Adenosine is a purine nucleoside that regulates many physiological functions which includes respiratory regulation, neural function ,platelet aggregation, hormonal action ,lymphocyte differentiation, vascular tone, negative chronotropic and dromotropic effect on heart , also mediates inhibition of neurotransmitter release and lipolysis . These physiological function have been largely revised.(1),(2)
These functions are mediated through different adenosine receptor. There are four subtypes of AR-A1,A2A-AR,A2B-AR,A3-AR each of these receptors has distinct tissue distribution and effector coupling. They belong to super family of G-protein coupled receptors (3).among these receptors A1,A3AR1 are closely related based on their sequence similarity while A2A,A2B AR also similarly related. A1 and A3 are primarly couple to G(subi) –family of G-protein.A2A and A2B are mostly coupled to GS like G- protein. Each of these receptors plays an essential role in responding to adenosine in central nervous system(4) ,regulating pain (5) . cerebral blood flow(6). Basal gangalia function (7) respiration (8) and sleep (9.) thus these receptors can be therapeutic targets for several diseases. Development of more selective agonists and antagonists for adenosine receptor subtype provide aclass of therapeutics for treatment of numerous human diseases such as apain (10). parkinsons disease (11) asthma(12) huntingtons disease(13).A search for new leads acting on specific adenosine acting on specific adenosine receptors may provide a key for novel therapeutics
. A2A-AR subtype is linked to and G(S) and G(OLF) protein and up on activation the intracellular levels of Camp are increased . the expression A2A AR expression is higest in brain, .spleen,thymus,leucocyte and blood platelets and intermediate in heart lungs and blood vessel.(14)(15)..Crystal structure of A2A AR was determined in 2008,physiological functions A2A AR are regulation of sensori motors integration in basal ganglia., inhibition of platelet aggregation and polymorpho nuclear leucocytes, vasodilation protection against ischemic damage, stimuation of sensory nerve activity . (17) these wide range of functions implies their significant role in the body and use of chemical moieties to alter these function in disease state (may be agonists or antagonists).
A2A AR antagonist have their role in parkinsons disease, (18) keep regulations (19) controlling alcohol abuse (20) invivo receptor imaging (21) there can also be used an anti depressant drug. (22) A2 AR agonists can be a treatment for ischemic renal injure (23) paraoxysmal supro ventricular tachycardia. They can be used as vasodilators (24) antithrombic agent (25) antinflamatory (26) . they can also be used in treatment of asthma( 27), arthritis(28) sepsis (29) inflamatory bowel disease (30) and reduced skin pressure ulcer formation (26) and accelerator wound healing,(31)
Structure of Adenosine
In view of the role of A2A AR in these diseases afurther study in to the subject may reveal beneficial (facts) information for the treatment of such dieases. These receptors became agood targeting strategy to bring out novel therapeutics for effective treatment of dieases..So a 3D QSAR study was taken up on the ligands of A2A receptors to identify a new lead molecule based on pharmacophore model generated.
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