NMDA receptor antagonists for neuroprotection

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.