Purinergic receptors are involved in many physiological and pathological conditions of cells. Adenosine 5’-triphosphate (ATP) is a cotransmitter with classical transmitters in both the peripheral and central nervous systems. In addition, purines are powerful extracellular messengers to non-neuronal cells, including secretory, exocrine and endocrine, endothelial, immune, musculo-skeletal and inflammatory cells. Purinergic signaling alterations may occur due to abnormal receptor expression or extracellular nucleotide levels. Synthetic modulators for receptors and enzymes involved in the purinergic signaling machinery have been developing. 
In the gastrointestinal tract, purine nucleosides and nucleotides modulate motor, secretory, and sensory functions and dysfunctions. Synthetic purinergic receptor/enzyme modulators help to restore normal motor, secretory, and sensory functions. Currently, potent and selective purinergic signaling modulators as novel therapeutic tools for gastrointestinal diseases are developed. 
Moreover, there was recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer. 
 G. Burnstock, “Purinergic signalling: Therapeutic developments,” Frontiers in Pharmacology, vol. 8. Frontiers Media S.A., Sep. 01, 2017, doi: 10.3389/fphar.2017.00661.
 D. Dal Ben et al., “Approaches for designing and discovering purinergic drugs for gastrointestinal diseases,” Expert Opin. Drug Discov., vol. 15, no. 6, pp. 687–703, 2020, doi: 10.1080/17460441.2020.1743673.
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