Ishida T, In Y, Inoue M, Kurihara T, Moriomoto K, Morisaka K, Shibata K
Osaka University of Pharmaceutical Sciences, Japan.
Chem Pharm Bull (Tokyo). 1990 Jul;38(7):1803-9. doi: 10.1248/cpb.38.1803.
To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational characteristics using X-ray diffraction and proton nuclear magnetic resonance (1H-NMR) methods, and for antiulcer activities on rats and H2-receptor antagonist activities in guinea pig. The ortho isomer 1, which preferentially formed an intramolecular N-H (amino)...N (imidazole) hydrogen bond, showed the highest antiulcer activity with half the efficacy of cimetidine. On the other hand, none of 1, 2 and 3 showed significant H2-receptor antagonist activity. Based on these results, the conformational characteristic for the exhibition of antiulcer activity has been discussed.
为了通过实验阐明所提出的H2受体拮抗剂可能存在的立体结构-活性关系，合成了三种5-氨基苯基咪唑（1、2和3），其中各自的氨基位于苯环的邻位、间位和对位，并使用X射线衍射和质子核磁共振（1H-NMR）方法研究了它们的构象特征，以及对大鼠的抗溃疡活性和对豚鼠的H2受体拮抗剂活性。优先形成分子内N-H（氨基）...N（咪唑）氢键的邻位异构体1显示出最高的抗溃疡活性，其效力为西咪替丁的一半。另一方面，1、2和3均未显示出显著的H2受体拮抗剂活性。基于这些结果，讨论了表现出抗溃疡活性的构象特征。
