Synthesis and biological properties of 9-(trans-4-hydroxy-2-buten-1-yl)adenine and guanine: open-chain analogues of neplanocin A.
Alkylation of adenine (5a) or 2-amino-6-chloropurine (5b) with excess trans-1,4-dichloro-2-butene (4), effected by K2CO3 in dimethyl sulfoxide or tetra-n-butylammonium fluoride in tetrahydrofuran, led in 90-95% regioselectivity to 9-alkylpurines 6a and 6b. The title compounds 2a and 2b were obtained by refluxing intermediates 6a and 6b in 0.1 M NaOH or HCl. Adenine derivative 2a is a substrate for adenosine deaminase whereas both 2a and 2b exhibit 50% inhibition of the growth of murine leukemia L 1210 cell culture at 1 mM concentration.
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D058892:Adenosine Deaminase Inhibitors; D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; C050959:9-(4-hydroxy-2-buten-1-yl)adenine; C050960:9-(4-hydroxy-2-buten-1-yl)guanine; D006147:Guanine; C031096:neplanocin A; D000225:Adenine; D000241:Adenosine