Carbocyclic Analog of Purine Ribonucleosides with Antileukemic Activity

• Published in: Journal of pharmaceutical sciences 1973-05, Vol.62 (5), p.858-859
• Main Authors: Fulmer Shealy, Y., Clayton, Joe D.
• Format: Article
• Language: English
• Subjects: 5-d]pyrimidine (carbocyclic analog of purine nucleoside); 5-d]pyrimidines-synthesis of 8-azaadenosine analog of purine nucleoside; antileukemic activity; Antileukemic activity-synthesis of a v-triazolo; Antileukemic activity—synthesis of a v-triazolo[4,5-d]pyrimidine (carbocyclic analog of purine nucleoside); Aza Compounds - therapeutic use; Carbocyclic analogs of purine nucleosides (8- azaadenosine analog)—synthesis, antileukemic activity; Carbocyclic analogs of purine nucleosides (8-azaadenosine analog)-synthesis; Carcinoma, Squamous Cell - drug therapy; Cells, Cultured; Humans; Leukemia - drug therapy; Neoplasms, Experimental - drug therapy; Purine ribonucleosides-synthesis of carbocyclic analog with antileukemic activity; Purines - chemical synthesis; Purines - therapeutic use; Ribonucleosides - chemical synthesis; Ribonucleosides - therapeutic use; Triazoles - therapeutic use; v-Triazolo; v-Triazolo[4,5-d]pyrimidines—synthesis of 8-azaadenosine analog of purine nucleoside, antileukemic activity
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600620547

Carbocyclic analogs of several naturally occurring and biologically active purine nucleosides have been synthesized (1–4). In these analogs a methylene group occupies the position of the ring oxygen atom of the ribo- or deoxyribofuranosides. Because of the presence of a stable carbon-nitrogen bond at position 9 of the purine moiety, these analogs are not subject to cleavage by enzymes that remove or transfer the ribofuranosyl moiety of the nucleosides or nucleotides. Biochemical studies (5–7) have shown that the racemic analog (III) of adenosine can serve either as a substrate for or as an inhibitor of some of the enzymes involved in purine nucleotide metabolism, one of the more interesting findings being the inhibition of guanylic acid kinase by the phosphate (7). The antibiotic aristeromycin (8). the optically active form (9, 10) of the adenosine analog, inhibits certain plant pathogens (8, 11). Several racemic carbocyclic analogs of purine nucleosides are cytotoxic to neoplastic cells growing in culture (4). In this communication, antileukemic activity in vivo by a carbocyclic analog, the 8-azaadenosine analog (II), is reported.