Huckvale Rosemary, Mortensen Martin, Pryde David, Smart Trevor G, Baker James R
Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK.
Department of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Org Biomol Chem. 2016 Jul 12;14(28):6676-8. doi: 10.1039/c6ob01101b.
The design and synthesis of azogabazine is described, which represents a highly potent (IC50 = 23 nM) photoswitchable antagonist of the GABAA receptor. An azologization strategy is adopted, in which a benzyl phenyl ether in a high affinity gabazine analogue is replaced by an azobenzene, with resultant retention of antagonist potency. We show that cycling from blue to UV light, switching between trans and cis isomeric forms, leads to photochemically controlled antagonism of the GABA ion channel.
本文描述了偶氮加巴嗪的设计与合成，它是一种高效的（IC50 = 23 nM）GABAA受体光开关拮抗剂。采用了一种偶氮化策略，即将高亲和力加巴嗪类似物中的苄基苯基醚替换为偶氮苯，同时保留拮抗剂活性。我们发现，从蓝光切换到紫外光，反式和顺式异构体形式之间的转换，会导致GABA离子通道的光化学控制拮抗作用。
