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NMDA RECEPTOR ANTAGONISTS FOR NEUROPROTECTION

机译:NMDA受体对神经保护的拮抗剂

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.
机译:提供了化合物,药物组合物和治疗或预防与NMDA受体活性相关的疾病的方法,包括神经性疼痛,中风,创伤性脑损伤,癫痫和相关神经学事件或神经变性。化合物是通式I的,或者提供了一种药学上可接受的盐,酯,前药或其衍生物:其中:每(L)K-Ar1是取代的或未取代的,单环或双环芳基或杂芳基; W是键,烷基或链烯基; X是键,NR1或O,每个R1和R2独立地为H,烷基,链烯基或芳烷基或R1和R 2,形成5-8元环; R3-R6选自某些特异性取代基或羰基; Y是键,O,S,SO,SO2,CH2,NH,N(烷基)或NHC(O); Z是OH,NR6R7,NR8SO2(烷基),NR8C(O)NR6R7,NR8C(O)O(烷基),NR8-二羟基噻唑或NR8-二氢咪唑或其中Z可以与AR 2熔断以形成选定的杂环。

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