192989-86-9Relevant articles and documents
Subtype-selective N-methyl-D-aspartate receptor antagonists: Synthesis and biological evaluation of 1-(heteroarylalkynyl)-4-benzylpiperidines
Wright,Gregory,Kesten,Boxer,Serpa,Meltzer,Wise,Espitia,Konkoy,Whittemore,Woodward
, p. 3408 - 3419 (2007/10/03)
4-[4-(4-Benzylpiperidin-1-yl)but-1-ynyl]phenol (8) and 4-[3-(4-benzylpiperidin-1-yl)prop-1-ynyl]-phenol (9) are potent NR1A/2B receptor antagonists (IC50 values 0.17 and 0.10 μM, respectively). Administered intraperitoneally, they both potentia
Subtype-selective N-methyl-D-aspartate receptor antagonists: Synthesis and biological evaluation of 1-(arylalkynyl)-4-benzylpiperidines
Wright, Jon L.,Gregory, Tracy F.,Bigge, Christopher F.,Boxer, Peter A.,Serpa, Kevin,Meltzer, Leonard T.,Wise, Lawrence D.,Cai, Sui Xiong,Hawkinson, Jon E.,Konkoy, Christopher S.,Whittemore, Edward R.,Woodward, Richard M.,Zhou, Zhang-Lin
, p. 2469 - 2477 (2007/10/03)
A search of our compound library for compounds with structural similarity to ifenprodil (5) and haloperidol (7) followed by in vitro screening revealed that 4-benzyl-1-(4-phenyl-3-butynyl)piperidine (8) was a moderately potent and selective antagonist of the NR1A/2B subtype of NMDA receptors. Substitution on the benzyl group of 8 did not significantly affect NR1A/2B potency, while addition of hydrogen bond donors in the para position of the phenyl group enhanced NR1A/2B potency. Addition of a hydroxyl moiety to the 4-position of the piperidine group slightly reduced NR1A/2B potency while reducing α-1 adrenergic and dopamine D2 receptor binding affinities substantially, resulting in improved overall selectivity for NR1A/2B receptors. Finally, the butynyl linker was replaced with propynyl or pentynyl. When the phenyl was para substituted with amine or acetamide groups, the NR1A/2B potency order was butynyl > pentynyl >> propynyl. For the para methanesulfonamide or hydroxyl groups, the order was butynyl ? propynyl > pentynyl. The hydroxyl propyne (48) and butyne (23) were among the most potent NR1A/2B antagonists from this study. They both potentiated the effects of L-DOPA in the 6-hydroxydopamine-lesioned rat, a model of Parkinson's disease, dosed at 10 mg/kg ip, but 48 was not active at 30 mg/kg po.
