Purine and Its Derivatives

Dear Colleagues,

The purine ring system (imidazo[4,5-d]pyrimidine) is among the most ubiquitous of all the heterocyclic compounds. Although purine itself has never been found in nature, substituted purines like adenine and guanine or their respective nucleoside/nucleotide derivatives are the most common class of nitrogen heterocycles which play crucial roles in a wide variety of functions of living species. As nucleotides (AMP, GMP), they are the building blocks of nucleic acids (RNA/DNA). They serve as energy cofactors (ATP, GTP), as part of coenzymes (NAD/FAD) in oxidation-reduction reactions, as important second messengers in many intracellular signal transduction processes (cAMP/cGMP, or as direct neurotransmitters by binding to purinergic receptors (adenosine receptors). Therefore, it is not surprising that the analogues of purines have found utility both as chemotherapeutics (antiviral, antibiotic, and anticancer agents) and pharmacodynamic entities (regulation of myocardial oxygen consumption and cardiac blood flow). They can also act as substrates or inhibitors of enzymes of purine metabolism (ADA, Guanase, HGPRTase, PNPase, etc) in order to exert their chemotherapeutic property. In addition, their ability to act as agonists or antagonists of A1/A2A receptors is the basis for modulation of pharmacodynamic property. Finally, they can be excellent probes for elucidation of biochemical mechanisms (e.g. fluorescent -adenosine) and biophysical characteristics of nucleic acids (e.g. 8-bromoguanosine).
The availability of new methods for metal-mediated coupling with aryl or heteroaryl halide substrates has expanded the range of synthetically accessible aryl-purine derivatives. For example, aryl boronic acids are now readily available reagents for metal-mediated C-C and C-N coupling reactions. The palladium and nickel catalysts catalyze the coupling reactions that result in C-C bond formation at positions C2, C6 and C8 of purines. The reactivity at C6 position has been successfully demonstrated using fluoro-, chloro-, bromo-, iodo-, sulfanyl, sulfonyloxy- and azole-substrates. Copper-mediated N-arylations are known to occur at positions N7 and N9. These methods are also applicable using solid-supported purine substrates and provide convenient access to structurally diverse purine derivatives with applications in drug discovery. 
Since the topic on “Purines and Its Derivatives” is obviously too vast and broad to cover it all in a single issue, and considering that this special issue is released as part of the journal “Pharmaceuticals”, we will mainly focus on medicinal and pharmaceutical aspects of purines that are deemed most important based on the recent literature published during the last 5 years or so. The following are only some of the representative topics, and in no way meant to be a comprehensive list. Any subject that deals with medicinal and pharmaceutical aspects of purines in the broadest sense will be given due consideration for inclusion.

(1) Role of purines in the regulation of metabolic networks and signal transduction: 
(2) Use of uric Acid and its derivatives in the treatment of multiple sclerosis (MS) and Parkinson’s disease (PD 
(3) Use of fludarabine and its analogs in the treatment of chronic lymphocytic leukemia (CLL)
(4) The role of purine-based cyclin-dependent kinase (CDK) inhibitors in promoting apoptosis of cancer cells
(5) C-8 Aryl purines and their nucleoside/nucleotide derivatives
(6) Purinome as the target for drug discovery 
(7) Use of cyclonucleosides in the treatment of viruses and cancer
(8)Synthesis and use of 8-Azapurines with antiviral and anticancer properties: 
(9) Synthesis and use of thiopurines in the treatment of leukemia 
(10) Targeting purine salvage pathway for development of antimalarials

Prof. Dr. Ramachandra S. Hosmane
Guest Editor

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