The synthesis and biological evaluation of new series of 6,7-dihydro-5H-cyclopenta[d]pyrimidine and 5,6,7,8-tetrahydroquinazoline derivatives as selective sigma-1 receptor (σ₁R) antagonists are reported. The receptor affinities of new compounds were evaluated in vitro in σ₁ and σ₂ receptor binding assays. The structure-active relationship study leads us to the most promising compound: 2-(4-chlorophenyl)-4-(3-(4-methylpiperidin-1-yl)propoxy)-5,6,7,8-tetra-hydroquinazoline (33). Compound 33 has exerted nanomolar affinity for σ₁R (K_iσ₁ = 15.6 nM) and high σ₁/σ₂ selectivity (K_iσ₂ >2000 nM), and identified to be a σ₁R antagonist. In animal model, compound 33 exhibited dose dependent anti-nociceptive effects in the formalin test. These results suggest that compound 33 could be a potent analgesic for pain treatment.

的合成和新系列6,7-二氢5的生物学评价ħ环戊二烯并[ d（]嘧啶和5,6,7,8-四氢喹唑啉衍生物作为选择性σ-1受体σ _1个R）报道拮抗剂。新化合物的受体亲和力在体外进行了评价σ ₁和σ ₂受体结合试验。通过结构-活性关系研究，我们得出了最有希望的化合物：2-（4-氯苯基）-4-（3-（4-甲基哌啶-1-基）丙氧基）-5,6,7,8-四氢喹唑啉（33）。化合物33具有用于施加纳摩尔亲和力σ _1个R（ķ_我σ₁  = 15.6 1nM）和高σ ₁ / σ ₂选择性（ķ_我σ ₂ > 2000纳米），和鉴定为σ ₁ - [R拮抗剂。在动物模型中，化合物33在福尔马林试验中表现出剂量依赖性的抗伤害感受作用。这些结果表明，化合物33可能是用于疼痛治疗的有效止痛药。