8-Phosphorus substituted isosteres of purine and deazapurines.
Synthesis of 8-phosphorus substituted isosteres of purine [pyrimidino (4,5-d)-1,3,2-diazaphosphole], 1-deazapurine [pyridino (2,3-d)-1,3,2-diazaphosphole] and 3-deazapurine [pyridino (4,5-d)-1,3,2-diazaphosphole] has been achieved by the reaction of equimolar amounts of triphenylphosphite and 4,5-diaminopyrimidine, 2,3-diaminopyridine and 3,4-diaminopyridine, respectively. These compounds hydrolyzed (cleavage of the phosphorus-nitrogen bounds) in aqueous solutions to provide the corresponding diaminopyrimidine or diaminopyridines. These three new basic ring systems constitute the first reported synthesis of purines in which ring carbon atom is substituted with a phosphorus atom. 8-Phosphorus substituted purine at a concentration of 4 X 10(-4)M caused a 50% inhibition in the growth of leukemia L1210 cells in culture. The biochemical rationale for the synthesis of these compounds is discussed.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D007939:Leukemia L1210 / Q000503:physiopathology; D008722:Methods; D051379:Mice; D010758:Phosphorus; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D013053:Spectrophotometry; D013329:Structure-Activity Relationship
D011687:Purines; D010758:Phosphorus