Synthesis of indolizine derivatives with selective antibacterial activity against Mycobacterium tuberculosis.
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.
Gundersen
Lise-Lotte
LL
Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo, Norway. l.l.gundersen@kjemi.uio.no
Charnock
Colin
C
Negussie
Ayele Hailu
AH
Rise
Frode
F
Teklu
Solomon
S
D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D007212:Indolizines / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014709:Vero Cells
D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D000995:Antitubercular Agents; D007212:Indolizines