Synthesis of potential anticancer agents: imidazo[4,5-c]pyridines and imidazo[4,5-b]pyridines.
The 1,2-dihydropyrido[3,4-b]pyrazines (1) are mitotic inhibitors with significant antitumor activity in mice. Also, the active imidazo[4,5-b]pyridine 3 was shown to cause the accumulation of cells at mitosis. Routes were developed for the synthesis of congeners of 3 by cyclization of 4-(substituted amino)-5,6-diaminopyridines with ethyl orthoformate. Oxidative cyclization of either 4,5- or 5,6-diaminopyridines with aryl aldehydes produced the [4,5-c] and [4,5-b] imidazopyridine ring systems, respectively. The latter reaction with 6-(substituted amino)-4,5-diaminopyridines gave imidazo[4,5-c]pyridine ring analogues of 1. Biological studies indicated that the target compounds were less active than 1 and 3.
Temple
C
C
Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35255-5305.
Rose
J D
JD
Comber
R N
RN
Rener
G A
GA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D007093:Imidazoles / Q000138:chemical synthesis* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007093:Imidazoles; D011725:Pyridines