公开(公告)号：US20070265286A1

公开(公告)日：2007-11-15

申请号：US11642979

申请日：2006-12-21

申请人： Andrew Thomas ,  Elaine Stokes ,  Laurent Hennequin

发明人： Andrew Thomas ,  Elaine Stokes ,  Laurent Hennequin

IPC分类号： A61K31/517 ,  A61P19/02 ,  A61P3/00 ,  A61P35/00 ,  A61P37/00 ,  C07D239/94

CPC分类号： C07D401/12

摘要： The invention relates to quinazoline derivatives of formula (I), wherein m is an integer from 1 to 3; R1 represents halogeno or C1-3alkyl; X1 represents —O—; R2 is selected from one of the following three groups: 1) C1-5alkylR3 (wherein R3 is piperidinyl-4-yl which may bear one or two substituents selected from hydroxy, halogeno, C1-4alkyl, C1-4hydroxyalkyl and C1-4alkoxy; 2) C2-5alkenylR3 (wherein R3 is as defined hereinbefore); 3) C2-5alkynylR3 (wherein R3 is as defined hereinbefore); and wherein any alkyl, alkenyl or alkynyl group may bear one or more substituents selected from hydroxy, halogeno and amino; and salts thereof; processes for their preparation, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.

摘要翻译： 本发明涉及式（I）的喹唑啉衍生物，其中m为1至3的整数; R 1表示卤代或C 1-3烷基; X 1表示-O-; R 2选自以下三个基团之一：1）C 1-5烷基R 3（其中R 3，R 3，R 3， SUP>是可以带有一个或两个选自羟基，卤代，C 1-4 - 烷基，C 1-4 - 羟基烷基和C 1-4烷氧基; 2）C 2-5烯基R 3（其中R 3如上定义）; 3）C 2-5炔基R 3（其中R 3如上定义）; 并且其中任何烷基，烯基或炔基可以具有一个或多个选自羟基，卤代和氨基的取代基; 及其盐; 其制备方法，含有式（I）化合物或其药学上可接受的盐作为活性成分的药物组合物。 式（I）化合物及其药学上可接受的盐抑制VEGF的作用，其在治疗许多疾病状态（包括癌症和类风湿性关节炎）中是有价值的。

公开(公告)号：US20070191421A1

公开(公告)日：2007-08-16

申请号：US11640768

申请日：2006-12-18

申请人： Bernd Buettelmann ,  Jiaqiang Dong ,  Bo Han ,  Henner Knust ,  Andrew Thomas

发明人： Bernd Buettelmann ,  Jiaqiang Dong ,  Bo Han ,  Henner Knust ,  Andrew Thomas

IPC分类号： A61K31/4745 ,  C07D471/02

CPC分类号： C07D471/04

摘要： The present invention is concerned with aryl-isoxazol-4-yl-imidazo[1,5-a]pyridine derivatives of formula wherein: R1, R2, and R3 are as defined herein and pharmaceutically acceptable acid addition salts thereof. These compounds have high affinity and selectivity for GABA A α5 receptor binding sites. The invention also relates to methods for enhancing cognition and treating cognitive disorders like Alzheimer's disease.

摘要翻译： 本发明涉及下式的芳基 - 异恶唑-4-基 - 咪唑并[1,5-a]吡啶衍生物其中：R 1，R 2，R 2，R 3和本文所定义的药学上可接受的酸加成盐。 这些化合物对GABA Aα5受体结合位点具有高亲和力和选择性。 本发明还涉及用于增强认知和治疗认知障碍如阿尔茨海默病的方法。

公开(公告)号：US20070161654A1

公开(公告)日：2007-07-12

申请号：US11640622

申请日：2006-12-18

申请人： Bernd Buettelmann ,  Bo Han ,  Henner Knust ,  Andrew Thomas

发明人： Bernd Buettelmann ,  Bo Han ,  Henner Knust ,  Andrew Thomas

IPC分类号： A61K31/506 ,  A61K31/4439 ,  A61K31/42 ,  C07D413/14

CPC分类号： C07D413/04

摘要： The present invention is concerned with aryl-isoxazol-4-yl-imidazole derivatives of formula I: wherein R1 to R6 are as defmed in the specification and pharmaceutically acceptable acid addition salts thereof. This class of compounds has high affinity and selectivity for GABA A α5 receptor binding sites and might be useful as cognitive enhancer or for the treatment of cognitive disorders like Alzheimer's disease.

摘要翻译： 本发明涉及式I的芳基 - 异恶唑-4-基 - 咪唑衍生物：其中R 1至R 6如本说明书和药学上可接受的酸所定义 其加成盐。 这类化合物对GABA Aα5受体结合位点具有高亲和力和选择性，可用作认知增强剂或用于治疗认知障碍如阿尔茨海默病。

公开(公告)号：US20070085606A1

公开(公告)日：2007-04-19

申请号：US11489892

申请日：2006-07-20

申请人： Andrew Thomas ,  Steven Besser

发明人： Andrew Thomas ,  Steven Besser

IPC分类号： H03F3/45

CPC分类号： H03G1/0088 ,  G01N29/36 ,  G01N29/40 ,  G01N29/4463 ,  G01N2291/106 ,  G01S7/52033 ,  H03G3/001

摘要： In a non-destructive test instrument, there is provided a time variable gain (TVG) amplifier wherein the gain of the amplifier is dynamically changed to optimize the amplitude of a flaw echo signal. The TVG digital memory for a given TVG curve specifies and controls not only the start gain value, and the end game value, but the gain rate of change slope as well to generate TVG curve line segments.

摘要翻译： 在非破坏性测试仪器中，提供了一种时间可变增益（TVG）放大器，其中动态地改变放大器的增益以优化缺陷回波信号的幅度。 用于给定TVG曲线的TVG数字存储器不仅指定并控制起始增益值和结束游戏值，而且还对变化斜率的增益率以及产生TVG曲线线段进行控制。

公开(公告)号：US20070084289A1

公开(公告)日：2007-04-19

申请号：US11490334

申请日：2006-07-20

申请人： Andrew Thomas ,  Steven Besser ,  Jason Toomey

发明人： Andrew Thomas ,  Steven Besser ,  Jason Toomey

IPC分类号： G01N29/00

CPC分类号： G01N29/262 ,  G01N29/043 ,  G01N29/42 ,  G01N29/44 ,  G01N29/4463 ,  G01N29/449 ,  G01N2291/044 ,  G01N2291/102

摘要： An ultrasonic inspection system utilizes a tunable digital filter with 4× interpolation. The system is used for scanning objects to be tested and includes a transmit/receive device to generate a test signal and receive an echo signal. A signal processing circuit processes the echo signal with one or more digital to analog converters for converting an analog version of the echo signal to a digital echo signal in the form of streaming digital data which is stored in a memory. The data is stored at a first data rate and read out at the second, slower data rate. An averaging decimator receives and processes the data from the memory and supplies it to an IIR filter and subsequently to an FIR filter and ultimately to a box car filter to effect processing thereon which increases the perceived resolution of the data by a given factor, preferably by a factor of 4.

摘要翻译： 超声波检测系统采用4x插值的可调数字滤波器。 该系统用于扫描要测试的对象，并且包括发射/接收装置以产生测试信号并接收回波信号。 信号处理电路用一个或多个数模转换器来处理回波信号，用于将回波信号的模拟版本转换成存储在存储器中的流式数字数据形式的数字回波信号。 数据以第一数据速率存储，并以第二个较慢的数据速率读出。 平均抽取器接收并处理来自存储器的数据并将其提供给IIR滤波器并随后提供给FIR滤波器并且最终提供给盒式汽车滤波器以对其进行处理，从而将数据的感知分辨率提高给定因子，优选地通过 一个因素4。

公开(公告)号：US20060261303A1

公开(公告)日：2006-11-23

申请号：US10553057

申请日：2004-04-29

申请人： Andrew Thomas ,  Mark Profaca

发明人： Andrew Thomas ,  Mark Profaca

IPC分类号： F16K3/00

CPC分类号： F02D9/14 ,  F02M9/02 ,  F16K3/03

摘要： A throttle valve (1) for an inlet of an internal combustion piston engine comprising an aperture (9) adapted to be variably opened and closed between a first fully opened configuration and a second near closed configuration. The aperture (9) is variably opened and closed by a plurality of coplanar plates (10) mounted about the periphery of the aperture and movable towards the central region of the aperture.

摘要翻译： 一种用于内燃活塞发动机入口的节流阀（1），其包括适于在第一完全打开构型和第二近闭合构造之间可变地打开和关闭的孔（9）。 孔（9）由围绕孔的周边安装的多个共面板（10）可变地打开和关闭，并且可朝向孔的中心区域移动。

公开(公告)号：US20060135552A1

公开(公告)日：2006-06-22

申请号：US11301696

申请日：2005-12-13

申请人： Parichehr Malherbe ,  Raffaello Masciadri ,  Roger Norcross ,  Hasane Ratni ,  Andrew Thomas

发明人： Parichehr Malherbe ,  Raffaello Masciadri ,  Roger Norcross ,  Hasane Ratni ,  Andrew Thomas

IPC分类号： A61K31/4743 ,  C07D498/02

CPC分类号： C07D495/04 ,  C07D495/14

摘要： The present invention relates to compounds of formula I wherein R1, R2, R3, R4, and R5 are as defined in the specification. Compounds of the invention are active on the GABAB receptor and are useful for treating a variety of CNS disorders, including anxiety, depression, epilepsy, schizophrenia, cognitive disorders, spasticity-and skeletal muscle rigidity, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, cerebral palsy, neuropathic pain and craving associated with cocaine and nicotine, psychosis, panic disorder, posttraumatic stress disorders and gastrointestinal disorders.

摘要翻译： 本发明涉及式Ⅰ化合物，其中R 1，R 2，R 3，R 4， 和R 5如说明书中所定义。 本发明的化合物对GABA B受体具有活性，可用于治疗各种CNS疾病，包括焦虑，抑郁，癫痫，精神分裂症，认知障碍，痉挛性和骨骼肌僵硬，脊髓损伤，多发性硬化，肌萎缩性侧索硬化 ，脑性麻痹，神经性疼痛和与可卡因和尼古丁有关的渴望，精神病，恐慌症，创伤后应激障碍和胃肠道疾病。

公开(公告)号：US20060128691A1

公开(公告)日：2006-06-15

申请号：US11297691

申请日：2005-12-08

申请人： Bernd Buettelmann ,  Henner Knust ,  Andrew Thomas

发明人： Bernd Buettelmann ,  Henner Knust ,  Andrew Thomas

IPC分类号： A61K31/551 ,  C07D487/14

CPC分类号： C07D487/14

摘要： The present invention is concerned with substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of the formula I wherein R1 is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, nitro, cycloalkyl, —O(CH2)mO(CH2)mOH or —C≡C—R′; R2 is hydrogen or methyl; R3 is lower alkyl, lower alkyl substituted by halogen, lower alkenyl, lower alkenyl substituted by halogen, lower alkynyl, —(CH2)n-cycloalkyl, —(CR′R″)m—CH3, phenyl that is unsubstituted or substituted by halogen, pyridinyl or thienyl each of which is unsubstituted or substituted by lower alkyl, —(CH2)n—NH-cycloalkyl, lower alkenyl-cycloalkyl, lower alkynyl-(CR′R″)mOH, or lower alkynyl-phenyl wherein the phenyl ring is unsubstituited or substituted by halogen, CF3, lower alkyl or lower alkoxy; R′ is hydrogen or lower alkyl; R″ is hydrogen, hydroxy or lower alkyl; n is 0, 1 or 2; m is 1, 2 or 3; and o is 1 or 2; and pharmaceutically acceptable acid addition salts thereof. This class of compounds have high affinity and selectivity for GABA A α5 receptor binding sites. Thus, the invention also relates to methods of enhancing cognition and treating cognitive disorders like Alzheimer's disease.

摘要翻译： 本发明涉及式I的取代的咪唑并[1,5-a] [1,2,4]三唑并[1,5-d] [1,4]苯并二氮杂衍生物，其中R 1， >是氢，卤素，低级烷基，被卤素取代的低级烷基，低级烷氧基，被卤素取代的低级烷氧基，硝基，环烷基，-O（CH 2 CH 2）m O （CH 2）2 OH或-C≡C-R'; R 2是氢或甲基; R 3是低级烷基，被卤素取代的低级烷基，低级烯基，被卤素取代的低级链烯基，低级炔基， - （CH 2 SO 2）n

公开(公告)号：US20060084801A1

公开(公告)日：2006-04-20

申请号：US11252026

申请日：2005-10-17

申请人： Henner Knust ,  Andrew Thomas

发明人： Henner Knust ,  Andrew Thomas

IPC分类号： C07D487/22

CPC分类号： C07D487/14

摘要： The invention relates to halogen substituted imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]benzodiazepine derivatives of formula I wherein R1, R2, R3, R4 and n are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The compounds can be used as a cognitive enhancer or for the treatment of cognitive disorders, anxiety, Alzheimer's disease and schizophrenia.

摘要翻译： 本发明涉及式I的卤素取代咪唑并[1,5-a] [1,2,4]三唑并[1,5-d] [1,4]苯并二氮杂衍生物，其中R 1， R 2，R 3，R 4和n如说明书中所定义及其药学上可接受的酸加成盐。 这些化合物可以用作认知增强剂或用于治疗认知障碍，焦虑，阿尔茨海默病和精神分裂症。

公开(公告)号：US20050283019A1

公开(公告)日：2005-12-22

申请号：US11213052

申请日：2005-08-26

申请人： Synese Jolidon ,  Rosa Rodriguez Sarmiento ,  Andrew Thomas ,  Rene Wyler

发明人： Synese Jolidon ,  Rosa Rodriguez Sarmiento ,  Andrew Thomas ,  Rene Wyler

IPC分类号： A61P3/00 ,  A61K31/15 ,  A61K31/167 ,  A61K31/216 ,  A61K31/275 ,  A61P3/04 ,  A61P25/00 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P25/32 ,  A61P25/34 ,  A61P29/00 ,  A61P43/00 ,  C07C231/02 ,  C07C233/15 ,  C07C233/25 ,  C07C233/33 ,  C07C233/60 ,  C07C235/16 ,  C07C237/04 ,  C07C237/22 ,  C07C243/14 ,  C07C243/28 ,  C07C255/19 ,  C07C255/23 ,  C07C255/25 ,  C07C255/58 ,  C07C259/06 ,  C07C323/41

CPC分类号： C07C259/06 ,  C07C233/15 ,  C07C233/25 ,  C07C233/33 ,  C07C233/60 ,  C07C235/16 ,  C07C237/04 ,  C07C237/22 ,  C07C243/14 ,  C07C243/28 ,  C07C255/19 ,  C07C255/23 ,  C07C255/25 ,  C07C323/41 ,  C07C2601/02

摘要： This invention relates to N-acylamino aryl derivatives of the formula where R1R21, R22, R23, R24, R3, R4, R5, R6, R7, R8, R, and n are as defined herein and where X is —CHRO, —OCHR—, —CH2S—, —SCH2—, —CH2CH2—, —CH═CH— or —C≡C—. The compounds of the invention are selective monoamine oxidase B inhibitors, and they are therefore useful in the treatment of diseases mediated by monoamine oxidase B, for example, for the treatment of Alzheimer's disease or senile dementia.

摘要翻译： 本发明涉及下式的N-酰基氨基芳基衍生物：其中R 1，R 2，R 22，R 23， >，R 24，R 3，R 4，R 5，R 6， R 7，R 8，R 8和n如本文所定义，并且其中X是-CHRO，-OCHR - ， - CH 2 ，-SCH 2 - ， - CH 2 CH 2 - ， - CH-CH-或-C≡C-。 本发明的化合物是选择性单胺氧化酶B抑制剂，因此它们可用于治疗由单胺氧化酶B介导的疾病，例如用于治疗阿尔茨海默氏病或​​老年痴呆症。