An-Najah Staff

Adenosine is a ubiquitous autocoid with multiple effects on the human body. Adenosine can bind to four different P1-purinoreceptors (A₁, A_2A, A_2B, A₃) which belong to the broad group of receptors coupled to G-proteins and which modulate the activity of adenylate cyclase.¹ A₁-Adenosine receptors are found in many tissues including the heart, kidney, brain and spinal cord, adipose and thyroid tissues, lung, and immune system cells. In 1990, Bruns and co-workers^2 and 3 reported that 2-amino-3-benzoylthiophene derivatives both enhanced the binding of agonists to the A₁-adenosine receptor and (usually at higher concentrations) acted as competitive antagonists at these receptors. Among the synthesized compounds, PD 81,723 ((2-amino-4,5-dimethyl-3-thienyl)-[3-(trifluoromethyl)phenyl]methanone) was identified as the compound with the best ratio of enhancement to antagonistic action at the A₁-adenosine receptor.³ To study the role of various substitutions on the phenyl ring and the importance of the 4,5-dimethyl group on the thienyl ring, Baraldi⁴ and Ijzerman⁵ have described the synthesis and biological evaluation of mostly novel PD 81,723 analogues. The purpose of our investigation was to synthesize and evaluate a new series of derivatives of PD 81,723 and to establish the structural requirements and the structure–activity relationship for enhancement of the action of an agonist at the human A₁-adenosine receptor.