P2X receptors are potential therapeutic targets for the treatment of various neurodegenerative disorders, pain, inflammation, hypertension, and cancer. Adamantane ring has been reported to exhibit significant inhibitory potential towards P2X receptors, especially for P2X7R. We have utilized uniqueness of adamantane moiety in our synthesized compounds and introduced various substitutions that enhanced the potency as well as selectivity for P2XR subtypes. Among synthesized derivatives, 4n and 5b were found to be most potent and selective inhibitors for h-P2X4R and h-P2X7R, respectively. 4n was found to be highly selective for h-P2X4R with IC₅₀ ± SEM = 0.04 ± 0.01 μM, that is 22 times more potent than BX-430, a standard selective inhibitor of h-P2X4R. 5b has IC₅₀ ± SEM of 0.073 ± 0.04 μM, which is comparable with the known antagonists of h-P2X7R. 4n and 5b were studied for mode of inhibition of P2XRs and both were found to be negative allosteric modulators. In silico studies were also conducted to find the type of interactions as well as mode of inhibition.

P2X 受体是治疗各种神经退行性疾病、疼痛、炎症、高血压和癌症的潜在治疗靶点。据报道，金刚烷环对 P2X 受体具有显着的抑制潜力，尤其是对 P2X7R。我们在我们合成的化合物中利用了金刚烷部分的独特性，并引入了各种取代，以增强 P2XR 亚型的效力和选择性。在合成的衍生物中，4n 和 5b 被发现分别是h -P2X4R 和h -P2X7R 最有效和选择性的抑制剂。发现 4n 对h -P2X4R 具有高度选择性，IC ₅₀± SEM = 0.04 ± 0.01 μM，比标准的h -P2X4R选择性抑制剂 BX-430 强 22 倍。图5b 的 IC ₅₀ ± SEM 为 0.073 ± 0.04 μM，与已知的h -P2X7R 拮抗剂相当。研究了 4n 和 5b 的 P2XR 抑制模式，发现两者都是负变构调节剂。还进行了计算机研究以发现相互作用的类型以及抑制模式。