Structure-affinity relationships of the affinity of 2-pyrazolyl adenosine analogues for the adenosine A2A receptor.
The structure-affinity relationships of two novel 2-substituted adenosine series containing a substituted pyrazole attached at the N-1 or C-4 position for the adenosine (ADO) A2A receptor are described. Compounds in the 2-(N-1-pyrazolyl) adenosine series IV provided the highest affinity for the ADO A2A receptor as compared to the 2-(C-4-pyrazolyl) series V. The main structural differences between the two series point to the N-1 nitrogen of series IV imparting more favorable binding interactions with the receptor than those of series V.
Palle
Venkata P
VP
Department of Bioorganic Chemistry, CV Therapeutics, 3172 Porter Drive, Palo Alto, CA 94304, USA. jeff.zablocki@cut.com
Elzein
Elfatih O
EO
Gothe
Scott A
SA
Li
Zhihe
Z
Gao
Zhenhai
Z
Meyer
Stephanie
S
Blackburn
Brent
B
Zablocki
Jeff A
JA
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology*
C471906:2-pyrazolyl adenosine; D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D014665:Vasodilator Agents; D000241:Adenosine