公开(公告)号：US20090253710A1

公开(公告)日：2009-10-08

申请号：US12165308

申请日：2008-06-30

申请人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

发明人： Dennis C. Liotta ,  James P. Snyder ,  Stephen F. Traynelis ,  Lawrence Wilson ,  Cara Mosley ,  Raymond J. Dingledine ,  Scott Myers ,  Yesim Altas Tahirovic

IPC分类号： A61K31/496 ,  C07D241/04 ,  C07D401/04 ,  A61P25/00 ,  A61K31/495

CPC分类号： C07D209/34 ,  C07C217/20 ,  C07C235/20 ,  C07C311/08 ,  C07D211/52 ,  C07D213/74 ,  C07D215/227 ,  C07D233/32 ,  C07D233/34 ,  C07D235/26 ,  C07D263/58 ,  C07D295/088

摘要： Provided are compounds, pharmaceutical compositions and methods of treatment or prophylaxis of disorders associated with NMDA receptor activity, including neuropathic pain, stroke, traumatic brain injury, epilepsy, and related neurologic events or neurodegeneration. Compounds are of the general Formula I, or a pharmaceutically acceptable salt, ester, prodrug or derivative thereof are provided: wherein: each (L)k-Ar1 is a substituted or unsubstituted, mono or bicyclic aryl or heteroaryl; W is a bond, alkyl, or alkenyl; X is a bond, NR1 or O and each R1 and R2 is independently H, alkyl, alkenyl or aralkyl or R1 and R2 taken together form a 5-8 membered ring; R3−R6 are selected from certain specific substituents or a carbonyl; Y is a bond, O, S, SO, SO2, CH2, NH, N(alkyl), or NHC(═O); and Z is OH, NR6R7, NR8SO2(alkyl), NR8C(O)NR6R7, NR8C(O)O(alkyl), NR8-dihydrothiazole, or NR8-dihydroimidazole or wherein Z can fuse with Ar2 to form selected heterocycles.

摘要翻译： 提供了治疗或预防与NMDA受体活性相关的病症的化合物，药物组合物和方法，包括神经性疼痛，中风，创伤性脑损伤，癫痫以及相关的神经系统事件或神经变性。 化合物为通式I，或其药学上可接受的盐，酯，前药或衍生物：其中：（L）k-Ar1为取代或未取代的单或双环芳基或杂芳基; W是键，烷基或烯基; X是键，NR 1或O，并且每个R 1和R 2独立地是H，烷基，烯基或芳烷基，或者R 1和R 2一起形成5-8元环; R 3 -R 6选自某些具体取代基或羰基; Y是键，O，S，SO，SO 2，CH 2，NH，N（烷基）或NHC（-O）; 并且Z是OH，NR 6 R 7，NR 8 SO 2（烷基），NR 8 C（O）NR 6 R 7，NR 8 C（O）O（烷基），NR 8 - 二氢噻唑或NR 8 - 二氢咪唑，或其中Z可与Ar 2融合形成选定的杂环。