δ-Selective compounds 1 and 2 (DS1, compound 22; DS2, compound 16) were introduced as functionally selective modulators of δ-containing GABA type A receptors (GABA_AR). In our hands, [³H]EBOB-binding experiments with recombinant GABA_AR and compound 22 showed no proof of δ-selectivity, although there was a minimally higher preference for the α4β3δ and α6β2/3δ receptors with respect to potency. In order to delineate the structural determinants of δ preferences, we synthesized 25 derivatives of DS1 and DS2, and investigated their structure–activity relationships (SAR). Four of our derivatives showed selectivity for α6β3δ receptors (29, 38, 39, and 41). For all of them, the major factors that distinguished them from compound 22 were variations at the para-positions of their benzamide groups. However, two compounds (29 and 39), when tested in the presence of GABA, revealed effects at several additional GABA_AR. The newly synthesized compounds will still serve as useful tools to investigate α6β3δ receptors.

中文翻译：

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含δ-亚基的γ-氨基丁酸_A型（GABA _A）受体的咪唑并吡啶衍生物的结构-功能评价

引入δ-选择性化合物1和2（DS1，化合物22； DS2，化合物16）作为含δ的GABA A型受体（GABA _A R）的功能选择性调节剂。在我们手中，用重组GABA _A R和化合物22进行的[ ³ H] EBOB结合实验没有显示δ选择性的证据，尽管就效力而言，对α4β3δ和α6β2/3δ受体的偏爱程度最低。为了描述δ偏好的结构决定因素，我们合成了DS1和DS2的25个导数，并研究了它们的构效关系（SAR）。我们的衍生品四个表现出对α6β3δ受体的选择性（29，38，39和41）。对于所有这些化合物，使它们与化合物22区别开的主要因素是其苯甲酰胺基对位的变异。但是，当在GABA存在下测试时，两种化合物（29和39）显示出对另外几种GABA _A R的影响。新合成的化合物仍将用作研究α6β3δ受体的有用工具。