公开(公告)号：US06271234B1

公开(公告)日：2001-08-07

申请号：US09266534

申请日：1999-03-11

申请人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri ,  Elena Poggesi

发明人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri ,  Elena Poggesi

IPC分类号： A61K31496

CPC分类号： C07D213/75

摘要： Disclosed herein are novel compounds and methods for the treatment of disorders of the lower urinary tract. The novel compounds are 1,4-disubstituted piperazine derivatives. The methods comprise the administration of the novel compounds of the invention, and other compounds that bind to 5HT1A receptors, for treating disorders of the lower urinary tract.

摘要翻译： 本文公开了用于治疗下尿路疾病的新型化合物和方法。 新化合物是1,4-二取代的哌嗪衍生物。 所述方法包括施用本发明的新化合物和结合5HT1A受体的其它化合物，用于治疗下尿路的疾病。

公开(公告)号：US08580962B2

公开(公告)日：2013-11-12

申请号：US13180166

申请日：2011-07-11

申请人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri ,  Davide Graziani ,  Carlo De Toma ,  Katia Dimitrova Karamfilova

发明人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri ,  Davide Graziani ,  Carlo De Toma ,  Katia Dimitrova Karamfilova

IPC分类号： A61K31/44 ,  C07D213/00

CPC分类号： C07D498/10 ,  C07D491/10

摘要： The invention is directed to methods of using antagonists selective for the metabotropic mGlu5 receptor to treat conditions of neuromuscular dysfunction of the lower urinary tract in a mammal. Provided are methods of treating a mammal suffering from a condition of neuromuscular dysfunction of the lower urinary tract by administering a selective mGlu5 antagonist. The selective mGlu5 antagonist may be administered alone or in combination with one or more additional therapeutic agents for treating such a condition. Also provided are methods of identifying selective mGlu5 antagonists that are useful for treating neuromuscular dysfunction of the lower urinary tract in a mammal. Methods for treating migraine and gastroesophageal reflux disease (GERD) using selective mGlu5 antagonists are also disclosed.

摘要翻译： 本发明涉及使用选择性代谢型mGlu5受体的拮抗剂治疗哺乳动物下泌尿道神经肌肉功能障碍的方法。 提供了通过施用选择性mGlu5拮抗剂治疗患有下尿路神经肌肉功能障碍的哺乳动物的方法。 选择性mGlu5拮抗剂可以单独施用或与一种或多种用于治疗这种病症的其它治疗剂组合施用。 还提供鉴定可用于治疗哺乳动物下泌尿道神经肌肉功能障碍的选择性mGlu5拮抗剂的方法。 还公开了使用选择性mGlu5拮抗剂治疗偏头痛和胃食管反流病（GERD）的方法。

公开(公告)号：US20120059015A1

公开(公告)日：2012-03-08

申请号：US13180166

申请日：2011-07-11

申请人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri ,  Davide Graziani ,  Carlo De Toma ,  Katia Dimitrova Karamfilova

发明人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri ,  Davide Graziani ,  Carlo De Toma ,  Katia Dimitrova Karamfilova

IPC分类号： A61K31/423 ,  A61K31/4439 ,  A61P1/04 ,  A61K31/427 ,  A61P13/10 ,  A61P13/00 ,  C07D498/10 ,  A61K31/497

CPC分类号： C07D498/10 ,  C07D491/10

摘要： The invention is directed to methods of using antagonists selective for the metabotropic mGlu5 receptor to treat conditions of neuromuscular dysfunction of the lower urinary tract in a mammal. Provided are methods of treating a mammal suffering from a condition of neuromuscular dysfunction of the lower urinary tract by administering a selective mGlu5 antagonist. The selective mGlu5 antagonist may be administered alone or in combination with one or more additional therapeutic agents for treating such a condition. Also provided are methods of identifying selective mGlu5 antagonists that are useful for treating neuromuscular dysfunction of the lower urinary tract in a mammal. Methods for treating migraine and gastroesophageal reflux disease (GERD) using selective mGlu5 antagonists are also disclosed.

摘要翻译： 本发明涉及使用选择性代谢型mGlu5受体的拮抗剂治疗哺乳动物下泌尿道神经肌肉功能障碍的方法。 提供了通过施用选择性mGlu5拮抗剂治疗患有下尿路神经肌肉功能障碍的哺乳动物的方法。 选择性mGlu5拮抗剂可以单独施用或与一种或多种用于治疗这种病症的其它治疗剂组合施用。 还提供鉴定可用于治疗哺乳动物下泌尿道神经肌肉功能障碍的选择性mGlu5拮抗剂的方法。 还公开了使用选择性mGlu5拮抗剂治疗偏头痛和胃食管反流病（GERD）的方法。

公开(公告)号：US20120028931A1

公开(公告)日：2012-02-02

申请号：US12882169

申请日：2010-09-14

申请人： Amedeo Leonardi ,  Carlo Riva ,  Luciano Guarneri ,  Davide Graziani ,  Fabio Marinoni ,  Gianni Motta ,  Ilaria Bettinelli

发明人： Amedeo Leonardi ,  Carlo Riva ,  Luciano Guarneri ,  Davide Graziani ,  Fabio Marinoni ,  Gianni Motta ,  Ilaria Bettinelli

IPC分类号： A61K31/616 ,  A61K31/4545 ,  C07D409/14 ,  C07D401/14 ,  C07D417/14 ,  C07D413/14 ,  A61K31/497 ,  A61K31/454 ,  A61K31/4439 ,  A61K31/55 ,  C07D495/04 ,  A61K31/4725 ,  A61K31/46 ,  A61K31/517 ,  A61P13/00 ,  A61P13/10 ,  A61P25/00 ,  A61P25/22 ,  A61P25/30 ,  A61P25/04 ,  A61P43/00 ,  A61P1/04 ,  C07D405/14

CPC分类号： C07D405/14 ,  C07D403/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： Compounds I (R1 is an optionally substituted C1-C13 heteromonocyclic, heterobicyclic or heterotricyclic group containing from 1 to 5 heteroatoms selected from N, O and S; R2 is H, an optionally substituted monocyclic aromatic group, or a C1-C5 heteroaromatic group containing from 1 to 4 heteroatoms selected from N, O and S; R3 is an optionally substituted C1-C13 heteromonocyclic, heterobicyclic or heterotricyclic group containing from 1 to 5 heteroatoms selected from N, O and S; an optionally substituted mono-, bi- or tricyclic C6-C14 aryl group, an optionally substituted C3-C6 cycloalkyl group, or an optionally substituted C3-C6 cycloalkenyl group; each R4, independently for each position capable of substitution, is H or C1-C6 alkyl; R5 is H, halogen or C1-C6 alkyl; m is 0, 1 or 2; n is 0, 1 or 2; p is 0, 1, 2, 3, 4, 5, or 6; and is an optional double bond) and their enantiomers, diastereomers, N-oxides and pharmaceutically acceptable salts, and pharmaceutical compositions containing them, are useful for the treatment of neuromuscular dysfunction of the lower urinary tract and also for the treatment of gastrooesophageal reflux disease; anxiety disorder; abuse, substance dependence and substance withdrawal disorders; neuropathic pain disorder, migraine and fragile X syndrome disorders.

摘要翻译： 化合物I（R1是含有1至5个选自N，O和S的杂原子的任选取代的C 1 -C 13杂单环，杂双环或异三环基团; R 2是H，任选取代的单环芳族基团或含有C 1 -C 5杂芳族基团 1至4个选自N，O和S的杂原子; R 3是任选取代的含有1至5个选自N，O和S的杂原子的C1-C13杂单环，杂双环或异三环;任选取代的单 - ，二 - 三环C 6 -C 14芳基，任选取代的C 3 -C 6环烷基或任选取代的C 3 -C 6环烯基;每个R 4独立地为每个能够取代的位置是H或C 1 -C 6烷基; R 5是H，卤素 或C 1 -C 6烷基; m为0,1或2; n为0,1或2; p为0,1,2,3,4,5或6;并且为任选的双键）及其对映异构体， 非对映异构体，N-氧化物和药学上可接受的盐，以及含有的药物组合物 它们可用于治疗下尿路神经肌肉功能障碍，也可用于治疗胃食管反流病; 焦虑症 滥用，物质依赖和物质戒断障碍; 神经性疼痛障碍，偏头痛和脆弱X综合征障碍。

公开(公告)号：US20070270436A1

公开(公告)日：2007-11-22

申请号：US11751322

申请日：2007-05-21

申请人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri

发明人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri

IPC分类号： A61K31/496 ,  C07D403/02 ,  C07D405/02

CPC分类号： C07D403/04 ,  C07D235/06 ,  C07D295/13 ,  C07D319/16 ,  C07D405/12 ,  C07D413/12

摘要： Described are novel amino- and iminoalkyl piperazines having affinity for serotonergic receptors and pharmacological compositions thereof. These compounds and their isomers, including optical isomers, enantiomers, diastereomers, N-oxides, polymorphs, hydrates, solvates and pharmaceutically acceptable salts are useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract and CNS diseases and/or disorders associated with 5-HT1A receptor dysfunction.

摘要翻译： 描述了对5-羟色胺能受体具有亲和力的新型氨基和亚氨基烷基哌嗪及其药理学组合物。 这些化合物及其异构体，包括光学异构体，对映异构体，非对映异构体，N-氧化物，多晶型物，水合物，溶剂合物和药学上可接受的盐可用于治疗下尿路神经肌肉功能障碍和CNS疾病和/或相关疾病的患者 具有5-HT 1A受体功能障碍。

公开(公告)号：US5453518A

公开(公告)日：1995-09-26

申请号：US45420

申请日：1993-04-09

申请人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri

发明人： Amedeo Leonardi ,  Gianni Motta ,  Carlo Riva ,  Luciano Guarneri

IPC分类号： A61K31/35 ,  A61K31/352 ,  A61K31/385 ,  A61K31/47 ,  A61P13/02 ,  A61P15/00 ,  C07D311/30 ,  C07D405/06 ,  C07D405/12 ,  C07D409/12 ,  C07D311/22 ,  C07D339/08

CPC分类号： C07D405/12 ,  A61K31/35 ,  A61K31/385 ,  A61K31/47 ,  C07D311/30 ,  C07D409/12

摘要： A compound of the general formula: ##STR1## wherein X represents --CO--, --COO--, --CONH--, --CON(CH.sub.3)--, --CH.sub.2 NH--, --CH.sub.2 N(CH.sub.3)--, --CH.sub.2 NHCO--, --CH.sub.2 N(CH.sub.3)CO--, --CH.sub.2 O--, --CH.sub.2 S--, --CH.sub.2 SO--, or --CH.sub.2 SO.sub.2 --; n represents an integer from 1 to 4; and B represents one of the following groups: ##STR2## wherein R.sub.1 represents a lower alkyl (C.sub.1 -C.sub.4) group; R.sub.2 represents a hydrogen atom or a lower alkyl (C.sub.1 -C.sub.4) group; R.sub.3 represents a hydrogen atom or OR.sub.4 group wherein R.sub.4 represents a lower alkyl (C.sub.1 -C.sub.4) group; p represents an integer from 1 to 3; and Y represents a valence bond (Y1), or one of the following groups: ##STR3## wherein R.sub.2 is as above defined as well as the enantiomers, diastereomers, N-oxides, prodrugs, metabolites, prodrugs of metabolites, and pharmaceutically acceptable salts of these compounds. The compounds are long-lasting antispasmodic therapeutic agents and are particularly useful for the treatment of lower urinary tract disorders.

摘要翻译： 其中X表示-CO - ， - COO - ， - CONH - ， - CON（CH 3） - ， - CH 2 NH-， - CH 2 N（CH 3） - ， - CH 2 NHCO-， - CH 2 N（ CH3）CO-，-CH2O-，-CH2S-，-CH2SO-或-CH2SO2-; n表示1〜4的整数， B表示下列基团之一：其中R 1表示低级烷基（C 1 -C 4）基团; R2表示氢原子或低级烷基（C1-C4）基团; R3表示氢原子或OR4基团，其中R4表示低级烷基（C1-C4）基团; p表示1〜3的整数， Y表示价键（Y1）或以下组之一：图像（Y2）（Y3）（B2）（B3）其中R2如上所定义，以及 对映异构体，非对映体，N-氧化物，前体药物，代谢物，代谢物前药以及这些化合物的药学上可接受的盐。 这些化合物是持久的抗痉挛治疗剂，并且特别可用于治疗下尿路疾病。

公开(公告)号：US06440963B1

公开(公告)日：2002-08-27

申请号：US09969538

申请日：2001-10-01

申请人： Amedeo Leonardi ,  Rodolfo Testa ,  Luciano Guarneri

发明人： Amedeo Leonardi ,  Rodolfo Testa ,  Luciano Guarneri

IPC分类号： A61K3154

CPC分类号： C12Q1/26 ,  A61K31/00 ,  A61K31/18 ,  A61K31/365 ,  A61K31/415 ,  A61K31/4162 ,  A61K31/42 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/5415 ,  G01N2333/90245 ,  G01N2500/10

摘要： The treatment of neuromuscular dysfunction of the lower urinary tract by compounds which selectively inhibit the COX-2 isozyme is described. The compounds concerned inhibit the COX-2 isozyme with a potency at least 10-fold, and preferably at least 100-fold, greater than their potency on the COX-1 isozyme.

摘要翻译： 描述了通过选择性抑制COX-2同功酶的化合物治疗下尿路神经肌肉功能障碍。 所涉及的化合物以COX-1同功酶的效力至少抑制COX-2同功酶的效力至少10倍，优选至少100倍。

公开(公告)号：US20080153888A1

公开(公告)日：2008-06-26

申请号：US11962552

申请日：2007-12-21

申请人： Amedeo Leonardi ,  Luciano Guarneri ,  Patrizia Angelico

发明人： Amedeo Leonardi ,  Luciano Guarneri ,  Patrizia Angelico

IPC分类号： A61K31/4245 ,  A61K31/198 ,  A61K31/197 ,  A61P13/02 ,  A61K31/192 ,  A61K31/41

CPC分类号： A61K45/06 ,  A61K31/197

摘要： The invention relates to a method of treating at least one symptom of lower urinary tract disease in a subject in need of treatment comprising administering to said subject a combination of an α2δ calcium channel subunit (A2d) ligand and a non-steroidal anti-inflammatory drug (NSAID), wherein the administered amounts of A2d ligand and NSAID together comprise a therapeutically effective amount of an active combination of agents. The combination of A2d ligand and NSAID can result in a synergistic therapeutic effect, wherein the combined effect is greater than the additive effect resulting from separate, single administration of A2d ligand or NSAID. Combination of A2d ligand and NSAID is particularly useful in treatment of lower urinary tract disease which manifests symptoms of urinary incontinence.

摘要翻译： 本发明涉及一种治疗需要治疗的受试者的下尿路疾病的至少一种症状的方法，其包括向所述受试者施用α2-δ钙通道亚基（A2d）配体 和非甾体抗炎药（NSAID），其中所述A2d配体和NSAID的给药量一起包含治疗有效量的药剂的活性组合。 A2d配体和NSAID的组合可以产生协同的治疗效果，其中联合作用大于单独单次施用A2d配体或NSAID引起的加和效应。 A2d配体和NSAID的组合对尿失禁症状的下尿路疾病的治疗特别有用。

公开(公告)号：US20050165025A1

公开(公告)日：2005-07-28

申请号：US11041086

申请日：2005-01-21

申请人： Amedeo Leonardi ,  Luciano Guarneri ,  Rodolfo Testa

发明人： Amedeo Leonardi ,  Luciano Guarneri ,  Rodolfo Testa

IPC分类号： A61K31/495 ,  A61K31/496 ,  A61K45/06

CPC分类号： A61K31/451 ,  A61K31/4418 ,  A61K31/454 ,  A61K31/495 ,  A61K31/496 ,  A61K45/06 ,  A61K2300/00

摘要： Described is the novel use of combinations of molecules endowed with antagonistic activity toward the serotonin 5-HT1A or 5-HT1B receptor, and of molecules simultaneously endowed with antagonistic activity at both said receptors. These compounds and their enantiomers, diastereoisomers, N-oxides, polymorphs, solvates, prodrugs, and pharmaceutically acceptable salts are useful in the treatment of patients with neuromuscular dysfunction of the lower urinary tract. Also described are the pharmaceutical compositions containing them. There is also provided a method of therapeutic treatment of urinary disorders in a mammal, including man, comprising administering to said mammal, including man, in need of such treatment, a therapeutically effective amount of a composition according to the invention.

摘要翻译： 描述了赋予对5-羟色胺5-HT 1A或5-HT 1B 1受体具有拮抗活性的分子的组合以及同时具有拮抗活性的分子的组合的新颖用途 两者都是受体。 这些化合物及其对映体，非对映异构体，N-氧化物，多晶型物，溶剂合物，前药和药学上可接受的盐可用于治疗下泌尿道神经肌肉功能障碍的患者。 还描述了含有它们的药物组合物。 还提供了包括人在内的哺乳动物的尿失调的治疗性治疗方法，其包括对需要这种治疗的所述哺乳动物包括人施用治疗有效量的根据本发明的组合物。