公开(公告)号：US5716957A

公开(公告)日：1998-02-10

申请号：US469012

申请日：1995-06-05

申请人： Anthony H. Cincotta ,  Albert H. Meier

发明人： Anthony H. Cincotta ,  Albert H. Meier

IPC分类号： A61K31/00 ,  A61K31/13 ,  A61K31/137 ,  A61K31/15 ,  A61K31/166 ,  A61K31/195 ,  A61K31/221 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/405 ,  A61K31/435 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4515 ,  A61K31/454 ,  A61K31/46 ,  A61K31/475 ,  A61K31/48 ,  A61K31/496 ,  A61K31/54 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/695 ,  A61K38/22 ,  A61K45/00 ,  A61K45/06 ,  A61P3/06 ,  A61P3/08 ,  A61P3/10 ,  C07D457/00 ,  C07D457/04 ,  G01N33/74 ,  A61K31/495

CPC分类号： G01N33/74 ,  A61K31/00 ,  A61K31/13 ,  A61K31/137 ,  A61K31/15 ,  A61K31/166 ,  A61K31/195 ,  A61K31/221 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/405 ,  A61K31/435 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4515 ,  A61K31/454 ,  A61K31/46 ,  A61K31/475 ,  A61K31/48 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/54 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/695 ,  A61K38/2257 ,  A61K45/06 ,  Y10S514/866 ,  Y10S514/909

摘要： A process for the long term modification and regulation of lipid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species. The dopamine agonist is administered at the time of, or just after the time of peak plasma prolactin concentration found in lean animals of the same species and the prolactin stimulator is administered at a time just before the plasma prolactin rhythm reaches its peak in lean animals. Insulin resistance, and hyperinsulinemia or hyperglycemia, or both, can also be controlled in humans on a long term basis by treatment corresponding to that of the treatment for obesity. The short term daily injections reset hormonal timing in the neural centers of the brain to produce long term effects.

摘要翻译： 长期改变和调节脂质和葡萄糖代谢的过程 - 通常通过给脊椎动物施用来减少肥胖，胰岛素抵抗和高胰岛素血症或高血糖或两者（这些是非胰岛素依赖型或II型糖尿病的标志） 动物或人类的多巴胺激动剂和催乳素刺激剂。 多巴胺激动剂和催乳素刺激剂分别以每天的剂量施用，取决于类似物种的脂肪和瘦成员的正常昼夜节律。 基于妊娠峰值催乳素的昼夜节律，峰值催乳素和糖皮质激素峰值，为类似物种的瘦胰岛素敏感成分建立的血液水平，以每日定时序列治疗肥胖物种的身体脂肪沉积物减少。 多巴胺激动剂在同一物种的瘦动物中发现的血浆催乳素浓度峰值之前或之后施用，并且在等离子体催乳素节律在瘦动物中达到峰值之前的时间施用催乳素刺激剂。 胰岛素抵抗和高胰岛素血症或高血糖或两者也可以通过与肥胖症治疗相对应的治疗长期控制。 短期每日注射在脑神经中枢复位激素时间产生长期效应。

公开(公告)号：US4839363A

公开(公告)日：1989-06-13

申请号：US149012

申请日：1988-01-27

申请人： Enzo Brambilla ,  Sergio Mantegani ,  Lorenzo Pegrassi ,  Alessandro Rossi ,  Aldemio Temperilli

发明人： Enzo Brambilla ,  Sergio Mantegani ,  Lorenzo Pegrassi ,  Alessandro Rossi ,  Aldemio Temperilli

IPC分类号： A61K31/48 ,  A61P25/00 ,  C07D457/00 ,  C07D457/02

CPC分类号： C07D457/00 ,  C07D457/02

摘要： Ergoline derivatives of the formula I ##STR1## wherein R.sub.1 represents a hydrogen atom or a methyl group; R.sub.2 represents a hydrogen atom or a methoxy group;R.sub.3 represents a hydrocarbon group having from 1 to 4 carbon atoms;X represents a nitrogen atom and Y represents an oxygen atom, a ##STR2## group wherein R.sub.4 represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl or a phenyl group, R.sub.5 represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl, a phenyl, an amino or di(C.sub.1 -C.sub.4 alkyl)amino group and the nitrogen atom of the group ##STR3## is not joined to the nitrogen atom represented by X, or Y represents a nitrogen atom and X represents an oxygen atom or a ##STR4## group wherein R.sub.4 is as above defined; and the pharmaceutically acceptable salt thereof; are useful for treatment of Parkinsonism and dyskinetic symptoms.

公开(公告)号：US3954772A

公开(公告)日：1976-05-04

申请号：US504395

申请日：1974-09-09

申请人： Nicholas J. Bach ,  David A. Hall ,  Edmund C. Kornfeld

发明人： Nicholas J. Bach ,  David A. Hall ,  Edmund C. Kornfeld

IPC分类号： C07D457/02 ,  C07D457/10 ,  C07D457/00

CPC分类号： C07D457/02 ,  C07D457/10

摘要： Descarboxylysergic acid prepared from 2,3-dihydro-8.beta.-hydroxy-6-methyl-9-ergolene or from penniclavine has oxytocic, serotonin antagonist, prolactin inhibition and muscle contracting activities.

摘要翻译： 由2,3-二氢-8β-羟基-6-甲基-9-己二醇或从扁豆素制备的解咖啡酸具有催产素，5-羟色胺拮抗剂，催乳素抑制和肌肉收缩活性。

公开(公告)号：US10342792B2

公开(公告)日：2019-07-09

申请号：US16009078

申请日：2018-06-14

申请人： ProLynx LLC

发明人： Gary W. Ashley ,  Eric L. Schneider

IPC分类号： A61K47/10 ,  A61K47/20 ,  A61K47/60 ,  C08G65/48 ,  C08G83/00 ,  A61K31/4745 ,  C07D457/00 ,  C07D491/22 ,  C07D519/00

摘要： Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism.

公开(公告)号：US10016411B2

公开(公告)日：2018-07-10

申请号：US15026579

申请日：2014-10-03

申请人： ProLynx LLC

发明人： Gary W. Ashley ,  Eric L. Schneider

IPC分类号： A61K31/4745 ,  A61K47/48 ,  C07D457/00 ,  C08G83/00 ,  C07D519/00 ,  A61K47/10 ,  A61K47/20 ,  C07D491/22 ,  C08G65/48

CPC分类号： A61K31/4745 ,  A61K47/10 ,  A61K47/20 ,  A61K47/60 ,  C07D457/00 ,  C07D491/22 ,  C07D519/00 ,  C08G65/329 ,  C08G65/33396 ,  C08G65/48 ,  C08G83/002

摘要： Conjugates of SN-38 that provide optimal drug release rates and minimize the formation of the corresponding glucuronate are described. The conjugates release SN-38 from a polyethylene glycol through a β-elimination mechanism.

公开(公告)号：US08765760B2

公开(公告)日：2014-07-01

申请号：US13347541

申请日：2012-01-10

申请人： John Emmerson Campbell ,  Philip Jones ,  Michael Charles Hewitt

发明人： John Emmerson Campbell ,  Philip Jones ,  Michael Charles Hewitt

IPC分类号： A61K31/495 ,  C07D457/00 ,  C07D471/00 ,  C07D495/00 ,  C07D497/00

CPC分类号： C07D519/00 ,  A61K31/4375 ,  A61K31/4745 ,  A61K31/4985 ,  A61K31/519 ,  A61K31/5383 ,  A61K45/06 ,  C07D471/04 ,  C07D487/04

摘要： Provided herein are compounds of formula (I): A-L-B  (I) and pharmaceutically acceptable salts and stereoisomers thereof, wherein A is wherein X is (i) CR1 or N, or (ii) O or NR2, each Y is independently N or CR3, and each Z is independently N or C, wherein R1, R2 and R3 are defined in the specification; L is a linker, and B is a multicyclic ring; methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. The compounds provided herein are inhibitors of phosphodiesterases and useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, e.g., neurological disorders, psychosis, schizophrenia, obesity and diabetes.

摘要翻译： 本文提供式（I）的化合物：其中A是其中X是（i）CR 1或N，或（ii）O或NR 2，其中每个Y独立地是N或CR 3 并且每个Z独立地为N或C，其中R1，R2和R3在说明书中定义; L为连接体，B为多环; 其合成方法，包含该化合物的药物组合物及其使用方法。 本文提供的化合物是磷酸二酯酶的抑制剂，并且可用于治疗，预防和/或治疗各种疾病，例如CNS障碍和代谢性疾病，例如神经障碍，精神病，精神分裂症，肥胖症和糖尿病。

公开(公告)号：US20100152223A1

公开(公告)日：2010-06-17

申请号：US12525240

申请日：2008-01-30

申请人： Zoran Ham ,  Andrej Premrl

发明人： Zoran Ham ,  Andrej Premrl

IPC分类号： A61K31/437 ,  C07D457/00 ,  A61P25/28 ,  A61P25/00

CPC分类号： C07D457/06

摘要： The present invention relates to a cabergoline crystal form L, its preparation from halogenated aromatic solvents and aliphatic hydrocarbons and to pharmaceutical compositions containing the new form.

摘要翻译： 本发明涉及一种卡麦角林晶形L，其由卤代芳族溶剂和脂族烃的制备以及含有新形式的药物组合物。

公开(公告)号：US20020002170A1

公开(公告)日：2002-01-03

申请号：US09906249

申请日：2001-07-16

发明人： Rainer M. Luond ,  Markus Banziger ,  Peter Frey

IPC分类号： A61K031/496 ,  A61K031/48 ,  A61K031/473 ,  C07D457/00

CPC分类号： C07D401/06 ,  C07D221/08 ,  C07D401/14 ,  C07D451/08 ,  C07D457/02

摘要： The invention provides a compound of formula I 1 wherein R, X, Y1 and Y2 are as defined in the description, and a process for preparing them. The compounds of formula I are useful as pharmaceuticals.

摘要翻译： 本发明提供式I化合物，其中R，X，Y 1和Y 2如说明书中所定义，及其制备方法。 式I的化合物可用作药物。

公开(公告)号：US5654313A

公开(公告)日：1997-08-05

申请号：US465674

申请日：1995-06-06

申请人： Anthony H. Cincotta ,  Albert H. Meier

发明人： Anthony H. Cincotta ,  Albert H. Meier

IPC分类号： A61K31/00 ,  A61K31/13 ,  A61K31/137 ,  A61K31/15 ,  A61K31/166 ,  A61K31/195 ,  A61K31/221 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/405 ,  A61K31/435 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4515 ,  A61K31/454 ,  A61K31/46 ,  A61K31/475 ,  A61K31/48 ,  A61K31/496 ,  A61K31/54 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/695 ,  A61K38/22 ,  A61K45/00 ,  A61K45/06 ,  A61P3/06 ,  A61P3/08 ,  A61P3/10 ,  C07D457/00 ,  C07D457/04 ,  G01N33/74 ,  A61K31/44 ,  A61K31/495

CPC分类号： G01N33/74 ,  A61K31/00 ,  A61K31/13 ,  A61K31/137 ,  A61K31/15 ,  A61K31/166 ,  A61K31/195 ,  A61K31/221 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/405 ,  A61K31/435 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4515 ,  A61K31/454 ,  A61K31/46 ,  A61K31/475 ,  A61K31/48 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/54 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/695 ,  A61K38/2257 ,  A61K45/06 ,  Y10S514/866 ,  Y10S514/909

摘要： A process for the long term modification and regulation of lipid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species. The dopamine agonist is administered at the time of, or just after the time of peak plasma prolactin concentration found in lean animals of the same species and the prolactin stimulator is administered at a time just before the plasma prolactin rhythm reaches its peak in lean animals. Insulin resistance, and hyperinsulinemia or hyperglycemia, or both, can also be controlled in humans on a long term basis by treatment corresponding to that of the treatment for obesity. The short term daily injections reset hormonal timing in the neural centers of the brain to produce long term effects.

摘要翻译： 长期改变和调节脂质和葡萄糖代谢的过程 - 通常通过给脊椎动物施用来减少肥胖，胰岛素抵抗和高胰岛素血症或高血糖或两者（这些是非胰岛素依赖型或II型糖尿病的标志） 动物或人类的多巴胺激动剂和催乳素刺激剂。 多巴胺激动剂和催乳素刺激剂分别以每天的剂量施用，取决于类似物种的脂肪和瘦成员的正常昼夜节律。 基于妊娠峰值催乳素的昼夜节律，峰值催乳素和糖皮质激素峰值，为类似物种的瘦胰岛素敏感成分建立的血液水平，以每日定时序列治疗肥胖物种的身体脂肪沉积物的减少。 多巴胺激动剂在同一物种的瘦动物中发现的血浆催乳素浓度峰值之前或之后施用，并且在等离子体催乳素节律在瘦动物中达到峰值之前的时间施用催乳素刺激剂。 胰岛素抵抗和高胰岛素血症或高血糖或两者也可以通过与肥胖症治疗相对应的治疗长期控制。 短期每日注射在脑神经中枢复位激素时间产生长期效应。

公开(公告)号：US5554623A

公开(公告)日：1996-09-10

申请号：US249808

申请日：1994-05-26

申请人： Anthony H. Cincotta ,  Albert H. Meier

发明人： Anthony H. Cincotta ,  Albert H. Meier

IPC分类号： A61K31/00 ,  A61K31/13 ,  A61K31/137 ,  A61K31/15 ,  A61K31/166 ,  A61K31/195 ,  A61K31/221 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/405 ,  A61K31/435 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4515 ,  A61K31/454 ,  A61K31/46 ,  A61K31/475 ,  A61K31/48 ,  A61K31/496 ,  A61K31/54 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/695 ,  A61K38/22 ,  A61K45/00 ,  A61K45/06 ,  A61P3/06 ,  A61P3/08 ,  A61P3/10 ,  C07D457/00 ,  C07D457/04 ,  G01N33/74 ,  A61K31/44

CPC分类号： G01N33/74 ,  A61K31/00 ,  A61K31/13 ,  A61K31/137 ,  A61K31/15 ,  A61K31/166 ,  A61K31/195 ,  A61K31/221 ,  A61K31/35 ,  A61K31/352 ,  A61K31/40 ,  A61K31/405 ,  A61K31/435 ,  A61K31/439 ,  A61K31/445 ,  A61K31/4515 ,  A61K31/454 ,  A61K31/46 ,  A61K31/475 ,  A61K31/48 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/54 ,  A61K31/5415 ,  A61K31/55 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/695 ,  A61K38/2257 ,  A61K45/06 ,  Y10S514/866 ,  Y10S514/909

摘要： A process for the long term modification and regulation of lipid and glucose metabolism--generally to reduce obesity, insulin resistance, and hyperinsulinemia or hyperglycemia, or both (these being the hallmarks of noninsulin dependent, or Type II diabetes)--by administration to a vertebrate, animal or human, of a dopamine agonist and a prolactin stimulator. The dopamine agonist and prolactin stimulator are administered in daily dosages, respectively, at a time of day dependent on the normal circadian rhythm of fat and lean members of a similar species. Decreases in body fat deposits result by treatment of an obese species on a daily timed sequence based on circadian rhythms of the peak prolactin, or peak prolactin and peak glucocorticosteroid, blood level established for lean insulin sensitive members of a similar species. The dopamine agonist is administered at the time of, or just after the time of peak plasma prolactin concentration found in lean animals of the same species and the prolactin stimulator is administered at a time just before the plasma prolactin rhythm reaches its peak in lean animals. Insulin resistance, and hyperinsulinemia or hyperglycemia, or both, can also be controlled in humans on a long term basis by treatment corresponding to that of the treatment for obesity. The short term daily injections reset hormonal timing in the neural centers of the brain to produce long term effects.

摘要翻译： 长期改变和调节脂质和葡萄糖代谢的过程 - 通常通过给脊椎动物施用来减少肥胖，胰岛素抵抗和高胰岛素血症或高血糖或两者（这些是非胰岛素依赖型或II型糖尿病的标志） 动物或人类的多巴胺激动剂和催乳素刺激剂。 多巴胺激动剂和催乳素刺激剂分别以每天的剂量施用，取决于类似物种的脂肪和瘦成员的正常昼夜节律。 基于妊娠峰值催乳素的昼夜节律，峰值催乳素和糖皮质激素峰值，为类似物种的瘦胰岛素敏感成分建立的血液水平，以每日定时序列治疗肥胖物种的身体脂肪沉积物减少。 多巴胺激动剂在同一物种的瘦动物中发现的血浆催乳素浓度峰值之前或之后施用，并且在等离子体催乳素节律在瘦动物中达到峰值之前的时间施用催乳素刺激剂。 胰岛素抵抗和高胰岛素血症或高血糖或两者也可以通过与肥胖症治疗相对应的治疗长期控制。 短期每日注射在脑神经中枢复位激素时间产生长期效应。