Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor
Section snippets
Chemical Methods
The formation of 2-amino-3-benzoylthiophene from the base-catalyzed condensation of carbonyl compounds and nitriles, known as the ‘Gewald reaction’,6 was reported 35 years ago. Nevertheless, it was not until 1990 that synthesis of 2-amino-3-benzoylthiophenes by this method received renewed attention. The same method has been used for the synthesis of our new 2-amino-3-benzoylthiophene derivatives 3a–x and 4a–v wherein the appropriate carbonyl compounds were reacted with benzoylacetonitrile
Biological Methods
Chinese hamster ovary cells expressing human recombinant A1-adenosine receptors (CHO: huA1 cells) at a density of approximately 8000 fmol/mg protein were prepared as previously described7 and aliquots of these cells at low passage numbers were frozen and stored in liquid nitrogen. Cells were removed from liquid nitrogen storage when needed, and grown in Ham's F-12 culture medium with 10% fetal bovine serum and 0.5 mg/ml of antibiotic G-418.8 Aliquots of cells were placed into 12-well culture
Results and Discussion
The effects of the newly-synthesized derivatives of PD 81,723 on CHO cells expressing the cloned human A1-adenosine receptor are shown in Table 2. Allosteric enhancers of agonist binding to the A1-adenosine receptor have been shown to increase agonist binding in equilibrium binding studies,2 to slow dissociation of the agonist-receptor complex in kinetic studies,2 and to cause leftward shifts of the agonist concentration-response relationship in studies of isolated tissues.7, 8 In the current
Acknowledgements
We wish to thank Medco Research for support of this research.
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