Progress towards novel adenosine receptor therapeutics gleaned from the recent patent literature

Abstract

Adenosine receptor research is a thriving field with continuing claims of exciting new compounds with high specificity and intriguing examples of new uses for such ligands.

Development of novel adenosine receptor ligands based on the 3-amidocoumarin scaffold

“…The 3-amino-4-hydroxycoumarin was prepared by a reduction of the commercially available 3-nitro-4-hydroxycoumarin, in ethanol, with Pd/C as catalyst, in H 2 atmosphere, with a yield of 90% [13]. An acylation reaction of the 3-aminocoumarins with the conveniently substituted acid chloride, using pyridine in dichloromethane, from 0°C to room temperature, afforded the differently substituted 3-amidocoumarins (1)(2)(3)(4)(5)(6)(7)(8) in yields between 80% and 90% [14][15][16][17][18]. …”

“…Their presence on almost every cell in different organs makes them an interesting target for the pharmacological intervention in many pathophysiological situations [4]. Adenosine plays its many roles through binding to one or more of the four AR subtypes A 1 , A 2A , A 2B and A 3 [5]. All the AR subtypes are closely related to specific biochemical processes, therefore they are involved in different pathologies.…”

“…Finally, A 3 AR ligands have been linked to inflammatory diseases, such as rheumatoid arthritis and psoriasis, liver cancer, neurodegeneration, hepatitis, asthma and to the protective effects in cardiac ischemia and liver regeneration [4]. In the last years, the search for selective and potent ligands toward individual AR subtypes has been intensified, as the role of these AR in many therapeutic areas is continuously expanding [4][5][6].…”

Coumarins and adenosine receptors: New perceptions in structure–affinity relationships

“…[4] Pharmacological modulation of AR pathways opens a new window for drug treatment of a variety of pathologies, such as asthma, neurodegenerative disorders, cancer, inflammatory and ischaemicrelated diseases. [5][6][7][8][9] Coumarins are naturally occurring heterocyclic compounds with an in-depth history in Medicinal Chemistry, [10] as they have been exploited in quite more projects aiming to find, for instance, anticancer, antioxidant, antiinflammatory, antimicrobial and antiviral agents. [11] Although benzopyran is considered a privileged structure, few studies have been addressed towards its application in the discovery of new AR ligands.…”

Structure-Based Approaches to Ligands for G-Protein-Coupled Adenosine and P2Y Receptors, from Small Molecules to Nanoconjugates

“…Ligands of the ARs include clinical candidate drugs and typically have a well explored structure activity relationship (SAR). 4 , 5 However, P2YRs in some cases lack selective ligands altogether. 6 Also, many of the known P2YR ligands suffer from limited stability and bioavailability because of phosphate groups.…”