Gundersen Lise-Lotte, Charnock Colin, Negussie Ayele Hailu, Rise Frode, Teklu Solomon
Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo, Norway.
Eur J Pharm Sci. 2007 Jan;30(1):26-35. doi: 10.1016/j.ejps.2006.09.006. Epub 2006 Oct 1.
1-substituted indolizines with activity against Mycobacterium tuberculosis have been synthesized. The most active compounds carry an hydroxyphenylmethyl- or hydroxyalkyl substituent in the indolizine 1-position. The alkyl chain should be moderately long (C-5 or C-6). Aryl groups in the 2- and 3-position of the indolizine are also required. Removal of the 3-substituent resulted in significant loss of activity. A nitrile substituent in the 7-position is beneficial for both chemical stability and bioactivity. The compounds studied display a narrow antibacterial spectrum and appear to be quite selective antimycobacterial compounds. Moderate activity against certain pathogenic protozoa was also observed.
已合成出对结核分枝杆菌具有活性的1-取代中氮茚。活性最高的化合物在中氮茚的1-位带有羟苯基甲基或羟烷基取代基。烷基链应有适度的长度（C-5或C-6）。中氮茚的2-位和3-位也需要芳基。去除3-取代基会导致活性显著丧失。7-位的腈取代基对化学稳定性和生物活性都有利。所研究的化合物显示出较窄的抗菌谱，似乎是相当有选择性的抗分枝杆菌化合物。还观察到对某些致病原生动物有适度活性。
