Developing new and selective 5-HT₇R ligands may have a key impact on the treatment of central nervous system diseases including depression. We have found that indoleaminotriazine core fused with alkyl aryl moiety exhibits high affinity and selectivity to 5-HT₇R. SAR analysis demonstrated that the ethyl or ethoxy group (5c 5-HT₇R K_i = 8 nM; 5d 5-HT₇R K_i = 55 nM) is the optimal carbon linker between triazine and aryl moiety. The results of the molecular dynamics simulations show stable interaction with E7.34 upon binding to a 5-HT₇R. Compounds 5c and 5d were tested for early ADMET parameters. Compounds are not hepatotoxic and exhibit moderate potential interaction with other drugs metabolized by CYP3A4 or CYP2D6.

开发新的选择性5-HT ₇ R配体可能对中枢神经系统疾病（包括抑郁症）的治疗产生关键影响。我们发现与烷基芳基部分稠合的吲哚氨基三嗪核心对5-HT ₇ R表现出高亲和力和选择性.SAR分析表明，乙基或乙氧基（5c 5-HT ₇ R K _i  = 8 nM; 5d 5-HT ₇ R K _i  = 55 nM）是三嗪和芳基部分之间的最佳碳连接基。分子动力学模拟的结果表明，与5-HT ₇ R结合后，与E7.34稳定相互作用。化合物5c和测试5d的早期ADMET参数。该化合物无肝毒性，与其他经由CYP3A4或CYP2D6代谢的药物具有中等潜在的相互作用。