公开(公告)号：US09873702B2

公开(公告)日：2018-01-23

申请号：US14960012

申请日：2015-12-04

申请人： Subramaniam Ananthan ,  Richard B. Rothman

发明人： Subramaniam Ananthan ,  Richard B. Rothman

IPC分类号： C07D487/04 ,  C07D239/95 ,  C07D401/04 ,  C07D403/04 ,  C07D401/14 ,  C07D409/04 ,  C07D471/04 ,  C07D473/00

CPC分类号： C07D487/04 ,  C07D239/95 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D409/04 ,  C07D471/04 ,  C07D473/00

摘要： The present disclosure relates to certain amine derivatives of fused bicyclic heterocycles that inhibit the amine reuptake function of the biogenic amine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET). Compounds of the present disclosure are potent inhibitors of the reuptake of dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) with full or partial maximal efficacy. The compounds with partial maximal efficacy in inhibiting reuptake of all three biogenic amines are herein referred to as partial triple uptake inhibitors (PTRIs). Compounds of the present disclosure are useful for treating depression, pain and substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

公开(公告)号：US07541364B2

公开(公告)日：2009-06-02

申请号：US11718565

申请日：2004-08-27

申请人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

发明人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

IPC分类号： A61K31/4748 ,  C07D491/12

CPC分类号： C07D491/18

摘要： Compounds represented by the formula: wherein R is C1-6 alkyl; C4-6 cycloalkylalkyl; or C3-6 alkenyl; R′ is H or C1-6 alkyl; X is H or OH; Y is alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl or aroyl; and Z is CH or N; provided that X is H, when Z is CH and R is C4 cycloalkylalkyl or C4 alkenyl; prodrugs thereof; and pharmaceutically acceptable salts thereof are provided. Compounds of the above formula are useful as analgesics for treating pain; as immunomodulators, to modulate the behavioral effects of drugs of abuse and to modulate the development of tolerance and dependence to μ agonists.

摘要翻译： 由下式表示的化合物：其中R是C 1-6烷基; C4-6环烷基烷基; 或C 3-6烯基; R'是H或C 1-6烷基; X是H或OH; Y是烷基，环烷基，芳基，杂芳基，芳基烷基或芳酰基; Z为CH或N; 条件是X为H，当Z为CH且R为C 4环烷基烷基或C 4链烯基时; 其前药; 及其药学上可接受的盐。 上述化合物可用作治疗疼痛的止痛剂; 作为免疫调节剂，调节滥用药物的行为效应，调节对mu激动剂的耐受性和依赖性的发展。

公开(公告)号：US10087148B2

公开(公告)日：2018-10-02

申请号：US14960023

申请日：2015-12-04

申请人： Subramaniam Ananthan ,  Richard B. Rothman

发明人： Subramaniam Ananthan ,  Richard B. Rothman

IPC分类号： C07D239/94 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： The present disclosure relates to certain amine derivatives of fused bicyclic heterocycles that inhibit the amine reuptake function of the biogenic amine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET). Compounds of the present disclosure are potent inhibitors of the reuptake of dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) with full or partial maximal efficacy. The compounds with partial maximal efficacy in inhibiting reuptake of all three biogenic amines are herein referred to as partial triple uptake inhibitors (PTRIs). Compounds of the present disclosure are useful for treating depression, pain and substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

公开(公告)号：US20160159751A1

公开(公告)日：2016-06-09

申请号：US14960023

申请日：2015-12-04

申请人： Subramaniam ANANTHAN ,  Richard B. ROTHMAN

发明人： Subramaniam ANANTHAN ,  Richard B. ROTHMAN

IPC分类号： C07D239/94 ,  C07D403/12 ,  C07D401/14 ,  C07D401/12

CPC分类号： C07D239/94 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

摘要： The present disclosure relates to certain amine derivatives of fused bicyclic heterocycles that inhibit the amine reuptake function of the biogenic amine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET). Compounds of the present disclosure are potent inhibitors of the reuptake of dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) with full or partial maximal efficacy. The compounds with partial maximal efficacy in inhibiting reuptake of all three biogenic amines are herein referred to as partial triple uptake inhibitors (PTRIs). Compounds of the present disclosure are useful for treating depression, pain and substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

摘要翻译： 本公开涉及抑制生物胺转运蛋白，多巴胺转运蛋白（DAT），血清素转运蛋白（SERT）和去甲肾上腺素转运蛋白（NET））的胺再摄取功能的稠合双环杂环的某些胺衍生物。 本公开的化合物是具有完全或部分最大功效的多巴胺（DA），5-羟色胺（5-羟色胺，5-HT）和去甲肾上腺素（NE））再摄取的有效抑制剂。 在抑制所有三种生物胺的再摄取中具有部分最大功效的化合物在本文中称为部分三重摄取抑制剂（PTRI）。 本公开的化合物可用于治疗抑郁症，疼痛和药物滥用以及物质滥用和对诸如可卡因，甲基苯丙胺，尼古丁和酒精的物质的成瘾的复发。 该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

公开(公告)号：US20080194568A1

公开(公告)日：2008-08-14

申请号：US11718565

申请日：2004-08-27

申请人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

发明人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

IPC分类号： A61K31/485 ,  A61K31/5025 ,  C07D489/02 ,  A61P29/00 ,  A61P25/30

CPC分类号： C07D491/18

摘要： Compounds represented by formula (I) wherein R is C1-6cycloalkylalkyl; or C3-6 alkenyl; R′ is H or C1-6 alkyl; X is H or OH; Y is alkyl, cycloalkyl, aryl, heteroaryl or aroyl; and Z is CH or N; provided that X is H, when Z is CH and R is C4 cycloalkylalkyl or C4 alkenyl; prodrugs thereof; and pharmaceutically acceptable salts thereof are provided. Compounds of the above formula are useful as analgesics for treating pain; as immunomodulators, to modulate the behavioral effects of drugs of abuse and to modulate the development of tolerance and dependence of μ agonists.

摘要翻译： 由式（I）表示的化合物，其中R是C 1-6环烷基烷基; 或C 3-6烯基; R'是H或C 1-6烷基; X是H或OH; Y是烷基，环烷基，芳基，杂芳基或芳酰基; Z为CH或N; 条件是X是H，当Z是CH且R是C 4环烷基烷基或C 1-4链烯基时; 其前药; 及其药学上可接受的盐。 上述化合物可用作治疗疼痛的止痛剂; 作为免疫调节剂，调节滥用药物的行为效应，并调节mu激动剂的耐受性和依赖性的发展。

公开(公告)号：US06387389B1

公开(公告)日：2002-05-14

申请号：US09269926

申请日：1999-06-30

申请人： Richard B. Rothman ,  Kenner C. Rice ,  David Lewis ,  Dorota Matecka ,  John R. Glowa

发明人： Richard B. Rothman ,  Kenner C. Rice ,  David Lewis ,  Dorota Matecka ,  John R. Glowa

IPC分类号： A61F1300

CPC分类号： C07D295/088 ,  A61K31/495 ,  C07D215/26 ,  C07D243/04 ,  C07D295/092 ,  C07D307/52 ,  C07D333/20

摘要： The present invention provides sustained-release derivatives of hydroxylated analogs of substituted 1-[2[bis(aryl)methoxy]ethyl]-piperazines and -homopiperazines, pharmaceutical compositions comprising the same, and a method of using such sustained-release derivatives to bind the dopamine transporter to achieve a desired effect, such as antagonism of dopamine reuptake inhibitors, such as cocaine, or dopamine releasers or norepinephrine and/or serotonin reuptake inhibitors, such as methamphetamine.

摘要翻译： 本发明提供了取代的1- [2 [双（芳基）甲氧基]乙基] - 哌嗪和高 - 哌嗪嗪的羟基化类似物的缓释衍生物，包含它们的药物组合物和使用这种缓释衍生物结合的方法 多巴胺转运蛋白以达到所需效果，例如多巴胺再摄取抑制剂如可卡因或多巴胺释放剂或去甲肾上腺素和/或5-羟色胺再摄取抑制剂如甲基苯丙胺的拮抗作用。

公开(公告)号：US5336483A

公开(公告)日：1994-08-09

申请号：US3731

申请日：1993-01-13

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 ,  A61K49/02

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 L and .sup.125 ; 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123L和125; 并且其中R是烷基，环烷基低级烷基或烯丙基。

公开(公告)号：US20160159809A1

公开(公告)日：2016-06-09

申请号：US14960012

申请日：2015-12-04

申请人： Subramaniam ANANTHAN ,  Richard B. ROTHMAN

发明人： Subramaniam ANANTHAN ,  Richard B. ROTHMAN

IPC分类号： C07D487/04 ,  C07D239/95 ,  C07D473/00 ,  C07D403/04 ,  C07D471/04 ,  C07D401/14 ,  C07D401/04 ,  C07D409/04

CPC分类号： C07D487/04 ,  C07D239/95 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D409/04 ,  C07D471/04 ,  C07D473/00

摘要： The present disclosure relates to certain amine derivatives of fused bicyclic heterocycles that inhibit the amine reuptake function of the biogenic amine transporters, dopamine transporter (DAT), serotonin transporter (SERT) and norepinephrine transporter (NET). Compounds of the present disclosure are potent inhibitors of the reuptake of dopamine (DA), serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) with full or partial maximal efficacy. The compounds with partial maximal efficacy in inhibiting reuptake of all three biogenic amines are herein referred to as partial triple uptake inhibitors (PTRIs). Compounds of the present disclosure are useful for treating depression, pain and substance abuse and relapse to substance abuse and addiction to substances such as cocaine, methamphetamine, nicotine and alcohol. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

摘要翻译： 本公开涉及抑制生物胺转运蛋白，多巴胺转运蛋白（DAT），血清素转运蛋白（SERT）和去甲肾上腺素转运蛋白（NET））的胺再摄取功能的稠合双环杂环的某些胺衍生物。 本公开的化合物是具有完全或部分最大功效的多巴胺（DA），5-羟色胺（5-羟色胺，5-HT）和去甲肾上腺素（NE））再摄取的有效抑制剂。 在抑制所有三种生物胺的再摄取中具有部分最大功效的化合物在本文中称为部分三重摄取抑制剂（PTRI）。 本公开的化合物可用于治疗抑郁症，疼痛和药物滥用以及物质滥用和对诸如可卡因，甲基苯丙胺，尼古丁和酒精的物质的成瘾的复发。 该摘要旨在作为用于在特定技术中进行搜索的扫描工具，而不意在限制本发明。

公开(公告)号：US07951817B2

公开(公告)日：2011-05-31

申请号：US12407000

申请日：2009-03-19

申请人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

发明人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

IPC分类号： A61K31/4748 ,  C07D491/12

CPC分类号： C07D491/18

摘要： Compounds represented by the formula:wherein R is C1-6 alkyl; C4-6 cycloalkylalkyl; or C3-6 alkenyl; R′ is H or C1-6 alkyl; X is H or OH; Y is alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl or aroyl; and Z is CH or N; provided that X is H, when Z is CH and R is C4 cycloalkylalkyl or C4 alkenyl; prodrugs thereof; and pharmaceutically acceptable salts thereof are provided. Compounds of the above formula are useful as analgesics for treating pain; as immunomodulators, to modulate the behavioral effects of drugs of abuse and to modulate the development of tolerance and dependence to μ agonists.

摘要翻译： 由下式表示的化合物：其中R是C 1-6烷基; C4-6环烷基烷基; 或C 3-6烯基; R'是H或C 1-6烷基; X是H或OH; Y是烷基，环烷基，芳基，杂芳基，芳基烷基或芳酰基; Z为CH或N; 条件是X为H，当Z为CH且R为C 4环烷基烷基或C 4链烯基时; 其前药; 及其药学上可接受的盐。 上述化合物可用作治疗疼痛的止痛剂; 作为免疫调节剂，调节滥用药物的行为效应，并调节对μ激动剂的耐受性和依赖性的发展。

公开(公告)号：US20090239892A1

公开(公告)日：2009-09-24

申请号：US12407000

申请日：2009-03-19

申请人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

发明人： Subramaniam Ananthan ,  Richard B. Rothman ,  Edward J. Bilsky ,  Frank Porreca

IPC分类号： A61K31/485 ,  C07D491/18 ,  A61P25/00

CPC分类号： C07D491/18

摘要： Compounds represented by the formula:wherein R is C1-6 alkyl; C4-6 cycloalkylalkyl; or C3-6 alkenyl; R′ is H or C1-6 alkyl; X is H or OH; Y is alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl or aroyl; and Z is CH or N; provided that X is H, when Z is CH and R is C4 cycloalkylalkyl or C4 alkenyl; prodrugs thereof; and pharmaceutically acceptable salts thereof are provided. Compounds of the above formula are useful as analgesics for treating pain; as immunomodulators, to modulate the behavioral effects of drugs of abuse and to modulate the development of tolerance and dependence to μ agonists.

摘要翻译： 由下式表示的化合物：其中R是C 1-6烷基; C4-6环烷基烷基; 或C 3-6烯基; R'是H或C 1-6烷基; X是H或OH; Y是烷基，环烷基，芳基，杂芳基，芳基烷基或芳酰基; Z为CH或N; 条件是X为H，当Z为CH且R为C 4环烷基烷基或C 4链烯基时; 其前药; 及其药学上可接受的盐。 上述化合物可用作治疗疼痛的止痛剂; 作为免疫调节剂，调节滥用药物的行为效应，调节对mu激动剂的耐受性和依赖性的发展。