公开(公告)号：US06310064B1

公开(公告)日：2001-10-30

申请号：US09347659

申请日：1999-07-06

申请人： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

发明人： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

IPC分类号： C07D47104

CPC分类号： C07D471/04 ,  A61K31/495 ,  C07D487/04

摘要： Certain aralkyl diazabicycloalkyl compounds are disclosed for treatment of CNS disorders, such as cerebral ischemia, psychosis, and convulsions. For example, compounds of interest are of the formula:

摘要翻译： 公开了某些芳烷基二氮杂双环烷基化合物用于治疗中枢神经系统疾病，例如脑缺血，精神病和抽搐。例如，感兴趣的化合物具有下式：

公开(公告)号：US5958920A

公开(公告)日：1999-09-28

申请号：US954284

申请日：1997-10-20

申请人： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

发明人： Wayne Bowen ,  Brian R. de Costa ,  Celia Dominguez ,  Xiao-Shu He ,  Kenner C. Rice

IPC分类号： A61K31/495 ,  C07D471/04 ,  C07D487/04 ,  C07D31/495 ,  C07D31/55

CPC分类号： C07D471/04 ,  A61K31/495 ,  C07D487/04

摘要： Certain aralkyl diazabicycloalkyl compounds are disclosed for treatment of CNS disorders, such as cerebral ischemia, psychosis and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein m is three or four; wherein z is selected from the group consisting of ##STR2## wherein when Z is ##STR3## n and p are integers of from one to four, with a sum of four or five, and when Z is ##STR4## n and p are integers of from one to three, with a sum of three or four; wherein A is selected from the group consisting of aryl, heteroaryl, aryloxy, heteroaryloxy, aralkoxy, heteroaralkoxy, arylamino, heteroarylamino, aralkylamino, heteroaralkylamino, arylthio, heteroarylthio, aralkylthio, and heteroaralkylthio; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from the group consisting of hydrido, hydroxy, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, aryl, alkoxy, aryloxy, aralkoxy, alkoxyalkyl, halo, haloalkyl, hydroxyalkyl, cyano, amino, monoalkylamino, dialkylamino, carboxy, carboxyalkyl, alkanoyl, alkenyl and alkynyl; or a pharmaceutically acceptable salt thereof.

摘要翻译： 公开了某些芳烷基二氮杂双环烷基化合物用于治疗中枢神经系统疾病，如脑缺血，精神病和抽搐。 特别感兴趣的化合物具有下式：其中m为三或四; 其中z选自其中当Z为n且p为1至4的整数时，其总数为4或5，当Z为n且p为1至3的整数时，其总和为 三或四; 其中A选自芳基，杂芳基，芳氧基，杂芳氧基，芳烷氧基，杂芳烷氧基，芳基氨基，杂芳基氨基，芳烷基氨基，杂芳烷基氨基，芳硫基，杂芳硫基，芳烷硫基和杂芳烷硫基。 其中前述A基团中的任一个可以进一步被一个或多个独立地选自羟基，羟基，烷基，环烷基，环烷基烷基，芳烷基，芳基，烷氧基，芳氧基，芳烷氧基，烷氧基烷基，卤素，卤代烷基， ，氰基，氨基，单烷基氨基，二烷基氨基，羧基，羧基烷基，烷酰基，烯基和炔基; 或其药学上可接受的盐。

公开(公告)号：US5468854A

公开(公告)日：1995-11-21

申请号：US95937

申请日：1993-07-22

申请人： R. Tyler McCabe ,  Brian R. de Costa

发明人： R. Tyler McCabe ,  Brian R. de Costa

IPC分类号： G01N33/533 ,  G01N33/94 ,  C07D487/04 ,  C07D519/00

CPC分类号： G01N33/533 ,  G01N33/94

摘要： Conjugates of fluorescent labels with specific, selective, and high affinity ligands for receptors have been synthesized and used to directly measure binding to receptors. In the examples, fluorescein conjugates of the high-affinity benzodiazepine receptor ligands Ro 15-1788 and Ro 7-1986 were synthesized. The binding of these fluorescent ligands (BD 621, BD 623 and BD 607) to benzodiazepine receptors was characterized by direct fluorescence measurement. Both the equilibrium dissociation constants (K.sub.D) of BD 621 and BD 607 and the maximum number of binding sites (B.sub.max) estimated by fluorescence monitoring were consistent with values obtained by using radioligand binding techniques. The binding of BD 621 and BD 607 assessed by fluorescence measurement was reversible, abolished by photoaffinity labeling with Ro 15-4513, and unaffected by a variety of substances that do not bind to benzodiazepine receptors. The potencies of chemically diverse benzodiazepine receptor compounds to inhibit fluorescent ligand binding were highly correlated, with potencies obtained from radioligand binding techniques. These findings demonstrate that direct fluorescence measurement techniques can be used to quantitate ligand-receptor interactions.

摘要翻译： 已经合成了具有特异性，选择性和高亲和力受体配体的荧光标记物的缀合物，并用于直接测量与受体的结合。 在实施例中，合成了高亲和力苯并二氮杂受体配体Ro 15-1788和Ro 7-1986的荧光素缀合物。 通过直接荧光测定来表征这些荧光配体（BD 621，BD 623和BD 607）与苯并二氮杂受体的结合。 BD 621和BD 607的平衡解离常数（KD）和通过荧光监测估计的最大结合位点数（Bmax）均与通过使用放射性配体结合技术获得的值一致。 通过荧光测量评估的BD 621和BD 607的结合是可逆的，通过用Ro 15-4513的光亲和标记来消除，并且不受不与苯并二氮杂受体结合的各种物质的影响。 化学多样的苯并二氮杂受体化合物抑制荧光配体结合的效力与放射性配体结合技术获得的效力高度相关。 这些发现表明直接荧光测量技术可用于定量配体 - 受体相互作用。

公开(公告)号：US5130330A

公开(公告)日：1992-07-14

申请号：US473008

申请日：1990-01-31

申请人： Brian R. de Costa ,  Kenner C. Rice ,  Nancy M. Gray ,  Patricia C. Contreras ,  Arthur E. Jacobson ,  Andrew Thurkauf ,  Lilian A. Radesca ,  Wayne D. Bowen

发明人： Brian R. de Costa ,  Kenner C. Rice ,  Nancy M. Gray ,  Patricia C. Contreras ,  Arthur E. Jacobson ,  Andrew Thurkauf ,  Lilian A. Radesca ,  Wayne D. Bowen

IPC分类号： A61K31/40 ,  A61K31/4025 ,  A61P25/00 ,  C07D295/12 ,  C07D295/135 ,  C07D405/12

CPC分类号： C07D295/135

摘要： Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychotic disorders and convulsions. Compounds of particular interest are of the formula ##STR1## wherein R.sup.1 is selected from hydrido, loweralkyl, cycloalkylalkyl of four to six carbon atoms, and loweralkenylloweralkyl; wherein each of R.sup.2 and R.sup.3 is independently selected from hydrido and loweralkyl; wherein each of R.sup.4 through R.sup.7, R.sup.10 and R.sup.11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is a number selected from four through six; wherein p is a number selected from zero through four; wherein q is a number selected from three through five; wherein A is selected from phenyl, naphthyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

摘要翻译： 描述某些含氮环杂环烷基氨基芳基化合物用于治疗中枢神经系统疾病如脑缺血，精神病和惊厥。 特别感兴趣的化合物具有下式：其中R 1选自4至6个碳原子的氢，低级烷基，环烷基烷基和低级链烯基低级烷基; 其中R2和R3各自独立地选自氢和低级烷基; 其中R 4至R 7，R 10和R 11各自独立地选自氢，羟基，低级烷基，苄基，苯氧基，苄氧基和卤代低级烷基; 其中n是选自四至六的数; 其中p是选自零至四的数字; 其中q是选自三至五的数; 其中A选自苯基，萘基和噻吩基; 其中前述A基团中的任一个可以进一步被一个或多个独立地选自氢，羟基，低级烷基，低级烷氧基，卤素，卤代低级烷基，氨基，单低级烷基氨基和二低级烷基氨基的取代基取代。 或其药学上可接受的盐。