MXPA06008521A - Myocardial persufion imaging using adenosine receptor agonists - Google Patents

Abstract

A myocardial imaging method that is accomplished by administering one or more adenosime A2A adenosine receptor agonist to a human undergoing myocardial imaging as well as pharmaceutical compositions comprising at least one A2a receptor agonist, at least one liquid carrier, and at least one co-solvent.

Description

FORMATION OF MYOCARDIAL PERFUSION IMAGES USING AGENISTS OF ADENOSINE RECEPTORS BACKGROUND OF THE INVENTION FIELD OF THE INVENTION The invention relates to methods of imaging that have been made possible by administering doses of one or more adenosine adenosine receptor agonists of adenosine A2A to a mammal that is undergoing imaging of the myocardium. This invention also relates to pharmaceutical compositions useful in methods of myocardial imaging. DEPARTURE OF THE TECHNIQUE Myocardial perfusion imaging (MPI) is a useful diagnostic technique for the detection and characterization of coronary artery disease. Perfusion imaging uses materials such as radionuclides to identify areas of insufficient blood flow. In MPI, blood flow is measured at rest, and the result is compared to the blood flow measured during exercise in a camper (cardiac stress test), such exercise is necessary to stimulate blood flow. Unfortunately, many patients are not able to exercise at the levels necessary to provide sufficient blood flow, due to medical conditions such as peripheral vascular diseases, arthritis and the like. Therefore a pharmacological agent that increases cardiac blood flow (CBF) for a short period of time would be of great benefit, particularly one that does not cause peripheral vasodilatation. Vasodilators, for example dipyridamole, have been used for this purpose in patients before radionuclide imaging. Dipyridamole is an effective vasodilator, but side effects such as pain and nausea limit the use of the treatment of this compound. Adenosine, a naturally occurring nucleoside, is also useful as a vasodilator. Adenosine exerts its biological effects by interacting with a family of adenosine receptors characterized as subtypes Ai, A2A, A2B and A3. Adenoscan® (Fujisaea Healthcare Inc) is a formu- lation of an adenosine of natural origin. Adenoscan® has been marketed as an adjuvant in perfusion studies using radioactive thallium-201. However its use is limited due to side effects such as dizziness, chest problems, the urgent need to exhale deeply, headache and throat, neck and jaw. These adverse effects of adenosine are due to the activation of other subtypes of adenosine receptors other than A2A, which mediate the vasodilatory effects of adenosine. Additionally, the short half-life of adenosine requires multiple treatments during the procedure, further limiting its use. Adenoscan® is contraindicated in many patients including those with sinus node disease with second or third degree blockage, bronchoconstrictive or bronchospastic lung disease and patients with known hypersensitivity to the drug.

Other potent and selective agonists are known for the adenosine A2A receptor. For example MRE-0470 (Medco) is an adenosine A2A receptor agonist which is a potent and selective adenosine derivative. MRC-0470 (Medco) is an adenosine A2A agonist that is used as an adjuvant in imaging. In general, compounds such as those having a high affinity for the A2A receptor and consequently, a long duration of action which is undesirable in imaging. Therefore there is still a need for a method to produce rapid and maximal coronary vasodilatation in mammals without causing the corresponding peripheral vasodilatation, which will be useful for imaging with radionuclide agents. Preferred compounds would be selective for the adenosine A2A receptor and will have a short period of action (although they act for longer than compounds such as adenosine), avoiding the need for multiple doses. SUMMARY OF THE INVENTION The following are several aspects of the present invention. A method for producing coronary vasodilatation without peripheral vasodilatation in a human consisting of administering to the human at least 10 μg of at least one receptor agonist A2A- A method for producing coronary vasodilatation without peripheral vasodilation in a human consisting of administering to the human no more than 1000 μg of an A2A receptor agonist.

A method for producing coronary vasodilatation without 'peripheral vasodilation in a human which' consists in administering to the human an A2A receptor agonist in an amount in the range of from about 10 to 600 μg. A method for producing coronary vasodilatation without peripheral vasodilatation in a human consisting of administering to the human approximately 300 μg of at least one 'A2A receptor agonist. A method for producing coronary vasodilatation without peripheral vasodilation in a human consisting of administering to the human approximately 400 μg of at least one A2A receptor agonist - A method for producing coronary vasodilatation without peripheral vasodilation in a human consisting of administering to the human about 500 μg of at least one A2A receptor agonist. A method for producing coronary vasodilatation without peripheral vasodilation in a human consisting of administering to the human approximately 600 μg of at least one A2A receptor agonist. A method for producing coronary vasodilation without peripheral vasodilation in a human consisting of administering to the human approximately 700 μg of at least one A2A receptor agonist. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount in the range of about 10 to 600 μg and in wherein the A2A receptor agonist is administered in a single dose. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein in a single dose approximately 300 μg of the A2A receptor agonist is administered. A method for the perfusion imaging of a human myocardium consisting in administering a radionuclide and an A2A receptor agonist wherein in a single dose approximately 400 μg of the A2A receptor agonist is administered. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein in a single dose approximately 500 μg of the A2A receptor agonist is administered. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein in a single dose approximately 600 μg of the A2A receptor agonist is administered. A method for the formation of perfusion images of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein in a single dose approximately 700 μg of the A2A receptor agonist is administered. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount in the range of about 10 to 600 μg and wherein the A2A receptor agonist is administered by means of an intravenous bolus. A method for perfusion imaging the myocardium of a human consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount in the range of about 0.05 to 60 μg / kg and wherein the A2A receptor agonist is administered by means of an intravenous bolus. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in a amount in the range of about 0. 1 to 30 μg / kg and wherein the A2A receptor agonist is administered by means of an intravenous bolus. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount not greater than about 20 μg / kg - to a supine patient and wherein the A2A receptor agonist is administered by means of an intravenous bolus. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount not greater than about 10 μg / kg to a patient standing and wherein the A2A receptor agonist is administered by means of an intravenous bolus. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount in the range of about 10 to 600 μg and in where the A2A receptor agonist is administered in about 20 seconds. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist in an amount in the range of about to 600 μg and wherein the A2A receptor agonist is administered in less than about 10 seconds. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount greater than about 10 μg. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount greater than about 100 μg. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount not greater than about 600 μg. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount not greater than about 500 μg. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is administered in an amount of about 1000 μg to 500 μg and preferably about 400 μg. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the A2A receptor agonist is selected from the group consisting of CVT-3033, CVT-3146 and combinations thereof . A method for the perfusion imaging of a human myocardium consisting of administering to humans a radionuclide and about 300 μg of a compound selected from the group consisting of CVT-3033, CVT-3146. A method for the perfusion imaging of a human myocardium consisting in administering to the human a radionuclide and approximately 400 μg of a compound selected from the group consisting of CVT-3033, CVT-3146. A method for the perfusion imaging of a human myocardium which consists in administering to the human a radionuclide and approximately 500 μg of a compound selected from the group consisting of CVT-3033, CVT-3146. . A method for the perfusion imaging of a human myocardium which consists of administering to humans a radionuclide and approximately 600 μg of a compound selected from the group consisting of CVT-3033, CVT-3146. A method for the perfusion imaging of a human myocardium which consists of administering to humans a radionuclide and approximately 700 μg of a compound selected from the group consisting of CVT-3033, CVT-3146. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist in which the myocardium is examined in an area of insufficient blood flow after the administration of the radionuclides and the agonist of A2A receiver. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist in which the myocardium is examined in an area of insufficient blood flow after administration of the radionuclides and the receptor agonist A2A, starting with the myocardial examination in the course of 1 minute from the moment in which the A2A receptor is administered. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the administration of the A2A receptor agonist causes an increase of at least 2.5 times in the coronary blood flow. A method for training of images by perfusion of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the administration of the A2A receptor agonist causes an increase of at least 2.5 times in the coronary blood flow which is reached in the course of about 1 minute from the moment when the A2A receiver is admired. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the radionuclides and the A2A receptor agonist are administered separately. A method for the perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein the radionuclides and the A2A receptor agonist are administered simultaneously. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein administration of the A2A receptor agonist causes an increase of at least 2.5 times in coronary blood flow for less than about 5 minutes. A method for perfusion imaging of a human myocardium consisting of administering a radionuclide and an A2A receptor agonist wherein administration of the A2A receptor agonist causes an increase of at least 2.5 times in coronary blood flow for less than about 3 minutes. A method for perfusion imaging of a human myocardium consisting of administering CVT-3146 in an amount in the range of about 10 to 600 μg in a single intravenous bolus. A method for perfusion imaging of a human myocardium which consists of administering CVT-3146 in an amount in the range of about 1 00 to 500 μg and more preferably of about 400 μg in a single intravenous bolus. A method for perfusion imaging of a human myocardium consisting of administering CVT-3146 in an amount in the range of about 10 to 600 μg which is independent of the weight of the human receiving the dose. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the A2A receptor agonist is selected from the group consisting of CVT-3033, CVT-3146 and combinations thereof . Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the liquid carrier consists of water, distilled water, deionized water, saline solution, a buffer, or combinations thereof . Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent consists of methylboronic acid, borate buffer, propylene glycol or polyethylene glycol. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is methylboronic acid. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is methylboronic acid and wherein the A2A receptor agonist is CVT-3146. Pharmaceutical compositions containing CVT-3146, at least one liquid carrier and at least one co-solvent, wherein the cosolvent is methylboronic acid and wherein CVT-3146 is present in an amount in the range of about 50 micrograms / ml to about 250 micrograms / ml and the methylboronic acid is present in an amount of about 0.4% to 0.6% (p: v). Pharmaceutical compositions containing CVT-3146, at least one liquid carrier and at least one co-solvent, wherein the cosolvent is methylboronic acid has a pH of about 9.1 to 9.4. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is a borate buffer and preferably about 0.5% (p: v) methylboronic acid . Pharmaceutical compositions containing at least one A2A receptor agonist; at least one liquid carrier and at least one co-solvent, wherein the co-solvent is a borate buffer and preferably about 0.5% (p: v) of methylboronic acid and wherein the composition further contains a buffer to carry the pH of the composition at about 9.3. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is a borate buffer and the A2A receptor agonist is CVT-3146 which is preferably present in the composition in an amount of about 50 to 150 micrograms / ml. Pharmaceutical compositions containing at least one A2A receptor uri agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is a borate buffer and the A2A receptor agonist is CVT-3146 which is preferably present in the composition in an amount of about 50 to 150 micrograms / ml and wherein the composition also contains about 0.55% (p: v) chloride of. sodium and 50 mM sodium bicarbonate. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is propylene glycol and propylene glycol is present in an amount of about 5% to 25% ( p: v) and preferably in an amount of about 8% to 20% (p: v). Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is propylene glycol and propylene glycol is present in an amount of about 5% to 25% ( p: v) wherein the liquid carrier includes a buffer to bring the pH of the composition to about 6 to 8. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent , wherein the co-solvent is propylene glycol and the propylene glycol is present in an amount of. about 5% to 25% (w: v) and the composition also contains EDTA. Pharmaceutical compositions containing at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the co-solvent is propylene glycol and propylene glycol is present in an amount of about 5% to 25% ( p: v) and preferably in an amount of about 8% to 20% (p: v), wherein the A2A receptor agonist is CVT-3146 which is preferably present in the composition in an amount of about 50 to 1 50 micrograms. A method for producing coronary vasodilatation without peripheral vasodilation consisting of administering to a human the pharmaceutical composition consisting of at least one A2A receptor agonist, when at least one liquid carrier and at least one cosolvent. A method for producing coronary vasodilatation without peripheral vasodilation consisting of administering to a human the pharmaceutical composition consisting of at least one A2A receptor agonist, at least one carrier liquidated and at least one cosolvent, wherein the A2A receptor agonist it's CVT-3146. A method for producing coronary vasodilatation without peripheral vasodilation consisting of administering to a human the pharmaceutical composition consisting of at least one A2A receptor agonist, at least one liquid carrier and at least one cosolvent, wherein the A2A receptor agonist is CVT-3146 and wherein the pharmaceutical composition is administered by intravenous bolus. A method for producing coronary vasodilatation without peripheral vasodilation consisting of administering to a human the pharmaceutical composition consisting of at least one A2A receptor agonist, at least one liquid carrier and at least one co-solvent, wherein the A2A receptor agonist is CVT-3146 and wherein the pharmaceutical composition is administered by intravenous bolus and wherein the pharmaceutical composition is administered in about 10 to 20 seconds. A method for producing coronary vasodilatation without peripheral vasodilation consisting of administering to a human the pharmaceutical composition consisting of at least one A2A receptor agonist, at least one liquid carrier and at least one cosolvent, wherein the A2A receptor agonist is CVT-3146 and where the total amount of CVT-3146 that is administered is. is in the range of about 100 to 500 μg and more preferably of about 400 μg. In all the above methods the dose is preferably administered in a single dose. In all of the above methods, at least one radionuclide is administered before, with or after administration of the A2A receptor agonist to facilitate myocardial imaging. In all of the above methods, the dose is preferably administered in 60 seconds or less, preferably in 30 seconds or less, and more preferably in 20 seconds or less. DESCRIPTION OF THE FIGURES Figure 1 shows intracoronary Doppler flow profiles that after administration of 18 μg of adenosine IC bolus (top) and 30 μg IV bolus of CVT-3146; Figure 2 is a graph showing the dose ratio of CVT-3146 on peak coronary flow rates; Figure 3 is a table that reports the length of time the coronary flow velocity is greater than or equal to 2.5 times the coronary flow rate base for different doses of CVT-3 46 where "n" refers to the number of patients dosed humans; Figure 4 is a graph of the time course of the average peak rate (APV) ratio for human patients receiving 400 μg intravenous bolus of CVT-3146; Figure 5 is a graph of the heart rate time course of human patients receiving 400 μg of intravenous bolus CVT-3146; Figure 6 is the time course of blood pressure of human patients receiving 400 μg of intravenous bolus CVT-3146; and Figure 7 is a table of adverse events; . Figure 8 is a plot of the change over time of the measured plasma concentration of CVT-3146 in healthy male volunteers in a supine position. The different curves refer to different amounts of CVT-3146 administered to patients; Figures 9 and 10 are graphs of the mean change in heart rate of healthy male volunteers either standing or supine over time for different bolus dosing levels of CVT-3146; Figure 11 is a graph of the maximum load of the heart rate in relation to the total dose of CVT-3146 administered to male human patients standing or in supine position. In the graph the term "DBS" refers to the observed data point while "adjus refers to a signature adjusto the observed data points; Figure 12 is a graph of the heart rate (area under the curve) AUC (0-15 minutes) of the change from the baseline in relation to the total dose of CVT-3146 administered to unemployed or supine human individuals; Figure 13 is a graph of the maximum change in base heart rate at a plasma concentration of CVT-3146 for patients in a supine position; Figure 14 is a graph of the heart rate (area under the curve - time vs. effector) AUCE (0-15 minutes) of change of baseline vs. (AUC plasma AUC (0-15 minutes) for patients in a supine position Figure 15 is a graph of the time profiles of change in heart rate from baseline versus mean plasma concentration over time for a dose of 20 μg / kg of CVT-3146; Figure 16 is a graph of the average peak blood flow velocity over time after the administration of CVT-3146 measured in the pulmonary artery (PA), for four arteries of the limbs (FA) the arterial vasculature of the brain (BA) and the left circumflex coronary artery. Figure 17 is a graph of the percentage change in heart rate (HR) and blood pressure (BP) for various doses of CVC-3146; and Figure 18 is a graph of the change in blood flow LBF and RBF after administering ADO or CVT-3146 growths to awake dogs. DISCLOSURE OF THE INVENTION Strong A24 agonists are useful as adjuncts in imaging when they are added either prior to dosing with an imaging agent or simultaneously with an imaging agent. Suitable imaging agents include 201Talium or 99mTechnecio-Sestamini, 99mTcTeboroxima and new and potent A24 agonists have been identified that elevate CBF but do not significantly increase peripheral blood flow. The A2 agonists and especially CVT-3146 and CVT-3033 have a rapid onset and a short duration when administered. An unexpecand recently identified benefit of these new compounds is that they are very useful when administered in a very small amount in a single bolus intravenous (i.v.) injection. Receptor agonists of A24 can be administered in amounts as small as 10 μg and as high as 600 μg or more and still be effective with few or no side effects. An optimal dose may include only 10 μg and at most 600 μg or more and still be effective with few laeral effec ions. An optimal dose may include only 10 μg and when many approximately 1000 μg or more of an A2 receptor agonist. More preferably an optimal dose will be in the range of about 1 to 500 μg of at least one agonist of the A24 receptor. It is preferred that the A24 receptor agonist be administered in a single bolus injection in a selecamount of between about 300 μg., 400 μg, 500 μg, 600 μg and 700 μg. These amounts are unexpectedly small when compared to the adenosine which is typically administered conIminally by IV infusion at a dose of approximately 140 μg / kg / min. Cantráriamenfe to adenosine, the same dosage of the agonisías of receptors A24, and in paríicular CVT-3146 and CVT-3033 can be administered to a human patient without íomar in the weight of the patient. Thus the administration of a single uniformity of A24 receptor agonists by intravenous bolus for myocardial imaging is dramatically simpler and less prone to error than administration depends on the time and weight of adenosine. The dose of agonisia of receptacle A2 administered to a human patient, however, can be determined by weight. Typically, a dose based on weight will be in the range of about 0.05 to 60 μg / kg and more preferably about 0.1 to 20 μg / kg. CVT-3146 in particular is generally well tolerated when administered in a dose of 10 to 10 μg / kg in unemployed patients and 20 μg / kg in patients in the supine position. The agonisies A2 of this invention can be administered orally, intravenously, through the epidermis by means of other methods known in the art for administering analogous agents, with intravenous bolus administration being preferred. In another mode, the bolus dose occurs in 60 seconds or less. In still another embodiment, bolus dosing occurs in about 30 seconds or less and more preferably in about 20. seconds or 'less or in approximately 1 0 seconds or less. The A2 agonists of this invention will preferably be administered in a single dose. The term "single dose" generally refers to a single dose administered rapidly from an epileptic canine of at least one agony of recipient A24. The term "" Single dose "does not include a dose or doses administered for an extended period of time, for example by means of i.v. keep going. One aspect of the invention is directed to pharmaceutical compositions. The term "pharmaceutical composition" refers to a combination of one or more agonist compounds of the A24 receptor agonist of this invention with at least one liquid carrier which together form a solution or suspension. Freeze-dried powders including compositions of this invention fall within the scope of the invention. The scope of the "pharmaceutical compositions" whenever the powders are intended will be reconstiuted by the addition of a suitable liquid portion prior to use Examples of suitable liquid carriers include but are not limited to water, paraffinised water, deionized water, saline, amorphous solutions , normal saline solutions, isoxy, dexory in water, and combinations thereof These pharmaceutical compositions are generally suitable for injection The term "amorphous solution" or "buffer" as used herein refers to a solution containing tannin a weak acid and its weak conjugate base. they are used in pharmaceutical compositions of this invention in order to resist changes in pH. Nonimitable examples of buffer solutions are solutions that contain sodium bicarbonate and sodium phosphate. The A24 receptor agonists of this invention are prepared and then administered with or without an intermediate storage, as a pharmaceutical composition. Several properties considered in formulating the pharmaceutical compositions of this invention include but were not limited to the shelf life of the product, the solubility of the recepfor A2A agonism, the solubility of the receptor agony, the pH of the composition, the irritation of the veins, hemolysis, storage conditions (eg the pharmaceutical composition will be stored at ambient temperature or other temperature) and the ability to withstand the sterilization procedure. One method to achieve the desired pharmaceutical composition properties is to include a co-solvent in the pharmaceutical composition. The co-solvent may be selected from any liquid or compound in solution that imparts the desired properties to the pharmaceutical compositions. Examples of useful co-solvents, include, but are not limited to, methyloboronic acid, boral acid amorphous, propylene glycol or polyethylene glycol. The amount of co-solvent in the pharmaceutical composition will depend on the properties, as well as the solubility and stability of the A2A receptor agonisia. A preferred A2A receptor agonism of the invention is CVT-3146. CVT-3146 has a solubility in water of approximately 50 micrograms / ml. Therefore, CVT-3146 can be dissolved and administered in water as long as the desired amount of weight of CVT-3146 can be administered in an acceptable volume. For example, a preferred dose of about A00 micrograms can be administered in 8 ml of water. If this volume is too large for administration purposes or if the pharmaceutical composition is stored at a temperature different from the ambient (RT), then additional ingredients may be added to the composition to increase the solubility of CVT-3146 in the composition and / or to provide the resulting pharmaceutical composition with other improved properties such as improved stability and storage properties. The pharmaceutical compositions of this invention including CVT-3146 can include up to about 1 milligram / ml of CVT-3146. It is preferred that pharmaceutical compositions including CVT3146 include from about 50 to 250 micrograms / ml, and more preferably from about 50 to 150 micrograms / μl of CVT-3146. In order to improve the solubility and storage properties, the A2A receptor agonisias of this invention can be administered in a pharmaceutical composition including methylboronic acid co-solvent (M BA). The methylboronic acid is added to the pharmaceutical composition to improve the solubility of the agonist and its shelf life. MBA increases the pH of the resulting composition. The solubility of CVT-3146 is a pharmaceutical composition that includes MBA tends to decrease as the pH of the composition approaches the neutro. Therefore with CVT-3146, the pH of an MBA-containing composition is about 8.5 to 10 with a pH of about 9.1 to 9.4 being preferred and the most preferred pH being about 9.3. This corresponds to a composition that includes from about 50 to 250 mg / ml of MBA. As an alternative to MBA, CVT-3146 can be combined with a borate buffer solution. Typically, a borage solution can consist of an aqueous solution of sodium bromide that has been adjusted to the desired pH as a pH of 9.3 using an acid or a base. Pharmaceutical compositions containing MBA may suffer from storage problems. In fact MBA can cause delamination when it is packaged in certain type of glass I containers. This problem can be solved by storing the pharmaceutical compositions containing MBA in plastic containers or in a more resistant type of glass I. If pharmaceutical compositions are desired which contain an A2A receptor agonist having a pH close to neutral, then an allynaire is to combine the A2A receptor agonists with a propylene glycol co-solvent. { PG). The amount of PG used in the composition may be in the range of about 5% to 25% by volume, with a range of from about 8% to about 20% by volume when using CVT-3 46. An alternative to PG is polyethylene glycol PEG. A PEG will have an average molecular weight of approximately 200 to 400. Preference is given to the composition CVT3146 which includes PG or PEG will have a pH of from or about 6 to 8 with a pH of about 7 being preferred. Any physiologically acceptable absorber capable of adjusting the pH of the composition to the desired value can be used. . Additional optional optional ingredients such as EDTA and dimethylacetamide can also be used in the composition.

The pharmaceutical compositions of this invention can include one or more anti-oxidants such as hydroxyanisoles (BHA). A first class of compounds which are polysis and selective agonies for the adenosine A2A receptor which are useful in the methods of this invention are the 2-adenosine N-pyrazole compounds having the formula: wherein R1 = CO2OH, -CONR5R6; R3 is independently selected from the group consisting of alkyl with from 1 to 1 5 carbon atoms, halo, NO2, CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2 , SO2NR20COR22, SO2NR20CO2R22, SO2NR20CON (R20) 2, N (R20) 2NR20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, CO2R20, CON (R20), CONR20SO2R22, NR20SO2R22, SO2R20CO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20, and OCON (R20) 2-CONR7R8, alkenyl with 2 to 15 carbon atoms, alkynyl with 2 to 15 carbon atoms, heteroaryl, aryl and heteroaryl, wherein the alkyls of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected from the group consisting of halo, alkyl, NO2, heterocyclyl, aryl, heteroaryl, CF3, CN, OR20, SR20, N (R20 ) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2N R20COR22, SO2N R20CO2R22, SO2NR20CON (R20) 2, N (R20) 2NR20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20 , CO2R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 and wherein optionally substituted heteroaryl, aryl and heterocyclyl substituents are optionally susíiuidos with halo, NO2, arquilo, CF3, amino, mono- or dialkylamino, alkyl or aryl or heieroarii amide, NCOR22, NR 0SO2R22, COR20, CO2R20, CON (R20) 2, NR20 (CON (R20) 2, OC (O) R20, OC (O) N (R20) 2 , SR20, S (O) R22, SO2R22, SO2N (R20) 2, CN or OR20, R5 and R6 is selected individually from H, and alkyl having from 1 to 15 carbon atoms which is optionally susiiuid with from 1 to 2 susíiuuyeníes independently selected from the group of halo, NO2, heterocyclyl, aryl, heeroaryl, CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2NR20COR22, SO2N R20CO2R22, SO2NR20CON ( R20) 2, N (R20) 2NR20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, CO2R20, CON (R20), WITH R20SO2R22, NR20SO2R22, SO2R20CO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20, and OCON (R20) 2, and wherein the heteroaryl derivatives of aryloyl, aryl and optionally optionally substituted heterocyclics are optionally susiituted with halo, NO2, alkyl, CF3, amino, monoalkylamino, dialkylamino, alkylamide, arylamide, heteroarylamide, NCOR22, NR20SO2R22, COR20, CO2R20, CON (R20) 2, NR20 (CON (R20) 2, OC (O) R20, OC (O) N (R20) 2, SR20, S (O) R22, SO2R22, SO2N (R20) 2, CN or OR20; R7 is selected from the group consisting of hydrogen, alkyl having from 1 to 15 carbon atoms, alkenyl having from 2 to 15 carbon atoms, alkynyl having from 2 to 15 carbon atoms, heteroaryl, aryl and heteroaryl, wherein the amino acids of alkyl, alkenyl, alkynyl, aryl, heteroaryl and heteroaryl are optionally susiuuid with from 1 to 3 substituents independently selected from the group consisting of halo, NO2, heterocyclyl, aryclo, heteroaryl, CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2NR20COR22, SO2NR20CO2R22, SO2NR20CON (R20) 2, N (R20) 2N R20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, C02R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, 'OCON R20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 and wherein the optionally substituted heteroaryl, aryl and heteroarylcyl substituents are optionally halogen, NO2, alkyl, CF3, amino, mono- or dialkylamino, alkyl or aryl or heeroaryl amide, NCOR22, NR20SO2R22, COR20, CO2R20, CON (R20) 2, NR20 (CON (R20) 2, OC (O) R20, OC (O) N (R20) 2, SR20, S (O) R22, SO2R22, SO2N (R 0) 2, CN or OR20; R8 is selected from the group consisting of hydrogen, alkyl having 1 to 1 5 carbon atoms, alkenyl having 2 to 15 carbon atoms, alkynyl having 2 to 15 carbon atoms, heterocyclyl, aryl. and heteroaryl, wherein the substituents of alkyl, alkenyl, alkynyl, aryl, heterocyclyl and heteroaryl are optionally substituted with from 1 to 3 substituents independently selected from the group consisting of halo, NO2, heterocyclyl, aryl, heteroaryl, CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2NR20COR22, SO2NR20CO2R22, SO2NR20CON (R20) 2, N (R20) 2NR20COR22, NR20CO2R22, NR 0CON (R20) 2, NR20C (NR20 ) NHR23, COR20, CO2R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 and wherein the optionally substituted heteroaryl, aryl and heteroaryl substituents are optionally substituted with halo, NO2, alkyl, CF3, amino, mono- or dialkylamino, alkyl or aryl or heteroaryl amide, NCOR22, NR20SO2R22, COR20, CO2R20, CON (R20) 2, NR0 (CON (R20) 2, OC (O) R20, OC (O) N (R20) 2, SR20, S (O) R22 , SO2R22, SO2N (R20) 2, CN or OR20, R20 is selected from the group consisting of H, alkyl having from 1 to 15 carbon atoms, alkenyl having from 2 to 15 carbon atoms, alkynyl having from 2 to 15 atoms from carbon, heteroaryl, aryl and heteroaryl, wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl and heteroaryl substituents are optionally substituted with 1 to 3 independently selected halo, alkyl, mono- or dialkylamine, alkyl- or aryl - or heyeroarylamide, CN, OC -? - 6 alkyl, CF3, aryl and heeroaryl, R22 is selected from the group consisting of alkyl with from 1 to 15 carbon atoms, alkenyl with 2 to 15 carbon atoms, alkynyl with 2 to 15 carbon atoms, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkenyl, alkynyl, heterocyclyl, aryl and heteroaryl substituents are optionally substituted with from 1 to 3 substituents independently selected from halo, alkyl, mono- or dialkylamino, alkyl- or aryl- or heteroarylamide, CN, O-C1-6 alkyl, CF3, aryl and heteroaryl; and wherein R2 and R4 are selected from the group consisting of H, alkyl and aryl having from 1 to 6 carbon atoms, wherein the alkyl and aryl substituents are optionally substituted with halo, CN, CF3, OR20 and N (R20) 2 with the proviso that when R2 is not hydrogen then R4 is hydrogen, and when R4 is not hydrogen then R2 is hydrogen. In a related group of compounds of this invention R 3 is selected from the group consisting of alkyl with from 1 to 15 carbon atoms, halo, CF 3, CN, OR 20, SR 20, S (O) R 22, SO 2 R 22, SO 2 N (R 20) 2 , COR20, CO2R20, -CONR7R8, aryl and heeroaryl wherein the alkyl, aryl and heteroaryl derivatives are optionally substituted with 1 to 3 independently selected subsides of the halo, aryl, heteroaryl, CF3, CN, OR20, SR20, S (O) R22 group. , SO2R22, SO2N (R20) 2, COR20, CO2R20 or CON (R20) 2, and wherein each of the heteroaryl and aryl subsides is optionally substituted with halo, alkyl, CF3, CN and OR20; R5 and R6 are selected from the group of H and alkyl with from 1 to 15 carbon atoms including a sub-aryl group. optional and each optional aryl substitute which is optionally susíiido cpn halo or CF3; R7 is selected from the group consisting of alkyl with from 1 to 15 carbon atoms, alkynyl with from 2 to 15 carbon atoms, aryl and hepheroaryl, wherein the allyl, alkynyl, aryl and heteroaryl substituents are optionally substituted with from 1 to 3 independent substituents selected from the group ^ consisting of halo, aryl, heteroaryl, CF3, CN, OR20, and each heteroaryl and aryl is optionally substituted with halo, alkyl, CF CN or OR20; R8 is selected from the group consisting of hydrogen and alkyl with from 1 to 15 carbon atoms; R 20 is selected from the group consisting of H, alkyl and aryl having 1 to 4 carbon atoms, wherein the alkyl and aryl substitutes are optionally substituted with one alkyl substituent; and R22 is selected from the group consisting of alkyl and aryl having from 1 to 4 carbon atoms which are optionally substituted with from 1 to 3 alkyl groups. In another related class of compounds R1 is CH2OH; R3 is selected from the group consisting of CO2R20, -CONR7R8 and aryl wherein the optionally aryl substituted aryl is optionally substituted with 1 to 2 substituents independently selected from the group consisting of halo, alkyl having 1 to 6 carbon atoms, CF3 and OR20; R7 is selected from the group consisting of hydrogen, alkyl or aryl having from 1 to 8 carbon atoms, wherein the alkyl and aryl substituents are optionally susíiuuidos with a susíiuyenyen selected from the group consisting of halo, aryl, CF3 CN or OR20 and in where each optional aryl agent is optionally suspended with halo, alkyl, CF3, CN or OR20; R8 is selected from the group consisting of hydrogen and alkyl with from 1 to 8 carbon atoms; and R20 is selected from hydrogen and alkyl with from 1 to 4 carbon atoms. I still have a related class of compounds of this invention, R1-CH2OH; R3 is selected from the group consisting of CO2R20, -CONR7R8 and aryl which is optionally substituted with a substituent selected from the group consisting of halo, alkyl having from 1 to 3 carbon atoms and OR20; R7 is selected from hydrogen, and alkyl having from 1 to 3 carbon atoms; R8 is hydrogen and R20 is selected from hydrogen and alkyl having from 1 to 4 carbon atoms. In this preferred embodiment R3 is selected most preferably from -CO2Et and -CONHEt. In still another related class of compounds R1 = - CONHEi, R3 is selected from the group consisting of CO2R20, -CONR7R8, and aryl in that aryl is optionally susíiuido with from 1 to 2 susíiuuyeníes independently selected from the group consisting of halo, alkyl with 1 to 3 carbon atoms, CF3 or OR20; R7 is selected from the group consisting of hydrogen and alkyl having from 1 to 8 carbon atoms optionally susiiuuid with a susiiuyenyen selected from the group consisting of halo, CF3, CN or OR20; R8 is selected from the group consisting of hydrogen and alkyl having from 1 to 3 carbon atoms; R20 is selected from the group consisting of hydrogen and alkyl with from 1 to 4 carbon atoms. In this most preferred embodiment, R8 is preferably hydrogen, R7 is preferably selected from the group consisting of hydrogen, and alkyl having from 1 to 3 carbon atoms, and R20 is selected preferentially from the group consisting of hydrogen and alkyl having from 1 to 4 atoms of carbon. Specific useful compounds are selected from 1-. { 9 - [(4S, 2R, 3R, 5R) -3,4-Dihydroxy-5- (2-hydroxymethyl) oxolan-2-yl] -6-aminopurin-2-yl} 3-yl pyrazole-4-carboxylic acid, (4S, 2R, 3R, 5R) -2-. { 6-amino-2- [4- (4-chlorophenyl) pyrazolyl] purin-9-yl} -5 (hydroxymethyl) oxolahe-3,4-diol, (4S, 2R, 3R, 5R) -2-. { 6-amino-2- [4- (4-methoxyphenyl) pyrazolyl] purin-9-yl} -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2. { 6-amino-2- [4- (4-meitylphenyl) pyrazolyl] purin-9-yl} -5- (hydroxymethyl) oxolane-3,4-diol, (1 -. {9 - [(4S, 2R, 3R, 5R) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl) ] -6-aminopurin-2-yl.} Pyrazol-4-yl) -N-methylcarboxamide, 1 - acid. { 9 - [(4S, 2R, 3R, 5R) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-y1] -6-aminopurin-2-yl} pyrazole-4-carboxylic acid, (1 - {9- [(4S, 2R, 3R, 5R) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -6- aminopurin-2-yl.] pyrazol-4-yl) -N, N-dimethylalkylcarboxamide, (1 -. {9 - [(4S, 2R, 3R, 5R) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -6-aminopurin-2-yl.} pyrazol-4-yl) -N-eylcarboxamide, 1 -. { 9 - [(4S, 2R, 3R, 5R) -3,4-dihydroxy-5-hydroxymethyl) oxolan-2-yl] -6-aminopurin-2-yl} pyrazole-4-carboxamide, 1 -. { 9 - [(4S, 2R, 3R, 5R) -3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -6-aminopurin-2-yl} pyrazol-4-yl) -N- (cyclopentylmethyl) carboxamide, (1 -. {9 - [(4S, 2R, 3R, 5R) 3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -6-aminopurin-2-yl.} Pyrazol-4-yl) -N - [(4-chlorophenyl) -methylcarboxamide, 2 - [(-. {9 - [(4S, 2R, 3R, 5R) - 3,4-Dihydroxy-5 ~ (hydroxymethyl) -oxolan-2-yl] -6-aminopurin-2-yl.}. Pyrazol-4-yl) -carbonylamino etheyl ether and mixtures thereof. A second class of compounds that are selective and selective adenosine A2A receptor agonies that are useful in the methods of this invention are the 2-adenosine C-pyrazole compounds that follow the formula: wherein R1 is -CH2OH, -C (= O) NR5Re R2 is independently selected from the group consisting of alkyl with 1 to 1 5 carbon atoms, alkenyl with 2 to 15 carbon atoms, alkynyl with 2 to 15 carbon atoms, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkenyl, alkynyl, aryl, heteroaryl and heteroaryl substituents are optionally substituted with from 1 to 3 independently selected substituents from the group consisting of halo, NO2, heteroaryl, aryl, heteroaryl , CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2 ,. SO2NR20COR22, SO2NR20CO2R22, SO2NR20CON (R20) 2, N (R20) 2N R20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, CO2R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 and wherein each optionally optionally available heteroaryl, aryl, and heteroarylcyl optionally is optionally substituted with halo, NO2, alkyl, CF3, amino, mono- or dialkylamino, alkyl or aryl or heeroaryl amide, NCOR22, NR20SO2R22, COR20, CO2R20, CON (R20) 2, NR 0 (CON (R20) 2, OC (O) R20, OC (O) N (R20) 2, SR20, S (O) R22, SO2R22, SO2N (R0) 2, CN or OR20, R3, R4 are selected individually from the group consisting of hydrogen, alkyl having from 1 to 15 carbon atoms, alkenyl having from 2 to 15 carbon atoms, alkynyl having from 2 to 15 carbon, heyerocyclyl, aryl and heeroaryl, halo, NO2, CF3, CN, OR20, SR-20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2NR20COR22, SO2NR 0CO2R22, SO2NR20CON (R20) 2, N (R20) 2NR20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, CO2R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 wherein the alkyl substitutes, alken ilo, alkynyl, aryl, heterocyclyl, and heteroaryl are optionally substituted with from 1 to 3 suspends and are selected from the group consisting of halo, NO2, heteroaryl, aryl, heteroaryl, CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2NR20COR22, SO2NR20CO2R22, SO2NR20CON (R20) 2, N (R20) 2NR2) COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, CO2R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 and wherein each optionally optionally available heteroaryl, aryl and heterocyclyl ether is optionally Substituted with halo, NO2, alkyl, CF3, amino, mono- or dialkylamino, alkyl or aryl or heeroaryl amide, NCOR22, NR20SO2R22, COR20, CO2R20, CON (R20) 2, NR20 (CON (R20) 2, OC (O) R20, OC (O) N (R20) 2, SR20, S (O) R22, SO2R22, SO2N (R20) 2, CN or OR20; R5 and R6 each individually are hydrogen, alkyl having 1 to 1 5 carbon atoms with 1 to 2 independently selected substitutents of the group consisting of halo, NO2, heterocyclyl, aryl, heteroaryl, CF3, CN, OR20, SR20, N (R20) 2, S (O) R22, SO2R22, SO2N (R20) 2, SO2NR20COR22, SO2N R20CO2R22, SO2NR20CON (R20) 2, N (R20) 2NR20COR22, NR20CO2R22, NR20CON (R20) 2, NR20C (NR20) NHR23, COR20, CO2R20, CON (R20) 2, CONR20SO2R22, NR20SO2R22, SO2NR20SO2R22, OCONR20SO2R22, OC (O) R20, C (O) OCH2OC (O) R20 and OCON (R20) 2 and wherein each optional heteroaryl, aryl and optionally substituted heteroaryl groups are optionally substituted with halo, NO2, alkyl, CF3, amino, mono- or dialkylamino, alkyl or aryl or heeroaryl amide, NCOR22, NR20SO2R22, COR20, CO2R20, CON (R20) 2, NR20 (CON (R20 ) 2, OC (O) R20, OC (O) N (R20) 2, SR20, S (O) R22, SO2R22, SO2N (R0) 2, CN or OR20; R20 is selected from the group consisting of H, alkyl with from 1 to 15 carbon atoms, alkenyl with 2 to 15 carbon atoms, alkynyl with from 2 to 15 carbon atoms, heyerocyclyl, aryl and heteroaryl, wherein the alkyl, alkenyl, alkynyl, aryl, heterocyclyl and heteroaryl substituents are optionally susfifed with from 1 to 3 independently selected halogen substituents. , alkyl, mono- or dialkylamino, alkyl- or aryl- or heyeroarylamide, CN, O-C1-6 alkyl, CF3, aryl and heeroaryl; and R22 is selected from the group consisting of alkyl having from 1 to 15 carbon atoms, alkenyl having from 2 to 1 5 carbon atoms, alkynyl having from 2 to 15 carbon atoms, heterocyclyl, aryl and heteroaryl, wherein the substituents of alkyl, alkenyl, alkynyl, heterocyclyl, aryl and heteroaryl is optionally susíifuido with from 1 to 3 susíiuuyeníes independently selected from halo, alkyl, mono- or dialkylamino, alkyl- or aryl- or heeroarylamide, CN, O-C1-6 alkyl , CF3, aryl and heteroaryl; and wherein when R1 is CH2OH, R3 is H, R4 is H, the pyrazole ring is linked through C4, and R2 is not H. When the selected compound has one of the following formulas: it is preferred that R1 is -.CH2OH; R2 is selected from the group consisting of hydrogen, alkyl having from 1 to 8 carbon atoms wherein the alkyl is optionally susíiuuido with a susíifuyenie selected independently from the group consisting of aryl, CF3, CN, and wherein each optional susiiuyenyenie of airlo is optionally Substituted with halo, alkyl, CF3 or CN; and R3 and R4 are independently selected from the group consisting of hydrogen, methyl and more preferably each of R3 and R4 are hydrogen. When the compound of this invention has the following formula: then it is preferred that R1 is -.CH2OH; R2 is selected from the group consisting of hydrogen, alkyl having from 1 to 6 carbon atoms wherein the alkyl is optionally substituted with phenyl. More preferably R2 is selected from benzyl and pentyl, R3 is selected from the group consisting of hydrogen, alkyl having from 1 to 6 carbon atoms, aryl, wherein the alkyl and aryl groups are optionally substituted with from 1 to 2 substituents selected independently from each other. of the group consist of halo, aryl, CF3, CN and wherein each optional aryl substituent is optionally substituted with halo, alkyl, CF3 or CN; and R 4 is selected from the group consisting of hydrogen and alkyl with from 1 to 6 carbon atoms, and more preferably R 4 of hydrogen and me yl. A ciase. More specific compound is selected from the group consisting of (4S, 2R, 3R, 5R) -2-. { 6-amino-2- [l-benzylpyrazol-4-yl] purin-9-yl} -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2- [6-amino-2- (1-pentylprazo l-4-yl) purin-9il] -5 (hydroxymethyl) oxo n-3, 4-d iol, (4S, 2R, 3R, 5R) -2- [6-amino-2- (1-methylpyrazol-4-yl) purin-9 -yl] -S- (hydroxymethyl) oxolane-3,4-dioi, (4S, 2R, 3R, 5R) -2-. { 6-amino-2- [1- (methyleryl) pyrazol-4-yl] purin-9-yl} -S- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, SR) -2-. { 6-amino-2- [1 - (3-phenylpropyl) pyrazol-4-yl] purin-9-yl} -S- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2-. { 6-amino-2- [1 - (4-y-buylbenzyl) pyrazol-4-yl] purin-9-yl} -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2- (6-amino-2-pyrazol-4-yl] purin-9-yl) -5- (hydroxymethyl) ) oxolane-3,4-diol, (4S, 2R, 3R, SR.) -2-. {6-amino-2- [1 -pene-4-enylpyrazol-4-yl] purin-9-yl.} . -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2-. {6-amino-2- [1 -decylpyrazol-4-yl] purin-9-yl. .5. -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2-. {6-amino-2- [1 - (cyclohexyl) pyrazol-4-yl] purin- 9-yl.). -5- (Hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2-. {6-amino-2- [1- (2-phenylethyl) ) pyrazoloi-4-yl] purin-9-yl.}. -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, SR) -2-. {6-amino- 2- [1 - (3-Cyclohexylpropyl) pyrazol-4-yl] purin-9-yl}. -5- (hydroxymethyl) oxolane-3,4-diol, (4S, 2R, 3R, 5R) -2-. { 6-amino-2- [1 - (2-cyclohexylleyl) pyrazol-4-yl] purin-9-yl}. -5- (hydroxymethyl) oxolane-3,4-diol and its combinations A very useful and potent and selective agonist of the adenosine A2A receptor is CVT-3146 or (1 -. {9 - [(4S, 2R, 3R, SR) -3,4-dihydroxy-S- (hydroxymethyl) oxo fan-2-il] -6-am i nope urin-2-yl] pyrazol-4-yl) -N-mephrine carboxamide which has the formula: Another preferred compound that is useful as a selective adenosine A2A receptor agonist with a short duration of action is a compound of the formula: CVT-3033 CVT-3033 is particularly useful as an aid in the formation of cardiological images. The first classes of compounds identified above are described in greater detail in the North American countries. 6,403,567 and 6,214,807 whose descriptions are incorporated herein by reference. The following definitions apply to the terms used here. "Halo" or "halogen" in combination means all halogens, that is chlorine (Cl), fluor (F), bromine (Br), iodine (I). "Hydroxy" refers to the -OH group. "Thiol" or "mercapto" refer to the -SH group. "Alkyl" alone or in combination means a radical derived from alkane containing from 1 to 20, preferably from 1 to 15 carbon atoms (unless specifically defined). It is a straight chain alkyl or a branched alkyl or cycloalkyl. Preferred, the linear or branched alkyl groups contain from 1 to 15, preferably from 1 to 8, even more preferably from 1 to 6, even more preferably from 1 to 4 and most preferably from 1 to 2 carbon atoms, as metyl, ethylene, propyl, isopropyl, builo, isobuilo, and the like. The term "lower alkyl" is used herein to describe the straight chain alkyl groups described immediately above. Preferably, the cycloalkyl groups are monocyclic, bicyclic or tricyclic ring systems of 3-8, more preferably 3-6 ring members per ring, eg cyclopropyl, cyclopenyl, cyclohexyl, adamantyl and the like. Alkyl also includes a straight or branched chain alkyl containing or interrupted by a cycloalkyl moiety. The straight or branched chain alkyl group is attached at any available point to produce a stable compound. Examples of this include but are not limited to 4- (isopropyl) -cyclohexylethyl or 2-methyl-cyclopropylpentyl. A substituted alkyl is a straight chain alkyl group, a branched alkyl or cycloalkyl previously defined, independently substituted with 1 to 3 halo, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, acyloxy, aryloxy, heteroaryloxy, amino optionally mono or substituents or substituents - or disubstituted with alkyl, aryl or heteroaryl groups, amidino, urea optionally substituted with alkyl, aryl, heteroaryl or heterocyclyl, aminosulfonyl optionally N-mono- or N, N-di-substituted with alkyl, aryl or heteroaryl, alkylsulfonylamino, arylsulfonylamino groups , heteroarylsulphonylamino, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino or the like. "Alkenyl" alone or in combination means a straight, branched or cyclic hydrocarbon containing from 2-20, preferably 2-17, more preferably 2-1-0, even more preferably 2-8, most preferably from 2 to 4 carbon atoms. carbon and at least one carbon-to-carbon double bond, preferably 1 -3, more preferably 1 -2, more preferably one. In the case of a cycloalkyl group, the conjugation of more than one carbon-to-carbon double bond is not enough to make the ring aromatic. The carbon-carbon double bonds can be contained within a cycloalkyl portion, with the exception of cyclopropyl or denitro of a straight chain or a branched portion. Examples of alkenyl groups include ethenyl, propenyl, isopropenyl, butenyl, cyclohexenyl, cyclohexenalkyl and the like. A substituted alkenyl is the straight chain, branched chain alkynyl or cycloalkenyl group previously defined, independently substituted with 1 to 3 groups or halo, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, acyloxy, aryloxy, heteroaryloxy, amino optionally mono or substituents. - or disubstituted with alkyl, aryl or hephenoaryl, amidino, optionally substituted urea groups with alkyl, aryl, heteroaryl or heterocyclyl aminosulfonyl groups optionally N-mono- or N, N-disubstituted with alkyl, aryl or heteroaryl groups, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino , alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamine, carboxy, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl or the like attached in any available puncture to produce a stable compound. "Alkynyl" alone or in combination means a straight or branched hydrocarbon containing 2-20, preferably 2-17, more preferably 2-1 0, still more preferably 2-8, more preferably 2-4 carbon atoms- which connue when minus one, preferably a triple carbon to carbon bond. Examples of alkynyl groups include ethynyl, propynyl, butynyl and the like. A substituted alkynyl refers to a straight-chain or branched alkynyl previously defined, independently substituted with 1 to 3 substituent groups or halo, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, acyloxy, aryloxy, heteroaryloxy, amino optionally mono- or disusifluido with alkyl, aryl or heteroaryl, amidino, urea optionally susíiuuido groups with alkyl, aryl, heleroaryl or heyerocyclyl aminosulfonyl optionally N-mono- or N, N-disusiiuuido with alkyl, aryl or heteroaryl groups , alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, carboxy, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl or the like are attached in any available pen to produce a stable compound. "Alkenyl alkenyl" refers to a group -R-CR '= CR' "R" ", wherein R is lower alkyl or substituted lower alkyl, R ', R" R "" may independently be hydrogen, halogen, alkyl lower, substituted lower alkyl, acyl, aryl, substituted aryl, heteroaryl or substituted hetearyl as defined below. "Alkynyl alkynyl" refers to -RCp-R 'groups wherein R is lower alkyl or substituted lower alkyl, R' is hydrogen, lower alkyl, substituted lower alkyl, acyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl as defined go ahead "Alkoxy" denoted the group -OR, wherein R is lower alkyl, lower alkyl, acyl, aryl, aryl, aralkyl, substituted aralkyl, heteroalkyl, heteroarylalkyl, cycloalkyl, substituted cycloalkyl, cycloheylalkyl or substituted cycloheteroalkyl as defined. "Alkylthio" denotes the group -SR, S- (O) n =, 2-R, wherein R is lower alkyl, substituted lower alkyl, aryl, susiioid aryl, aralkyl or aralkyl susiiuuide fal as defined herein. "Acyl" denoted groups -C (O) R, wherein R is hydrogen, lower alkyl substituted with lower alkyl, aryl, aryl, and the like as defined herein. "Aryloxy" denotes -OAr groups, where Ar is an aryl, substituted aryl, heteroaryl or substituted aryl group as defined herein. "Amino" denotes the group NRR ', wherein R and R' may independently be hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, or heteroaryl as defined herein or acyl. "Amido" denoted the group -C (O) NRR ', wherein R and R' can independently be hydrogen, lower alkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl, heteroaryl heteroaryl as defined herein. "Carboxyl" denoted the group -C (O) OR, wherein R is hydrogen, lower alkyl, lower alkyl, aryl, aryl, heteroaryl, heteroaryl, and heteroaryl, as defined herein. "Aryo" alone or in combination means phenyl or optionally carbocyclic naphthyl fused to a cycloalkyl or preferably 5-7, more preferably 5-6, null, and / or optionally substituted with 1 to 3 groups of halo, hydroxy, and halogen subsides. alkoxy, alkyl, alkylsulphinyl, alkylsulfonyl, acyloxy, aryloxy, hephenoaryloxy, amino optionally mono- or di-substituted with alkyl, aryl or heteroaryl groups, amidino, urea optionally substituted with alkyl, aryl, heteroaryl or heterocyclyl groups, aminosulfonyl optionally N-mono- or N-substituted with alkyl, aryl or heteroaryl, alkylsulfonylamino, arylsulphonylamino, heteroarylsulfonylamino, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, or the like. "Substituted aryl" refers to aryl optionally substituted with one or more functional groups for example halogen, lower alkyl, lower alkoxy, alkylthio, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocycle, hearyaryl, substituted heteroaryl, nitro , cyano, thiol, sulfamido and the like. "Heterocycle" refers to a saturated, unsaturated or aromatic carbocyclic group having a single ring (eg, morpholino, pyridyl or furyl) or multiple fused rings (eg, napthyridyl, quinoxalyl, quinolinyl, indolizinyl, or benzo [b] -iienyl) and that they have at least one heteroatom, such as N, O or S, within the ring, which may optionally be unsuspensed or suspended with, for example, halogen, lower alkyl, lower alkoxy, alkyl, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heteroaryl, heteroaryl , suspended substance, nitrogen, cyano, thiol, sulfonamide and the like. "Heteroaryl" alone or in combination means a monocyclic aromatic ring structure containing 5 or 6 atoms in the ring, or a bicyclic aromatic group having 8 to 10 atoms containing one or more preferably 1-4, more preferably 1 -3. , still more preferably 1 -2, independently selected heteroaíómos of the group O, S and N, and optionally susíiuuido with 1 to 3 groups or susíituyentes of halo, hidoxi, aloxi, alquilíio, alquilsulfinilo, alquilsulfonilo, aciloxi, ariloxi, heteroaryloxy, amino optionally mono- or disubstituted with alkyl, aryl or heteroaryl groups, amidino, urea optionally substituted with alkyl, aryl, heteroaryl or heterocyclic groups, aminosulfonyl optionally N-mono- or N, N-di-substituted with alkyl, aryl or heteroaryl groups, alkylsulfonylamino , arylsulfonyl-amino, heteroarylsulfonyl-amino, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino or the like. Heteroaryl is also intended to include oxidized S or N, such as sulfinyl, sulfonyl and ring N-ring nitrogen. A carbon or nitrogen atom is the point of attachment of the ring, heteroaryl ester in such a way that an aromatic ring is retained esíbale. Examples of heteroaryl groups are pyridinyl, pyridazinyl, pyrazinyl, quinazolinyl, purinyl, indolyl, quinolinyl, pyrimidinyl, pyrrolyl, oxazolyl, thiazolyl, thienyl, isoxazolyl, oxatadiazolyl, isoiadinyl, tetrazolyl, imidazolyl, triazinyl, furanyl, benzofuryl, indolyl and the like. A solid product has a substrate attached to a carbon or nickel available to produce a stable com- pound. "Heterocyclyl" alone or in combination means a non-aromatic cycloalkyl group having from 5 to 10 atoms in which from 1 to 3 carbon atoms in the ring are replaced by the hetero atoms of O, S or N, and are optionally benzo fused or heteroaryl fused with 5-6 ring members and / or are optionally substituted as in the case of Heterocyclic cycloalkyl is also preferred to include oxidized S or N, such as sulfinyl, sulfonyl and N-oxide of a tertiary ring nitrogen. The point of attachment is a carbon or nihorogen atom. Examples of heyerocyclyl groups are iorahydroguranyl, dihydropyridinyl, piperidinyl, pyrrolidinyl, piperazinyl, dihydrobenzofuranyl, dihydroindolyl and the like. A substituted heyerocyclyl contains a nickarogen substitute bonded to a carbon or nihologen available to produce a compound. "Substituted heteroaryl" refers to an optionally mono or poly-substituted heterocycle with one or more functional groups, for example halogen, lower alkyl, lower alkoxy, alkylthio, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocycle, heterocycle Substituted, heteroaryl, substituted heteroaryl, niid, cyano, thiol, sulfamido and the like. "Aralkyl" refers to the group -R-Ar wherein Ar is an aryl group and R is lower alkyl or a substituted lower alkyl group. The aryl groups may optionally be unsubstituted or substituted with, for example, halogen, lower alkyl, alkoxy, alkylthio, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocycle, heterocycle, substituted heteroaryl, heteroaryl, substituted heteroaryl, ni, cyano. , thiol, sulfamido and the like. "Heteroalkyl" refers to the group -R-Het wherein Hei is a heterocycle group and R is a lower alkyl group. The heteroalkyl groups may optionally be unsubstituted or substituted with, for example, halogen, lower alkyl, lower alkoxy, alkyl, acetylene, amino, amido, carboxyl, hydroxyl., aryl, aryloxy, heterocycle, heteroaryl, substituted heteroaryl, nitro, cyano, thiol, sulfamido and the like. "Heteroarylalkyl" refers to the group -R-HetAr where HetAr is a heteroaryl group and R is lower alkyl or substituted lower alkyl. The heteroarylalkyl groups may optionally be unsubstituted or substituted by, for example, halogen, lower alkyl, lower alkoxy, alkyl, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heteroaryl, heteroaryl, substituted heteroaryl, nitro, cyano, thiol, sulfamido and the like. "Cycloalkyl" refers to a cyclic or polycyclic divalent alkyl group containing from 3 to 15 carbon atoms. "Substituted cycloalkyl" refers to a cycloalkyl group containing one or more substituents with for example halogen, lower alkyl, substituted lower alkyl, alkoxy, alkylthio, acetylene, aryl, aryloxy, heterocycle, substituted heterocycle, heteroaryl, substituted heteroaryl, nitro, cyano, thiol, sulfamido and the like. "Cycloheteroalkyl" refers to a cycloalkyl group in which one or more of the ring carbon atoms is replaced with a hetero-atom (for example N, O, S or P). "Substituted cyclohexylalkyl" refers to a cycloheteroalkyl group as herein containing one or more substituents, such as halogen optionally unsubstituted or substituted by, for example, halogen, lower alkyl, lower alkoxy, alkyl, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocycle, heteroaryl, substituted heteroaryl, nitro, cyano, thiol, sulfamido and the like. "Alkyl cycloalkyl" denotes the group -R-cycloalkyl wherein cycloalkyl is a cycloalkyl group and R is a lower alkyl or lower alkyl substituted. The cycloalkyl groups can optionally be unsubstituted or substituted with, for example, halogen, lower alkyl, lower alkoxy, alkylthio, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocycle, heteroaryl, substituted heteroaryl, nitro, cyano, thiol, sulfamido. and similar. "Alkyl-cycloheteroalkyl" denotes the group -R-cycloheylalkyl wherein R is a lower alkyl or a lower alkyl is substituted. Cyclohepheralkyl groups may optionally be unsubstituted or substituted with for example halogen, lower alkyl, lower alkoxy, alkylthio, acetylene, amino, amido, carboxyl, hydroxyl, aryl, aryloxy, heterocycle, heteroaryl, substituted heteroaryl, nitro, cyano, thiol, sulfamido and similar. The first class of idenified compounds can be prepared as indicated in the 1-4 schemes. The compounds having the general formula IV can be prepared in the manner shown in scheme 1. Scheme 1 Compound I can be prepared by reacting compound 1 with substituted 1,3-dicarbonyl in a mixture of AcOH and MeOH at 80 ° C (Holzer et al, J. Heteorcycl. Chem. (1993) 30, 865). Compound II, which can be obtained by reacting compound I with 2,2-dimethoxypropane in the presence of an acid, can be oxidized to carboxylic acid III, based on structurally similar compounds using potassium permanganate or pyridinium chlorochromate (M Hudiicky, (1990) Oxidations in Organic Chemistry, ACS Monographs, American Chemical Society, Washington DC). The reaction of a primary or secondary amine having the formula HN R6R7, and the compound III using the DCC coupling conditions (M. Fujino et al., Chem. Pharm. Bull. (1 974), 22, 1 857), PyBOP (J. Martinez et al., J. Med. Chem. (1988) 28, 1874) or PyBrop (J. Caste et al., Tetrahedron (1991), 32, 1967) compound IV can be produced. Esq uema 2.

Compound V can be prepared as shown in the scheme. "The derivative of Tri TBDMS 4 can be obtained by bringing compound 2 with TBDMSCI and imidazole in DMF followed by hydrolysis of ethyl ester using NaOH The reaction of a primary or secondary amine with the formula HNR6R7, and compound 4 using the DCC coupling conditions (M. Fujino et al., Chem. Pharm. Bull. (1974), 22, 1 857), PyBOP (J. Martinez et al., J. Med. Chem. (1988) 28, 1874) or PyBrop (J. Caste et al., Tetrahedron (1991), 32, 1967) can be produced compound V. Scheme 3 A specific synthesis of compound 11 is illustrated in scheme 3. Commercially available guanosine 5 is converted to triaceate 6 as previously described (MJ Robins and B. Uznanski, Can J. Chem (1988), 59, 2601). -2607). Compound 7, prepared by the following procedure described in the literature of Cersfer ef. to the. (JF Cerster, AF Lewis, and RK Robins, Org. Synthesis, 242-243), is converted to compound 9 in two clauses as described previously (V. Nair et al., J. Org. Chem., (1988 ), 53, 3051-3057). Compound 1 is obtained by reacting hydrazine hydrazine with compound 9 in 80 ° C ethylene. The condensation of compound 1 with ethoxycarbonylmallodaldehyde in a mixture of AcOH and MeOH at 80 ° C produces the compound 1 0. The heating of the compound 1 0 in an excess of methylamine gives compound 1 1. Scheme 4 VI VB The syn- thesis of 1, 3-dialdehyde Vi l is described in scheme 4. The reaction of 3,3-diethoxypropionate or 3,3-diethoxypropionitrile or 1,1-diethoxy-2-nitroethane VI (R3 = CO2R, CN or NO2) with ethyl or methyl formate in the presence of NaH can produce the dialdehyde VI I (Y. Yamamoto et al., J. Org. Chem. (1989) 54, 4734). The second class of the compound described above can be prepared in the manner described in schemes 1-5. The compounds having the general formula I I: Scheme 1 were prepared by means of palladium-mediated coupling of compound 1 with halo-pyrazoles represented by formula VII I (scheme 4) in the presence or absence of copper salts (K. Kato et al., J. Org. Chem. , 62, 6833-6841; Palladium Reagents and Catalysts-Innovations in Organic Synthesis, Tsuji, John Wiley and Sons, 1995) followed by deprotection either TBAF or NH4F / Markiewicz et al.

Tetrahedron Lett (1988), 29, 1561). The preparation of compound 1 has been previously described (copper (K. Kato et al., J. Org. Chem. 1997, 62, 6833-6841) and is shown in scheme 5. Compounds of general formula VI can be prepared as as shown in scheme 2. Scheme 2 Compound I, which can be obtained by reacting II with 2,2-dimefoxipropane in the presence of an acid, can be oxidized to IV carboxylic acid, based on structurally similar compounds using potassium permangana or pyridium chlorochromate, etc. (Jones et al., J. Am. Chem. Soc. (1949), 71, 3994; Hidlicky, Oxidaiions in Organic Chemistry, American chemical Society, Washingfon D.C., 1990) to give compound IV. The reaction of the primary or secondary amine of the formula NHR5R6, and the compound V using the DCC coupling conditions (M. Fujino et al., Chem. Pharm. Bull. (1974), 22, 1 857), PyBOP (J. Martínez et al., J. Med, Chem. (1988) 28, 1874) or PyBrop (J. Caste et al., Tetrahedron (1 991), 32, 1 967) can be produced. The deprotection of compound V can be can be carried out by means of heating with 80% aqueous acetic acid (TW Green and PG Wuts (1 991), Protecive Groups in Organic Synthesis, A, Wiley-lnterscience publication) or with anhydrous HCl (4N) to obtain the compound of the general formula VI. Alternatively, the compounds with the general formula I I can be prepared by means of the Suzuki type coupling as shown in scheme 3. Scheme 3 2-Iodoadenosine 6 can be prepared in four steps from guanosine 2 following the procedures described in the literature (MJ Robins et al., Can. J. chem. (1981), 59, 2601-2607; JF Cerster et al. , Org Synthesis, -242-243; V. Nir et al., J. Org. Chem., (1988), 53, 3051-3057). Suzuki coupling mediated with palladium of 6 with suitably substituted pyrazole boronic acids XVII in the presence of a base can provide the final compounds with general formula II (A. Suzuki, Acc. Chem. Res.) (1982 ), 15, 178). If necessary the 2 ', 3', 5 'hydroxyl in 6 can be protected as TBDMS ether before the Suzuki coupling. The compounds of the general formula VIII can be obtained commercially or can be prepared following the steps shown in scheme 4. Scheme 4 the condensation of the compounds 1, 3-diketo of formula IX with hydrazine in a suitable solvent can give pyrazoles with the general formula X (RH Wiley et al., Synthsis Org, Coil, Vol. IV (1 963), 351 These pyrazoles can be n-Alkylated with different alkyl halides to give the compounds of the formula XI which after the iodation gives 4-iodo derivatives with the general formula VI II (R. Huttel et al., Justis Liebigs An., Chem. (1 955), 593, 200) The 5-iodopyrazoles with the general formula XV can be prepared following the steps indicated in scheme 5. Scheme 5 the condensation of the 1,3-diketo compounds of the formula XI I with hydrazine in an appropriate solvent can give pyrazoles with the general formula XI I I. These pyrazoles can be n-Alkylated with different alkyl halides to give the compounds of the formula XIV. Extraction of 5-H with a strong base by suffocation with iodine can provide 5-iodo derivatives with the general formula XV (F. Effenberger et al., J .. Org. Chem. (1984), 49, 4687 ). The 4- or 5-iodopyrazoles can be transformed into the corresponding boronic acids as shown in scheme 6. The transmetalization with n-buLi followed by the treatment with trimethyl borate can give compounds of the general formula XVI which after hydrolysis can provide boronic acids with formula XVI I (FC Fischer et al., RECU EI L (1 965), 84, 439).

Hydrolysis 2-staniladenosine 1 was prepared in fresh air from the commercial 6-chloropupe riboside following the procedure of the hterauration (K. Kato et al., J. Org. Chem. 1997, 62, 6833-6841). The derivative of Tri TBDMS was obtained by treating 8 with TBDMSC1 and midazole in DM F. Lithiation with LTMP followed by quenching with tri n-butylline chloride gave exclusively the 2-esfanyl derivative. The amonolysis in 2-propanol gave 2-esfanyladenosine 1. Coupling of 1 with 1-benzyl-4-iodopyrazole in the presence of Pd (PPh3) 4 and Cul resulted in 1 1 (K. Kato et al., J. Org. Chem. 1997, 62, 6833-6841). Deprotection of the 2 ', 3' and 5 'hydroxyl silyl groups with 0.5M ammonium fluoride in methanol yielded 12 with a good yield (scheme 7). Scheme 7 The methods used to prepare the compounds of this invention are not limited to those described above. Additional methods can be found in the following sources and are included as references (J. March, Advanced Organic Chemisfry, Reaction Mechanisms and Studies (1992), A. Wiley Interscience Publications, and Tsuji, Palladium Reagents and Catalysts-Innovations in Organic Synthesis. , Tsuji, John Wiley and Sons, 1995). If the final compound of this invention contains a basic group, an acid addition salt can be prepared. The acid addition salts of the compounds are prepared in the standard manner in a suitable solvent from the related compound and an excess of acid, such as hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, maleic, succinic, or methanesulfonic acid. The hydrochloric salt form is especially useful. If the final compound contains an acidic group, cationic salts can be prepared. Typically the parent compound is prepared with an excess of alkaline reagent such as hydroxide, carbonate or alkoxide, which contains the appropriate cation. The cations Na +, K +, Ca + 2 and NH + are examples of cations present in pharmaceutically acceptable salts. Certain of the compounds form internal salts or zwitterions that may also be acceptable. EXAMPLES In the following examples three differential aqueous pharmaceutical formulations of CVT-3146 were used. Examples 1-7 employ the pharmaceutical compositions (a) and (b). The pharmaceutical compositions (a) and (b) were aseptically introduced into a 1 ml glass bottle of 1 μl. (a) a pharmaceutically-aqueous composition consisting of 200 micrograms / ml of CVT-3146 in 0.5% (w: v) of methylboronic acid buffered with sodium bicarbonate at a pH of 9.3. (b) a pharmaceutically-aqueous composition consisting of 200 micrograms / ml of CVT-3146 in 0.1% (w: v) of methylboronic acid, 50 mM of sodium bicarbonate buffer adjusted to a pH of 9.3 with the addition of 0.55% (p: v) of NaCl to produce a pharmaceutical composition. Example 8 employs a pharmaceutical composition consisting of an aqueous composition of 100 micrograms / ml of CVT-3146 in 15% (p: v) of propylene glycol and 1 00 mM of phosphate buffer at a pH of 7 with 0.1% EDTA. The formulation is stored in type I glass bottles, 5 ml per bottle.

EXAMPLE 1 BACKGROUND: CVT-3146 (CVT9 with an initial half-life of 3 minutes with rapid onset and end of action, is> 1 00 times more potent than adenosine (Ado) in increasing coronary blood flow velocity The purpose of this open label test is to determine the amount and duration of the effect of CVT-3146 (1 0-500 μg) on human CBFv. METHODS: Patients who are undergoing a coronary caiarization clinically indicated with no more than 70% esignosis or in any coronary artery and no more than 50% of the study vessel studied, with a Doppler flow wire, selected by means of a Doppler flow wire. To measure the baseline and peak lines of CBFv after an intracoronary injection (IC) of 1 8 μg of Ado. Twenty-one patients, who were considered to have met the screening criteria of a peak proportion of baseline CBFv of> 2.5 in response to adenosine, received a rapid (£ 1 0 seconds) peripheral bolus vv of CVT-3146; Doppler signals were stable and unresectable during the course of the increase in CBFv in 17 patients. RESULTS: CVT-3146 caused a rapid increase in CBFv near the peak of 30 to 40 seconds after the start of the bolus. CVT-3146 at a dose of 100 μg (n = 3), 300 μg (n = 4), and 500 μg (n = 2) induced a peak to baseline ratio of 3.2 + 0.6 (mean + SD) similar to that obtained through IC Ado (3.2 +. 0.5). The duration of the increase in CBFv (increase> 2 in CBFv) depends on the dose; at 300 μg the duration was 4.0 + 4.9 minutes and at 500 μg it was 6.9 + 7.6 minutes. At 500 μg (n = 3) the maximum increase in heart rate (HR) was 18.7 + 4.0 and the maximum reduction in systolic blood pressure (BP) was 8.7 + 7.6. Adverse events (AEs) were infrequent and included nausea, dizziness, and headaches; and they were moderate and limited. AE were not observed in 4 patients who received a dose of 500 μg. CONCLUSION: In humans the peak of CBFv after CVT-3146 (bolus IV) is comparable to CBF after IC Ado without major changes in HR or BP. The magnitude of the agent and the duration of the effect, the profile of adverse events and the administration of the bolus make the CVT-3146 a pharmacological tension agent useful for the imaging of perfusion of the myocardium. EXAMPLE 2 This example is a study carried out to determine the range of doses at which the A2A receptor agonist, CVT-.3146 can be administered and be effective as a coronary vasodilator. The study included patients who underwent coronary catheterization clinically indicated with no more than 70% esignosis in any coronary artery and no more than 50% stenosis of the sphincter vessel fibrin CVIFv terminated by means of a Doppler flow wire. The selected individuals were selected after measuring the baseline and peak lines of CBFv after an intrarchial injection (IC) of 18 μg of Ado. Twenty-three patients, who were considered to meet the study criteria of having a peak to baseline rate of CBFv of > 2.5 in response to adenosine.

CVT-3146 was administered to individuals challenged by IV bolus in less than 10 seconds in doses ranging from 10 μg to 500 μg. The effectiveness of both compounds was measured by monitoring the rate of coronary flow. Other coronary parameters that were monitored included heart rate and blood pressure. These parameters were measured to evaluate the time to the response at the peak dose, the magnitude of the dose to the dose and the duration of the dose response. Adverse events were also moniiored. Coronary blood flow velocity was measured in the left anterior descending coronary artery (LAD) or the left circumflex coronary artery (LCx). The velocity measurements were taken following the techniques of standard heartbeat of the heart and inserting a Flowir wire with a Doppler puncture of 0.014 inches into the LAD or LCx vessel and then moni- torate the blood flow velocity. further, hemodynamic and electrocardiographic measurements were recorded continuously. In general, 36 human individuals were evaluated (n = 36). Of the 36, 1 8 were women and 1 8 men. Their average age was 53.4 years and they were at an age in the range of 24-72 years of age. Of the 36 subjects evaluated, the LAD vessel of 31 individuals was monitored, and the LCx vessel of 4 individuals. The following doses (μg) of CVT-3146 were administered to the subjects in a single iv bolus: 10 (n = 4), 30 (n = 6 =; 1 00 (n = 4), 300 (n = 7); 400 (n = 9) M; 500 (n = 6). The results of the study are reported in figures 1-6. The graph of Figure 1 shows that CVT-3146 increases the peak flow rate in amounts up to 10 μg and reaches a flat peak velocity after administration of less than approximately 100 μg of CVT-3146. Other test results and conclusions include: "peak flow was reached in approximately 30 seconds with all doses; • At doses above approximately 100 μg, the peak values were equivalent to 18 μg of adenosine administered IC; • CVT-3146 was generally well tolerated reporting adverse events in the annexed figure as figure 7; • At 400 μg: o the rate of coronary blood flow > . 2.5 times above the baseline was maintained for 2.8 min. or the maximum increase in heart rate (1 8 + 8 bpm) is reported approximately 1 minute after dosing, or the maximum decrease in systolic BP (20 ± 8 mmHg) occurs approximately 1 minute after dosing. or the maximum decrease in diastolic BP (20 ± 8 mmHg) occurs approximately 1 minute after dosing. EXAMPLE 3 This example is a study conducted to evaluate (1) the maximum tolerated dose of CVT-3146 and (2) the pharmacokinetic profile of CVT-3146 in healthy volunteers, after a single IV bolus dose. Methods The study was carried out using twenty-six healthy non-smoking male individuals between the ages of 1 8 and 59 and in a range of 1 5%) of their ideal body weight. Study design The study was conducted as a phase 1 study, with a single center, double blind, alloy, placebo, transposition and ascending dose. The randomization was with respect to CVT-3146 or placebo, both in supine or upright positions. CVT-3146 was administered as an IV bolus (20 seconds) in ascending doses of 0.1, 0.3, 1 .3, 1 0, 20 and 30 μg / kg. Individuals received either CVT-3146 or placebo on day 1 in the supine position, then the transposition procedure on day 2 in the supine position. On day 3, individuals received CVT-3146 or placebo standing, then the day of the transposition on day 4 standing. Determinations The safety of the patient was monitored by means of ECG, laboratory tests, and the recording of vital signs and adverse events. Pharmacokinetics: Plasma samples were extracted during the supine phase (days 1 and 2), 0,2,3,4, 5,7, 10, 15,20,30,45 minutes after each dose and 1, 1. 5, 2,4,6,8, 12 and 23 hours after dosing. Urine was collected for 24 hours to observe the excretion of CVT-3146. Pharmacodynamics: • The study evaluated the relationship of cardiac changes to the dose in the erect and supine positions and the plasma concentration of the supine position. Some of the results of the study were reported in figures 8-14. Resulíados Seguridad In general, adverse events reflected the pharmacological effect of CVT-3146 and were related to vasodila- tion or an increase in heart rate (H R). In general, the adverse effects were mild and mild to moderate in severity. There were no serious adverse events. Three events were classified as severe inínsidad. (Table 1 ). Table 1: Adverse events classified as severe infancy.

An open three compartment model was fitted to the data using the observed Tmax (1 -4 min) as the duration of a zero order infusion. Spirits of reliable parameters were obtained for the dose of 1 -30 μg / kg. The parameters are summarized in the following (table 2): Table 2 Average Pharmacokinetic Parameters (SD) d (3 CVT-3146 using a three compartment model) Dosage { μg / kg) 1 3 10 20 30 Total N 3 4 4 8 3 22 CL (tfl / mtti) 737 668 841 743 1021 768 (IOS) (167) (120) (123) (92.7) (168) Vc () 9.84 (4.12) 13.7 (6.06) 17 (6.11) 12.5 15.7 13.8 (5.83) (4.59) (5.67) V = s (L) 69.0 (28.2) 90.0 (29.6) IG1 (l U) 75.2 «9.6 75.5 (10.6) (10-9) (24.4) VitLi media ce 2.14 111 4.15 4.69 3.00 3.73 (mip) (1.38) (2.14) (2.75) (4.01) (1.05) (2.SS) Vicia me tlia ß 8.93 17.2 50.2 32.6 14.0 27.2 (min) (4.10) (11.4) (52.1) (32.4) (4.98) (31.0) Average life? 99.0 130 132 I I7 99.4 S6.4 (min) (28.6) (23 1) (2G.5) (36.0) (8.10) (57.5) K21 (l / min) 0.246 0.203 0.187 0.3S7 0.0948 0.258 (0.255) (0.272) (0.305) (0.615) (0.0443) (0.410) K3I (1 / mm) O.0I SQ8 0.0152 0.01 or 0.0141 0.0148 0.0143 (0.00548) (0.00490) (0.00592) (0.00728) (0.000900) (.0O5S0) CL = release Vc = central volume of distribution Vss = volume of distribution in the constant state K21 = constant of transfer speed from the first peripheral compartment to the center l K31 = constant of transfer speed from the second peripheral compartment to the center central Results • CVT-3146 was well tolerated, the AEs mainly represented their pharmacological effects as adenosine A2A receptor agonism. • The tolerable average dose of CVT-3146 was 10 μg / kg of foot and 20 μg / kg in the supine position. • CVT-3146 does not require dosage adjusted to the weight • There was no delay in the changes in plasma concentration and changes in heart rate. • 'The relationship between the HR increase and the dose or concentration is adequately described with the sigmoidal Emax model. Example 4 CVT-3146 is a new selective adenosine A2A receptor agonist which is being developed as a pharmacological tensor for the perfusion imaging of the radionuclide myocardium. It has previously been shown that CVT-3146 causes coronary vasodilation without significantly affecting peripheral end-tidal resistance or renal blood flow in awake dogs. The objective of this study was to deduce the differential effects of CVT-3146 on the blood flow velocity in several vascular beds. The effect of CVT-3146 was on the velocity of blood flow in the coronary arteries (LCX), the cerebral arterial vasculature (BA), the antephase artery GFA) and in the pulmonary artery (BP) of a diameter affordable on an anesthetized dog. CVT-3146 (1.0 μg / kg) was administered as an intravenous bolus, in an improved blood flow that was specific to the site. The effects of CVT-3146 were quantified as the peak mean blood flow velocity. (APV) using a catheter with an intravascular Doppler transducer tip. Heart rate (HR) and arterial blood pressure (BP) were also monitored. APV increased 3.1 ± 0.2, 1 .4 ± 0.1, 1 .2 ± 0.1, and 1 .1 ± 0.01 times in LCX, BA, FA and PA, respectively, manifesting a range of local polypeptide of the order of LXC > > BA »FA» PA (figure 16). The effect of CVT-3146 on blood flow velocity was of long duration; reaching its peak in less than 30 seconds and dissipating in less than ten minutes. The increasing velocity of blood flow was associated with a small transient increase in GR (16 bpm) and a reduction in BP (12 mmHg). In conclusion, this study showed that CVT-3146 is a long-term vasodilator that lasts for a long time and that it is selected for the coronary vasculature. Example 5 Presenting the test was performed to determine if CVT-3146, a selective adenosine A2A receptor agonism causes sympathetic excitation. CVT (0.31 μg / kg-50μg / kg) was administered in the form of a bolus i.v. Rapidly to despierías and moniíorearon heart rate (HR) and blood pressure (BP). CVT-3146 caused an increase in BP and systolic pressure (SP) at lower doses while at higher doses there was a reduction in BP and SP. CVT-3146 caused a dose-dependent increase in HR (Figure 17). The increase in HR was evident at the lowest dose of CVT to the lime there was no appreciable increase in BP. ZM241 385 (30 μg / kg, N = 5), an A2A receptor agonist, attenuated the reduction in BP (CVT-3146; 14 ± 3, ZM: 1 ± 1%) and the increase in HR (CVT: 27 ± 3%, ZM: 1 8 ± 3%) caused by CVT-3146. The pre-tramemia with mefroprolol (MET, 1 mg / kg, n = 5), a beía-. Blocker increased the increase in HR (CVT: 27 + 3%, MET: 15 ± 2%), but there was no effect on the hypotension caused by CVT-3146. In the presence of hexamethonium (HEX, 10 mg / kg, n = 5), a ganglionic blocker was prevented, tachycardia (CVT: 27 + 3%, HEX: -1 ± 2%), but BP was further reduced (CVT: -1 1 ± 2%, HEX: - 49 + 5 &). CVT-23146 (10 μg / kg, n = 6) also significantly (p> 0.05) increased plasma norepinephrine (control: 146 + 1 1, CVT-3146 269 ± 22 ng / ml) and epinephrine levels (control : 25: f: 5, CTR: 100: F: 20 ng / ml). The separation of the effects HR or BP by dose, time and pharmacological interventions provides evidence that the akchydia caused by CVT-3146 is independent of the decrease in BP, suggesting that CVT-3146, by means of the activation of A2A receptors can cause direct stimulation of the sympathetic nervous system. Example 6 Imaging of the micoardium by perfusion (M PI) with pharmacological stress SPECT with adenosine (A) is a highly accepted technique with excellent diagnostic and prognostic value and proven safety. However, laeral effec ions are common and AV nodal blockage and severe dizziness occur poorly. Agents such as CVT-3146 selectively act on the adenosine A2A receptor and prevent stimulation of other receptor subtypes that can prevent such adverse reactions. To determine the ability of CVT-3146 to produce coronary hyperaemia and accurately detect CAD, 35 individuals (26 men, 9 women, 67 ± 10 years) underwent MPI studies under tension / rest with A and CVT-3146, with 1 0.0 ± 9.1 days between studies. The previous Ml were anoyed for 12 patients, and the majority had a previous revascularization [CABG (n = 19), PCI (n = 22)]. CVT-3146 [400 mcg (n = 18), 50 mcg (n = 17) was administered as an IV bolus immediately followed by a saline solution and then a Tc-99m radiopharmaceutical (sesiamibi (n = 34), felrofosmin (n = 1 )] SPECT images were processed uniformly, interspersed with conírol studies (normal and fixed defects only), and were interpreted by means of fres observers in a blind form using a 1 7 segmenfos model. also made a comparison in the same pan of images A and CVT-3146 to determine the relative differences using 5 regions per phase The scores added after the stress were similar with visual methods (A = 1 3.9 ± 1 .5, CVT-3146 = 13.2 ± 1 .3, P = n.s) and quantitative methods of analysis (A = 1 34.7 ± 1 .5, CVT-3146 = 1 3.6 ± 1 .6, ^ p = n .s.). Similarly, the comparisons between the scores added at rest and the summed differences were identical. The direct comparison also revealed that there were no differences in the detection of ischemia, with a regional agreement for the extension and severity of ischemia of 86.3% and 83.4% respectively. No dose-dependent effect of CVT-3146 on the detection of ischemia was observed. One conclusion of the study is that CVT-3146 administered by a logistically simple bolus injection provides a similar ability to detect quantifying ischemia of the myocardium with SPECT MPI as seen with the infusion of A. Example 7 CVT-3146 is a receptor agonist of adenosine A2A that produces coronary hyperemia and potentially less adverse effects due to its limited stimulation of receptor subtypes not participating in coronary vasodilation. This study evaluated the effectiveness of CVT-3146 as an agent of pharmacological stress. 36 individuals (27 men, 9 women, 67 ± 1 09 years) were treated with two doses of CVT-3146 [400 mcg (n = 18), 50 mcg (n = 18), administered as an IV bolus, as part of a proocule of imaging by perfusion of the myocardium by pharmacological stress. Adverse effects (AE) were present in 26 patients (72% >) including chest discomfort (33%), headache (25%), and abdominal pain (11%) with a similar incidence for both doses . Hot flashes, dyspnea, and dizziness were more frequent in the 500 mcg group (44%, 44%, and 28% respectively) than in the 400 mcg group (17%, 17%, and 1 1% > respectively). AE were mild to moderate (96%) and were resolved in the course of 1 5 minutes without any delay (91%). A serious AE occurred with the exacerbation of a migraine headache that required hospitalization. The abnormalities in the ST and T waves were developed with CVT-3146 in 7 and 5 points, respectively. An AV block of 2o was observed. and 3rd grade and there were no serious arriímias. The peak hemodynamic effects are shown in Table 3 and observed at 4 minutes for the diastolic blood pressure (BP) 8 minutes for the diastolic BP and within 2 minutes for the heart rate (HR). The effect on BP was minimal and the systolic BP did not fall below 90 mmHg with either dose. The mean change in HR response was greater for doses of 500 mcg (44.2%) than for 400 mcg (34.8% > P = n.s.). Thirty minutes after CVT-3146, BP changes deviated < 2% of the baseline but HR remained above the baseline at 8.6%. The results of this study indicate that CVT-3146 is well tolerated and has acceptable hemodynamic effects. Minimal differences were observed in the BP and HR responses between the 400 mcg and 500 mcg doses, but the AEs were more frequent at higher doses. CVT-3146 seems safe and well tolerated for perfusion imaging with bolus-mediated drug delivery. Hemodialysis changes (mean ± SD). Table 3 Absolute change Relative change Heart rate +21.9 ± 10.4 laidos per minute + 36.7% + 21.0% sisolic BP -5.9 ± 10.7 mm Hg -4.1% ± 7.6% dialysis BP -5.4 + 7.2 mmHg -7.9% ± 1 0.5% EXAMPLE 8 In this study, the vasodilatory effects of CVT-3146 were purchased with those of ADO in different vascular beds in post-emergence dogs. Dogs were chronically isolated to measure blood flow in coronary (CBF =), mesenteric (MBF), hind limb (LBF), and renal (RBF) vascular beds and hemodynamics. The bolus injections (iv) of CVT-3146 (0.1 to 2.5 μg / kg) and ADO (1 0 to 250 μg / kg) caused significant increases in CBF (35 + 6 to 205 ± 23% and 48 ± 13 to 163 + 16%) and MBF (18 + 4 at 88 ± 14% and 36 ± 8 at 84 ± 5%).

The results of the study show that CVT-3146 is a longer and longer coronary vasodilator compared to ADO (the duration of CBF above 2 times the baseline; CVT-3146 (2.5 μg / kg): 130 ± 19s; ADO (250 μg / kg): 16 + 3s, P < 0.5). As shown in Figure 1 8 (mean ± SE, n = 6), CVT-3146 caused a smaller increase in LBF than ADO. ADO caused a vasoconstriction (RBD (-5 ± 2 to -1 1 ± 4%, P <0.05, in comparison with ADO) .In conclusion, CVT-3146 is a more selective coronary vasodilator and could be the ADO. There is no significant effect on the blood flow in dogs, and the characteristics of CVT-3146 make it the ideal candidate for myocardial imaging by radionuclide perfusion.The invention has now been described in full, it will be evident to those with experience. It is common in the art that many changes and modifications can be made without departing from the spirit or scope of the invention.

Claims (31)

1. CLAIMS 1. A pharmaceutical composition consisting of at least one A2A receptor at least one liquid carrier and at least one co-solvent.
2. 2. The pharmaceutical composition according to claim 1, wherein the A2A receptor agonist is selected from the group consisting of CVT-3033, CVT-3146 and combinations thereof.
3. 3. The pharmaceutical composition according to claim 1, wherein the liquid carrier consists of water, paraffined water, deionized water, saline solution, amorigner, or combinations thereof.
4. 4. The pharmaceutical composition according to claim 1, wherein the co-solvent consists of meiilboronic acid, amorphous boral, propylene glycol or polyethylene glycol.
5. 5. The pharmaceutical composition according to claim 4, wherein the co-solvent is meilboronic acid.
6. 6. The pharmaceutical composition according to claim 5, wherein the agonism of the A2A receptor is CVT-3146.
7. 7. The pharmaceutical composition according to claim 6, wherein the CVT-3146 is present in a range in the range of about 50 micrograms / ml to about 250 micrograms / ml and the methylboronic acid is present in an amount of about 0.4% to 0.6% (p: v).
8. 8. The pharmaceutical composition according to claim 7, wherein the liquid portion is at least one amorphous.
9. The pharmaceutical composition according to claim 8, wherein the pH of the composition is from about 8.5 to 10.
10. The pharmaceutical composition according to claim 9, wherein the pH is from about 9.1 to 9.4. eleven .
11. The pharmaceutical composition according to claim 3, wherein the co-solvent is a borate buffer.
12. 12. The pharmaceutical composition according to claim 6, wherein the co-solvent is about 0.5% (w: v) of meilboronic acid.
13. The pharmaceutical composition according to claim 12, wherein the composition further contains a buffer to bring the pH of the composition to about 9.3.
14. 14. The pharmaceutical composition according to claim 1, wherein the CVT-3146 is present in a quantity of about 50 to 150 micrograms / ml.
15. 1 5. The pharmaceutic composition according to. Claim 14, in which the composition also contains approximately 0.55% (w: v) of sodium chloride and 50 mM of sodium bicarbonate.
16. 16. The pharmaceutical composition according to claim 4, wherein the co-solvent is propylene glycol and the propylene glycol is present in a quantity of about 5% to 25% (p: v).
17. 17. The pharmaceutical composition according to claim 16, wherein the propylene glycol is present in a quantity of about 8% to 20%) (p: v).
18. The pharmaceutical composition according to claim 17, wherein the liquid carrier includes a amorphous to bring the pH of the composition to about 6 to 8.
19. The pharmaceutical composition according to claim 18, wherein the composition also contains EDTA .
20. The pharmaceutical composition according to claim 5, wherein the agonist of recepfor A2A is CVT-3146 and the CVT-3146 is present in an amount of about 50 to 150 micrograms / ml. twenty-one .
21. A method for producing a coronary vasodilatory without peripheral vasodilatation consisting of nistering to a human the pharmaceutical composition of claims 1 or 5 or 16, wherein the composition contains from about 1 to 600 μg of at least one agonism of the A2A receptor. .
22. 22. The method according to claim 21, wherein the A2A receptor agonist is CVT-3146.
23. 23. The method according to claim 22 wherein the composition is nistered by intravenous bolus.
24. The method according to claim 23 in which the composition is nistered in about 10 to 20 seconds.
25. 25. A method for perfusion imaging of a human myocardium consisting of nistering a radionuclide and the composition of the claims 1 or 5 or 16 either simultaneously or sequentially to a human in whom the myocardium is examined in an area of insufficient blood flow after administration of the radionuclides and composition.
26. 26. A method according to claim 25 in which the myocardial examination begins approximately 1 minute after the radionuclides and the composition have been administered.
27. 27. A method according to claim 26 in which the A2A receptor agonist causes an increase of at least 2.5 times in coronary blood flow which is reached in less than about 5 minutes.
28. 28. A method according to claim 25 in which the agonisia of the A2A receptor in the composition is CVT-3146 and the CVT-3146 is administered in a quantity in an amount of about 10 to 600 micrograms in a single intravenous bolus.
29. 29. The method according to claim 28 wherein the amount of CVT-3146 is from about 100 to 500 micrograms.
30. 30. The method according to claim 28, wherein the capacity of CVT-3146 is approximately 400 micrograms.
31. 31 The method according to claim 28 in which the composition is administered in about 1 0 to 30 seconds or less.