公开(公告)号：US08106056B2

公开(公告)日：2012-01-31

申请号：US11762239

申请日：2007-06-13

Applicant: Andrew C. McCreary ,  Gustaaf J. M. Van Scharrenburg ,  Martinus Th. M. Tulp

Inventor： Andrew C. McCreary ,  Gustaaf J. M. Van Scharrenburg ,  Martinus Th. M. Tulp

IPC: A61K31/497 ,  A61K31/195 ,  A61K31/16 ,  A61K31/135

CPC classification number: A61K31/137 ,  A61K31/198 ,  A61K31/496 ,  A61K2300/00

Abstract: The present invention relates to a composition containing bifeprunox or its N-oxide, or at least one pharmacologically acceptable salt thereof: and L-DOPA or at least one pharmacologically acceptable salt thereof, for simultaneous, separate or sequential use in the treatment of disorders requiring recovery of dopaminergic function, including Parkinson's disease and restless leg syndrome.

Abstract translation: 本发明涉及含有双岐杆菌或其N-氧化物或其至少一种药理学可接受的盐的组合物：和L-DOPA或其至少一种药理学上可接受的盐，用于同时，分开或顺序地用于治疗所需疾病 恢复多巴胺能功能，包括帕金森病和不宁腿综合征。

公开(公告)号：US07786126B2

公开(公告)日：2010-08-31

申请号：US11762206

申请日：2007-06-13

Applicant: Andrew C. McCreary ,  Gustaaf J. M. Van Scharrenburg ,  Martinus Th. M. Tulp

Inventor： Andrew C. McCreary ,  Gustaaf J. M. Van Scharrenburg ,  Martinus Th. M. Tulp

IPC: A61K31/497 ,  A61K31/195 ,  A61K31/135

CPC classification number: A61K31/137 ,  A61K31/198 ,  A61K31/496 ,  A61K2300/00

Abstract: A composition containing SLV308 or its N-oxide, or at least one pharmacologically acceptable salt thereof: and L-DOPA or at least one pharmacologically acceptable salt thereof, for simultaneous, separate or sequential use in the treatment of disorders requiring recovery of dopaminergic function using this composition, including Parkinson's disease and restless leg syndrome.

Abstract translation: 含有SLV308或其N-氧化物或其至少一种药学上可接受的盐的组合物：和L-DOPA或其至少一种药理学上可接受的盐，用于同时，分别或顺序地用于治疗需要恢复多巴胺能功能的疾病，其使用 这种组合物，包括帕金森病和不宁腿综合征。

公开(公告)号：US07244734B2

公开(公告)日：2007-07-17

申请号：US10946176

申请日：2004-09-22

Applicant: Wouter I. Iwema Bakker ,  Gustaaf J. M. Van Scharrenburg ,  Adrianus Van Den Hoogenband ,  Andrew C. McCreary

Inventor： Wouter I. Iwema Bakker ,  Gustaaf J. M. Van Scharrenburg ,  Adrianus Van Den Hoogenband ,  Andrew C. McCreary

IPC: A01N43/58 ,  A01N43/60 ,  A61K31/50 ,  A61K31/495 ,  C07D401/00

CPC classification number: C07D471/04

Abstract: The invention relates to hexahydro-pyrido[1,2-a]pyrazine derivatives having interesting neurokinin-NK1 receptor antagonistic activity. The invention also relates to methods for the preparation of these compounds, to pharmaceutical compositions containing a pharmacologically active amount of at least one of these compounds as an active ingredient, as well as to the use of these compositions for the treatment of disorders in which neurokinin receptors are involved. The invention relates to compounds represented by the general formula (1) wherein the symbols have the meanings as given in the description.

Abstract translation: 本发明涉及具有感兴趣的神经激肽-NN1受体拮抗活性的六氢 - 吡啶并[1,2-a]吡嗪衍生物。 本发明还涉及制备这些化合物的方法，含有药理学活性量的这些化合物中的至少一种作为活性成分的药物组合物，以及这些组合物用于治疗神经激肽 受体参与。 本发明涉及由通式（1）表示的化合物，其中符号具有说明书中给出的含义。

公开(公告)号：US06780864B1

公开(公告)日：2004-08-24

申请号：US09831149

申请日：2001-08-14

Applicant: Roelof Feenstra ,  Johannes A. M. Van Der Heijden ,  Cornelis G. Kruse ,  Stephen K. Long ,  Johannes Mos ,  Gerben M. Visser ,  Gustaaf J. M. Van Scharrenburg ,  Gerrit P. Toorop

Inventor： Roelof Feenstra ,  Johannes A. M. Van Der Heijden ,  Cornelis G. Kruse ,  Stephen K. Long ,  Johannes Mos ,  Gerben M. Visser ,  Gustaaf J. M. Van Scharrenburg ,  Gerrit P. Toorop

IPC: C07D26358

CPC classification number: C07D263/58 ,  C07D209/34 ,  C07D235/26 ,  C07D277/68 ,  C07D401/04 ,  C07D413/04 ,  C07D417/04 ,  Y02P20/55

Abstract: The invention relates to a group of novel piperazine and piperidine derivatives of formula (I), wherein: S1 is hydrogen, halogen, alkyl (1-3C), CN, CF3, OCF3, SCF3, alkoxy (1-3C), amino or mono- or dialkyl (1-3C) substituted amino, or hydroxy; X represents NR3, S, CH2, O, SO or SO2, wherein R3 is H or alkyl (1-3C); . . . Z represents ═C or —N; —R1 independently represent H or alkyl (1-3C), or R1 and R2 together can form a bridge 2 or 3 C-atoms; R4 is hydrogen or alkyl (1-3C); Q is methyl, ethyl, ethyl substituted with one or more fluorine atoms, cyclopropyl—methyl, optionally substituted with one or more fluorine atoms, and salts and prodrugs thereof. It has been found that these compounds have both partial dopamine D2-receptor agonism and partial serotonin 5-HT1A-receptor agonism mediated activities.

Abstract translation: 本发明涉及一组式（I）的新的哌嗪和哌啶衍生物，其中：S1为氢，卤素，烷基（1-3C），CN，CF3，OCF3，SCF3，烷氧基（1-3C），氨基或 单或二烷基（1-3C）取代的氨基或羟基; X表示NR 3，S，CH 2，O，SO或SO 2，其中R 3是H或烷基（1-3C）; 。 。 。 Z表示= C或-N; -R1独立地表示H或烷基（1-3C），或者R1和R2一起可以形成桥2或3个C原子; R4是氢或烷基（1-3C）; Q是甲基，乙基，被一个或多个氟原子取代的乙基，任选被一个或多个氟原子取代的环丙基甲基，及其盐和前药。 已经发现这些化合物具有部分多巴胺D2受体激动和部分5-羟色胺5-HT 1A受体激动介导的活性。

公开(公告)号：US07596407B2

公开(公告)日：2009-09-29

申请号：US11088880

申请日：2005-03-25

Applicant: Johanna A. Bouwstra ,  Dirk-Jan van den Berg ,  Frederik J. Verbaan ,  Rajkumar V. Conjeevaram ,  Ajay K. Banga ,  Viswatej Vemulapalli ,  Hendrik Teunissen ,  Gustaaf J. M. van Scharrenburg

Inventor： Johanna A. Bouwstra ,  Dirk-Jan van den Berg ,  Frederik J. Verbaan ,  Rajkumar V. Conjeevaram ,  Ajay K. Banga ,  Viswatej Vemulapalli ,  Hendrik Teunissen ,  Gustaaf J. M. van Scharrenburg

IPC: A61N1/30

CPC classification number: A61N1/325 ,  A61N1/0436 ,  A61N1/044

Abstract: The invention is related to an iontophoretic method for the delivery of a compound of the formula wherein R is defined herein, and pharmaceutically acceptable salts and prodrugs thereof; and, wherein the method comprises: (a) applying a transdermal device to the skin of a living body, wherein the transdermal device has a reservoir containing the compound of formula I or a composition thereof and optionally a pharmaceutically acceptable electrolyte; (b) causing current to flow through the skin so as to iontophoretically deliver the compound of formula I. The invention is further related to iontophoretic systems and to kits containing the iontophoretic system combined with one or more cartridges containing a compound of formula I, and to cartridges containing a compound of formula I.

Abstract translation: 本发明涉及用于递送下式化合物的离子电渗法：其中R如本文所定义，及其药学上可接受的盐和前药; 并且其中所述方法包括：（a）将透皮装置施加到活体的皮肤，其中所述透皮装置具有含有式I化合物或其组合物和任选的药学上可接受的电解质的储库; （b）引起电流流过皮肤，以离子电渗方式递送式I化合物。本发明还涉及离子电渗疗法系统和含有与一种或多种含有式I化合物的药筒组合的离子电渗疗法系统的试剂盒，以及 包含式I化合物的药筒。

公开(公告)号：US20090215796A1

公开(公告)日：2009-08-27

申请号：US12391393

申请日：2009-02-24

Applicant: Juliana B. Bronzova ,  Gustaaf J. M. Van Scharrenburg ,  Serge V. Van De Witte ,  Hendrik Teunissen

Inventor： Juliana B. Bronzova ,  Gustaaf J. M. Van Scharrenburg ,  Serge V. Van De Witte ,  Hendrik Teunissen

IPC: A61K31/496 ,  A61P25/16 ,  A61P25/00

CPC classification number: A61K31/496

Abstract: The present invention is directed to compositions, kits, and methods for a titration schedule to facilitate the treatment of a central nervous system condition or disorder by administering a plurality of dosage units of a composition comprising a compound 7-(4-methyl)-1-piperazinyl-2(3H)-benzoxazolone (INN pardoprunox).

Abstract translation: 本发明涉及用于滴定方案的组合物，试剂盒和方法，以便于通过施用包含化合物7-（4-甲基）-1的组合物的多个剂量单位来治疗中枢神经系统病症或病症 - 哌嗪基-2（3H） - 苯并恶唑酮（INN pardoprunox）。

公开(公告)号：US07297699B2

公开(公告)日：2007-11-20

申请号：US11129465

申请日：2005-05-16

Applicant: Roelof W. Feenstra ,  Johannes A. M. van der Heijden ,  Cornelis G. Kruse ,  Stephen K. Long ,  Gustaaf J. M. van Scharrenburg

Inventor： Roelof W. Feenstra ,  Johannes A. M. van der Heijden ,  Cornelis G. Kruse ,  Stephen K. Long ,  Gustaaf J. M. van Scharrenburg

IPC: A61K31/496 ,  C07D263/58 ,  C07D277/68

CPC classification number: C07D263/58 ,  C07D413/12

Abstract: The invention relates to a group of novel piperazine and piperidine derivatives of the formula wherein Y is hydrogen, halogen, alkyl (1-3C), or CN, CF3, OCF3, SCF3, alkoxy(1-3C), amino or mono- or dialkyl(1-3C) substituted amino or hydroxy, X is O, S, SO or SO2, —Z represents —C, ═C or —N, R1 and R2 independently represent hydrogen or alkyl (1-3C), Q is benzyl or 2-, 3- or 4-pyridylmethyl, wich groups may be substited with one or more more substituents from the group halogen, nitro, cyano, amino, mono- or di (1-3C)alkylamino, (1-3C) alkoxy, CF3, OCF3, SCF3, (1-4C)-alkyl, (1-3C)alkylsulfonyl or hydroxy, and salts and prodrugs thereof. It has been found that these compounds have interesting pharmacological properties due to a combination of (partial) agonism towards the members of the dopamine D2-receptor subfamily and affinity for relevant serotonin and/or noradrenergic receptors

Abstract translation: 本发明涉及下式的一组新的哌嗪和哌啶衍生物其中Y是氢，卤素，烷基（1-3C）或CN，CF 3，OCF 3， >，SCF 3，烷氧基（1-3C），氨基或单或二烷基（1-3C）取代的氨基或羟基，X是O，S，SO或SO 2， SUB，-Z表示-C，-C或-N，R 1和R 2独立地表示氢或烷基（1-3C），Q是苄基或2 - ，3-或4-吡啶基甲基，其基团可以被一个或多个取代基取代，所述取代基可以是卤素，硝基，氰基，氨基，单或二（1-3C）烷基氨基，（1-3C）烷氧基，CF OCF 3，SCF 3，（1-4C） - 烷基，（1-3C）烷基磺酰基或羟基，及其盐和前体药物 其中。 已经发现，这些化合物由于（多）向多巴胺D 2受体亚家族的成员的组合以及对相关的5-羟色胺和/或去甲肾上腺素能受体的亲和力而具有令人感兴趣的药理学性质

公开(公告)号：US06911448B2

公开(公告)日：2005-06-28

申请号：US10257677

申请日：2001-05-10

Applicant: Roelof W. Feenstra ,  Johannes A. M. van der Heijden ,  Cornelis G. Kruse ,  Stephen K. Long ,  Gustaaf J. M. van Scharrenburg

Inventor： Roelof W. Feenstra ,  Johannes A. M. van der Heijden ,  Cornelis G. Kruse ,  Stephen K. Long ,  Gustaaf J. M. van Scharrenburg

IPC: C07D413/10 ,  A61K31/423 ,  A61K31/428 ,  A61K31/4439 ,  A61K31/445 ,  A61K31/4523 ,  A61K31/496 ,  A61P25/00 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P25/30 ,  A61P43/00 ,  C07D263/54 ,  C07D263/58 ,  C07D277/62 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  A61K31/454

CPC classification number: C07D263/58 ,  C07D413/12

Abstract: The invention relates to a group of novel piperazine and piperidine derivatives of the formula wherein Y is hydrogen, halogen, alkyl (1-3C), or CN, CF3, OCF3, SCF3, alkoxy(1-3C), amino or mono- or dialkyl(1-3C) substituted amino or hydroxy, X is O, S, SO or SO2, ---Z represents —C, ═C or —N, R1 and R2 independently represent hydrogen or alkyl (1-3C), Q is benzyl or 2-, 3- or 4-pyridylmethyl, wich groups may be substited with one or more more substituents from the group halogen, nitro, cyano, amino, mono- or di (1-3C)alkylamino, (1-3C) alkoxy, CF3, OCF3, SCF3, (1-4C)-alkyl, (1-3C)alkylsulfonyl or hydroxy, and salts and prodrugs thereof. It has been found that these compounds have interesting pharmacological properties due to a combination of (partial) agonism towards the members of the dopamine D2-receptor subfamily and affinity for relevant serotonin and/or noradrenergic receptors

Abstract translation: 本发明涉及下式的一组新的哌嗪和哌啶衍生物其中Y是氢，卤素，烷基（1-3C）或CN，CF 3，OCF 3， >，SCF 3，烷氧基（1-3C），氨基或单或二烷基（1-3C）取代的氨基或羟基，X是O，S，SO或SO 2， Z表示-C，-C或-N，R 1和R 2独立地表示氢或烷基（1-3C），Q表示苄基 或2-，3-或4-吡啶基甲基，其可以被一个或多个取代基取代为卤素，硝基，氰基，氨基，单或二（1-3C）烷基氨基，（1-3C）烷氧基 ，CF 3 3，OCF 3，SCF 3，（1-4C） - 烷基，（1-3C）烷基磺酰基或羟基，和盐 及其前体药物。 已经发现，这些化合物由于（多）向多巴胺D 2受体亚家族的成员的组合以及对相关的5-羟色胺和/或去甲肾上腺素能受体的亲和力而具有令人感兴趣的药理学性质

公开(公告)号：US06793928B1

公开(公告)日：2004-09-21

申请号：US09555139

申请日：2000-12-13

Applicant: Gustaaf J. M. van Scharrenburg ,  Rudi Brands ,  Lolke de Haan ,  Willem Ronald Verweij ,  Jan C. Wilschut ,  Etienne Agsteribbe

Inventor： Gustaaf J. M. van Scharrenburg ,  Rudi Brands ,  Lolke de Haan ,  Willem Ronald Verweij ,  Jan C. Wilschut ,  Etienne Agsteribbe

IPC: A61K39108

CPC classification number: C07K14/005 ,  A61K38/00 ,  A61K39/12 ,  A61K39/145 ,  A61K39/39 ,  A61K2039/541 ,  A61K2039/543 ,  A61K2039/55544 ,  C07K14/245 ,  C12N2760/16122 ,  C12N2760/16134 ,  C12N2760/16222 ,  C12N2760/16234

Abstract: The present invention relates to a vaccine containing at least one particulate immunogen and an adjuvanting amount of B subunits of heat-labile enterotoxin characteristic of E. Coli. More in particular, this invention relates to vaccines wherein the adjuvanting LTB is free from contaminating A subunits or holotoxin. To this end, preferably, use is made of LTB prepared by recombinant DNA techniques. The particulate immunogens can relate to or can be derived from e.g. viruses, bacteria or fungi. This vaccine is particularly suitable for the induction of a protective response against said particulate immunogen upon mucosal (e.g. intra-nasal) administration. It was found that such administration results in both systemic and mucosal protection against the pathogen to which the particulate immunogen relates.

Abstract translation: 本发明涉及含有至少一种颗粒免疫原和佐剂量的大肠杆菌特征的热不稳定肠毒素B亚基的疫苗。 更具体地，本发明涉及疫苗，其中佐剂LTB不含有污染的A亚单位或全毒素。 为此，优选使用通过重组DNA技术制备的LTB。 颗粒免疫原可以涉及或可以衍生自例如 病毒，细菌或真菌。 该疫苗特别适用于在粘膜（例如鼻内）施用时诱导针对所述颗粒免疫原的保护性应答。 发现这种给药导致针对颗粒免疫原所涉及的病原体的全身和粘膜保护。

公开(公告)号：US07678789B2

公开(公告)日：2010-03-16

申请号：US11349910

申请日：2006-02-09

Applicant: Roelof W. Feenstra ,  Hiskias G. Keizer ,  Maria L. Pras-Raves ,  Bernard J Van Vliet ,  Gustaaf J. M. Van Scharrenburg

Inventor： Roelof W. Feenstra ,  Hiskias G. Keizer ,  Maria L. Pras-Raves ,  Bernard J Van Vliet ,  Gustaaf J. M. Van Scharrenburg

IPC: A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/4535 ,  A61K31/4436 ,  A61K31/41 ,  C07D417/04 ,  C07D413/04 ,  C07D285/01

CPC classification number: C07D285/01 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

Abstract: The present invention relates to 5-imino-5H-[1,2,4]-dithiazol-3-yl-amine and [1,2,4]-dithiazolidine-3,5-diylidene-diamine derivatives as inducers of gluthathione-S-transferase (GST) and NADPH quinone oxidoreductase (NQO), to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said [1,2,4]-dithiazoli(di)ne derivatives. The invention also relates to the use of a compound disclosed herein for the treatment of adverse conditions associated with cytotoxicity in general and apoptosis in particular. The invention relates to compounds of the general formula (I): wherein wherein the symbols have the meanings given in the specification.

Abstract translation: 本发明涉及5-亚氨基-5H- [1,2,4] - 二噻唑-3-基 - 胺和[1,2,4] - 二噻唑烷-3,5-二亚胺基二胺衍生物作为谷胱甘肽 - S-转移酶（GST）和NADPH醌氧化还原酶（NQO），用于制备这些化合物的方法和用于合成所述[1,2,4] - 二噻唑（di）ne衍生物的新中间体。 本发明还涉及本文公开的化合物用于治疗与一般细胞毒性和特别是细胞凋亡相关的不利条件的用途。 本发明涉及通式（I）的化合物：其中符号具有说明书中给出的含义。