Hasegawa T, Nigo T, Kakita T, Toyoda H, Toya H, Ueda I
Institute of Scientific and Industrial Research, Osaka University, Japan.
Chem Pharm Bull (Tokyo). 1993 Oct;41(10):1760-8. doi: 10.1248/cpb.41.1760.
The synthesis and antiulcer activity of highly strained cage compounds such as pentacyclo[4.2.0.0(2,5).0(3,8).0(4,7)]-octane (cubane), pentacyclo[4.3.0.0(2,5).0(3,8).0(4,7)]nonane (homocubane) and pentacyclo[5.3.0.0(2,4).0(3,6).0(5,8)]decane are described. Of the compounds obtained, N-[3-(3-piperidinomethylphenoxy)propyl]-4-piperidinocarbonylpen tacyclo [4.2.0.0(2,5).0(3,8).0(4,7)]octane carboxamide (26a) and N-[3'-(3'-piperidinomethylphenoxy)propyl]-1-bromo-9, 9-ethylenedioxypentacyclo[4.3.0.0(2,5).0(3,8).0(4,7)[nonane]-4- carboxamid e (26q) showed more potent antiulcer activity with very good cytoprotective ability in the HCl.ethanol-treated rat model. Compounds 26a and 26q exhibited H2-receptor antagonist potency (in vitro) comparable to that of ranitidine, but did not inhibit histamine-stimulated acid secretion (in vivo) in the gastric fistula rat model, when orally administered in the dose range at which antiulcer and cytoprotective activities were seen. The structure-activity relationships are discussed.
本文描述了高张力笼状化合物如五环[4.2.0.0(2,5).0(3,8).0(4,7)]辛烷（立方烷）、五环[4.3.0.0(2,5).0(3,8).0(4,7)]壬烷（高立方烷）和五环[5.3.0.0(2,4).0(3,6).0(5,8)]癸烷的合成及其抗溃疡活性。在所得到的化合物中，N-[3-(3-哌啶甲基苯氧基)丙基]-4-哌啶羰基五环[4.2.0.0(2,5).0(3,8).0(4,7)]辛烷甲酰胺（26a）和N-[3'-(3'-哌啶甲基苯氧基)丙基]-1-溴-9,9-亚乙基二氧五环[4.3.0.0(2,5).0(3,8).0(4,7)]壬烷-4-甲酰胺（26q）在盐酸-乙醇处理的大鼠模型中表现出更强的抗溃疡活性和非常好的细胞保护能力。化合物26a和26q在体外表现出与雷尼替丁相当的H2受体拮抗剂效力，但在胃瘘大鼠模型中，当以观察到抗溃疡和细胞保护活性的剂量范围口服给药时，它们并不抑制组胺刺激的胃酸分泌。文中讨论了构效关系。
