Role of strong intramolecular N-H...N hydrogen bonds in determining the conformation of adenosine-receptor antagonists.
Over the last few years many efforts have been devoted to the discovery of new adenosine antagonists which can selectively bind to one of the four adenosine receptors, called A(1), A(2A), A(2B) and A(3), in order to develop new drugs with few side effects. The present paper reports the crystal structures of four newly synthesized antagonists belonging to the chemical class of pyrazolo-triazolo-pyrimidine derivatives, which display good affinity and selectivity properties towards the A(2A) or A(3) receptor subtypes. These molecules assume an overall planar conformation due to the formation of strong intramolecular N-H...N hydrogen bonds. A systematic investigation on molecules containing the ureidic -NH-C(=O,S)-NH-C=N- fragment has shown that the formation of such interactions is a common feature for this class of compounds. The associated energy, evaluated through DFT calculations, is some 50.24 kJ mol(-1), leading to the conclusion that the hydrogen bond, and consequently the planar conformation, is retained not only in the solid state but also in solution during the interaction of the molecule with its receptor.
Ferretti
Valeria
V
Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, University of Ferrara, via L. Borsari 46, I-44100 Ferrara, Italy. frt@unife.it
Pretto
Loretta
L
Tabrizi
Mojgan Aghazadeh
MA
Gilli
Paola
P
D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D011720:Pyrazoles; D011743:Pyrimidines; D014230:Triazoles