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1. 发明申请

US20050148621A1 Acetylcholinesterase dual inhibitors 失效
标题翻译：乙酰胆碱酯酶双抑制剂
公开(公告)号：US20050148621A1
公开(公告)日：2005-07-07
申请号：US10887974
申请日：2004-07-09
申请人： Ana Gil , Isabel Diaz , Laura Arrieta , Diana Gordillo , Ana Huerta , Susana Morales-Alcelay , Maria Millan , Esther Palomero , Paola Egea , Celia Austria , Miguel Padilla , Pilar Ruiz
发明人： Ana Gil , Isabel Diaz , Laura Arrieta , Diana Gordillo , Ana Huerta , Susana Morales-Alcelay , Maria Millan , Esther Palomero , Paola Egea , Celia Austria , Miguel Padilla , Pilar Ruiz
IPC分类号： A61P25/28 , C07D401/12 , A61K31/473 , C07D43/02
CPC分类号： C07D401/12
摘要： The invention provides compounds of formula: which have a tacrine moiety connected to an heterocyclic moiety through a linker. Through careful selection of the substituents and the linker, the activity and selectivity towards acetylcholinesterase can be modulated. The compounds show potent AChE inhibition activities together with modifications in the β-amyloid aggregation properties by binding simultaneously to the catalytic and peripheral AChE sites. They are useful in the treatment of AChE mediated diseases, such as the Alzheimer's disease.
摘要翻译：本发明提供下式的化合物：其具有通过接头与杂环部分连接的他克林部分。通过仔细选择取代基和接头，可以调节对乙酰胆碱酯酶的活性和选择性。化合物通过同时结合催化和外周AChE位点显示出有力的AChE抑制活性以及β-淀粉样蛋白聚集性质的修饰。它们可用于治疗AChE介导的疾病，例如阿尔茨海默氏病。

2. 发明申请

US20060142323A1 Dual binding site acetylcholinesterase inhibitors for the treatment of alzheimer's disease 审中-公开
标题翻译：双重结合位点乙酰胆碱酯酶抑制剂治疗阿尔茨海默病
公开(公告)号：US20060142323A1
公开(公告)日：2006-06-29
申请号：US10530667
申请日：2003-10-07
申请人： Ana Gil , Isabel Diaz , Laura Arrieta , Diana Gordillo , Ana Huerta , Susana Morales-Alcelay , Maria Millan , Esther Palomero , Paolo Egea , Celia De Austria , Miguel Padilla
发明人： Ana Gil , Isabel Diaz , Laura Arrieta , Diana Gordillo , Ana Huerta , Susana Morales-Alcelay , Maria Millan , Esther Palomero , Paolo Egea , Celia De Austria , Miguel Padilla
IPC分类号： A61K31/473 , C07D401/02
CPC分类号： C07D401/12 , C07D219/12 , C07D417/12
摘要： A family of compounds of formula (I) wherein: X is one of the following radicals: which behaves as dual site acetyl-cholinesterase inhibitors and which are especially useful for the treatment of cognitive disorders as senile dementia, cerebrovascular dementia, mild cognition impairment, attention deficit disorder, and/or neurodegenerative dementing disease with aberrant protein aggregations as specially Alzheimer's disease, Parkinson disease, ALS, or prion diseases, as Creutzfeldt-Jakob disease or Gerst-mann-Straussler-Scheiner disease.
摘要翻译：一种式（I）化合物，其中：X是以下基团之一：其表现为双位点乙酰胆碱酯酶抑制剂，并且其特别可用于治疗认知障碍，如老年痴呆，脑血管性痴呆，轻度认知障碍，注意力缺陷障碍和/或异常蛋白质聚集作为特异性阿尔茨海默氏病，帕金森病，ALS或朊病毒疾病的神经退行性痴呆疾病，如克雅氏综合征或杰斯特 - 曼 - 斯特劳斯勒 - 舍勒病。

3. 发明申请

US20070088080A1 Gsk-3 inhibitors isolated from marine organisms 审中-公开
标题翻译：从海洋生物分离的Gsk-3抑制剂
公开(公告)号：US20070088080A1
公开(公告)日：2007-04-19
申请号：US10596188
申请日：2004-12-02
申请人： Diana Gordillo , Isabel Diaz , Ana Martinez-Gil , Gema Del Pliego , Ana Huerta , Ma Jose Puerto , Ester Aparicio , Dario Navarro , Miguel Padilla
发明人： Diana Gordillo , Isabel Diaz , Ana Martinez-Gil , Gema Del Pliego , Ana Huerta , Ma Jose Puerto , Ester Aparicio , Dario Navarro , Miguel Padilla
IPC分类号： A61K31/365 , C07D405/02
CPC分类号： C07D407/06
摘要： The present invention provides the use of a compound of formula (I); wherein: n is 0, 1, 2, or 3, the bonds shown with the dashed lines are saturated, or unsaturated with one or more double bonds; R, and R′are independently selected from hydrogen, alkyl, aryl, —OH, —OR″ —SH, —SR″—NH, —NHR″, ═O, ═NH, ═NR″; R″ is independently selected from alkyl, aryl, in the preparation of a medicament for the treatment of a disease requiring a GSK-3 inhibitor. Also provided is a compound of formula (II); wherein n is 0, 1, 2, or 3 the bonds shown with the dashed lines are saturated, or unsaturated with one or more double bonds. Also provided are methods of treating chronic neurodegenerative conditions.
摘要翻译：本发明提供式（I）化合物的用途; 其中：n为0,1,2或3，用虚线表示的键是饱和的或具有一个或多个双键的不饱和键; R和R'独立地选自氢，烷基，芳基，-OH，-OR“-SH，-SR”-NH，-NHR“， - O，-NH，-NR” 在制备用于治疗需要GSK-3抑制剂的疾病的药物中，R“独立地选自烷基，芳基。还提供了式（II）的化合物; 其中n为0,1,2或3，虚线所示的键为饱和的，或具有一个或多个双键的不饱和键。还提供了治疗慢性神经变性病症的方法。

4. 发明申请

US20050222220A1 GSK-3 inhibitors 有权
标题翻译： GSK-3抑制剂
公开(公告)号：US20050222220A1
公开(公告)日：2005-10-06
申请号：US11098610
申请日：2005-04-05
申请人： Miguel Padilla , Mercedes Cascon , Isabel Diaz , Ana Gil , Gema del Pliego , Ana Huerta , Maria Puerto
发明人： Miguel Padilla , Mercedes Cascon , Isabel Diaz , Ana Gil , Gema del Pliego , Ana Huerta , Maria Puerto
IPC分类号： A61K31/433 , A61P3/10 , A61P25/28 , C07D285/08 , C07D417/04 , C07D285/14
CPC分类号： C07D285/08 , C07D417/04
摘要： Provided are thiadiazolidine compounds of formula I wherein R1 is an organic group having at least 8 atoms selected from C or O, which is not linked directly to the N through a —C(O)— and comprising at least an aromatic ring, and their pharmaceutical compositions. These compounds are selective GSK-3 inhibitors and have improved bioavailability. They are useful for the treatment of GSK-3 mediated diseases, among others Alzheimer's disease, type II diabetes, depression and brain injury.
摘要翻译：提供式I的噻二唑烷化合物，其中R 1是具有至少8个选自C或O的原子的有机基团，其不直接通过-C（O）直接与N连接，并且包含至少一个芳环，及其药物组合物。这些化合物是选择性GSK-3抑制剂并具有改善的生物利用度。它们可用于治疗GSK-3介导的疾病，其中包括阿尔茨海默病，II型糖尿病，抑郁症和脑损伤。

5. 发明授权

US3968334A Audiometric method and apparatus for testing the effectiveness of hearing protective devices 失效
标题翻译：用于测试听力保护装置有效性的听力测量方法和装置
公开(公告)号：US3968334A
公开(公告)日：1976-07-06
申请号：US513604
申请日：1974-10-10
申请人： Miguel Padilla
发明人： Miguel Padilla
IPC分类号： A61B5/12 , H04R29/00
CPC分类号： A61B5/12
摘要： A novel method and apparatus is disclosed for audiometrically testing the effectiveness and fitting of insert-type hearing protective devices whereby each ear is enclosed in a separate and portable audiometric enclosure having a telephonic earphone arrangement, the interior of each enclosure being freely spaced from the respective pinna of the ear to avoid any physical contact therebetween that may otherwise distort the ear canal supporting the protective device to be tested. Predetermined audiometric signals may be transmitted to each ear separately, both with and without the protective device, to obtain the difference of hearing thresholds and thereby determine separately, if needed, the fitting of each protective device, and its "real ear attenuation".
摘要翻译：公开了一种新颖的方法和装置，用于对插入式听力保护装置的有效性和装配进行听力测试，其中每个耳朵被封闭在具有电话耳机装置的单独的便携式听觉外壳中，每个外壳的内部与相应的耳朵的耳廓以避免其间的任何物理接触，否则可能使支撑待测试的保护装置的耳道变形。可以将预定的听力信号分别传送到每个耳朵，无论是否有保护装置，以获得听力阈值的差异，从而如果需要，分别确定每个保护装置的装配以及其“真正的耳朵衰减”。

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