Synthesis of 2-alkynyl substituted 4'-thioadenosine derivatives and their binding affinities at the adenosine receptors.
On the basis of high binding affinity of 2-hexynyl-N(6)-methyladenosine and N(6)-substituted-4'-thioadenosine derivatives at the A3 adenosine receptor (AR), novel 2-alkynyl-substituted-N(6)-methyl-4'-thioadenosine derivatives, combining the characteristics of two classes of nucleosides were designed and synthesized from D-gulonic gamma-lactone via palladium-catalyzed cross coupling reaction as a key step. Among compounds tested, only compound 3b showed moderate binding affinity at the human A3 adenosine receptor without binding affinities at other subtypes.
Liang
Cheng-Wu
CW
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Choi
Won Jun
WJ
Jeong
Lak Shin
LS
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002384:Catalysis; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000378:metabolism
D007202:Indicators and Reagents; D018047:Receptors, Purinergic P1; D013872:Thionucleosides; C050070:4'-thioadenosine; D010165:Palladium; D000241:Adenosine