, James, C.
IPC分类号： C07D498/22 , C07D519/00 , A61K31/40 , A61K31/55 , C07H19/044 , C07H9/06
CPC分类号： C07D487/14 , A61K31/407 , A61K31/5377 , A61K31/553 , A61K31/7056 , A61K2300/00
摘要： The invention features novel derivatives of K-252a, as well as novel bis-N-substituted derivatives of staurosporine. Also, a method for treating diseased neuronal cells involving the administration of either the novel staurosporine derivatives or specified functional derivatives of K-252a.
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公开(公告)号：EP0789578B1
公开(公告)日：2003-06-04
申请号：EP95939165.7
申请日：1995-11-14
申请人： CEPHALON, INC.
IPC分类号： A61K38/05 , C07K5/04 , C07C229/00
CPC分类号： C07D209/48 , A61K31/18 , A61K31/216 , A61K31/22 , A61K31/277 , A61K31/353 , A61K31/4035 , A61K38/00 , C07C279/36 , C07C311/09 , C07C311/47 , C07C311/64 , C07C337/08 , C07C2601/08 , C07D311/70 , C07F5/025 , C07K5/0207 , C07K5/06095
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公开(公告)号：EP0788501A1
公开(公告)日：1997-08-13
申请号：EP95937391.0
申请日：1995-10-04
发明人： LEWIS, Michael, E. , KAUER, James, C. , NEFF, Nicola , GLICKSMAN, Marcie , ROBERTS-LEWIS, Jill , MURAKATA, Chikara , SAITO, Hiromitsu , MATSUDA, Yuzuru , KANAI, Fumihiko , KANEKO, Masami
CPC分类号： C07D487/14 , A61K31/407 , A61K31/5377 , A61K31/553 , A61K31/7056 , A61K2300/00
摘要： The invention features novel derivatives of K-252a e.g. (II-4) as well as novel bis-N-substituted derivatives of staurosporine of Formula (I). The invention also features a method for treating diseased neuronal cells involving the administration of either the novel staurosporine derivatives or specified functional derivatives of K-252a. In the formula (I): [Stau] -N(CH3)-W-N(CH3)-[Stau], [Stau] represents a residue of formula (a) and W represents a radical of the formula: -C(=Y)-NH-W'-NH-C(=Y)- where W' is a hydrocarbylene radical of 2-20 carbon atoms and Y is O or S. In formula (II-4) R?1, R2, Z1, and Z2¿ are each H; X is CH¿2?OH; and R is OCH3.
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5.发明公开TREATING DISORDERS BY APPLICATION OF INSULIN-LIKE GROWTH FACTORS AND ANALOGS 失效病THROUGH胰岛素样生长因子和模拟应用处理。
公开(公告)号：EP0476044A1
公开(公告)日：1992-03-25
申请号：EP90909874.0
申请日：1990-06-05
申请人： CEPHALON, INC.
发明人： LEWIS, Michael, E. , KAUER, James, C. , SMITH, Kevih, R. , CALLISON, Kathleen, V. , BALDINO, Frank, Jr.
CPC分类号： C07K14/65 , A61K38/30 , C07K1/113 , Y10S514/885 , Y10S514/903
摘要： Selon un procédé d'amélioration des chances de survie de cellules neuronales menacées d'un mammifère, on administre au mammifère une quantité efficace d'au moins une des substances suivantes: IGF-I (facteur de croissance I similaire à l'insuline); un dérivé fonctionnel d'IGF-II, à condition que lorsque IGF-I ou IGF-II sont administrés, on administre également du NGF (facteur de croissance des nerfs) ou un dérivé fonctionnel du NGF.
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公开(公告)号：EP0789578A1
公开(公告)日：1997-08-20
申请号：EP95939165.0
申请日：1995-11-14
申请人： CEPHALON, INC.
IPC分类号： A61K31 , A61K38 , A61K45 , A61P19 , A61P21 , A61P43 , C07C279 , C07C311 , C07C337 , C07D209 , C07D311 , C07F5 , C07K5
CPC分类号： C07D209/48 , A61K31/18 , A61K31/216 , A61K31/22 , A61K31/277 , A61K31/353 , A61K31/4035 , A61K38/00 , C07C279/36 , C07C311/09 , C07C311/47 , C07C311/64 , C07C337/08 , C07C2601/08 , C07D311/70 , C07F5/025 , C07K5/0207 , C07K5/06095
摘要： Disclosed herein are inhibitors of the multicatalytic protease enzyme which are represented by general formula (I). Constituent members and preferred constituent members are disclosed herein. Methodologies for making and using the disclosed compounds are also set forth herein.
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7.发明授权Use of IGF1 or IGF2 for the manufacture of a medicament in the treatment of amyotrophic lateral sclerosis 失效使用IGF1或IGF2的用于制备药物用于肌萎缩性侧索硬化的治疗
公开(公告)号：EP0476044B1
公开(公告)日：1997-07-30
申请号：EP90909874.1
申请日：1990-06-05
申请人： CEPHALON, INC.
发明人： LEWIS, Michael, E. , KAUER, James, C. , SMITH, Kevih, R. , CALLISON, Kathleen, V. , BALDINO, Frank, Jr.
IPC分类号： A61K38/30
CPC分类号： C07K14/65 , A61K38/30 , C07K1/113 , Y10S514/885 , Y10S514/903
摘要： A method of enhancing the survival of neuronal cells in a mammal, the cells being at risk of dying, the method comprising administering to the mammal an effective amount of at least one of the following substances: IGF-I; a functional derivative of IGF-I; IGF-II; or a functional derivative of IGF-II, provided that if IGF-I or IGF-II is administered, NGF or a functional derivative of NGF is also administered.
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公开(公告)号：EP0651754A1
公开(公告)日：1995-05-10
申请号：EP93917337.0
申请日：1993-07-26
发明人： LEWIS, Michael, E. , NEFF, Nicola , ROBERTS-LEWIS, Jill , MURAKATA, Chikara 2-11-2-702, Bessho , SAITO, Hiromitsu 5-15-23, Tokura , MATSUDA, Yuzuru 1-22-7, Nukuiminami-cho , KAUER, James, C.
CPC分类号： C07D487/14 , A61K31/407 , A61K31/5377 , A61K31/553 , A61K31/7056 , A61K2300/00
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公开(公告)号：EP0518955A1
公开(公告)日：1992-12-23
申请号：EP91905743.0
申请日：1991-03-04
申请人： CEPHALON, INC.
CPC分类号： C07K7/06 , A61K38/00 , C07C237/22 , C07C279/14 , C07K5/0207 , C07K5/06052 , C07K5/06191 , C07K5/0806 , C07K5/0808 , C07K5/0812 , C07K5/0819 , C07K5/0823 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K5/1027 , C07K7/02 , C12N9/6421 , C12N9/6424 , C12Q2337/12 , G01N2333/4709 , G01N2800/2821
摘要： On décrit l'identification, la caractérisation et la purification de deux protéases de sérine analogues à la chymotrypsine, appelées "chymase" et "protéase multicatalytique". La chymase et la protéase multicatalytique font toutes deux preuve d'une activité enzymatique capable de cliver entre la méthionine-L et l'acide aspartique, une activité nécessaire à la production de bêta-amyloïde. Des procédés sont décrits, destinés à quantifier les activités de la chymase et de la protéase multicatalitique dans le cerveau (ainsi que d'autres échantillons de tissus et de fluides) pour permettre de diagnostiquer la maladie d'Alzheimer, et pour permettre le développement d'inhibiteurs comme agents thérapeutiques ralentissant la progression de la maladie. De nouvelles compositions ont été préparées et identifiées comme étant des inhibiteurs des deux enzymes. Des substrats sont aussi décrits. Des méthodes de traitement de la maladie d'Alzheimer et l'identification des protéases capables de produire la protéine bêta-amyloïde sont fournies, ainsi que des méthodes de clonage et de séquentiation de chymase et de protéase multicatalytique du cerveau humain, et de la préparation de sondes à anticorps et à acide nucléique pour elles.
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