Synthesis and biological activity of 2'-deoxy-4'-thio-pyrazolo[3,4-d]pyrimidine nucleosides.
The coupling of 4-aminopyrazolo [3, 4-d]pyrimidine with the appropriate thio sugar gave a 3:1 ratio of alpha,beta blocked 4-amino-1-(2-deoxy-4-thio-D-erythropentofuranosyl)-1H pyrazolo[3,4-d]pyrimidine nucleosides. The mixture was deblocked, both the anomers were separated, and the beta-anomer was readily deaminated by adenosine deaminase. The nucleosides have been characterized, and their anomeric configurations have been determined by proton NMR. All three nucleosides were evaluated against a panel of human tumor cell lines for cytotoxicity in vitro. The details of a convenient and high yielding synthesis of these nucleosides are described.
Tiwari
K N
KN
Southern Research Institute, Birmingham, Alabama, USA.
Fowler
A S
AS
Secrist
J A
JA
D000241:Adenosine / Q000737:chemistry*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008967:Molecular Biology / Q000379:methods*; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D011522:Protons; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011741:Pyrimidine Nucleosides / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*
D009705:Nucleosides; D011522:Protons; D011684:Purine Nucleosides; D011741:Pyrimidine Nucleosides; D011743:Pyrimidines; D000241:Adenosine; C030986:pyrimidine