Skip to main content
. Author manuscript; available in PMC: 2012 Oct 10.
Published in final edited form as: J Med Chem. 1985 Sep;28(9):1334–1340. doi: 10.1021/jm00147a038

Table I.

Effect of Functionalization on the Activity of 1,3-Dialkyl-8-(p-hydroxyphenyl)xanthines at A1- and A2-Adenosine Receptors

graphic file with name nihms406018t1.jpg
Ki,a nM
compd R′ A1 receptor A2 receptors ratio A1/A2
R = CH3
   2a H 50 ± 20 130 ± 30 2.6
   8a HO2CCH2 500 ± 200 430 ± 80 0.86
   9a graphic file with name nihms406018t2.jpg 26 ± 5 20 ± 7 0.77
R = n-C3H7
   2b H 2.9 ± 0.8 50 ± 10b 17
   8b HO2CCH2 58 ± 3 34 ± 13 0.59
   9b graphic file with name nihms406018t3.jpg 36 ± 23 750 ± 370 21
   9c graphic file with name nihms406018t4.jpg 4.1 ± 1.5 62 ± 37 15
   10 CH3CH2OCOCH2 42 ± 3 30 ± 12 0.71
   11 graphic file with name nihms406018t5.jpg 96 ± 25 > 1000 (30% inhibn) > 10
   12 graphic file with name nihms406018t6.jpg 9.0 ± 0.7 40 ± 14 4.4
   13a H2NCOCH2 6.0 ± 1.0 47 ± 2 7.8
   13b (CH3)2 NCOCH2 32 ± 7 68 ± 39 2.1
   13c H2N(CH2)2NHCOCH2 1.2 ± 0.5 49 ± 17 41
   13d H2N( CH2)8NHCOCH2 5 ± 2 470 ± 170 94
   13e H2NNHCOCH2 59 ± 0.7 32 ± 4 0.54
   14a CH3CONH(CH2)2NHCOCH2 24 ± 3.5 62 ± 3 2.6
   14b graphic file with name nihms406018t7.jpg 54 ± 2 180 ± 80 3.3
   16 graphic file with name nihms406018t8.jpg 2.2 ± 0.7 320 ± 70 145
a

IC50 values for A1 receptors were obtained from antagonism of binding of 1 nM [3H]cyclohexyladenosine to rat cerebral cortical membranes. IC50 values for A1 receptors were obtained from antagonism of 3H-labeled cyclic AMP accumulation elicited by 15 µM 2-chloroadenosine in [3H]adenine-labeled guinea pig cerebral cortical slices. Ki values were calculated from the equation Ki = IC50/(1 + concentration of adenosine analogue/Ka for adenosine analogue). Values are means ± SEM for two to four experiments. Each experiment contained triplicate determinations.

b

Values from ref 4.