公开(公告)号：US20050209273A1

公开(公告)日：2005-09-22

申请号：US11133678

申请日：2005-05-20

申请人： Dominique Mabire ,  Marc Venet ,  Sophie Coupa ,  Alain Poncelet ,  Anne Lesage

发明人： Dominique Mabire ,  Marc Venet ,  Sophie Coupa ,  Alain Poncelet ,  Anne Lesage

IPC分类号： A61K31/47 ,  A61K31/4704 ,  A61K31/4709 ,  A61K31/473 ,  A61K31/4741 ,  A61K31/4743 ,  A61K31/4745 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61P3/08 ,  A61P5/00 ,  A61P9/10 ,  A61P25/00 ,  A61P25/04 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/20 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/30 ,  A61P29/00 ,  A61P43/00 ,  C07D215/04 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D215/22 ,  C07D215/227 ,  C07D215/36 ,  C07D215/38 ,  C07D215/48 ,  C07D215/50 ,  C07D215/54 ,  C07D215/60 ,  C07D219/02 ,  C07D221/10 ,  C07D221/12 ,  C07D221/16 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/06 ,  C07D453/06 ,  C07D471/04 ,  C07D487/04 ,  C07D491/04 ,  C07D491/048 ,  C07D491/052 ,  C07D495/04 ,  C07F7/08 ,  C07F7/10 ,  C07D453/02 ,  C07D43/02

CPC分类号： C07D215/04 ,  C07D215/12 ,  C07D215/14 ,  C07D215/18 ,  C07D215/227 ,  C07D215/36 ,  C07D215/38 ,  C07D215/48 ,  C07D215/50 ,  C07D215/54 ,  C07D221/10 ,  C07D221/12 ,  C07D221/16 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12 ,  C07D417/04 ,  C07D453/06 ,  C07D471/04 ,  C07D491/04 ,  C07D495/04 ,  C07F7/0812

摘要： The present invention concerns compounds of formula. In a preferable embodiment, X represents O; R1 represents C1-4alkyl; cycloC3-12alkyl or (cycloC3-12alkyl)C1-6alkyl, wherein one or more hydrogen atoms in a C1-6alkyl-moiety or in a cycloC3-12alkyl-moiety optionally may be replaced by C1-6alkyloxy, aryl, halo or thienyl; R2 represents hydrogen; halo; C1-6alkyl or amino; R3 and R4 each independently represent hydrogen or C1-6alkyl; or R2 and R3 may be taken together to form —R2—R3—, which represents a bivalent radical of formula -Z4-CH2—CH2—CH2— or -Z4-CH2—CH2— with Z4 being O or NR11 wherein R11 is C1-6alkyl; and wherein each bivalent radical is optionally substituted with C1-6alkyl; or R3 and R4 may be taken together to form a bivalent radical of formula —CH2—CH2—CH2—CH2—; R5 represents hydrogen; Y represents O; and aryl represents phenyl optionally substituted with halo. The invention also relates to the use of a compound according to the invention as a medicament and in the manufacture of a medicament for treating or preventing glutamate-induced diseases of the central nervous system, as well as formulations comprising such a compound and processes for preparing such a compound.

公开(公告)号：US20070254904A1

公开(公告)日：2007-11-01

申请号：US11547705

申请日：2005-04-04

申请人： Frans Janssens ,  Bruno Schoentjes ,  Sophie Coupa ,  Alain Poncelet ,  Yvan Simonnet

发明人： Frans Janssens ,  Bruno Schoentjes ,  Sophie Coupa ,  Alain Poncelet ,  Yvan Simonnet

IPC分类号： A61K31/438 ,  A61P1/12 ,  A61P13/00 ,  A61P25/18 ,  A61P25/24 ,  C07D401/02

CPC分类号： C07D471/10

摘要： This invention concerns substituted diaza-spiro-[4.5]-decane derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK2 antagonistic activity, a combined NK1/NK3 antagonistic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment and/or prophylaxis of schizophrenia, emesis, anxiety and depression, irritable bowel syndrome (IBS), circadian rhythm disturbances, pre-eclampsia, nociception, pain, in particular visceral and neuropathic pain, pancreatitis, neurogenic inflammation, asthma, chronic obstructive pulmonary disease (COPD) and micturition disorders such as urinary incontinence. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

摘要翻译： 本发明涉及具有神经激肽拮抗活性，特别是NK 1拮抗活性的组合NK 1 / NK 2的取代的二氮 - 螺 - [4.5] - 癸烷衍生物 组合的NK 1 / NK 3拮抗活性和组合的NK 1 / NK 2拮抗活性， 拮抗活性，它们的制备，包含它们的组合物及其作为药物的用途，特别是用于治疗和/或预防精神分裂症，呕吐，焦虑和抑郁症，肠易激综合征（肠易激综合征 IBS），昼夜节律障碍，先兆子痫，伤害感受，疼痛，特别是内脏和神经性疼痛，胰腺炎，神经源性炎症，哮喘，慢性阻塞性肺病（COPD）和排尿障碍如尿失禁。 根据本发明的化合物可以由通式（I）表示，并且还包括其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。

公开(公告)号：US20070232636A1

公开(公告)日：2007-10-04

申请号：US11547889

申请日：2005-04-04

申请人： Frans Janssens ,  Bruno Schoentjes ,  Sophie Coupa ,  Alain Poncelet ,  Yvan Simonnet

发明人： Frans Janssens ,  Bruno Schoentjes ,  Sophie Coupa ,  Alain Poncelet ,  Yvan Simonnet

IPC分类号： A61K31/438 ,  C07D215/00

CPC分类号： C07D471/10 ,  C07D519/00

摘要： This invention concerns substituted diaza-spiro-[5.5]-undecane derivatives having neurokinin antagonistic activity, in particular NK1 antagonistic activity, a combined NK1/NK2 antagonistic activity, a combined NK1/NK3 antagonistic activity and a combined NK1/NK2/NK3 antagonistic activity, their preparation, compositions comprising them and their use as a medicine, in particular for the treatment and/or prophylaxis of schizophrenia, emesis, anxiety and depression, irritable bowel syndrome (IBS), circadian rhythm disturbances, pre-eclampsia, nociception, pain, in particular visceral and neuropathic pain, pancreatitis, neurogenic inflammation, asthma, COPD and micturition disorders such as urinary incontinence. The compounds according to the invention can be represented by general Formula (I) and comprises also the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the N-oxide form thereof and prodrugs thereof, wherein all substituents are defined as in Claim 1.

摘要翻译： 本发明涉及具有神经激肽拮抗活性，特别是NK 1拮抗活性的组合NK 1 / NK 2的取代的二氮 - 螺 - [5.5] - 十一烷衍生物 组合的NK 1 / NK 3拮抗活性和组合的NK 1 / NK 2拮抗活性， 拮抗活性，它们的制备，包含它们的组合物及其作为药物的用途，特别是用于治疗和/或预防精神分裂症，呕吐，焦虑和抑郁症，肠易激综合征（肠易激综合征 IBS），昼夜节律紊乱，先兆子痫，伤害感受，疼痛，特别是内脏和神经性疼痛，胰腺炎，神经源性炎症，哮喘，COPD和排尿障碍如尿失禁。 根据本发明的化合物可以由通式（I）表示，并且还包括其药学上可接受的酸或碱加成盐，其立体化学异构形式，其N-氧化物形式及其前药，其中所有取代基定义为 在权利要求1中。