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In the present study we synthesized aza-analogs of 8-styrylxanthines, in which the ethenyl bridge is replaced by an imine, amide, or azo function, in order to investigate structure-activity relationships of the 8-substituent of A2A-selective xanthine derivatives. Thus, various 8-substituents were combined with theophylline or caffeine, respectively, and affinities of the novel compounds for adenosine A1- and A2a-receptors were determined and compared with those of analogous 8-styrylxanthine derivatives. 8-(Benzylideneamino)caffeine derivatives exhibited high affinity and selectivity for A2A-adenosine receptors, but were unstable in aqueous buffer solution at physiological pH values. 8-(Phenylazo)caffeine derivatives were less potent than corresponding 8-styrylcaffeine derivatives at adenosine receptors. The most potent azo compound of the present series was 8-(m-chlorophenylazo)caffeine (14b) exhibiting a Ki value of 400 nM at A2A-adenosine receptors and 20-fold selectivity versus A1-receptors. Due to the facile synthetic access to 8-(phenylazo)xanthine derivatives, which are obtained by coupling of 8-unsubstituted xanthines with phenyldiazonium salts, 14b may be an interesting new lead compound for the development of more potent and selective A2A-antagonists with azo structure.
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
June 2014,
Bioorganic & medicinal chemistry,
C E Müller, and
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U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
June 1998,
Bioorganic & medicinal chemistry,
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
January 2001,
Farmaco (Societa chimica italiana : 1989),
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
July 2008,
Bioorganic & medicinal chemistry letters,
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
January 2003,
Current topics in medicinal chemistry,
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
May 2013,
Bioorganic & medicinal chemistry letters,
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
November 2020,
Journal of medicinal chemistry,
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
September 2020,
Pharmaceuticals (Basel, Switzerland),
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
January 2022,
Current medicinal chemistry,
C E Müller, and
R Sauer, and
U Geis, and
W Frobenius, and
P Talik, and
M Pawlowski
March 2008,
Bioorganic & medicinal chemistry letters,
