Lumma W C, Baldwin J J, Bicking J B, Bolhofer W A, Hoffman J M, Phillips B T, Robb C M, Torchiana M L, Schlegel H B, Smith G M
J Med Chem. 1984 Aug;27(8):1047-52. doi: 10.1021/jm00374a019.
The furan ring of the histamine H2 receptor antagonist 3-amino-4-[[2-[[[5-[(dimethylamino)methyl]-2-furanyl]-methyl] thio]ethyl]amino]-1,2,5-thiadiazole 1-oxide (1a) was replaced by thiophene, pyridine, benzene, and pyrrole. The relative receptor affinities of these analogues were estimated by in vitro and in vivo techniques. A theoretical model for the stacking interaction, observed by single crystal X-ray analysis of 1a, was developed, and the ability to enter into this type of interaction was estimated. The X-ray analysis of the pyridine analogue of 1a revealed no intramolecular stacking interaction. The theoretical studies were evaluated in light of the observed receptor affinities, and the relevance of the solid-state geometry of 1a to the receptor-bound geometry was assessed. It is suggested that the stacked geometry found in the X-ray structure of 1a does not represent a conformation that is relevant to that bound at the histamine H2 receptor.
组胺H2受体拮抗剂3-氨基-4-[[2-[[[5-[(二甲氨基)甲基]-2-呋喃基]甲基]硫代]乙基]氨基]-1,2,5-噻二唑1-氧化物(1a)的呋喃环被噻吩、吡啶、苯和吡咯取代。通过体外和体内技术评估了这些类似物的相对受体亲和力。通过对1a的单晶X射线分析观察到的堆积相互作用建立了理论模型，并评估了进入这种相互作用类型的能力。1a的吡啶类似物的X射线分析显示没有分子内堆积相互作用。根据观察到的受体亲和力对理论研究进行了评估，并评估了1a的固态几何结构与受体结合几何结构的相关性。有人提出，在1a的X射线结构中发现的堆积几何结构并不代表与组胺H2受体结合的构象。
