公开(公告)号：US4775759A

公开(公告)日：1988-10-04

申请号：US675276

申请日：1984-11-27

申请人： Kenner C. Rice ,  Candace B. Pert ,  Terrence R. Burke, Jr. ,  Steven M. Larson ,  William C. Eckelman ,  Michael A. Channing

发明人： Kenner C. Rice ,  Candace B. Pert ,  Terrence R. Burke, Jr. ,  Steven M. Larson ,  William C. Eckelman ,  Michael A. Channing

IPC分类号： A61K51/04 ,  C07D489/08 ,  A61K43/00 ,  A61K49/02

CPC分类号： C07D489/08 ,  A61K51/0455 ,  A61K2123/00

摘要： Fluorinated derivatives 3,14-dihydroxy-4,5.alpha.-epoxy-6.beta.-fluoro-17-methylmorphinan ("fluorooxymorphone"; FOXY, compound 10) and 17-cyclopropylmethyl-3,14-dihydroxy-4,5.alpha.-epoxy-6.beta.-fluoromorphinan (CYCLOFOXY, compound 18) are prepared based upon the structures of the potent opioid agonist oxymorphone 4 and the antagonist naltrexone 11, respectively. Fluorine was introduced in the final stages of synthesis by a facile nucleophilic displacement with fluoride ion of the 6.alpha.-triflate functions in 8 and 16. The synthetic procedures were suitable for the production of the corresponding positron emitting .sup.18 F-labeled analogs .sup.18 F-FOXY and .sup.18 F-CYCLOFOXY, which are useful for in vivo studies of the opioid receptor system using positron emission transaxial tomography. In addition, the tritiation of FOXY (10) to high specific activity is noted.

摘要翻译： 氟化衍生物3,14-二羟基-4,5α-环氧-6β-氟-17-甲基吗啡喃（“fluoroxymorphone”; FOXY，化合物10）和17-环丙基甲基-3,14-二羟基-4,5α-环氧 -6β-氟吗啡喃（CYCLOFOXY，化合物18）分别基于有效的阿片样物质激动剂oxymorphone4和拮抗剂纳曲酮11的结构制备。 在合成的最后阶段，氟在8和16中通过易位的亲核置换引入6α-三氟甲磺酸的氟离子。该合成方法适用于生产相应的正电子发射18F-标记的类似物18F-FOXY和 18F-CYCLOFOXY，其可用于使用正电子发射横轴断层扫描的阿片受体系统的体内研究。 此外，还注意到FOXY（10）对高比活性的研究。

公开(公告)号：US5856318A

公开(公告)日：1999-01-05

申请号：US910302

申请日：1997-08-11

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： C07D207/14 ,  C07D211/56 ,  C07D223/12 ,  C07D409/06 ,  A61K31/33 ,  A61K31/55 ,  C07D295/00 ,  C07D405/00

CPC分类号： C07D409/06 ,  C07D207/14 ,  C07D211/56 ,  C07D223/12

摘要： Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein each of R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from hydrido, lower alkyl, benzyl, and haloloweralkyl;wherein each of R.sup.2, R.sup.3 and R.sup.8 through R.sup.11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is an integer of from four to six; wherein m is an integer of from two to four; wherein A is selected from phenyl, naphthyl, benzothienyl, benzofuranyl 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，精神病和抽搐。 特别感兴趣的化合物具有下式：其中R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; 其中R2，R3和R8至R11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为4-6的整数; 其中m是2至4的整数; 其中A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基; 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。

公开(公告)号：US5679679A

公开(公告)日：1997-10-21

申请号：US348654

申请日：1994-12-02

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 diazabicyloalkyl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein: each of R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from the group consisting of hydrido, loweralkyl, benzyl and haloloweralkyl; each of R.sup.2, R.sup.3, and R.sup.8 through R.sup.11 is independently selected from the group consisting of hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; n is an integer of from three to four; m is an integer of two; A is selected from the group consisting of phenyl, naphthyl, benzothienyl, benzofuranyl and thienyl and 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, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

摘要翻译： 描述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：R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; R 2，R 3和R 8至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; n是3至4的整数; m是2的整数; A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基，其中任何前述A基团可以进一步被一个或多个独立地选自羟基，羟基，低级烷基，低级烷氧基，卤代 ，卤代低级烷基，氨基，单低级烷基氨基和二低级烷基氨基; 或其药学上可接受的盐。

公开(公告)号：US5679673A

公开(公告)日：1997-10-21

申请号：US344304

申请日：1994-11-21

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： C07D453/02 ,  C07D487/08 ,  A61K31/55 ,  C07D471/08

CPC分类号： C07D487/08 ,  C07D453/02

摘要： Certain aralkyl diazabicycloalkyl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein each of R, R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from hydrido, lower-alkyl, benzyl, and haloloweralkyl; wherein each of R.sup.2, R.sup.3 and R.sup.10 through R.sup.13 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein each of R.sup.8 and R.sup.9 is selected from hydrido, loweralkyl, benzyl and haloloweralkyl; wherein m is an integer of from two to four; wherein A is selected from phenyl, naphthyl, benzothiophenyl, benzofuranyl 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R，R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; 其中R2，R3和R10至R13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R8和R9各自选自氢，低级烷基，苄基和卤代低级烷基; 其中m是2至4的整数; 其中A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基; 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。

公开(公告)号：US5346908A

公开(公告)日：1994-09-13

申请号：US904354

申请日：1992-06-25

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： C07D207/14 ,  C07D211/56 ,  C07D223/12 ,  C07D409/06 ,  A61K31/55 ,  A61K31/40 ,  A61K31/445 ,  C07D211/08

CPC分类号： C07D409/06 ,  C07D207/14 ,  C07D211/56 ,  C07D223/12

摘要： Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychoses and convulsions. Compounds of particular interest are of the formula: ##STR1## wherein each of R.sup.1, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 is independently selected from hydrido, lower alkyl, benzyl, and haloloweralkyl; wherein each of R.sup.2, R.sup.3 and R.sup.8 through R.sup.11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is an integer of from four to six; wherein m is an integer of from two to four; wherein A is selected from phenyl, naphthyl, benzothienyl, benzofuranyl 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，精神病和抽搐。 特别感兴趣的化合物具有下式：其中R 1，R 4，R 5，R 6和R 7各自独立地选自氢，低级烷基，苄基和卤代低级烷基; 其中R2，R3和R8至R11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为4-6的整数; 其中m是2至4的整数; 其中A选自苯基，萘基，苯并噻吩基，苯并呋喃基和噻吩基; 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。

公开(公告)号：US5208338A

公开(公告)日：1993-05-04

申请号：US715762

申请日：1991-06-14

申请人： Brian R. de Costa ,  Michael J. Iadarola ,  Kenner C. Rice ,  Richard B. Rothman ,  Karen F. Berman

发明人： Brian R. de Costa ,  Michael J. Iadarola ,  Kenner C. Rice ,  Richard B. Rothman ,  Karen F. Berman

IPC分类号： C07D489/08 ,  G01N33/534 ,  G01N33/94

CPC分类号： G01N33/534 ,  C07D489/08 ,  G01N33/9486

摘要： The present invention is directed to radiolabeled N-substituted-6-iodo-3,14-dihydroxy-4,5.alpha.-epoxymorphinans, intermediates for producing the same, and a process for the preparation and methods of detecting opioid receptors.The radioimaging agent of the present invention has the following formula: ##STR1## wherein I is selected from the group consisting of .sup.123 I and .sup.125 I; and where R is alkyl, cycloalkylloweralkyl or allyl.

摘要翻译： 本发明涉及放射性标记的N-取代-6-碘-3,14-二羟基-4,5α-环氧吗啡喃，其制备方法及其制备方法和检测阿片受体的方法。 本发明的放射成像剂具有下式：其中I选自123I和125I的 并且其中R是烷基，环烷基低级烷基或烯丙基。

公开(公告)号：US06395900B1

公开(公告)日：2002-05-28

申请号：US09895956

申请日：2001-06-29

申请人： Andrew Coop ,  Kenner C. Rice

发明人： Andrew Coop ,  Kenner C. Rice

IPC分类号： C07D48902

CPC分类号： C07D489/02 ,  C07D489/00 ,  C07D489/08 ,  C07D489/12

摘要： The present invention provides a method for N-deprotecting an opioid compound, a method for N-deprotecting and O-demethylating an opioid compound, a method for O-demethylating an opioid compound, and a method for O-demethylating a nonpeptidic delta agonist compound or an opioid compound having a tertiary amide with no significant reaction at amide groups.

摘要翻译： 本发明提供了对阿片样物质进行N-去保护的方法，对于阿片样物质进行N-脱保护和O-脱甲基化的方法，对阿片样物质进行O-去甲基化的方法，以及将非肽δ激动剂化合物O-脱甲基化的方法 或具有在酰胺基上没有显着反应的叔酰胺的阿片样物质化合物。

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：US6046200A

公开(公告)日：2000-04-04

申请号：US9307

申请日：1998-01-20

申请人： Frank C. Tortella ,  Mark A. DeCoster ,  Kenner C. Rice ,  Sylvia N. Calderon

发明人： Frank C. Tortella ,  Mark A. DeCoster ,  Kenner C. Rice ,  Sylvia N. Calderon

IPC分类号： A61K31/4965 ,  A61K31/395 ,  A61K31/495 ,  A61K31/50

CPC分类号： A61K31/4965

摘要： Compounds of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are alkyl of 1-8 carbons have been shown to have both neuroprotective and analgesic activities. The compounds of the invention may be used in treatment of conditions that would normally result in neuronal damage, including those arising on account of cerebral ischemia/hypoxia or increase in intracranial pressure such as neoplasms, stroke, meningitis or trauma. Compositions of the invention can also be useful for treatment of toxin-related damage such as drug over-dose or exposure to toxins in the environment.

摘要翻译： 其中R1和R2为1-8个碳原子的烷基化合物已显示具有神经保护作用和止痛活性。 本发明的化合物可用于治疗通常导致神经元损伤的病症，包括因脑缺血/缺氧或颅内压升高如赘生物，中风，脑膜炎或创伤引起的损伤。 本发明的组合物还可用于治疗毒素相关的损伤，例如药物过量或暴露于环境中的毒素。

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。