Li Liantao, Kracht Julia, Peng Shiqi, Bernhardt Günther, Buschauer Armin
College of Pharmaceutical Sciences, Peking University, PR, China.
Bioorg Med Chem Lett. 2003 Apr 7;13(7):1245-8. doi: 10.1016/s0960-894x(03)00113-6.
Fluorescently labeled histamine H(1) receptor antagonists were synthesized starting from N-demethylmepyramine by introduction of omega-aminoalkyl chains (2-8 methylene groups in length) followed by derivatization of the terminal NH(2) group with various fluorophores (fluorescein, naphthofluorescein, rhodamine, tetramethylrhodamine, BODIPY, dansyl, and nitrobenzoxadiazole (NBD)). On the isolated guinea pig ileum and in a Ca(2+) assay on U373MG human glioblastoma cells the highest H(1) antagonistic activities were found in 5- and 6-carboxyfluorescein labeled compounds with hexa- and octamethylene spacers and in an analogous NBD-aminohexanoyl derivative (pA(2) or pK(B) values in the range: 8.3-9.0; compared to 9.3-9.4 for mepyramine).
从N - 去甲基美吡拉敏开始，通过引入ω - 氨基烷基链（长度为2 - 8个亚甲基），随后用各种荧光团（荧光素、萘荧光素、罗丹明、四甲基罗丹明、BODIPY、丹磺酰氯和硝基苯并恶二唑（NBD））对末端NH₂基团进行衍生化，合成了荧光标记的组胺H(1)受体拮抗剂。在分离的豚鼠回肠和U373MG人胶质母细胞瘤细胞的Ca(2+)检测中，发现具有六亚甲基和八亚甲基间隔基的5 - 和6 - 羧基荧光素标记的化合物以及类似的NBD - 氨基己酰衍生物具有最高的H(1)拮抗活性（pA(2)或pK(B)值范围：8.3 - 9.0；美吡拉敏为9.3 - 9.4）。
