Synthesis and ribonucleotide reductase inhibitory activity of analogues of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (IMPY).
A series of derivatives of the ribonucleotide reductase inhibitory anti-tumour agent 2,3-dihydro-1H-imidazo[1,2-b]pyrazole (IMPY), including all the methyl analogues, have been synthesised. IMPY itself caused 50% inhibition of L1210 tumour-derived ribonucleotide reductase at a concentration of 0.39 mM, comparable with enzyme obtained from other sources. The analogues proved to be no better than IMPY, either as inhibitors of this enzyme or of the growth of L1210 cells in vitro. No correlation was apparent between biological activity and position of substitution.
Goddard
A J
AJ
Drug Development Section, Institute of Cancer Research, Sutton, Surrey, UK.
Orr
R M
RM
Stock
J A
JA
Wilman
D E
DE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011720:Pyrazoles; D012264:Ribonucleotide Reductases; C000971:2,3-dihydro-1H-imidazo(1,2-b)pyrazole