COMPOUNDS SPECIFIC TO ADENOSINE A1, A2A, AND A3 RECEPTOR AND USES THEREOF

Abstract: This invention pertains to compounds which specifically inhibit the adenosine A1, A2A, and A3 receptors and the use of these compounds to treat a disease associated with A1, A2A, and A3 adenosine receptors in a subjects, comprising administering to the subject a therapeutically effective amount of the compounds.

Description: COMPOUNDS SPECIFIC TO ADENOSINE A lf A^, AND A 3 RECEPTORS AND USES THEREOF This application is a continuation-in-part and claims priority of U.S. Serial Nos. 09/728,316, filed December 1, 2000, 09/728,607, filed December 1, 2000, and 09/728,616, filed December 1, 2000, each of which is hereby incorporated by reference in its entirety. Throughout this application, reference is made to compounds that specifically bind to i) adenosine A x receptors (such as inter alia, pages 4-76, 130-175, and 257-287), ii) adenosine A 2a receptors (such as inter alia, pages 176-201, and pages 288-293), and adenosine A 3 receptors (such as inter alia, pages 202-256 and 294-300) . Background of the Invention Adenosine is an ubiquitous modulator of numerous physiological activities, particularly within the cardiovascular and nervous systems. The effects of adenosine appear to be mediated by specific cell surface receptor proteins. Adenosine modulates diverse physiological functions including induction of sedation, vasodilation, suppression of cardiac rate and contractility, inhibition of platelet aggregability, stimulation of gluconeogenesis and inhibition of lipolysis. In addition to its effects on adenylate cyclase, adenosine has been shown to open potassium channels, reduce flux through calcium channels, and inhibit or stimulate phosphoinositide turnover through receptor- mediated mechanisms (See for example, C.E. Muller and B. Stein "Adenosine Receptor Antagonists: Structures and Potential Therapeutic Applications," Current Pharmaceutical Design , 2:501 (1996) and C.E. Muller "A 1 -Adenosine Receptor Antagonists," Exp . Opin . Ther . Pa ten ts 1 ( 5) : 419 (1997)). Adenosine receptors belong to the superfamily of purine receptors which are currently subdivided into (adenosine) and P 2 (ATP, ADP, and other nucleotides) receptors. Four receptor subtypes for the nucleoside adenosine have been cloned so far from various species including humans . Two receptor subtypes (Aj and A 2a ) exhibit affinity for adenosine in the nanomolar range while two other known subtypes A 2b and A 3 are low-affinity receptors, with affinity for adenosine in the low-micromolar range. A x and A 3 adenosine receptor activation can lead to an inhibition of adenylate cyclase activity, while A 2a and A 25 activation causes a stimulation of adenylate cyclase. A few Ai antagonists have been developed for the treatment of cognitive disease, renal failure, and cardiac arrhythmias. It has been suggested that A 2a antagonists may be beneficial for patients suffering from Morbus Parkinson (Parkinson's disease) . Particularly in view of the potential for local delivery, adenosine receptor antagonists may be valuable for treatment of allergic inflammation and asthma. Available information (for example, Nyce & Metzger "DNA antisense Therapy for Asthma in an Animal Model" Na ture (1997) 385: 721-5) indicates that in this pathophysiologic context, Aj antagonists may block contraction of smooth muscle underlying respiratory epithelia, while A 2J -, or A 3 receptor antagonists may block mast cell degranulation, mitigating the release of histamine and other inflammatory mediators. A 2b receptors have been discovered throughout the gastrointestinal tract, especially in the colon and the intestinal epithelia. It has been suggested that A 2b receptors mediate cAMP response (Strohmeier eϋ al . , J. Bio . Chem. (1995) 270:2387-94). Adenosine receptors have also been shown to exist on the retinas of various mammalian species including bovine, porcine, monkey, rat, guinea pig, mouse, rabbit and human (See, Blazynski et al . , Discrete Distributions of Adenosine .Receptors in Mammalian .Retina, Journal of Neurochemis try, volume 54, pages 648-655 (1990); Woods et al . , Characterization of Adenosine A, -Receptor Binding Si tes in Bovine Retinal Membranes, Experimental Eye Research, volume 53, pages 325-331 (1991); and Braas et al . , Endogenous adenosine and adenosine receptors localized to ganglion cells of the retina , Proceedings of the Na tional Academy of Science, volume 84, pages 3906-3910 (1987)). Recently, Williams reported the observation of adenosine transport sites in a cultured human retinal cell line (Williams et al . , Nucleoside Transport Si tes in a Cul tured Human Retinal Cell Line Established By SV- 40 T An tigen Gene, Current Eye Research, volume 13, pages 109-118 (1994)). Compounds which regulate the uptake of adenosine uptake have previously been suggested as potential therapeutic agents for the treatment of retinal and optic nerve head damage. In U.S. Patent No. 5,780,450 to Shade, Shade discusses the use of adenosine uptake inhibitors for treating eye disorders. Shade does not disclose the use of specific A 3 receptor inhibitors. The entire contents of U.S. Patent No. 5,780,450 are hereby incorporated herein by reference. Additional adenosine receptor antagonists are needed as pharmacological tools and are of considerable interest as drugs for the above-referenced disease states and/or conditions. ■"'"TπffiT " f the Invention The present invention is based on compounds which selectivelv bind to adenosine A : receptor, thereby treating a disease associated with Ai adenosine receptor in a subject by administering to the subject a therapeutically effective amount of such compounds. The disease to be Treated are associated with cognitive disease, renal failure, cardiac arrhythmias, respiratory epithelia, transmitter release, sedation, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstriction, neutropil chemotaxis, reflux condition, or ulcerative condition. The present invention is based, at least in part, on the discovery that certain N-6 substituted 7-deazapurines, described infra , can be used to treat a N-6 substituted 7- deazapurine responsive state. Examples of such states include those in which the activity of the adenosine receptors is increased, e . g. , bronchitis, gastrointestinal disorders, or asthma. These states can be characterized in that adenosine receptor activation can lead to the inhibition or stimulation of adenylate cyclase activity. Compositions and methods of the invention include enantiomerically or diastereomerically pure N-6 substituted 7-deazapurines. Preferred N-6 substituted 7-deazapurines include those which have an acetamide, carboxamide, substituted cyclohexyl, e . g. , cyclohexanol, or a urea moiety attached to the N-6 nitrogen through an alkylene chain. The present invention pertains to methods for modulating an adenosine receptor (s) in a mammal by administering to the mammal a therapeutically effective amount of a N-6 substituted 7-deazapurine, such that modulation of the adenosine receptor's activity occurs. Suitable adenosine receptors include the families of A 1# A 2 , or A 3> In a preferred embodiment, the N-6 substituted 7-deazapurine is a adenosine receptor antagonist . The invention further pertains to methods for treating N-6 substituted 7-deazapurine disorders, e . g. , asthma, bronchitis, allergic rhinitis, chronic obstructive pulmonary disease, renal disorders, gastrointestinal disorders, and eye disorders, in a mammal by administering to the mammal a therapeutically effective amount of a N-6 substituted 7-deazapurine, such that treatment of the disorder in the mammal occurs. Suitable N-6 substituted 7 deazapurines include those illustrated by the general formula I : (I) and pharmaceutically acceptable salts thereof. R x and R 2 are each independently a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety or together form a substituted or unsubstituted heterocyclic ring. R 3 is a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. R 4 is a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. R5 and R 6 are each independently a halogen atom, e . g. , chlorine, fluorine, or bromine, a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety, or R 5 is carboxyl, esters of carboxyl, or carboxamides, or R 4 and R 5 or R 5 and R 6 together form a substituted or unsubstituted heterocyclic or carbocyclic ring. In certain embodiments, 1^ and R 2 can each independently be a substituted or unsubstituted cycloalkyl or heteroarylalkyl moieties. In other embodiments, R 3 is a hydrogen atom or a substituted or unsubstituted heteroaryl moiety. In still other embodiments, R , R= and R^ can each be independently a heteroaryl moieties. In a preferred embodiment , R^ :s a hydrogen atom, R 2 is a cyclohexanol, e . g . , trar.s - cyclohexanol, R 3 is phenyl, R^ is a ' hydrogen atom, Rt s a methyl group and Rg is a methyl group. In still another embodiment, R is a hydrogen atom, R 2 is R 3 is phenyl, R 4 is a hydrogen atom and R 5 and R are methyl groups . The invention further pertains to pharmaceutical compositions for treating a N-6 substituted 7-deazapurine responsive state in a mammal, e. g. , asthma, bronchitis, allergic rhinitis, chronic obstructive pulmonary disease, renal disorders, gastrointestinal disorders, and eye disorders. The pharmaceutical composition includes a therapeutically effective amount of a N-6 substituted 7-deazapurine and a pharmaceutically acceptable carrier. The present invention also pertains to packaged pharmaceutical compositions for treating a N-6 substituted 7- deazapurine responsive state in a mammal. The packaged pharmaceutical composition includes a container holding a therapeutically effective amount of at least one N-6 substituted 7-deazapurine and instructions for using the N-6 substituted 7-deazapurine for treating a N-6 substituted 7- deazapurine responsive state in a mammal . The invention further pertains to compounds of formula 1 wherein R ] _ is hydrogen; R 2 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl, or R 1 and R 2 together form a substituted or unsubstituted heterocyclic ring; R 3 is unsubstituted or substituted aryl; R 4 is hydrogen; and R 5 and R 6 are each independently hydrogen or alkyl, and pharmaceutically acceptable salts thereof. The deazapurines of this embodiment may advantageously be selective A- receptor antagonists. These compounds may be useful for numerous therapeutic uses such as, for example, the treatment of asthma, kidney failure associated with heart failure, and glaucoma. In a particularly preferred embodiment, the deazapurine is a water soluble prodrug that is capable of being metabolized in vivo to an active drug by, for example, esterase catalyzed hydrolysis. In yet another embodiment, the invention features a method for inhibiting the activity of an adenosine receptor (e.g., A 3 ) in a cell, by contacting the cell with N-6 substituted 7- deazapurine (e.g., preferably, an adenosine receptor antagonist) . In another aspect, the invention features a method for treating damage to the eye of an animal (e.g., a human) by administering to the animal an effective amount of an N-6 substituted 7-deazapurine of formula I. Preferably, the N-6 substituted 7-deazapurine is an antagonist of A 3 adenosine receptors in cells of the animal. The damage is to the retina or the optic nerve head and may be acute or chronic. The damage may be the result of, for example, glaucoma, edema, ischemia, hypoxia or trauma. The invention also features a pharmaceutical composition comprising a N-6 substituted compound of formula I. Preferably, the pharmaceutical preparation is an ophthalmic formulation ( e . g. , an periocular, retrobulbar or intraocular injection formulation, a systemic formulation, or a surgical irrigating solution) . In yet another embodiment, the invention features a compound having the formula II: (ID wherein X is N or CR 6 ; R τ and R 2 are each independently hydrogen, or substituted or unsubstituted alkoxy, aminoalkyl, alkyl, aryl, or alkylaryl, or together form a substituted or unsubstituted heterocyclic ring, provided that both R λ and R 2 are both not hydrogen; R 3 is substituted or unsubstituted alkyl, arylalkyl, or aryl; R 4 is hydrogen or substituted or unsubstituted C x - C 6 alkyl; L is hydrogen, substituted or unsubstituted alkyl, or R 4 and L together form a substituted or unsubstituted heterocyclic or carbocyclic ring; R 6 is hydrogen, substituted or unsubstituted alkyl, or halogen; Q is CH 2 , O, S, or NR 7 , wherein R 7 is hydrogen or substituted or unsubstituted C 1 - C 6 alkyl; and W is unsubstituted or substituted alkyl, cycloalkyl, aryl, arylalkyl, biaryl, heteroaryl, substituted carbonyl, substituted thiocarbonyl, or substituted sulfonyl; provided that if R 3 is pyrrolidine, ther. + s not methyl. The invention also pertains to pharmaceutically acceptable salts and prodrugs cf the compounds cf the invention. In an advantageous embodiment, X is CR 6 and Q is CK 1( C, S, or NK in formula II, wherein R f is as defined above. In another embodiment of formula II, X is N. The invention further pertains to a method for inhibiting the activity of an adenosine receptor (e.g., an A 2b adenosine receptor) in a cell by contacting the cell with a compound of the invention. Preferably, the compound is an antagonist of the receptor. The invention also pertains to a method for treating a gastrointestinal disorder (e.g., diarrhea) or a respiratory disorder (e.g., allergic rhinitis, chronic obstructive pulmonary disease) in an animal by administering to an animal an effective amount of a compound of formula II (e.g., an antagonist of A ;c ) . Preferably, the animal is a human. This invention also features a compound having the structure: IV wherein R: is trans-4 -hydroxy cyclohexyl, 2-methylamino carbonylamino cyclohexyl, 2-methylamino carbonylamino cyclohexyl, acetamido ethyl, or methylamino carbonylamino ethyl; wherein Ar is a substituted or unsubstituted four to s x membered ring. In one embodiment of the compound, Ar is phenyl, pyrrole, thiophene, furan, thiazole, imidazole, pyrazcle, 1,2,4- triazole, pyridine, 2 (IH) -pyridone, 4 (IK) -pyridone , pyrazme, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, IK-indole, indoline, benzopyrazole, 1, 3-benzodioxole, benzoxazoie, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoguinoline, benzimidazole, quinazoline, pyrido [2, 3- b]pyrazine, pyrido [3 , 4-b]pyrazine, pyrido [3 , 2-c] pyridazine, purido [3 , 4-b] -pyridine , lH-pyrazole [3 , 4 -d] pyrimidine , pteridine, 2 (IH) -quinolone, 1 (2H) -isoquinolone, 1,4- benzisoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline-N- oxide, benzoxazine, phthalazine, cinnoline, or having a structure : • wherein Y is carbon or nitrogen; wherein R2 and R: ' are independently H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, methoxy, methyl amino, or methyl thio; wherein R3 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Rι) (Rs)XRs. wherein X is 0, S, or NRe, wherein R? and Re are each independently H or alkyl, wherein Rs and Rt are each independently alkyl or cycloalkyl, or Rs, Rt and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members; 11 wherein R*. is H, alkyl, substituted alkyl, cycloalkyl. or a pharmaceutically acceptable salt, or a prcdruc derivative, or a biologically active metabolite; w t: the proviso that when R: is acetylamino ethyl, Ar is no: 4-pyridyl . This invention also pertains to a compound having the structure : V wherein R: is aryl, substituted aryl, or heteroaryl; wherein R: is H, alkyl, substituted alkyl, or cycloalkyl; wherein R.- is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Rβ) wherein Rt and Ri are each H or alkyl, wherein Ri and Rs are each alkyl or cycloalkyl, or R * R: and the nitrogen together form a ring system of between 4 and 7 members . This invention also features a method for inhibiting the activity of an h-^ adenosine receptor in a cell, which comprises contacting said cell with the above-mentioned compounds . Pet-ailed Description The features and other details of the invention w ll now oe more particularly described and pointed out m the claims. It will be understood that the particular embodiments of the invention are shown by way of illustration and not as limitations of the invention. The principle features of this invention can be employed in various embodiments without departing from the scope of the invention. The present invention pertains to methods for treating a N-6 substituted 7-deazapurine responsive state in a mammal. The methods include administration of a therapeutically effective amount of a N-6 substituted 7-deazapurine, described infra , to the mammal, such that treatment of the N-6 substituted 7- deazapurine responsive state in the mammal occurs. The language "N-6 substituted 7-deazapurine responsive state" is intended to include a disease state or condition characterized by its responsiveness to treatment with a N-6 substituted 7-deazapurine of the invention as described infra , e . g . , the treatment includes a significant diminishment of at least one symptom or effect of the state achieved with a N-6 substituted 7-deazapurine of the invention. Typically such states are associated with an increase of adenosine within a host such that the host often experiences physiological symptoms which include, but are not limited to, release of toxins, inflammation, coma, water retention, weight gain or weight loss, pancreatitis, emphysema, rheumatoid arthritis, osteoarthritis, multiple organ failure, infant and adult respiratory distress syndrome, allergic rhinitis, chronic obstructive pulmonary disease, eye disorders, gastrointestinal disorders, skin tumor ' promotion, immunodeficiency and asthma. (See for example, C.E. Muller and B. Stein "Adenosine Receptor Antagonists: Structures and Potential Therapeutic Applications," Current Pharmaceutical Design, 2:501 (1996) and C.E. Muller "A^Adenosine Receptor Antagonists," Exp. Opin . Ther. Patents 7(5):419 (1997) and I. Feoktistove, H. Polosa, S. T. Holgate and I. Eiaσgioni "Adenosine A 2 q receptors: a novel therapeutic target m asthma?" Tι?S 19; 148 (1998) ) . The effects often associated w th such symptoms include, but are not limited to, fever, shortness of breath, nausea, diarrhea, weakness, headache, and even death. Ir. one embodiment, a N-6 substituted 7-deazapurine responsive state includes those disease states which are mediated by stimulation of adenosine receptors, e.g., A ! , A 2 a . A? b , A- , etc., such that calcium concentrations in cells and/or activation of PLC (phospholipase C) is modulated. In a preferred embodiment, a N-6 substituted 7-deazapurine responsive state is associated with adenosine receptor (s), e . g. , the N-6 substituted 7-deazapurine acts as an antagonist. Examples of suitable responsive states which can be treated by the compounds of the invention, e.g., adenosine receptor subtypes which mediate biological effects, include central nervous system (CNS) effects, cardiovascular effects, renal effects, respiratory effects, immunological effects, gastro-intestinal effects and metabolic effects. The relative amount of adenosine in a subject can be associated with the effects listed below; that is increased levels of adenosine can trigger an effect, e.g., an undesired physiological response, e.g., an asthmatic attack. CNS effects include decreased transmitter release (A x ) , sedation IA 1 ) , decreased locomotor activity (A 2a ) , anticonvulsant activity, chemoreceptor stimulation (A 2 ) and hyperalgesia. Therapeutic applications of the inventive compounds include treatment of dementia, Alzheimer's disease and memory enhancement . Cardiovascular effects include vasodilation (A 2a ) , (A 2b ) and (A 3 ) , vasoconstriction (A x ) , bradycardia (A x ) , platelet inhibition (A 2a ) , negative cardiac inotropy and dromotropy (Aj) , arrhythmia, tachycardia and angiogenesis. Therapeutic applications of the inventive compounds include, for example, prevention of ischaemia-induced impairment of the heart and cardiotonics, myocardial tissue protection and restoration of cardiac function. Renal effects include decreased GFR (A x ) , mesang al cell contraction (AX , antidiuresis .A 1 ) and inhibition of rerun release (A : ) . Suitable therapeutic applications of the inventive compounds include use of the inventive compounds as diuretic, natriuretic, potassium-sparing, kidney- protective/prevention of acute renal failure, antihypertensive, anti-oedematous and anti-nephritic agents. Respiratory effects include bronchodilation (A 2 ), bronchoconstriction (A : ) , chronic obstructive pulmonary disease, allergic rhinitis, mucus secretion and respiratory depression (A 2 ) . Suitable therapeutic applications for the compounds of the invention include anti -asthmatic applications, treatment of lung disease after transplantation and respiratory disorders. Immunological effects include immunosuppression (A 2 ) , neutrophil chemotaxis (A x ) , neutrophil superoxide generation (A a ) and mast cell degranulation (A 2b and A 3 ) Therapeutic applications of antagonists include allergic and non allergic inflammation, e.g., release of histamine and other inflammatory mediators. Gastrointestinal effects include inhibition of acid secretion (A : ) therapeutic application may include reflux and ulcerative conditions Gastrointestinal effects also include colonic, intestinal and diarrheal disease, e.g., diarrheal disease associated with intestinal inflammation (A 2b ) . Eye disorders include retinal and optic nerve head injury and trauma related disorders (A 3 ) . In a preferred embodiment, the eye disorder is glaucoma. Other therapeutic applications of the compounds cf the invention include treatment of obesity (lipclyt r properties), hypertension, treatment cf depression, sedative, anxiolytic, as antileptics and as laxatives, e.g., effecting motility without causing diarrhea. The term "disease state" is intended to include tnose conditions caused by or associated with unwanted levels of adenosine, adenylyl cyclase activity, increased physiological activity associated with aberrant stimulation of adenosine receptors and/or an increase in cAMP. In one embodiment, the disease state is, for example, asthma, chronic obstructive pulmonary disease, allergic rhinitis, bronchitis, renal disorders, gastrointestinal disorders, or eye disorders. Additional examples include chronic bronchitis and cystic fibrosis. Suitable examples of inflammatory diseases include non-lymphocytic leukemia, myocardial ischaemia, angina, infarction, cerebrovascular ischaemia, intermittent claudication, critical limb ischemia, venous hypertension, varicose veins, venous ulceration and arteriosclerosis. Impaired reperfusion states include, for example, any post- surgical trauma, such as reconstructive surgery, thrombolysis or angioplasty. The language "treatment of a N-6 substituted 7-deazapurine responsive state" or "treating a N-6 substituted 7- deazapurine responsive state" is intended to include changes in a disease state or condition, as described above, such that physiological symptoms in a mammal can be significantly diminished or minimized. The language also includes control, prevention or inhibition of physiological symptoms or effects associated with an aberrant amount of adenosine. In one preferred embodiment, the control of the disease state or condition is such that the disease state or condition is eradicated. In another preferred embodiment, the control is selective such that aberrant levels of adenosine receptor activity are controlled while other physiologic systems and parameters are unaffected. The term "N-6 substituted 7-deazapurine" is art reco and is intended to include those compounds having zhe f I: N-6 "7 deaza site" (I) "N-substituted 7-deazapurine" includes pharmaceutically acceptable salts thereof, and, in one embodiment, also includes certain N-6 substituted purines described herein. In certain embodiments, the N-6 substituted 7-deazapurine is not N-6 benzyl or N-6 phenylethyl substituted. In other embodiments, R 4 is not benzyl or phenylethyl substituted. In preferred embodiments, R- and R 2 are both not hydrogen atoms. In still other preferred embodiments, R 3 is not a hydrogen atom. The language "therapeutically effective amount" of an N-6 substituted 7-deazapurine, described infra , is that amount of a therapeutic compound necessary or sufficient to perform its intended function within a mammal, e.g., treat a N-6 substituted 7-deazapurine responsive state, or a disease state in a mammal. An effective amount of the therapeutic compound can vary according to factors such as the amount of the causative agent already present in the mammal, the age, sex, and weight of the mammal, and the ability of the therapeutic compounds of the present invention to affect a N- 6 substituted 7-deazapurine responsive state in the mammal. One cf ordinary skill in the art would be able tc study the aforementioned factors and make a determination regarding the effective amount of the therapeutic compound without undue experimentation. An in vi zro or in vi vc assay also can be used to determine an "effective amount" of the therapeutic compounds described infra . The ordinarily skilled artisan would select an appropriate amount of the therapeutic compound for use in the aforementioned assay or as a theraDeutic treatment . A therapeutically effective amount preferably diminishes at least one symptom or effect associated with the N-6 substituted 7-deazapurine responsive state or condition being treated by at least about 20%, (more preferably by at least about 40%, even more preferably by at least about 60%, and still more preferably by at least about 80%) relative to untreated subjects. Assays can be designed by one skilled in the art to measure the diminishment of such symptoms and/or effects. Any art recognized assay capable of measuring such parameters are intended to be included as part of this invention. For example, if asthma is the state being treated, then the volume of air expended from the lungs of a subject can be measured before and after treatment for measurement of increase in the volume using an art recognized technique. Likewise, if inflammation is the state being treated, then the area which is inflamed can be measured before and after treatment for measurement of diminishment in the area inflamed using an art recognized technique. The term "cell" includes both prokaryotic and eukaryotic cells. The . term "animal" includes any organism with adenosine receptors or any organism susceptible to a N-6-substituted 7- deazapurine responsive state. Examples of animals include yeast, mammals, reptiles, and birds. It also includes transgenic animals . The term "mammal" is art recognized and is intended to include an animal, more preferably a warm-blooded animal, most preferably cattle, sheep, pigs, horses, dogs, cats, rats, mice, and humans. Mammals susceptible to a N-6 substituted 7-deazapurine responsive state, inflamma ion, emphysema, asthma, central nervous system conditions, or acute respiratory distress syndrome, for example, are included as part of this invention. In another aspect, the present invention pertains to methods for modulating an adenosine receptor (s) in a mammal by administering to the mammal a therapeutically effective amount of a N-6 substituted 7-deazapurine, such that modulation of the adenosine receptor in the mammal occurs. Suitable adenosine receptors include the families of A 1# A 2 , or A 3# In a preferred embodiment, the N-6 substituted 7- deazapurine is an adenosine receptor antagonist. The language "modulating an adenosine receptor" is intended to include those instances where a compound interacts with an adenosine receptor (s), causing increased, decreased or abnormal physiological activity associated with an adenosine receptor or subsequent cascade effects resulting from the modulation of the adenosine receptor. Physiological activities associated with adenosine receptors include induction of sedation, vasodilation, suppression of cardiac rate and contractility, inhibition of platelet aggregbility, stimulation of gluconeogenesis, inhibition of lipolysis, opening of potassium channels, reducing flux of calcium channels, etc. The terms "modulate", "modulating" and "modulation" are intended to include preventing, eradicating, or inhibiting the resulting increase of undesired physiological activity associated with abnormal stimulation of an adenosine receptor, e.g., in the context of the therapeutic methods of the invention. In another embodiment, the term modulate includes antagonistic effects, e . g. , diminishment cf the activity or production of mediators of allergy and allergic inflammation which results from the overstimulatio cf adenosine receptor(s). For example, the therapeutic deazapurines of the invention can interact with ar. adenosine receptor to inhibit, for example, adenylate cyclase activity. The language "condition characterized by aberrant adenosine receptor activity" is intended to include those diseases, disorders or conditions which are associated with aberrant stimulation of an adenosine receptor, in that the stimulation of the receptor causes a biochemical and or physiological chain of events that is directly or indirectly associated with the disease, disorder or condition. This stimulation of an adenosine receptor does not have to be the sole causative agent of the disease, disorder or condition but merely be responsible for causing some of the symptoms typically associated with the disease, disorder, or condition being treated. The aberrant stimulation of the receptor can be the sole factor or at least one other agent can be involved in the state being treated. Examples of conditions include those disease states listed supra , including inflammation, gastrointestinal disorders and those symptoms manifested by the presence of increased adenosine receptor activity. Preferred examples include those symptoms associated with asthma, allergic rhinitis, chronic obstructive pulmonary disease, emphysema, bronchitis, gastrointestinal disorders and glaucoma. The language "treating or treatment of a condition characterized by aberrant adenosine receptor activity" is intended to include the alleviation of or diminishment of at least one symptom typically associated with the condition. The treatment also includes alleviation or diminishment of more than one symptom. Preferably, the treatment cures, e.g., substantially eliminates, the symptoms associated with the condition. The present invention pertains to compounds, N-6 subs: .t ted 7-deazapurines, having the formula I: (I) wherein R j^ and R 2 are each independently a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety or together form a substituted or unsubstituted heterocyclic ring; R 3 is a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety; R 4 is a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. R 5 and R 6 are each independently a halogen atom, e.g., chlorine, fluorine, or bromine, a hydrogen atom or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety or R 4 and R 5 or R 5 and R 6 together form a substituted or unsubstituted heterocyclic or carbocyclic ring. Also included, are pharmaceutically acceptable salts of the N-6 substituted 7-deazapurines. In certain embodiments, R j and R 2 can each independently be a substituted or unsubstituted cycloalkyl or heteroarylalkyl moieties. In other embodiments, R 3 is a hydrogen atom or a substituted or unsubstituted heteroaryl moiety. In still other' embodiments, R 4 , R 5 and R 6 can each be independently a heteroaryl moiety. In one embodiment, R is a hydrogen atom, R 2 is a substituted or unsubstituted cyclohexane, cyclopentyl, cyclobutyl or cyclopropane moiety, R 3 is a substituted or unsubstituted phenyl moiety, R 4 is a hydrogen atom and R= and R $ are both methyl groups. In another embodiment, R 2 is ' a cyclohexanol. a cyclohexanediol, a cyclohexylsulfonamide, a cycichexanam de , a cyclohexylester, a cyclohexene, a cyclopentanol or a cyclopentanediol and R 3 is a phenyl moiety. In still another embodiment, R j is a hydrogen atom, R 2 is a cyclohexanol, R 3 is a substituted or unsubstituted phenyl, pyridine, furan, cyclopentane, or thiophene moiety, R 4 is a hydrogen atom, a substituted alkyl, aryl or arylalkyl moiety, and R5 and R 6 are each independently a hydrogen atom, or a substituted or unsubstituted alkyl, aryl, or alkylaryl moiety. In yet another embodiment, R- is a hydrogen atom, R is substituted or unsubstituted alkylamine, arylamine, or aikylarylamine, a substituted or unsubstituted alkylamide, arylamide or alkylarylamide, a substituted or unsubstituted alkylsulfonamide, arylsulfonamide or alkylarylsulfonamide, a substituted or unsubstituted alkylurea, arylurea or alkylarylurea, a substituted or unsubstituted alkylcarbamate, arylcarbamate or alkylarylcarbamate, a substituted or unsubstituted alkylcarboxylic acid, arylcarboxylic acid or alkylarylcarboxylic acid, is substituted or unsubstituted phenyl moiety, R 4 is a hydrogen atom and R 5 and R 6 are methyl groups . In still another embodiment, R 2 is guanidine, a modified guanidine, cyanoguanidine, a thiourea, a thioamide or an amidine . In one embodiment, R can be wherein R a -R c are each independently a hydrogen atom or a saturated or unsaturated alkyl, aryl or alkylaryl moiety and R 2d is a hydrogen atom or a saturated or unsaturated alkyl, aryl, or alkylaryl moiety, NR e R 2f , or OR σ , wherein R? e " R 2c are each independently a hydrogen atom or a saturated or unsaturated alkyl, aryl or alkylaryl moieties. Alternatively, R 2a and R 2t) together can form a carbocyclic or heterocyclic ring having a ring size between about 3 and 6 members, e . g. , cyclopropyl, cyclopentyl, cyclohexyl groups. In one aspect of the invention, both R 5 and R 6 are not methyl groups, preferably, one of R 5 and R 6 is an alkyl group, e.g., a methyl group, and the other is a hydrogen atom. In another aspect of the invention, when R 4 is 1-phenylethyl and R j is a hydrogen atom, then R 3 is not phenyl, 2- chlorophenyl , 3-chlorophenyl, 4-chlorophenyl , 3,4- dichlorophenyl, 3-methoxyphenyl or 4-methoxyphenyl or when R 4 and R 1 are 1-phenylethyl, then R 3 is not a hydrogen atom or when R 4 is a hydrogen atom and R 3 is a phenyl, then R } is not phenylethyl . In another aspect of the invention, when R 5 and R 6 together form a carbocyclic ring, e.g., or pyrimido[4,5-6] indole, then R 3 is not phenyl when R 4 is 1- (4-methylphenyl) ethyl, phenylisopropyl, phenyl or 1- phenylethyl or when R 3 is not a hydrogen atom when R 4 is 1- phenylethyl. The carbocyclic ring formed by R 5 and R 6 can be either aromatic or aliphatic and can have between 4 and 12 carbon atoms, e.g., naphthyl, phenylcyclohexyl, etc preferably between 5 and 7 carbon atoms, e.g., cyclopentyl or cyclohexyl. Alternatively, R 5 and R 6 together car. form a heterocyclic ring, such as those disclosed below. Typical heterocyclic rings include between 4 and 12 carbon atoms, preferably between 5 and 7 carbon atoms, and car. be either aromatic or aliphatic. The heterocyclic ring car. be further substituted, including substitution of one or more carbon atoms of the ring structure with one or more heteroatoms . In still another aspect of the invention, R 1 and R 2 form a heterocyclic ring. Representative examples include, but are not limited to, those heterocyclic rings listed below, such as morpholino, piperazine and the like, e.g., 4- hydroxypiperidines, 4-aminopiperidines . Where R-. and R 2 together form a piperazino group, wherein R 7 can be a hydrogen atom or a substituted or unsubstituted alkyl, aryl or alkylaryl moiety. In yet another aspect of the invention R 4 and R 5 together can form a heterocyclic ring, e.g., wherein the heterocyclic ring can be either aromatic or aliphatic and can form a ring having between 4 and 12 carbon atoms, e.g., naphthyl, phenylcyclohexyl, etc. and can be either aromatic or aliphatic, e.g., cyclohexyl, cyclopentyl. The heterocyclic ring can be further substituted, including substitution of carbon atoms of the ring structure with one or more heteroatoms. Alternatively, R 4 and R 5 together car. form a heterocyclic ring, such as those disclosed below. In certain embodiments, the N-6 substituted 7-deazapurine is not N-6 benzyl or N-6 phenylethyl substituted. In other embodiments, R 4 is not benzyl or phenylethyl substituted. In preferred embodiments, Rj_ and R 2 are both not hydrogen atoms. In still other preferred embodiments, R 3 is not K. The compounds of the invention may comprise water-soluble prodrugs which are described in WO 99/33815, International Application No. PCT/US98/04595, filed March 9, 1998 and published July 8, 1999. The entire content of WO 99/33815 is expressly incorporated herein by reference. The water- soluble prodrugs are metabolized in vivo to an active drug, e . g. , by esterase catalyzed hydrolysis. Examples of potential prodrugs include deazapurines with, for example, R 2 as cycloalkyl substituted with -OC(O) (Z)NH , wherein Z is a side chain of a naturally or unnaturally occurring amino acid, or analog thereof, an , 3, y, or ω amino acids, or a dipeptide. Preferred amino acid side chains include those of glycine, alanine, valine, leucine, isoleucine, lysine, α- methylalanine, aminocyclopropane carboxylic acid, azetidine- 2-carboxylic acid, β-alanine, γ-aminobutyric acid, alanine- alanine, or glycine-alanine . In a further embodiment, the invention features deazapurines of the formula (I) , wherein R is hydrogen; R 2 is substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl, or R χ and R 2 together form a substituted or unsubstituted heterocyclic ring; R 3 is unsubstituted or substituted aryl; R 4 is hydrogen,- and R 5 and R 6 are each independently hydrogen or alkyl, and pharmaceutically acceptable salts thereof. The deazapurines of this embodiment may potentially be selective A 3 receptor antagonists. In one embodiment, R is substituted (e.g., hydroxy substituted) or unsubstituted cycloalkyl . In an advantageous subembodi ent, Ri and R 4 are hydrogen, R 3 is unsubstituted or substituted phenyl, and R 5 and Rg are each alkyl. Preferably R 2 is mono-hydroxycyclopentyl or mono-hydroxycyclohexyl . R 2 also may be substituted with -NK-C(=0)E, wherein E s substituted or unsubstituted C ] _-C 4 alkyl (e.g., alkyiamme, e . g. , ethylamine . ) . R j and R 2 may also together form a substituted or unsubstituted heterocyclic ring, which may be substituted with an amine or acetamido group. In another aspect, R 2 may be -A-NHC(=0)B, wherein A is unsubstituted C : -C 4 alkyl (e.g., ethyl, propyl, butyl), and B is substituted or unsubstituted C : -C 4 alkyl (e.g., methyl, aminoalkyl, e.g., aminomethyl or aminoethyl, alkylamino, e.g., methylamino, ethylamino), preferably when R and R 4 are hydrogen, R 3 is unsubstituted or substituted phenyl, and R 5 and Rg are each alkyl . B may be substituted or unsubstituted cycloalkyl, e.g., cyclopropyl or 1-amino-cyclopropyl . In another embodiment, R 3 may be substituted or unsubstituted phenyl, preferably when R 5 and Rg are each alkyl. Preferably, R 3 may have one or more substituents (e.g., o- , m- or p- chlorophenyl , o- , m- or p- fluorophenyl) . Advantageously, R 3 may be substituted or unsubstituted heteroaryl, preferably when R 5 and Rg are each alkyl. Examples of heteroaryl groups include pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, pyrrolyl, triazolyl, thioazolyl, oxazolyl, oxadiazolyl, furanyl, methylenedioxyphenyl and thiophenyl. Preferably, R 3 is 2-pyridyl, 3-pyridyl, 4- pyridyl, 2-pyrimidyl or 3- pyrimidyl. Preferably in one embodiment, R 5 and Rg are each hydroge . In another, R 5 and R 6 are each methyl. In a particularly preferred embodiment, the deazapurines of the invention are water-soluble prodrugs that can be metabolized in vivo to an active drug, e.g. by esterase catalyzed hydrolysis. Preferably the prodrug comprises an R 7 group which is cycloalkyl substituted with -0C(0) (Z)NH 2 , wherein Z is a side chain of a naturally or unnaturally occurring amino acid, an analog thereof, an α, 5, y , or amino acid, or a dipeptide. Examples of preferred side chains include the side chains of glycine, alanine, valine, leucine, isoleucine, lysine, -methylalanine , aminocyclopropane carboxylic acid, azetidine-2-carboxylic acid, β-alanine, γ-aminobutyric acid, alanine-alanine, or glycine-alanine . In a particularly preferred embodiment, Z is a side chain of glycine, R 2 is cyclohexyl, R 3 is phenyl, and R 5 and R 6 are methyl . In another embodiment, the deazapurine is 4- (cis-3- hydroxycyclopentyl) amino-5 , 6-dimethyl-2-phenyl- 7H-pyrrolo [2,3d] pyrimidine . In another embodiment, the deazapurine is 4-(cis-3-(2- aminoacetoxy) cyclopentyl) amino-5, 6-dimethyl-2 -phenyl - 7H- pyrrolo [2 , 3d] pyrimidine trifluoroacetic acid' salt. In another embodiment, the deazapurine is 4- (3- acetamido) piperidinyl-5 , 6-dimethyl-2-phenyl- 7H-pyrrolo [2,3d] pyrimidine . In another embodiment, the deazapurine is 4-(2-N'- methylureapropyl) amino-5, 6-dimethyl-2-phenyl- 7H-pyrrolo [2, 3d] pyrimidine . In another embodiment, the deazapurine is -,'Z- ace t amidobutyl) amino-5, 6 -dimethyl-2 -phenyl- 7H-pyrrclo [2,3d: pyrimidine . In another embodiment, the deazapurine is 4-(2-N'- methylureabutyl) amino-5, 6-dimethyl-2 -phenyl- 7H-pyrrolo [2 , 3d] pyrimidine . In another embodiment, the deazapurine is 4- (2- aminocyclopropylacetamidoethyl) amino-2-phenyl- 7H-pyrrolo [2,3d] pyrimidine . In another embodiment, the deazapurine is 4- (trans-4- hydroxycyclohexyl) amino-2- (3-chlorophenyl) - 7H-pyrrolo [2, 3d] pyrimidine. In another embodiment, the deazapurine is 4- (trans-4- hydroxycyclohexyl) amino-2- (3-fluorophenyl) - 7H-pyrrolo [2 , 3d] pyrimidine . In another embodiment, the deazapurine is 4- (tran -4- hydroxycyclohexyl) amino-2- (4 -pyridyl ) - 7H-pyrrolo [2,3d] pyrimidine . In yet another embodiment, the invention features a method for inhibiting the activity of an adenosine receptor (e.g., A ; , A 2A , A 3B , or, preferably, A 3 ) in a cell, by contacting the cell with N-6 substituted 7-deazapurine (e.g., preferably, an adenosine receptor antagonist) . In another aspect, the invention features a method for treating damage to the eye of an animal (e.g., a human) by administering to the animal an effective amount of an N-6 substituted 7-deazapurine. Preferably, the N-6 substituted 7-deazapurine is an antagonist of A ; . adenosine receptors in cells of the animal. The damage is to the retina cr the optic nerve head and may be acute or chronic. The damage ma be the result of, for example, glaucoma, edema, ischemia, hypoxia or trauma. In a preferred embodiment, the invention features a deazapurine having the formula II, supra , wherein X is K or CR 6 ; R α and R ; are each independently hydrogen, or substituted or unsubstituted alkoxy, aminoalkyl, alkyl, aryl, or alkylaryl, or together form a substituted or unsubstituted heterocyclic ring, provided that both R 1 and R : are both not hydrogen; R 3 is substituted or unsubstituted alkyl, arylalkyl, or aryl; R 4 is hydrogen or substituted or unsubstituted C : -C 6 alkyl; L is hydrogen, substituted or unsubstituted alkyl, or R 4 and L together form a substituted or unsubstituted heterocyclic or carbocyclic ring,- R 6 is hydrogen, substituted or unsubstituted alkyl, or halogen; Q -is CH 2 , 0, S, or NR 7 , wherein R 7 is hydrogen or substituted or unsubstituted C^Cς alkyl; and W is unsubstituted or substituted alkyl, cycloalkyl, alkynyl, aryl, arylalkyl, biaryl, heteroaryl, substituted carbonyl, substituted thiocarbonyl, or substituted sulfonyl, provided that if R 3 is pyrrolidino, then R 4 is not methyl. In one embodiment, in compounds of formula II, X is CR 6 and Q is CH,, 0, S, or NH. In another embodiment, X is N. In a further embodiment of compounds of formula II, W is substituted or unsubstituted aryl, 5- or 6- member heteroaryl, or biaryl. W may be substituted with one or more substituents. Examples of substituents include: halogen, hydroxy, alkoxy, amino, aminoalkyl, aminocarboxyamide, CN, CF 3 ,.C0 2 Rβ, CONHR 8 , C0NR 8 R 9 , S0R 8 , S0 2 R 8 , and S0 2 NR g R 9 , wherein R 8 and Rα are each independently hydrogen, or substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. Preferably, W may be substituted or unsubstituted phenyl, e.g., methylenedioxyphenyl . W also may be a substituted or unsubstituted 5-membered heteroaryl ring, e.g., pyrrole, pyrazole, oxazole, imidazole, triazole, tetra∑cle, furan, thiophene, thiazole, and oxadiazole. Preferably, K may be a 6-member ■ heteroaryl ring, e.g., pyridyl, pyrimidyl, pyridazinyl, pyrazinal, and thiophenyl. In a preferred embodiment, W is 2-pyridyl, 3- pyridyl, 4-pyr dyi, 2- pyrimidyl, 4-pyrimidyl, or 5-pyrimidyl. In one advantageous embodiment of compounds of formula II, Q is NH and W is a 3-pyrazolo ring which is unsubstituted or N- substituted by substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. In another embodiment of compounds of formula II, Q is oxygen, and W is a 2-thiazolo ring which is unsubstituted or substituted by substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. In another embodiment of compounds of formula II, W is substituted or unsubstituted alkyl, cycloalkyl e.g., cyclopentyl, or arylalkyl. Examples of substituents include halogen, hydroxy , substituted or unsubstituted alkyl, cycloalkyl, aryl, arylalkyl, or NHR 10 , wherein R 10 is hydrogen, or substituted or unsubstituted alkyl, cycloalkyl, aryl, or arylalkyl. In yet another embodiment, the invention features a deazapurine of formula II wherein W is - (CH ; ) a -C(=0) Y or - (CH 2 ) S -C(=S) Y, and a is an integer from 0 to 3, Y is aryl, alkyl, arylalkyl, cycloalkyl, heteroaryl, alkynyl, NHR U R 12 , or, provided that Q is NH, 0R 13 , wherein R n , R 12 and R 13 are each independently hydrogen, or unsubstituted or substituted alkyl, aryl, arylalkyl, or cycloalkyl. Preferably, Y is a 5- or 6- member heteroaryl ring. Furthermore, W may be - (CH 2 ) t -S (=0) .Y, wherein j is 1 or 2, b is 0, 1, 2, or 3, Y is aryl, alkyl, arylalkyl, cycloalkyl, alkynyl, heteroaryl, NHR 14 R 15 , provided that when b s 1, ; :s CH 2 , , and wherein R , R :5 , and R 16 are each independently hydrogen, or unsubstituted or substituted alkyl, aryl, arylalkyl, or cycloalkyl. In another embodiment, R 3 is selected from the group consisting of substituted and unsubstituted phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinal, pyrrolyl, triazolyl , thioazolyl, oxazolyl, oxadiazolyl, pyrazolyl, furanyl, methylenedioxyphenyl , and thiophenyl. When R 3 is phenyl, it may be substituted with, for example, hydroxyl, alkoxy (e.g., methoxy), alkyl (e.g., tolyl) , and halogen, { e . g. , o- , m- , or p- fluorophenyl or o- , m- , or p- chlorophenyl) . Advantageously, R 3 may be 2-, 3-, or 4- pyridyl or 2- or 3- pyrimidyl . The invention also pertains to a deazapurine wherein R 6 is hydrogen or C 1 -C 2 alkyl. Preferably, R 6 is hydrogen. The invention also includes deazapurines wherein R : is hydrogen, and R 2 is substituted or unsubstituted alkyl or alkoxy, substituted or unsubstituted alkylamine, arylamine, or alkylarylamine, substituted or unsubstituted aminoalkyl, amino aryl, or aminoalkylaryl, substituted or unsubstituted alkylamide, arylamide or alkylarylamide, substituted or unsubstituted alkylsulfonamide, arylsulfonamide or alkylarylsulfonamide, substituted or unsubstituted alkylurea, arylurea or alkylarylurea, substituted or unsubstituted alkylcarbamate, arylcarba ate or alkylarylcarbamate, or substituted or unsubstituted alkylcarboxylic acid, arylcarboxylic acid or alkylarylcarboxylic acid. Preferably, R ; is substituted or unsubstituted cycloalkyl, e . g. , mono- or dihydroxy-substituted cyclohexyl or cyclopentyl (preferably, monohydroxy-substituted cyclohexyl or monohydroxy-substituted cyclopentyl) . 2/057267 31 Advantageously, R 2 may be of the following formula wherein A is ^ ^ -C^ alkyl, ^ -C-, cycloalkyl, a chair, of one to seven atoms, or a ring of three to seven atoms, optionally substituted with C l -C 6 alkyl, halogens, hydroxyl, carboxyl, thiol, or amino groups; wherein B is methyl, N(Me) 2 , N(Et) 2 , NHMe, NHEt, (CH,) r NH 3 +, NH(CH 2 ).CH 3 , (CH,) r NH : , (CH ) r CHCH, H 2 , (CH 2 ) r NHMe, (CH 2 ) r 0H, CH 2 CN, (CH,) B C0 2 H, CHR 19 R i? , or CHMeOH, wherein r is an integer from 0 to 2, m is l or 2, R 13 is alkyl, R :5 is NH Ξ t- or C0 2 H or R 16 and R 1? together are: CH NH \ / (CH 2 )p wherein p is 2 or 3; and R 17 is C^ -C f , alkyl, C 3 -C 7 cycloalkyl, a chain of one to seven atoms, or a ring of three to seven atoms, optionally substituted with C x -C 6 alkyl, halogens, hydroxyl, carboxyl, thiol, or amino groups . Advantageously, A is unsubstituted or substituted Cj-Cg alkyl. B may be unsubstituted or unsubstituted C 1 - C 6 alkyl. In a preferred embodiment, R 2 is of the formula -A-NHC(sO)B. In a particularly advantageous embodiment, A is -CH 2 CH 2 - and B is methyl . The compounds of the invention may comprise water-soluble prodrugs which are metabolized in vivo to an active drug, e . g. , by esterase catalyzed hydrolysis. Examples of potential prodrugs include deazapurines with, for example, R 2 as cycloalkyl substituted with -OC(O) (Z)NH 2 , wherein Z is a side chain of a naturally or unnaturally occurring amine acid, or analog thereof, an α, β, y, or ω amino acid, or a dipeptide. Preferred amino acid side chains include those cf glycine, alanine, valine, leucine, isoleucine, lysine, α- methylalanine, aminocyclopropane carboxylic acid, azetidine- 2-carboxylic acid, β-alanine, γ-aminobutyric acid, alanine- alanine, or glycine-alanine. In another embodiment , R : and R ; together are wherein n is 1 or 2, and wherein the ring may be optionally substituted with one or more hydroxyl, amino, thiol, carboxyl, halogen, CH 2 0H, CH 2 NHC (=0) alkyl , or Ctf 2 NHC(=0)NHalkyl groups. Preferably, n is 1 or 2 and said ring is substituted with -NHC (=0) alkyl . In one advantageous embodiment, R 1 is hydrogen, R : is substituted or unsubstituted C : -C ό alkyl, R 3 is substituted or unsubstituted phenyl, R 4 is hydrogen, L is hydrogen or substituted or unsubstituted C l -C 6 alkyl, Q is 0, S or NR 7 , wherein R is hydrogen or substituted or unsubstituted Ci-C 6 alkyl, and W is substituted or unsubstituted aryl. Preferably, R 2 is -A-NHC(=0)B, wherein A and B are each independently unsubstituted or substituted C 1 -C 1 alkyl. For example, A may be CH 2 CH 2 . B may be, for example, alkyl (e.g., methyl), or aminoalkyl (e.g., aminomethyl) . Preferably, R 3 is unsubstituted phenyl and L is hydrogen. R 6 may be methyl or preferably, hydrogen. Preferably, Q is 0, S, or NR 7 wherein R is hydrogen or substituted or unsubstituted C x - C 6 alkyl, e . g. , methyl. W is unsubstituted or substituted phenyl ( e. g. , alkoxy, halogen substituted). Preferably, W is p-fluorophenyl, p-chlorophenyl, or p-methoxypheny . K may also be heteroaryl, e.g., 2-pyridyl. In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6 -phenoxymethyl-2 -phenyl - 7H- pyrrolo [2,3d] pyrimidine . In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6- (4-fluorophenoxy) methyl -2- phenyl- H-pyrrolo [2 , 3d] pyrimidine . In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6- (4-chlorophenoxy)methyl-2- phenyl- 7H-pyrrolo [2 , 3d] pyrimidine . In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6- (4-methoxyphenoxy)methyl-2- phenyl- 7H-pyrrolo [2 , 3d] pyrimidine . In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6- (2-pyridyloxy) methyl-2 -phenyl- 7H-pyrrolo [2 , 3d] pyrimidine . In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6- (N-phenylamino) methyl -2 -phenyl- 7H- yrrolo [2 , 3d] pyrimidine . In a particularly preferred embodiment, the deazapurine is 4- (2-acetylaminoethyl) amino-6- (N-methyl-N-phenylamino) methyl- 2-phenyl - 7H-pyrrolo [2, 3d] pyrimidine. In a particularly preferred embodiment, the deazapurine is 4- (2-N' -methylureaethyl) amino-6-phenoxymethyl-2 -phenyl - 7H- pyrrolo [2 , 3d] pyrimidine . The invention further pertains to a method for inhibiting the activity of an adenosine receptor (e.g., an ^ adenosine receptor) in a cell by contacting the cell with a compound cf the invention. Preferably, the compound is an antagonist of the receptor. The invention also pertains to a method for treating a gastrointestinal disorder ( e . g. , diarrhea) in an animal by administering to an animal an effective amount of a compound of the invention (e.g., an antagonist of A 2b ) . Preferably, the animal is a human. In another embodiment, the invention relates to a pharmaceutical composition containing an N-6 substituted 7- deazapurine of the invention and a pharmaceutically acceptable carrier. The invention also pertains to a method for treating a N-6 substituted 7-deazapurine responsive state in an animal, by administering to a mammal a therapeutically effective amount of a deazapurine of the invention, such that treatment of a N-6 substituted 7-deazapurine responsive state in the animal occurs. Advantageously, the disease state may be a disorder mediated by adenosine. Examples of preferred disease states include: central nervous system disorders, cardiovascular disorders, renal disorders, inflammatory disorders, allergic disorders, gastrointestinal disorders, eye disorders, and respiratory disorders. The term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. The term alkyl further includes alkyl groups, which can further include oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more carbons of the hydrocarbon backbone, e.g., oxygen, nitrogen, sulfur or phosphorous atoms. In preferred embodiments, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., 2 -C3 0 for straight chain, 3 -C 30 for branched chain), and more preferably 20 or fewer. Likewise, preferred cycloalkyls have from 4-10 carbon atoms in their ring structure, and more preferably have 5, 6 or 7 carbons in the ring structure. Moreover, the term alkyl as used throughout the specification and claims is intended to include both "unsubstituted alkyis" and "substituted alkyis", the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl , alkoxycarbonyl, aminocarbonyl , alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino) , acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido) , amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. It will be understood by those skilled in the art that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. Cycloalkyls can be further substituted, e.g., with the substituents described above. An "alkylaryl" moiety is an alkyl substituted with an aryl ( e . g. , phenylmethyl (benzyl)). The term "alkyl" also includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyis described above, but that contain at least one double or triple bond respectively. The term "aryl" as used herein, refers to the radical of aryl groups, including 5- and 6-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, pyrrole, furan, thiophene, imidazole, benzoxazole, benzothiazole, triazole, tetrazole, pyrazole, pyridine, pyrazme, pyridazine and pyrimidine, and tne lικe. Aryl groups also include polycyclic fused aromatic groups such as naphthyl, qumolyl, mdolyl, and the like. Those aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles" , "heteroaryls" or "heteroaromatics" . The aromatic ring can be substituted at one or more ring positions with such substituents as described above, as for example, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl , alkoxycarbonyl, ammocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, cyano, ammo (including alkyl ammo, dialkylammo, arylamino, diarylam o, and alkylarylammo) , acylam o (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido) , amidmo, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety Aryl groups can also be fused or bridged with alicyclic or heterocyclic rings which are not aromatic so as to form a polycycle (e.g., tetralm) . The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous m length and possible substitution to the alkyis described above, but that contain at least one double or triple bond respectively. For example, the invention contemplates cyano and propargyl groups . Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure, even more preferably one to three carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths. The terms "alkoxyalkyl" , "polyaminoalkyl" and "thioalkoxyalkyl" refer to alkyl groups, as described above, which further include oxygen, nitrogen or sulfur atoms replacing, one or more carbons of the hydrocarbon backbone , e.g., oxygen, nitrogen or sulfur atoms. The terms "polycyclyl" or "polycyclic radical" refer tc the radical of two or more cyclic rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls) in which two or more carbons are common to two adjoining rings, e.g., the rings are "fused rings". Rings that are joined through non-adjacent atoms are termed "bridged" rings. Each of the rings of the polycycle can be substituted with such substituents as described above, as for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, aminocarbonyl , alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkyl amino, dialkylamino, arylamino, diarylamino, and alkylarylamino) , acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido) , amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkyl, alkylaryl, or an aromatic or heteroaromatic moiety The term "heteroato " as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, sulfur and phosphorus.- The term "amino acids" includes naturally and unnaturally occurring amino acids found in proteins such as glycine, alanine, valine, cysteine, leucine, isoleucine, serine, threonine, methionine, glutamic acid, aspartic acid, glutamine, asparagine, lysine, arginine, proline, histidine, phenylalanine, tyrosine, and tryptophan. Amino acid analogs include amino acids with lengthened or shortened side cnair.s or variant side chains with appropriate functional groups . Amino acids also include D and L stereoisomers of an a mc acid when the structure of the am o acid admits of stereoisomeric forms. The term "dipeptide" includes two or more amino acids linked together. Preferably, dipeptides are two amino acids linked via a peptide linkage. Particularly preferred dipeptides include, for example, alanine-alanine and glycine-alanine. It will be noted that the structure of some of the compounds of this invention includes asymmetric carbon atoms and thus occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. All such isomeric forms of these compounds are expressly included in this invention. Each stereogenic carbon may be of the R or S configuration. It is to be understood accordingly that the isomers arising from such asymmetry (e.g., all enantiomers and diastereomers) are included within the scope of this invention, unless indicated otherwise. Such isomers can be obtained in substantially pure form by classical separation techniques and by stereochemically controlled synthesis . The invention further pertains to pharmaceutical compositions for treating a N-6 substituted 7-deazapurine responsive state in a mammal, e.g., respiratory disorders (e.g., asthma, bronchitis, chronic obstructive pulmonary disorder, and allergic rhinitis) , renal disorders, gastrointestinal disorders, and eye disorders. The pharmaceutical composition includes a therapeutically effective amount of a N-6 substituted 7-deazapurine, described supra, and a pharmaceutically acceptable carrier. It is to be understood, that all of the deazapurines described above are included for therapeutic treatment. It is to be further understood that the deazapurines of the invention can be used alone or in combination with other deazapurines of the invention or in combination with additional therapeutic compounds, sucn a= antibiotics, antiinflammatories, or anticancer agents, foi example . The term "antibiotic" is art recognized and is intended tc include those substances produced by growing microorganisms and synthetic derivatives thereof, which eliminate or inhibit growth of pathogens and are selectively toxic to the pathogen while producing minimal or no deleterious effects upon the infected host subject. Suitable examples of antibiotics include, but are not limited to, the principle classes of aminoglycosides, cephalosporins, chloramphenicols , fuscidic acids, macrolides, penicillins, polymixins, tetracyclines and streptomycins . The term "antiinflammatory" is art recognized and is intended to include those agents which act on body mechanisms, without directly antagonizing the causative agent of the inflammation such as glucocorticoids, aspirin, ibuprofen, NSAIDS, etc. The term "anticancer agent" is art recognized and is intended to include those agents which diminish, eradicate, or prevent growth of cancer cells without, preferably, adversely affecting other physiological functions. Representative examples include cisplatin and cyclophosphamide. When the compounds of the present invention are administered as pharmaceuticals, to humans and mammals, they can be given per se or as a pharmaceutical composition containing, for example, 0.1 to 99.5% (more preferably, 0.5 to 90%) of active ingredient in combination with a pharmaceutically acceptable carrier. The phrase "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting a compound (s) of the present invention within or to the subject such that it can performs its intended function. Typically, such compounds are carried or transported from one organ, or portion cf the body, to another organ, or portion of the body. Each carrier must be "acceptable" in the sense of- being compatible with the other ingredients of the formulation and not injurious tc the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose,- starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes,- oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar,- buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations . As set out above, certain embodiments of the present compounds can contain a basic functional group, such as amino or alkylamino, and are, thus, capable of forming pharmaceutically acceptable salts with pharmaceutically acceptable acids. The term "pharmaceutically acceptable salts" in this respect, refers to the relatively non-toxic, inorganic and organic acid addition salts of compounds of the present invention. These salts can be prepared in si tu during the final isolation and purification of the compounds of the invention, or by separately reacting a purified compound of the invention in its free base form with a suitable organic or inorganic acid, and isolating the salt thus formed. Representative salts include the hydrobromide , hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, la rat≤, benzoate, lactate, phosphate, tosylate, citrate, naleate, fumarate, succinate, tartrate, napthylate, mesylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like. (See, e . g . , Berge et al . (1977) "Pharmaceutical Salts", J. Pharm . Sci . 66:1-19). In other cases, the compounds of the present invention may contain one or more acidic functional groups and, thus, are capable of forming pharmaceutically acceptable salts with pharmaceutically acceptable bases. The term "pharmaceutically acceptable salts" in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention. These salts can likewise be prepared in si tu during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically acceptable metal cation, with ammonia, or with a pharmaceutically acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. The term "pharmaceutically acceptable esters" refers to the relatively non-toxic, esterified products of the compounds of the present invention. These esters can be prepared in si tu during the final isolation and purification of the compounds, or by separately reacting the purified compound in its free acid form or hydroxyl with a suitable esterifying agent. Carboxylic acids can be converted into esters via treatment with an alcohol in the presence of a catalyst. Hydroxyl containing derivatives can be converted into esters via treatment with an esterifying agent such as alkanoyl halides. The term is further intended to include lower hydrocarbon groups capable of being solvated under physiological conditions, e.g., alkyl esters, methyl, ethyl and propyl esters. (See, for example, Berge et al . , supra . ) The invention further contemplates the use of prodrugs which are converted in vivo to the therapeutic compounds of tne invention (see, e.g., R.B. Silverman, 1992, "The Organic Chemistry of Drug Design and Drug Action", Academic Press, Chapter 8) . Such prodrugs can be used to alter the biodistribution (e.g., to allow compounds which would not typically enter the reactive site of the protease) or the pharmacokinetics of the therapeutic compound. For example, a carboxylic acid group, can be esterified, e.g., with a methyl group or an ethyl group to yield an ester. When the ester is administered to a subject, the ester is cleaved, enzymatically or non-enzymatically, reductively or hydrolytically, to reveal the anionic group. An anionic group can be esterified with moieties (e.g., acyloxymethyl esters) which are cleaved to reveal an intermediate compound which subsequently decomposes to yield the active compound. In another embodiment, the prodrug is a reduced form of a sulfate or sulfonate, e.g., a thiol, which is oxidized in vivo to the therapeutic compound. Furthermore, an anionic moiety can be esterified to a group which is actively transported in vivo, or which is selectively taken up by target organs. The ester can be selected to allow specific targeting of the therapeutic moieties to particular reactive sites, as described below for carrier moieties. Wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions. , mΛrn 02/057267 43 Examples of pharmaceutically acceptable antioxidants include: water soluble antioxidants, such as ascorbic acid, cysteine hydrochloride, sodium bisulfate, sodium metabis lfite, sodium sulfite and the like; oil-soluble antioxidants, such as ascorbyl palmitate, butylated hydroxyanisole (3KA. , butylated hydroxytoluene (BHT) , lecithin, propyl gallate, alpha- tocopherol, and the like,- and metal chelating agents, such as citric acid, ethylenediamine tetraacetic acid (EDTA) , sorbitol, tartaric acid, phosphoric acid, and the like. Formulations of the present invention include those suitable for oral, nasal, topical, transdermal, buccal, sublmgual, rectal, vaginal and/or parenteral administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. The amount of active ingredient which can be combined with a carrier material to produce a single dosage form will generally be that amount of the compound which produces a therapeutic effect. Generally, out of one hundred per cent, this amount will range from about 1 per cent to about ninety-nine percent of active ingredient, preferably from about 5 per cent to about 70 per cent, most preferably from about 10 per cent to about 30 per cent. Methods of preparing these formulations or compositions include the step of bringing into association a compound of the present invention with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing into association a compound of the present invention with liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product. Formulations of the invention suitable for oral administration may be in the form of capsules, cachets, pills, tablets, lozenges (using a flavored basis, usually sucrose and acacia or tragacanth) , powders, granules, or as a solution or a suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-cil liquid emulsion, or as an elixir or syrup, or as pastilles . sing an inert base, such as gelatin and glycerin, cr sucrose and acacia) and/or as mouth washes and the like, each containing a predetermined amount of a compound of the present invention as an active ingredient. A compound of the present invention may also be administered as a bolus, electuary or paste. In solid dosage forms of the invention for oral administration (capsules, tablets, pills, dragees, powders, granules and the like) , the active ingredient is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and/or any of the following: fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and/or silicic acid; binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and/or acacia; humectants, such as glycerol; disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, al ' ginic acid, certain silicates, and sodium carbonate; solution retarding agents, such as paraffin; absorption accelerators, such as quaternary ammonium compounds; wetting agents, such as, for example, cetyl alcohol and glycerol monostearate ; absorbents, such as kaolin and bentonite clay; lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and coloring agents. In the case of capsules, tablets and pills, the pharmaceutical compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like. A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, , mΛrn 02/057267 45 preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose', surface-active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets, and other solid dosage forms of the pharmaceutical compositions of the present invention, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical - formulating art. They may also be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile, other polymer matrices, liposomes and/or microspheres. They may be sterilized by, for example, filtration through a bacteria- retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in' sterile water, or some other sterile injectable medium immediately before use. These compositions may also optionally contain opacifying agents and may be of a composition that they release the active ingredient (s) only, or preferentially, in a certain portion of the gastrointestinal tract, optionally, in a delayed manner. Examples of embedding compositions which can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, if appropriate, with one or more of the above-described excipients. Liquid dosage forms for oral administration of the compounds of the invention include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixir ' s. In addition to the active ingredient, the liquid dosage forms may contain inert dilutents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-buty ene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycercl, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert dilutents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preservative agents. Suspensions, in addition to the active compounds, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof. Formulations of the pharmaceutical compositions of the invention for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing one or more compounds of the invention with one or more suitable nonirritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the rectum or vaginal cavity and release the active compound. Formulations of the present invention which are suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be appropriate. Dosage forms for the topical or transdermal administration of a compound of this invention include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants which may be required . The ointments, pastes, creams and gels may contain, m addition to an active compound of this invention, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and z c oxide, or mixtures thereof. Powders and sprays can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane. Transdermal patches have the added advantage of providing controlled delivery of a compound of the present invention to the body. Such dosage forms can be made by dissolving or dispersing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate of such flux can be controlled by either providing a rate controlling membrane or dispersing the active compound in a polymer matrix or gel. Ophthalmic formulations, eye ointments, powders, solutions and the like, are also contemplated as being within the scope of this invention. Preferably, the pharmaceutical preparation is an ophthalmic formulation (e.g., an periocular, retrobulbar or intraocular injection formulation, a systemic formulation, or a surgical irrigating solution) . The ophthalmic formulations of the present invention may include one or more deazapurines and a pharmaceutically acceptable vehicle. Various types of vehicles may be used. The vehicles will generally be aqueous in nature. Aqueous solutions are generally preferred, based on case of formulation, as well as a patient's ability to easily administer such compositions by means of instilling one to t wo drops of the solutions in the affected eyes. However, the deazapurines of the present invention may also be readily incorporated into other types of compositions, such as suspensions, viscous or semi-viscous gels or other types of solid or semi-solid compositions. The ophthalmic compositions of the present invention may also include various other ingredients, such as buffers, preservatives, co-solvents and viscosity building agents. An appropriate buffer system (e.g., sodium phosphate, sodium acetate or sodium borate) may be added to prevent pH drift under storage conditions. Ophthalmic products are typically packaged in multidose form. Preservatives are thus required to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thi erosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, polyquaternium-1 , or other agents known to those skilled in the art. Such preservatives are typically employed at a level of from 0.001 to 1.0% weight/volume ("% w/v") . When the deazapurines of the present invention are administered during intraocular surgical procedures, such as through retrobulbar or periocular injection and intraocular perfusion or injection, the use of balanced salt irrigating solutions as vehicles are most preferred. BSS ® Sterile Irrigating Solution and BSS Plus ® Sterile Intraocular Irrigating Solution (Alcon Laboratories, Inc., Fort Worth, Texas, USA) are examples of physiologically balanced intraocular irrigating solutions. The latter type of solution is described in U.S. Pat. No. 4,550,022 (Garabedian, eϋ al . ) , the entire contents of which are hereby incorporated in the present specification by reference. Retrobulbar and periocular injections are known to those skilled in the art and are described in numerous publications including, for example, Ophthalmic Surgery: Principles of Practi ce, Ed . , G. L. Spaeth. W. B. Sanders Co., Philadelphia, Pa., U.S.A., pages 85-87 (1990) . As indicated above, use of deazapurines to prevent or reduce damage to retinal and optic nerve head tissues at the cellular level is a particularly important aspect of one embodiment of the invention. Ophthalmic conditions which may be treated include, but are not limited to, retinopathies, macular degeneration, ocular ischemia, glaucoma, and damage associated with injuries to ophthalmic tissues, such as ischemia reperfusion injuries, photochemical injuries, and injuries associated with ocular surgery, particularly injuries to the retina or optic nerve head by exposure to light or surgical instruments. The compounds may also be used as an adjunct to ophthalmic surgery, such as by vitreal or subconjunctival injection following ophthalmic surgery. The compounds may be used for acute treatment of temporary conditions, or may be administered chronically, especially in the case of degenerative disease. The compounds may also be used prophylactically, especially prior to ocular surgery or noninvasive ophthalmic procedures, or other types of surgery. Pharmaceutical compositions of this invention suitable for parenteral administration comprise one or more compounds of the invention in combination with one or more pharmaceutically acceptable sterile isotonic aqueous or nonaqueous solutions, dispersions, suspensions' or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents. Examples of suitable aqueous and nonaqueous carriers which may be employed in the pharmaceutical compositions of the invention include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like) , and suitable mixtures thereof, vegetable oils, such as ciive oil, and injectable organic esters, such as ethyl oleate . Proper fluidity can be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms may be ensured by the inclusion of various antibacterial and antifungal agents, for example, paraben, chlorobutanol, phenol sorbic acid, and the like. It may also be desirable to include isotonic agents, such as sugars, sodium chloride, and the like into the compositions. In addition, prolonged absorption of the injectable pharmaceutical form may be brought about by the inclusion of agents which delay absorption such as aluminum monostearate and gelatin. In some cases, in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material having poor water solubility. The rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form. Alternatively, delayed absorption of a parenterally-administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle. Injectable depot forms are made by forming microencapsule matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (orthoesters) and poly (anhydrides) . Depot injectable formulations are also prepared by entrapping the drug m liposomes or microemulsions which are compatible with body tissue. The preparations of the present invention may be given orally, parenterally, topically, or rectally. They are of course given by forms suitable for each administration route. For example, they are administered in tablets or capsule form, by injection, inhalation, eye lotion, ointment, suppository, etc. administration by injection, infusion or inhalation; topical by lotion or ointment; and rectal by suppositories. Oral administration is preferred. The phrases "parenteral administration" and "administered parenterally" as used herein means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, . subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion. The phrases "systemic administration, " "administered systematically, " "peripheral administration" and "administered peripherally" as used herein mean the administration of a compound, drug or other material other than directly into the central nervous system, such that it enters the patient's system and, thus, is subject to metabolism and other like processes, for example, subcutaneous administration. These compounds may be administered to humans and other animals for therapy by any suitable route of administration, including orally, nasally, as by, for example, a spray, rectally, intravaginally, parenterally, intracisternally and topically, as by powders, ointments or drops, including buccally and sublingually. Regardless of the route of administration selected, the compounds of the present invention, which may be used in a suitable hydrated form, and/or the pharmaceutical compositions of the present invention, are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those of skill in the art . Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, or the ester, salt or amide thereof, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the effective amount of • the pharmaceutical composition required For example, the physician or veterinarian could start doses of the compounds of the invention employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. In general, a suitable daily dose of a compound of the invention will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above. Generally, intravenous and subcutaneous doses of the compounds of this invention for a patient, when used for the indicated analgesic effects, will range from about 0.0001 to about 200 mg per kilogram of body weight per day, more preferably from about 0.01 to about 150 mg per kg per day, and still more preferably from about 0.2 to about 140 mg per kg per day. If desired, the effective daily dose of the active compound may be administered as two, three, four, five, six or more sub-doses administered separately at appropriate intervals throughout the day, optionally, in unit dosage forms. While it is possible for a compound of the present invention to be administered alone, it is preferable to administer the compound as a pharmaceutical composition. The present invention also pertains to packaged pharmaceutical compositions for treating a N-6 substituted 7 deazapurine responsive state, e.g., undesirable increased adenosine receptor activity in a mammal . The packaged pharmaceutical compositions include a container holding a therapeutically effective amount of at least one deazapurine as described supra and instructions for using the deazapurine for treating the deazapurine responsive state in the mammal. The deazapurines of the invention can be prepared using standard methods for organic synthesis. Deazapurines can be purified by reverse phase HPLC, chromatography, recrystallization, etc. and their structures confirmed by mass spectral analysis, elemental analysis, IR and/or NMR spectroscopy. Typically, synthesis of the intermediates as well as the deazapurines of the invention is performed in solution. The addition and removal of one or more protecting group is also t ypical practice and is known to those skilled in the art . Typical synthetic schemes for the preparation cf deazapurine intermediates of the invention are outlined below in Scheme I. This invention further provides a compound having the structure (IV) : IV wherein R: is trans-4-hydroxy cyclohexyl, 2-methylamino carbonylamino cyclohexyl, acetylamino ethyl, or methylamino carbonylamino ethyl ; wherein Ar is a substituted or unsubstituted four to six membered ring, phenyl, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1, 2, 4-triazole, pyridine, 2 (IH) -pyridone, 4 (IH) -pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, lH-indole, indoline, benzopyrazole, 1, 3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoquinoline, . benzimidazole, quinazoline, pyrido [2, 3 -b] pyrazine, pyrido [3,4- b]pyrazine, pyrido[3 , 2-c] pyridazine, purido [3, 4-b] - pyridine, lH-pyrazole [3 , 4-d] pyrimidine, pteridine, 2 (IH) -quinolone, 1 (2H) -isoquinolone, 1, 4-benzisoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline- N-oxide, benzoxazine, phthalazine, cinnoline, or having a structure : wherein Y is carbon or nitrogen; wherein R: and R: ' are independently H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, methoxy, methyl amino, or methyl thio; wherein R 3 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R?) (R÷)XR;, wherein X is 0, S, or NR * , wherein R- and Ri are each independently H or alkyl, wherein RΪ and Re are each independently alkyl or cycloalkyl, or NRsRe is a substituted or unsubstituted ring of between 4 and 7 members ,- wherein R< is H, alkyl, substituted alkyl, cycloalkyl; or a pharmaceutically acceptable salt, a prodrug derivative, or a biologically active metabolite, with proviso that when R: acetylamino ethyl, Ar is not 4- pyridyl . In one embodiment of the compound having structure IV, NRsRe is a substituted or unsubstituted ring of between 4 and 7 members which is selected from the group consisting of: wherein m is o, i, or 2, wherein n is 0, 1, 2, or 3; wherein Re is hydrogen, -OH, -CH2OH, NHR11; wherein R11 is -C(=0)CH3, or -SO∑Me, or wherein R is H, alkyl, or aryl In another embodiment of the compound having structure IV, Ar has the structure : wherein Y is carbon or nitrogen; wherein R: is H, or halogen, -O-alkyl group, amine group, or sulfide group; wherein R 3 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R->) (Re)NRsRe, wherein Ri and Rε are each independently H or alkyl, wherein Rs and Rέ are each independently alkyl or cycloalkyl, or Rs, Rb and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members. In another embodiment of the compound, Y is carbon. In another embodiment of the compound, R: is hydrogen. In another embodiment of the compound, R* is hydrogen. In another embodiment of the compound, R 3 is hydrogen. In another embodiment of the compound, R3 and R4 are each methyl . In another embodiment of the compound, R3 is -C(R-) (Re)NRsRe, wherein R? and Rε are each independently H or alkyl, wherein Rs and Re are each independently alkyl or cycloalkyl, or R , R and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members . In another embodiment of the compound, Rz is halogen. In another embodiment of the compound, Y is nitrogen. In yet another embodiment of the compound, R: is hydrogen. In a further embodiment of the compound, Rs and R÷ are each hydroge . This invention also provides a compound having the structure V wherein R: is aryl, substituted aryl, or heteroaryl; wherein Rz is H, alkyl, substituted alkyl, or cycloalkyl; wherein R 3 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Re) (RONR^Rs, wherein Re and R7 are each H or alkyl, wherein R« and Rs are each alkyl or cycloalkyl, or R< Rs and the nitrogen together form a ring system of between 4 and 7 members . In one embodiment of the compound having structure V, ^ and R- are each H; wherein R 4 is H and Rs is -Rι:C (=0! R::- . In another embodiment of the compound having structure V, R and R- are each H; wherein the ring system is morpholino, thiomorpholino, N-4 -substituted piperazino, 2 -substituted piperazine, or Re substituted pyrrolidino, piperadine, wherein Re is H, OH, CH2OH, -C (=0)NR9R10, NR11, wherein R11 is -C(=0)CH3, -S02Me. In another embodiment of the compound, the compound has the following structure: (Compound 706) In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure: (Compound 1318-a) In another embodiment of the compound, the compound has the structure : (Compound 1318-b) In another embodiment of the compound, the compound has the structure : (Compound 1319) In another embodiment of the compound, the compound has the structure: (Compound 1320] In another embodiment of the compound, the compound has structure : (Compound 1321) A compound having the structure : wherein R 2 is a 5-6 membered aromatic ring; wherein R 3 and R < are independently H, or alkyl. In one embodiment of the compound, the compound has tne structure : (Compound 1500) In one embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has structure : In another embodiment of compound 1500, the compound has the structure: In a further embodiment of the compound, the compound has the structure : This invention also provides a compound having the structure .- VII wherein R 2 is a 5-6 membered aromatic ring; wherein R ; , and R< are independently H, or alkyl; alkyl; with the proviso that R 2 is not 4 -pyridyl. In one embodiment of the compound, the compound has the structure: (Compound 1501) This invention further provides a compound having the structure: VIII wherein R 2 is a substituted 5-6 membered aromatic ring; wherein R : . and R, are independently H, or alkyl. In one embodiment of the compound, the compound has the structure : .(Compound 1520! This invention also provides a compound having the structure IX wherein R 2 is a 5-6 membered aromatic ring; wherein X is oxygen, or sulfur. In one embodiment of the compound, the compound has the structure : (Compound 1503) This invention also provides a compound having the structure wherein R z is a 5-6 membered aromatic ring; wherein X is oxygen, or sulfur. In one embodiment of the compound, the compound has the structure : (Compound 1504) This invention further provides a method for treating a disease associated with Az. adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of a compound having. the formula IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, the subject is a mammal. In another embodiment of the method, the mammal is a human. In another embodiment of the method, the Ai adenosine receptor is associated with cognitive disease, renal failure, cardiac arrhythmias, respiratory epithelia, transmitter release, sedation, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstriction, neutropil chemotaxis, reflux condition, or ulcerative condition. This invention also provides a combination therapy for asthma, comprising compounds IV and V, and a steroid, β2 agonist, glucocoticoid, lucotriene antagonist, or anticolinegic agonist. Diseases associated with adenosine Ai, ^a, A2b and A3 receptors are disclosed in WO 99/06053 and WO- 09822465, WO-09705138, WO-09511681, WO-09733879, JP-09291089, PCT/US98/16053 and U.S. Patent No. 5,516,894, the entire content of which are fully incorporate herein by reference. This invention also provides a water-soluble prodrug of a compound having the structures IV, V, VI, VII, VIII, IX, or X, wherein said water-soluble prodrug that is metabolized in vivo to an active drug which selectively inhibit Ai adenosine receptor. In orie embodiment of the prodrug, said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. This invention also provides a pharmaceutical composition comprising the prodrug and a pharmaceutically acceptable carrier. This invention further provides a method for inhibiting the activity of an Ai adenosine receptor in a cell, which comprises contacting said cell with a compound having the structures IV, V, VI, VII, VIII, IX, pr X. In one embodiment of the method, the compound is an antagonist of said Ai adenosine receptor. This invention also provides for a method for treating a gastrointestinal disorder in an subject, comprising administering to the an effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, said disorder is diarrhea. In another embodiment of the method, the subject is a human. In another method of the method, the compound is an antagonist of Ai adenosine receptors. This invention also provides a method for treating respiratory disorder in a subject, comprising administering to the subject an effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, said disorder is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In another embodiment of the method, the subject is a human. In another embodiment of the method, said compound is an antagonist of Ai adenosine receptors . This invention further provides a method for treating damage to the eye of a subject which comprises administering to said subject an effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X. In one embodiment of the method, said damage comprises retinal or optic nerve head damage. In another embodiment of the method, said damage is acute or chronic. In another embodiment of the method, wherein said damage is the result of glaucoma, edema, ischemia, hypoxia or trauma. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of Aα adenosine receptors. This invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound having the structures IV, V, VI, VII, VIII, IX, or X, and a pharmaceutically acceptable carrier. In another embodiment of the pharmaceutical composition, said therapeutically effective amount is effective to treat a respiratory disorder or a gastrointestinal disorder. In another embodiment of the pharmaceutical composition, said gastrointestinal disorder is diarrhea. In another embodiment of the pharmaceutical composition, said respiratory disorder is asthma, allergic rhinitis, or chronic obstructive pulmonary disease. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In yet another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. In a further embodiment of the pharmaceutical preparation, said pharmaceutical composition is a surgical irrigating solution. This invention also provides a packaged pharmaceutical composition for treating a disease associated with Ai adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of an adenosine Al specific compound; and (b) instructions for using said compound for treating said disease in a subject. As used herein, "A compound is k x selective." means that a compound has a binding constant to adenosine Al receptor of at least ten time higher then that to adenosine A 2a , A 2b or A 3 . This invention also provides a method of preparing the compound having structure IV, comprising the steps of reacting to provide wherein P is a removable protecting group; treating the product of step a) under cyclization conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the chlorinated product of step c) with NH2R] to provide wherein Ri is trans-4 -hydroxy cyclohexyl, 2-methylamino carbonylamino cyclohexyl, acetylamino ethyl, or methylamino carbonylamino ethyl; wherein Ar is a substituted or unsubstituted four to six membered ring; wherein R< is H, alkyl, substituted alkyl, cycloalkyl; or a pharmaceutically acceptable salt, or a prodrug derivative, or a biologically active metabolite; with the proviso that when R: is acetylamino ethyl , Ar is not 4 -pyridyl. This invention also provides a method of preparing the compound having structure V, comprising the steps of reacting to provide wherein P is a removable protecting group; treating the product of step a) under cyclization conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the chlorinated product of step c) with to provide wherein R: is aryl, substituted aryl, heteroaryl; wherein Rr is H, alkyl, substituted alkyl, or cycloalkyl; wherein R3 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Re) (R-)NR<Rs, wherein Rό and R- are each H or alkyl, wherein R< and Rs are each alkyl or cycloalkyl, or NR<Rs is a ring system of between 4 and 7 members . Compounds represented by formula VI, VII, and VIII can be synthesized by any of the Schemes I-VIII. Compounds represented by formula IX, and X can be prepared by Scheme IX. The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in humans. This invention will be better understood from the Experimental Details which follow. However, one skilled in the art will readily appreciate that the specific methods and results discussed are merely illustrative of the invention as described more fully in the claims which follow thereafter. KYPERTMSNTA DETAILS The deazapurines of the invention can be prepared using standard methods for organic synthesis. Deazapurines can be purified by reverse phase HPLC, chromatography, recrystallization, etc. and their structures confirmed by mass spectral analysis, elemental analysis, IR and/or NMR spectroscopy. Typically, synthesis of the intermediates as well as the deazapurines of the invention is performed in solution. The addition and removal of one or more protecting group is also typical practice and is known to those skilled in the art. Typical synthetic schemes for the preparation of deazapurine intermediates of the invention are outlined below in Scheme I. Scheme I wherein R 3 , R5 and Rg are as defined above. In general, a protected 2-amino-3-cyano-pyrrole can be treated with an acyl halide to form a carboxyamido-3-cyano- pyrrole which can be treated with acidic methanol to effect ring closure to a pyrrolo [2, 3d] pyrimidine-4 (3H) -one (Muller, C.E. et al . J. Med. Chem. 40:4396 (1997)). Removal of the pyrrolo protecting group followed by treatment with a chlorinating reagent, e.g., phosphorous oxychloride, produced substituted or unsubstituted 4-chloro-7H- pyrrolo [2, 3d]pyrimidines. Treatment of the chloropyrimidine with amines afforded 7-deazapurines. For example, as shown in Scheme I, a N- (l-dl-phenylethyl) -2- amino-3-cyano-pyrrole was treated with an acyl halide in pyridine and dichloromethane. The resultant N- (l-d2- phenylethyl) -2-phenylcarboxyamido-3-cyano-pyrrole was treated with a 10:1 mixture of methanol/sulfuric acid to effect ring closure, resulting in a dl- 7H-7- (1- phenylethyl) pyrrolo [2, 3d] pyrimidine-4 (3H) -one. Removal of the phenylethyl group by treatment of the pyrimidine with polyphosphoric acid (PPA) followed by P0C1 3 afforded a key intermediate, the 4 -chloro-7H-pyrrolo [2, 3d] pyrimidine . Further treatment of the 4 -chloro-7H-pyrrolo [2, 3d] pyrimidine with various amines listed in Table 1 gives compounds of formula (I) and (II) . TABLE 1 A general approach to prepare 6-substituted pyrroles is depicted in the following scheme (Scheme II) . Scheme II wherein R^ through R5 are as defined above. Transesterification and alkylation of ethyl cyanoacetate with an α-haloketone affords a ketomethylester. Protection of the ketone followed by treatment with an amidine ( e . g. , alkyl, aryl or alkylaryl) hydrochloride produced the resultant ketal protected pyrimidine. Removal of the protecting group, followed by cyclization and treatment with phosphorous oxychloride afforded the chloride intermediate which could be further treated with an amine to afford an amine 6- substituted pyrrole. Additionally, alkylation of the pyrrole nitrogen can be achieved under art recognized conditions. A general approach to prepare 5-substituted pyrroles is depicted in the following scheme (Scheme III) . Scheme III wherein R 1 through Rg are defined as above and R is a removable protecting group. Condensation of malononitrile and an excess of a ketone followed by bromination of the product afforded a mixture of starting material, monobrominated and dibrominated products which were treated with an alkylamine, arylamine or alkylarylamine. The resultant amine product was acylated with an acid chloride and the monacylated pyrrole was cyclized in the presence of acid to afford the corresponding pyrimidine. The pyrrole protecting group was removed with polyphosphoric acid and treated with phosphorous oxychloride to produce a chlorinated product. The chlorinated pyrrole could subsequently be treated with an amine to produce an amino 5-substituted pyrrole. Alkylation of the pyrrole nitrogen can be achieved under art recognized conditions. Schemes IV and V depict methods for preparing the deazapurines 1 and 2 of the invention. wherein R 5 and Rg are as described above, e . g. , CH-. Specific Preparation of 6-methvl pyrrolopyrimidines : The key reaction toward 6-methylpyrrolopyrimidines (1) [R 5 = CH 3 ] was cyclization of a cyanoacetate with benzamidine to a pyrimidine. It was believed methyl cyanoacetate would cyclize more efficiently with benzamidine to a pyrimidine than the corresponding ethyl ester. Therefore, transesterification and alkylation of ethyl cyanoacetate in the presence of NaOMe and an excess of an α-haloacetyl moiety, e.g., chloroacetone, gave the desired methyl ester (3) in 79% yield (Scheme IV) . The ketoester (3) was protected as the acetal (4) in 81% yield. A new' cyclization method to the pyrimidine (5) was achieved with an amidine hydrochloride, e.g., benzamidine hydrochloride, with 2 equivalents of DBU to afford the 5 in 54% isolated yield. This method improves the yield from 20% using the published conditions, which utilizes NaOMe during the cyclization with guanidine. Cyclization to the pyrrole-pyrimidine (6) was achieved via deprotection of the acetal in aqueous HCl in 78% yield. Reaction of (6) with phosphorous oxychloride at reflux gave the corresponding 4-chloro derivative (7) . Coupling with trans-4-aminocyclohexanol in dimethyl sulfoxide at 135°C gave (1) in 57% from (7) . One skilled in the art will appreciate that choice of reagents allows for great flexibility in choosing the desired substituent R 5 . Scheme IV Specific Preparation of 5-methvlpvτrrftl npy-ifni ΪTIOC Knoevengel condensation of malononitrile and an excess ketone, e.g., acetone in refluxing benzene gave 8 in 50% yield after distillation. Bromination of 8 with N- bromosuccinimde in the presence of benzoyl peroxide in chloroform yielded a mixture of starting material, mono- (9), and di-brominated products (5/90/5) after distillation (70%) . The mixture was reacted with an α-methylalkylamine or α- methylarylamine, e . g. , α-methylbenzylamine, to deliver the aminopyrrole (10) . After passing through a short silica gel column, the partially purified amine (31% yield) was acylated with an acid chloride, e.g., benzoyl chloride to deliver mono- (11) , and diacylated (12) pyrroles, which were separated by flash chromatography. Acid hydrolysis of the disubstituted pyrrole (12) generated a combined yield of 29% for the acylpyrrole (11) . Cyclization in the presence of concentrated sulphuric acid and DMF yielded (13) (23%), which was deprotected with polyphosphoric acid to (14). Reaction of (14) with phosphorous oxychloride at reflux gave the corresponding 4-chloro derivative (15) . Coupling with trans- 4-aminocyclohexanol in dimethyl sulfoxide at 135°C gave (2) [R 6 = CH 3 ] in 30% from (14) (See Scheme V) . One skilled in the art will appreciate that choice of reagents allows for great flexibility in choosing the desired substituent R 6 . Scheme V Alternative Synthetic Route to R g -Substituted Pyrroles, e . σ. . «?-n«*fehγl pyr-rnlnpyr-imidings: This alternative route to Rg-substituted pyrroles, e . g. , 5- methylpyrrolopyrimidines, involves transesterification and alkylation of ethyl cyanoacetate to (16) (Scheme VI) . The condensation of (16) with benzamidine hydrochloride with 2 equivalents of DBU affords the pyrimidine (17) . Cyclization to the pyrrole-pyrimidine (14) will be achieved via deprotection of the acetal in aqueous HCl. Reaction of (14) with phosphorous oxychloride at reflux gave the corresponding 4-chloro derivative (15) . Coupling with trans-4- aminocyclohexanol in dimethyl sulfoxide at 135°C gives 2. This procedure reduces the number of synthetic reactions to the target compound (2) from 9 to 4 steps. Moreover, the yield is dramatically improved. Again, one skilled in the art will appreciate that choice of reagents allows for great flexibility in choosing the desired substituent R g . Scheme V A general approach to prepare des-methyl pyrrole is depicted in the following scheme (Scheme VII) Scheme V wherein R ! through R are defined as above Alkylation of an alkyl cyanoacetate with a diethyl acetal in the presence of a base afforded a cyano diethyl acetal which was treated with an amidine salt to produce a methyl pyrrolopyrimidine precursor. The precursor was chlorinated and treated with an amine to form the des-methyl pyrrolopyrimidine target as shown above . For example, Scheme VIII depicts the synthesis of compound (18). Scheme VTII Commercially available methyl cyanoacetate was alkylated with bromoacetaldehyde diethyl acetal in the presence of potassium carbonate and Nal to yield (19) . Cyclization to the pyrimidine (20) was achieved in two steps. Initially, the pyrimidine-acetal was formed via reaction of (19) with benzamidine hydrochloride with 2 equivalents of DBU. The resultant pyrimidine-acetal was deprotected without purification with aqueous 1 N HCl and the resultant aldehyde cyclized to the pyrrolo-pyrimidine (20) , which was isolated by filtration. Reaction of (20) with phosphorous oxychloride at reflux afforded the corresponding 4-chloro derivative (21). Coupling of the chloro derivative with trans-4- aminocyclohexanol in DMSO at 135°C gave compound (18) from compound (21) . Schemes II-VIII demonstrate that it is possible to functionalize the 5- and 6-position of the pyrrolopyrimidine ring. Through the use of different starting reagents and slight modifications of the above reaction schemes, various functional groups can be introduced at the 5- and 6-positions in formula (I) and (II). Table 2 illustrates some examples. Table 2. Selected list of 5- and 6 -substituted pyrrolopyrimidines . A skilled artisan will know that metabolism of the compounds disclosed herein in a subject produces certain biologically active metabolites which can serve as. drugs. The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in humans. Exemplification Preparation 1: A modification of the alkylation method of Seela and Lϋpke was used. To an ice-cooled (0 e C) solution of ethyl cyanoacetate (6.58 g, 58.1 mmol) in MeOH (20 mL) was slowly added a solution of NaOMe (25% w/v; 58.1 mmol). After 10 min, chloroacetone (5 mL; 62.8 mmol) was slowly added. After 4 h, the solvent was removed. The brown oil was diluted the EtOAc (100 mL) and washed with H 2 0 (100 mL) . The organic fraction was dried, filtered, and concentrated to a brown oil (7.79 g; 79%). The oil (3) (Scheme IV) was a mixture of methyl/ethyl ester products (9/1) , and was used without further purification. X H NMR (200 MHz, CDC1 3 ) δ_4.24 (q, J = 7.2 Hz, OCH 2 ), 3.91 (dd, IH, J= 7.2, 7.0 Hz, CH) , 3.62 (s, 3H, OCH 3 ), 3.42 (dd, IH, J- 15.0, 7.1 Hz, 1 X CH 2 ); 3.02 (dd, IH, J = 15.0, 7.0 Hz, 1 X CH 2 ); 2.44 (s, 3H, CH 3 ), 1.26 (t, J = 7.1 Hz, ester-CH 3 ) . ^eela, F.; Lϋpke, U. Chem. Ber. 1977, 110, 1462-1469. Preparation 2 : The procedure of Seela and Lύpke was used. Thus, protection of the ketone (3) (Scheme IV; 5.0 g, 32.2 mmol) with ethylene glycol (4 mL, 64.4 mmol) in the presence of TsOH (100 mg) afforded (4) as an oil (Scheme IV; 5.2 g, 81.0) after flash chromatography (Si0 2 ; 3/7 EtOAc/Hex, R f 0.35). Still contains "5% ethyl ester: X H NMR (200 MHz, CDC1 3 ) δ_4.24 (q, J = 7.2 Hz, OCH 2 ), 3.98 (s, 4H, 2 x acetal-CH 2 ), 3.79 (s, 3H, OCH 3 ) , 3.62 (dd, IH, J = 7.2, 7.0 Hz, CH) , 2.48 (dd, IH, J = 15.0, 7.1 Hz, 1 x CH 2 ), 2.32 (dd, IH, J = 15.0, 7.0 Hz, 1 x CH 2 ); 1.35 (s, 3H, CH 3 ) , 1.26 (t, J = 7.1 Hz, ester-CH 3 ) ; MS (ES) : 200.1 (M * +l) . : Seela, F.; Lϋpke, U. Chem. Ber. 1977, 110, 1462-1469. Preparation 3 : A solution of acetal (4) (Scheme IV, 1 g, 5.02 mmol;, benzamidine (786 mg, 5.02 mmol), and DBU (1.5 mL, 10.04 mmol) in dry DMF (15 mL) was heated to 85 C C for 15 h. The mixture was diluted with CHC1 3 (30 rnL) and washed with 0.5 N NaOK (10 mL) and H 2 0 (20 mL) . The organic fraction was dried, filtered and concentrated to a brown oil. Flash chromatography (Si0 2 ; 1/9 EtOAc/CH2Cl2, R f 0.35) was attempted, but material crystallized on the column. The silica gel was washed with MeOH. Fractions containing the product (5) (Scheme IV) were concentrated and used without further purification (783 mg, 54.3%): X H NMR (200 MHz, CDC1 3 ) δ 8.24 (m, 2H, Ar-H) , 7.45 (m, 3H, Ar-H), 5.24 (br s, 2H, NH 2 ), 3.98 (s, 4H, 2 x acetal- CH 2 ), 3.60-3.15 (m, 2H, CH 2 ) , 1.38 (s, 3H, CH 3 ) ; MS (ES) : 288.1 (M ' +l) . Preparation of compound (20) (Scheme VIII) : A solution of acetal (19) (4.43 g, 20.6 mmol) 1 , benzamine hydrochloride (3.22 g, 20.6 mmol), and DBU (6.15 mL, 41.2 mmol) in dry DMF (20 mL) was heated to 85°C for fifteen hours. The mixture was diluted with lOOmL of CHC1 ? , and washed with H : 0 (2 x 50 mL) . The organic fraction was dried, filtered, and concentrated to a dark brown oil . The dark brown oil was stirred in IN HCl (100 mL) for 2 hours at room temperature. The resulting slurry was filtered yielding the HCl salt of (20) as a tan solid (3.60 g, 70.6%); : H NMR (200 MHz, DMSO-d6) 11.92 (s IH) , 8.05 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 7.05 (s, IH, pyrrole- H) ; MS(ES) : 212.1 (M ' +l) . Preparation 4 : A solution of acetal (5) (700 mg, 2.44 mmol) in 1 N HCl (40 mL) was stirred for 2 h at RT. The resultant slurry was filtered yielding the HCl salt of 2-phenyl-6 -methyl-7H- pyrrolo[2,3d]pyrimidin-4 (3H) -one as a tan solid (498 mg, 78.0%): X H NMR (200 MHz, DMSO-dg) δ 11.78 (s, IH) , 8.05 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 6.17 (s, IH, pyrrole-H) , 2.25 (S, 3H, CH 3 ) ; MS (ES) : 226.1 (M'+l). Preparation 5 : A modification of the Chen et al . cyclization method was used. To an ice-cooled (0°C) solution of bromide (9), (Scheme V; 20.0 g, 108 mmol; 90% pure) in isopropyl alcohol (60 mL) was slowly added a solution of α-methylbenzylamine (12.5 mL, 97.3 mmol) . The black solution was allowed to warm to RT and stir for 15 h. The mixture was diluted with EtOAc (200 mL) and washed with 0.5 N NaOH (50 mL) . The organic fraction was dried, filtered, and concentrated to a black tar (19.2 g; 94%). The residue was partially purified by flash chromatography (Si0 2 ; 4/96 MeOH/CH 2 Cl 2 , R f 0.35) to a black solid (6.38 g, 31%) as the compound dl-l- (1 -phenylethyl) -2 - amino-3-cyano-4-methylpyrrole: MS (ES) : 226.1 (M " +l). : Chen, Y. L. ; Mansbach, R. S . ; Winter, S. M. ; Brooks, E.,- Collins, J. ; Corman, M. L. ; Dunaiskis, A. R. ,- Faraci, W. S.,- Gallaschun, R. J. ; Schmidt, A.; Schulz, D. W. J. Med . Chem. 1997, 40, 1749-1754. Preparation 6 : To a solution of dl-l- (1-phenylethyl) -2-amino-3-cyano-4, 5- dimethylpyrrole : (14.9 g, 62.5 mmol) and pyridine (10.0 mL) in dichloromethane (50.0 mL) was added benzoyl chloride (9.37 g, 66.7 mmol) at O^C. After stirring at 0°C for 1 hr, hexane (10.0 mL) was added to help precipitation of product. Solvent was removed in vacuo and the solid was recrystallized from EtOH/H : 0 to give 13.9 g (65%) of dl-l- (1-phenylethyl) -2- phenylcarbonylamino-3-cyano-4, 5-dimethylpyrrole. mp 218-221°C; : H NMR (200 MHz, CDCl δ_l .72 (s, 3H) , 1.76 (d, J = 7.3 Hz, 3H) , 1.98 (s, 3H) , 5.52 (q, J = 7.3 Hz, IH) , 7.14-7.54 (m, 9H) , 7.68-7.72 (dd, J = 1.4 Hz, 6.9 Hz , 2H) , 10.73 (s, IH) ; MS (ES) : 344.4 (M'+l) . Liebigs Ann. Chem. 1986, 1485-1505. The following compounds were obtained in a similar manner . Preparation 6A: dl-l- (1-phenylethyl) -2- (3-pyridyl) carbonylamino- 3 -cyano- 4 , 5- dimethylpyrrole . l H NMR (200 MHz, CDC1 3 ) δ_1.83 (d, J = 6.8 Hz, 3H) , 2.02 (s, 3H) , 2.12 (s, 3H) , 5.50 (q, J = 6.8 Hz, IH) , 7.14-7.42 (m, 5H) , 8.08 (m, 2H) , 8.75 (m, 3H) ; MS (ES) : 345.2 (M ' + l) . dl-l- (1-phenylethyl) -2- (2-furyl) carbonylamino-3-cyano-4 , 5- dimethylpyrrole . l H NMR (200 MHz, CDC1 3 ) δ 1.84 (d, J = 7.4 Hz, 3H) , 1.92 (s, 3H) , 2.09 (s, 3H) , 5.49 (q, J = 7.4 Hz, IH) , 6.54 (dd, J = 1.8 Hz, 3.6 Hz, IH) , 7.12-7.47 (m, 7H) ; MS (ES) : 334.2 (M ' +l) , 230.1. dl-l- (1-phenylethyl) -2- (3-furyl) carbonylamino-3-cyano-4 , 5- dimethylpyrrole . : H NMR (200 MHz, CDCl,) δ 1.80 (d, J = 7 Hz 3H) , 1.89 (S, 3H) , 2.05 (s, 3H) , 5.48 (q, J = 7 Hz, IH) , 6.59 (s, IH) , 7.12-7.40 (m, 6H) , 7.93 (s, IH) ; MS (ES) : 334.1 (M ' + l) , 230.0. dl-l- (1-phenylethyl) -2-cyclopentylcarbonylamino-3-cyano-4 , 5- dimethylpyrrole . "H NMR (200 MHz, CDCl,) δ 1.82 (d, J = 7.4 Hz, 3H) , 1,88 (s, 3H) , 2.05 (s, 3H) , 1.63-1.85 (m, 8H) , 2.63 (m, IH) , 5.43 (q, J = 7.4 Hz, IH) , 6.52 (s, IH) , 7.05-7.20 (m, 5H) ; MS (ES) : 336.3 (M ' +l) . dl-l- (1-phenylethyl) -2- (2-thieyl) carbonylamino-3-cyano-4 , 5- dimethylpyrrole, : H NMR (200 MHz, CDC1 3 ) δ 1.82 (d, J = 6.8 Hz, 3H) , 1.96 (s, 3H) , 2.09 (s, 3H) , 5.49 (q, J= 6.8 Hz, IH) , 7.05-7.55 (m, 8H) ; MS (ES) : 350.1 (M " +l) , 246.0. dl-l- (1-phenylethyl) -2- (3-thienyl) carbonylamino- 3 -cyano -4 , 5- dimethylpyrrole . J H NMR (200 MHz, CDCl 3 ) δ 1.83 (d, J = 7.0 Hz, 3H) , 1.99 (s, 3H) , 2.12 (s, 3H) , 5.49 (q, J = 7.0 Hz, IH) , 6.90 (m, IH) , 7.18-7.36 (m, 6H) , 7.79 (m, IH) ; MS (ES) : 350.2 (M ' +l) , 246.1. dl-l- (1-phenylethyl) -2- (4 -fluorophenyl) carbonylamino-3 -cyano- 4 , 5-dimethylpyrrole . X H NMR (200 MHz, CDCl. δ 1.83 (d, J = 7.4 Hz, 3H) , 1.96 (s, 3H) , 2.08 (s, 3H) , 5.51 (q, J = 7.4 Hz, IH) , 7.16-7.55 (m, 9H) ; MS (ES) : 362.2 (M ' +l) , 258.1. dl-l- (1-phenylethyl) -2- (3 -fluorophenyl) carbonylamino- 3-cyano- 4, 5-dimethylpyrrole. : H NMR (200 MHz, CDCl,) δ 1.83 (d, J = 7.4 Hz 3H) , 1.97 (s, 3H) , 2.10(8, 3H) , 5.50 (q, J = 7.4 Hz , IH) , 7.05-7.38 (m, 7 H) , 7.67-7.74 (m, 2H) ; MS (ES) : 362.2 (M ' +l), 258.1. dl-l- (1-phenylethyl) -2- (2-fluorophenyl) carbonylamino-3-cyano- 4, 5-dimethylpyrrole. H NMR (200 MHz, CDC1 3 ) δ 1.85 (d, J = 7.2 Hz, 3H) , 1.94 (s, 3H) , 2.11 (s, 3H) , 5.50 (q, J = 7.2 hz, IH) , 7.12-7.35 (m, 6H) , 7.53 (m, IH) , 7.77 (m, IH) , 8.13 (m, IH) ; MS (ES) : 362.2 (M ' +l), 258.0. dl-l- (1-phenylethyl) -2-isoproylcarbonylamino-3-cyano-4 , 5- dimethylpyrrole . : H NMR (200 MHz, CDCl 3 ) δ 1.19 (d, J = 7.0 Hz, 6H) , 1.82 ( , J = 7.2 Hz, 3H) , 1.88 (s, 3H) , 2.06 (s, 3H) , 2.46 (m, IH) , 5.39 (m, J = 7.2 Hz, IH) , 6.64 (s, IH) , 7.11- 7.36 (m, 5H) ; MS (ES) : 310.2 (M ' +l), 206.1 . In the case of acylation of dl-l- (1-phenylethyl) -2 -amino-3- cyano-4-methylpyrrole, monoacylated dl-l- (1-phenylethyl) -2- benzoylamino-3-cyano-4 -dimethylpyrrole and diacylated pyrrole dl-l- (1-phenylethyl) -2-dibenzoylamino-3-cyano-4-methylpyrrole were obtained. Monoacylated pyrrole: H NMR (200 MHz, CDC1 3 ) δ_7.69 (d, 2H, J = 7.8 Hz, Ar-H), 7.58-7.12 (m, 8H, Ar-H), 6.18 (s, IH, pyrrole-H) , 5.52 (q, IH, J = 7.2 Hz, CH-CH 3 ) , 2.05 (s, 3H, pyrrole-CH 3 ) , 1.85 (d, 3H, J » 7.2 Hz, CH-CH3) ; MS (ES) : 330.2 (M'+l); Diacylated pyrrole: X H NMR (200 MHz, CDC1 3 ) δ_7.85 (d, 2H, J = 7.7 Hz, Ar-H), 7.74 (d, 2H, J = 7.8 Hz, Ar-H), 7.52-7.20 (m, 9H, Ar-H), 7.04 (m, 2H, Ar-H), 6.21 (s, IH, pyrrole-H) , 5.52 (q, IH, J= 7.2 Hz, CH-CH 3 ), 1.77 (d, 3H, J = 7.2 HZ, CH-CH 3 ) , 1.74 (s, 3H, pyrrole-CH 3 ) ; MS ;ΞS; : 434.1 (M ' +l) . Preparation 7 : To a solution of dl-l- (1-phenylethyl) -2-phenylcarboxyamido-3- cyano-4, 5-dimethylpyrrole (1.0 g, 2.92 mmol) in methanol (10.0 mL) was added concentrated sulfuric acid (1.0 mL) at 0°C. The resulted mixture was refluxed for 15 hr and cooled down to room temperature. The precipitate was filtered to give 0.48 g (48%) of dl-5 , 6-dimethyl-2-phenyl-7H-7- (1- phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. Η NMR (200 MHz, CDC1 3 ) δ_2.02 (d, J = 7.4 Hz, 3H) , 2.04 (s, 3H) , 2.41 (s, 3H) , 6.25 (q, J = 7.4 Hz, IH) , 7.22-7.50 (m, 9H) , 8.07-8.12 (dd, J = 3.4 Hz, 6.8 Hz, 2H) , 10.51 (s, IH) ; MS (ES): 344.2 (M ' +l). The following compounds were obtained in a similar manner as that of Preparation 7: dl-5, 6 -dime thy1-2- (3-pyridyl) -7H-7- (1-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, CDC1 3 ) δ_2.03 (d, J = 7.2 Hz, 3H) , 2.08 (s, 3H) , 2.42 (s, 3H) , 6.24 (q, J = 7.2 Hz, IH) , 7.09-7.42 (m, 5H) , 8.48 (m, 2H) , 8.70 (m, 3H) ,- MS (ES) : 345.1 (M ' + l) . dl-5,6-dimethyl-2- (2-furyl) -7H-7- (1-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. ; H NMR (200 MHz, CDC1 3 ) δ 1.98 (d, J = 7.8 Hz, 3H) , 1.99 (s, 3H) , 2.37 (s, 3H) , 6.12 (q, J = 7.8 Hz, IH) , 6.48 (dd, J=1.8 Hz, 3.6 Hz, IH) , 7.17- 7.55 (m, 7H) , 9.6 (s, IH) ; MS (ES) : 334.2 (M'+l) . dl-5, 6-dimethyl-2- (3-furyl) -7H-7- ( 1-phenylethyl ) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. l H NMR (200 MHz, CDC1 3 ) δ 1.99 (d, J = 7 Hz, 3H) , 2.02 (s, 3H) , 2.42 (s, 3H) , 6.24 (q, J = 7 Hz, IH) , 7.09 (s, IH) , 7.18-7.32 (m, 5H) , 7.48 (s, IH) , 8.51 (s, IH) ; MS (ES) : 334.2 (M ' +l) . dl-5, 6-di ethyl-2-cyclo entyl-7H-7- (l-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, CDC ^ δ 1.95 (d, J = 7.4 Hz, 3H) , 2.00 (s, 3H) , 2.33 (s, 3H) , 1.66- 1.88 (m, 8H) , 2.97 (m, IH) , 6.10 (q, J = 7.4 Hz, IH) , 7.16- 7.30 (m, 5H) , 9.29 (s, IH) ; MS (ES) : 336.3 (M ' +l). dl-5, 6-dimethyl-2- (2-thienyl) -7H-7- (1-phenyle hyl) pyrrolo [2, 3d] pyrimidin-4 (3tf) -one. : H NMR (200 MHz, CDC1 3 ) δ 2.02(d, J = 7.2 Hz, 3H) , 2.06 (s, 3H) , 2.41 (s, 3H) , 6.13 (q, J = 7.2 Hz, IH) , 7.12 (dd, J = 4.8, 2.8 Hz, IH) , 7.26-7.32 (m, 5H) , 7.44 (d, J = 4.8 Hz, IH) , 8.01 (d, J = 2.8 Hz, IH) 11.25 (s, IH) ; MS (ES) : 350.2 (M' + l) . dl-5, 6 -dime thy 1-2- (3-thienyl) -7H-7- (1-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. *H NMR (200 MHz, CDC1 3 ) δ 2.00 (d, J = 7.4 Hz, 3H) , 2.05 (s, 3H) , 2.43 (s, 3H) , 6.24(q, J = 7.4 Hz, IH) , 7.24-7.33 (m, 5H) , 7.33-7.39 (m, IH) , 7.85 (m, IH) , 8.47 (m, IH) , 12.01 (s, IH) ; MS (ES) : 350.2 (M τ +1) . dl-5, 6-dimethyl-2- (4 -fluorophenyl) -7H-7- (1-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, CDC1 3 ) δ 2.01 (d, J = 6.8 Hz, 3H) , 2.05 (s, 3H) , 2.42 (s, 3H) , 6.26 (q, J = 6.8 Hz, IH) , 7.12-7.36 (m, 7H) , 8.23-8.30 (m, 2H) , 11.82 (s, IH) ; MS (ES) : 362.3 (M ' +l) . dl-5, 6-dimethyl-2- (3 -fluorophenyl ) -7H-7- (1-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, CDC1 3 ) δ 2.02 (d, J = 7.4 Hz, 3H) , 2.06 (s, 3H) , 2.44 (s, 3H) , 6.29 (q, J = 7.4 Hz, IH) , 7.13-7.51 (m, 7H) , 8.00-8.04 (m, 2H) , 11.72 (s, IH) ; MS (ES) : 362.2 (M'+l) . dl-5 , 6-dimethyl-2- (2 -fluorophenyl) -7H-7- (1-phenylethyl) pyrrolo[2,3d]pyrimidin-4(3tf)-one. ; H NMR (200 MHz, CDC1 3 ) δ 2.00 (d, J = 7.2 Hz, 3H) , 2.05 (s, 3H) , 2.38 (s, 3H) , 6.24 (q, J = 7.2 Hz, IH) , 7.18 - 7.45 (m, 8 H) , 8.21 (m, IH) , 9.54 (s, IH) ; MS (ES) : 362.2 (M ' +l) . dl-5, 6 -dimethyl -2 -isopropyl - IH- 7- (1-phenylethyl ) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, CDC1 : .) δ 1.30 (d, J = 6.8 Hz, 3H) , 1.32 (d, J = 7.0 Hz, 3H) , 2.01 (s, 3H) , 2.34 (s, 3H) , 2.90 (m, IH) , 6.13 (m, IH) , 7.17-7.34 (m, 5H) , 10.16 (s, IH) ; MS (ES) : 310.2 (M ' +l). Preparation 8 : A solution of dl-l- (1-phenylethyl) -2-benzoylamino-3-cyano-4- dimethylpyrrole (785 mg, 2.38 mmol) with concentrated H 2 S0 4 (1 mL) in DMF (13 mL) was stirred at 130°C for 48 h. The black solution was diluted with CHC1 3 (100 mL) and washed with 1 N NaOH (30 mL) , and brine (30 mL) . The organic fraction was dried, filtered, concentrated, and purified by flash chromatography (Si0 ; 8/2 EtOAc/Hex, R f 0.35) to a brown solid (184 mg, 24%) as dl-5 -methyl-2 -phenyl -7H-7- (1- phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one. H NMR (200 MHz, CDC1 3 ) δ_8.18 (m, 2H, Ar-H), 7.62-7.44 (m, 3H, Ar-H), 7.40- 7.18 (m, 5H, Ar-H), 6.48 (s, IH, pyrrole-H) , 6.28 (q, IH, J = 7.2 Hz, CH-CH 3 ), 2.18 (s, 3H, pyrrole-CH 3 ) , 2.07 (d, 3H, J = 7.2 Hz, CH-CH 3 ) ; MS (ES) : 330.2 (M + + 1). Preparation 9 : A mixture of dl-l- (1-phenylethyl) -2-amino-3-cyano-4 , 5- dimethylpyrrole (9.60 g, 40.0 mmol) and of formic acid (50.0 mL, 98%) was refluxed for 5 hr. After cooling down to room temperature and scratching the sides of flask, copious precipitate was formed and filtered. The material was washed with water until washings showed neutral pH to give dl-5, 6- dimethyl -7H-7- (1 -phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) - one. : H NMR (200 MHz, CDC1 3 ) δ 1.96 (d, J = 7.4 hz, 3H) , 2.00 (S, 3H) , 2.38 (S, 3H) , 6.21 (q, J = 7.4 Hz , IH) , 7.11-7.35 (m, 5H) , 7.81 (S, IH) , 11.71 (s, IH) ; MS (ES) : 268.2 (M'+l). Preparation 10 : dl-5, 6 -dimethyl -2 -phenyl - I -7- (1-phenylethyl) pyrrolo [2, 3d] pyrimidin-4 (3H) -one (1.0 g, 2.91 mmol) was suspended in polyphosphoric acid (30.0 mL) . The mixture was heated at 100"C for 4 hr. The hot suspension was poured onto ice water, stirred vigorously to disperse suspension, and basified to pH 6 with solid KOH. The resulting solid was filtered and collected to give 0.49 g (69%) of 5, 6 -dimethyl-2 -phenyl - 1H- pyrrolo [2, 3d] pyrimidin-4 ( 3H) -one. : H NMR (200 MHz, DMSO-d δ_2.17 (s, 3H) , 2.22 (s, 3H) , 7.45 (br, 3H) , 8.07 (br, 2H, ) , 11.49 (s, IH) , 11.82 (s, IH) ; MS (ES) : 344.2 (M'+l). The following compounds were obtained in a similar manner as that of Preparation 10: 5 -methyl -2 -phenyl-7H-pyrrolo [2, 3d] yrimidin-4 (3H) -one. MS (ES) : 226.0 (M'+l) . 5, 6 -dimethyl -2- (3-pyridyl) -7tf-pyrrolo [2, 3d] pyrimidin- (3H) - one. MS (ES) : 241.1 (M'+l). 5, 6-dimethyl-2- (2-furyl) -7H-pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, DMSO-d 6 ) δ 2.13 (s, 3H) , 2.18 (s, 3H) , 6.39 (dd, J = 1.8, 3.6 Hz, IH) , 6.65 (dd, J = 1.8 Hz, 3.6 Hz, IH) , 7.85 (dd, J = 1.8, 3.6 Hz, IH, ) , 11.45 (s, IH) , 11.60 (s, IH) ; MS (ES) : 230.1 (M'+l) . 5, 6-dimethyl-2- (3-furyl) -7H-pyrrolo [2, 3d] pyrimidin-4 (3H) -one. : H NMR (200 MHz, DMSO-d δ 2.14 (s, 3H) , 2.19 (s, 3H) , 6.66 (s, IH) , 7.78 (s, IH) , 8.35 (s, IH) , 11.3 (s, IH) , 11.4 (s, IH) ; MS (ES) : 230.1 (M ' +l) . 5, 6 -dimethyl-2 -cyclopentyl -7H-pyrrolo [2, 3d] pyrimidin-4 ( 3H) - one. : H NMR (200 MHz, DMSO-d δ 1.57-1.91 (m, 8 H) , 2.12 (s, 3H) , 2.16 (s, 3H) , 2.99 (m, IH) , 11.24 (s, IH) , 11.38 (s, IH) ; MS (ES) : 232.2 (M'+l) . 5, 6-dimethyl-2- (2-thienyl) -7H-pyrrolo [2, 3d] pyrimidin-4 i2H) - one. ] H NMR (200 MHz, DMSO-d 6 ) δ 2.14 (s, 3H) , 2.19 (s, 3H) , 7.14 (dd, J = 3.0, 5.2 Hz, IH) , 7.70 (d, J = 5.2 Hz IH) , 8.10 (d, J=3.0 Hz, IH) , 11.50 (s, IH) ; MS (ES) : 246.1 (M ' +l) . 5, 6-dimethyl-2- (3-thienyl) -7ff-pyrrolo [2, 3d] pyrimidin-4 (3H) - one. l H NMR (200 MHz, DMSO-d 6 ) δ 2.17 (s, 3H) , 2.21 (s, 3H) , 7.66(m, IH) , 7.75 (m, IH) , 8.43 (m, IH) , 11.47 (s, IH) , 11.69 (S, IH) ; MS (ES) : 246.1 (M ' +l) . 5 , 6-dimethyl-2- (4 -fluorophenyl) -7H-pyrrolo [2 , 3d] pyrimidin- 4(3H)-one. : H NMR (200 MHz, DMSO-d 6 ) δ 2.17 (s, 3H) , 2.21 (s, 3H) , 7.31 (m, 2H) , 8.12 (m, 2H) , 11.47 (s, IH) ; MS (ES) : 258.2 (M'+l) . 5, 6-dimethyl-2- (3 -fluorophenyl) -7H-pyrrolo [2, 3d] pyrimidin- 4(3H)-one. l E NMR (200 MHz, DMSO-d 6 ) δ 2.18 (s, 3H) , 2.21 (s, 3H), 7.33 (m, IH) , 7.52 (m, IH) , 7.85-7.95 (m, 2H) , 11.56 (s, IH) , 11.80 (S, IH) ; MS (ES) : 258.1 (M'+l). 5, 6 -dimethyl -2- (2 - fluorophenyl) -7H-pyrrolo [2, 3d] pyrimidin- 4(3H)-one. H NMR (200 MHz, DMSO-d 6 ) δ 2.18 (s, 3H) , 2.22 (s, 3H) , 7.27-7.37 (m, 2H) , 7.53 (m IH) , 7.68 (m, IH) , 11.54 (s, IH) , 11.78 (S, IH) ; MS (ES): 258.1 (M'+l). 5, 6-dimethyl-2-isopropyl-7H-pyrrolo [2, 3d] pyrimidin-4 (3H) -one. > H NMR (200 MHz, DMSO-d δ 1.17 (d, J= 6.6 Hz, 6H) , 2.11 (s, 3H) , 2.15 (s, 3H) , 2.81 (m, IH) , 11.20 (s, IH) , 11.39 (s, IH) ; MS (ES) : 206.1 (M'+l) . 5, 6 -dimethyl-7H-pyrrolo [2, 3d] pyrimidin-4 (3H) -one . l H NMR (200 MHz, DMSO-d 6 ) δ 2.13 (s, 3H) , 2.17 (s, 3H) , 7.65 (s, IH) ; MS (ES) : 164.0 (M ' +l) . Preparation 11: A solution of 5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidin-4 (3H) -one (1.0 g, 4.2 mmol) in phosphorus oxychloride (25.0 mL) was refluxed for 6 hr and then concentrated in vacuo to dryness. Water was added to the residue to induce crystallization and the resulting solid was filtered and collected to give 0.90 g (83%) of 4-chloro-5 , 6- dimethyl-2-phenyl -IH-pyrrolo [2, 3d] pyrimidine. H NMR (200 MHz, DMS0-d 6 ) δ_2.33 (s, 3H) , 2.33 (s, 3H) , 7.46-7.49 (m, 3H) , 8.30-8.35 (m, 2H) , 12.20 (s, IH) ; MS (ES) : 258.1 (M ' +l). The following compounds were obtained in a similar manner as that of Preparation 11: 4-chloro-5-methyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine . MS (ES) : 244.0 (M'+l) . 4-chloro-6-methyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine . MS (ES) : 244.0 (M'+l) . 4-chloro-2 -phenyl-7tf-pyrrolo [2, 3d] pyrimidine. *H NMR (200 MHz, DMSO-d6) 8.35 (2, 2H) , 7.63 (br s, IH) , 7.45 (m, 3H) , 6.47 (br s, IH) ; MS (ES) : 230.0 (M'+l). 4-chloro-5, 6 -dimethyl -2- (3 -pyridyl) -IH- pyrrolo [2,3d] pyrimidine. MS (ES) : 259.0 (M ' +l) . 4-chloro-5,6-dimethyl-2- (2-furyl) -IH- pyrrolo [2, 3d] pyrimidine. } H NMR (200 MHz, DMSO-d € ) δ 2.35 (s, 3H) , 2.35 (s, 3H) , 6.68 (dd, J = 1.8, 3.6 Hz, IH) , 7.34 (dd, J = 1.8 Hz, 3.6 Hz, IH) , 7.89 (dd, J = 1.8, 3.6 Hz, IH) ; MS (ES) : 248.0 (M'+l) . 4-chloro-5, 6 -dimethyl -2- (3-furyl) -IH- pyrrolo [2, 3d] pyrimidine. > H NMR (200 MHz, DMSO-d € ) δ 2.31 (s, 3H) , 2.31 (s, 3H) , 6.62 (S, IH) , 7.78 (s, IH) , 8.18 (s, IH) , 12.02 (s, IH) ; MS (ES) : 248.1 (M'+l) . 4-chloro-5,6-dimethyl-2 -cyclopentyl - IH- pyrrolo [2 , 3d] pyrimidine. ; H NMR (200 MHz, DMSO-d 6 ) δ 1.61- 1.96 (m, 8H) , 2.27 (s, 3H) , 2.27 (s, 3H) , 3.22 (m, IH) , 11.97 (s, IH) ; MS (ES) : 250.1 (M ' +l) . 4-chloro-5, 6-dimethyl-2- (2-thienyl) -IH- pyrrolo [2 , 3d] pyrimidine. Η NMR (200 MHz, DMSO-d β ) δ 2.29 (s, 3H) , 2.31 (s, 3H) , 7.14 (dd, J = 3.1 Hz, 4.0 Hz, IH) , 7.33 (d, J = 4.9 Hz, IH) , 7.82 (d, J = 3.1 Hz, IH) , 12.19 (s, IH) ; MS (ES) : 264.1 (M ' + l) . 4-chloro-5, 6-dimethyl-2- (3-thienyl) -7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, DMSO-d 6 ) δ 2.32 (s, 3H) , 2.32 (s, 3H) , 7.62 (dd, J = 3.0, 5.2 Hz, IH) , 7.75 (d, J = 5.2 Hz, IH) , 8.20 (d, J = 3.0 Hz, IH) ; MS (ES) : 264.0 (M ' +l) . 4-chloro-5, 6 -dimethyl -2- (4 -fluorophenyl) -IH- pyrrolo [2, 3d] pyrimidine. Η NMR (200 MHz, DMSO-d 6 ) δ 2.33(s, 3H) , 2.33 (s, 3H) , 7.30 (m, 2H) , 8.34 (m, 2H) , 12.11 (s, IH) ; MS (ES) : 276.1. (M ' +l) . 4-chloro-5, 6-dimethyl-2- (3 -fluorophenyl) -7H-pyrrolo [2, 3d] pyrimidine. ; H NMR (200 MHz, DMSO-d 6 ) δ 2.31(s, 3H) , 2.33 (s, 3H) , 7.29(m, IH) , 7.52 (m, IH) , 7.96 (m, IH) , 8.14(m, IH) , 11.57 (s, IH) ; MS (ES) : 276.1 (M'+l) . 4-chloro-5, 6- dimethyl -2- (2 -fluorophenyl) -7H-pyrrolo [2, 3d] pyrimidine. Η NMR (200 MHz, DMSO-d 6 ) δ 2.34 (s, 3H) , 2.34 (s, 3H) , 7.33 (m, 2H) , 7.44 (m, IH) , 7.99 (m, IH) , 12.23 (s, IH) ; MS (ES) : 276.1 (M'+l) . 4-chloro-5, 6 -dimethyl-2- isopropyl -7H- pyrrolo [2, 3d] pyrimidine. Η NMR (200 MHz, DMSO-d ) δ 1.24 (d, J = 6.6 Hz, 6H) , 2.28 (s, 3H) , 2.28 (s, 3H) , 3.08 (q, J = 6.6 Hz, IH) , 11.95 (s, IH) ; MS (ES) : 224.0 (M ' +l) . 4-chloro-5, 6 -dimethyl -7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, DMSO-d 6 ) δ 2.31 (s, 3H) , 2.32 (s, 3H) , 8.40 (s, IH) ; MS (ES) : 182.0 (M ' +l) . dl-4-chloro-5 , 6-dimethyl-2-phenyl- 1H-1 - (1-phenylethyl ) pyrro1c [2,3d] pyrimidine . Preparation 12: To a solution of dl-l, 2-diaminopropane (1.48 g, 20.0 mmol) and sodium carbonate (2.73 g, 22.0 mmol) in dioxane (100.0 mL) and water (100.0 mL) was added di- ert-dicarbonate (4.80 g, 22.0 mmol) at room temperature. The resulted mixture was stirred for 14 hr. Dioxane was removed in vacuo . The precipitate was filtered off and the filtrate was concentrated in vacuo to dryness. The residue was triturated with EtOAc and then filtered. The filtrate was concentrated in vacuo to dryness to give a mixture of d -l-amino-2- (1, 1- dimethylethoxy) carbonylamino-propane and dl -2-amino-l- (l, 1- dimethylethoxy) carbonylamino-propane which were not separable by normal chromatography method. The mixture was used for the reaction in Example 8. Preparation 13 : To solution of Fmoc-β-Ala-OH (1.0 g, 3.212 mmol) and oxalyl chloride (0.428 g, 0.29 mL, 3.373 mmol) in dichloromethane (20.0 mL) was added a few drops of N,N-dimethylformamide at 0 C C. The mixture was stirred at room temperature for 1 hr followed by addition of cyclopropylmethylamine (0.229 g, 0.28 mL, 3.212 mmol) and triethylamine (0.65 g, 0.90 mL, 6.424 mmol) . After 10 min, the mixture was treated with 1 M hydrochloride (10.0 mL) and the aqueous mixture was extracted with dichloromethane (3 x 30.0 mL) . The organic solution was concentrated in vacuo to dryness. The residue was treated with a solution of 20% piperidine in N,N-dimethylforamide (20.0 mL) for 0.5 hr. After removal of the solvent in vacuo, the residue was treated with 1 M hydrochloride (20.0 mL) and ethyl acetate (20.0 mL) . The mixture was separated and the aqueous layer was basified with solid sodium hydroxide to pH = 8. The precipitate was removed by filtration and the aqueous solution was subjected to ion exchange column eluted with 20% pyridine to give 0.262 g (57%) of N- cyclopropylmethyl β-alanine amide. 'H NMR (200 MHz, CD 3 OD) δ_0.22 (m, 2H) , 0.49 (m, 2H) , 0.96 (m, 2H) , 2.40 (t, 2K) , 2.92 (t, 2H) , 3.05 (d, 2H) ; MS (ES) : 143.1 (MM) . Preparation 14 : N- tert-butoxycarbonyl- rans- 1, 4-cyclohexyldiamine . trans-1, 4 -cyclonexyldiamine (6.08 g, 53.2 mmol) was dissolved in dichloromethane (lOOmL) . A solution of di-t- butyldicarbonate (2.32 g, 10.65 mmol in 40 mL dichloromethane) was added via cannula. After 20 hours, the reaction was partitioned between CHC1, and water. The layers were separated and the aqueous layer was extracted with CHCl, (3x) . The combined organic layers were dried over MgSO « , filtered and concentrated to yield 1.20 g of a white solid (53%). : H-NMR (200MHz, CDC1 3 ) : δ 1.0-1.3 (m, 4H) , 1.44 (s, 9H) , 1.8 -2.1 (m, 4H) , 2.62 (brm, IH) , 3.40 (brs, IH) , 4.37 (brs, 1H0; MS (ES) : 215.2 (M'+l). 4- (N-acetyl) -N- ert-butoxycarbonyl- rans- 1 , 4 -cyclohexyl diamine . N- ert-butoxycarbonyl- rans-1, 4-cyclohexyldiamine (530 mg, 2.47 mmol) was dissolved in dichloromethane (20 mL) . Acetic anhydride (250 mg, 2.60 mmol) was added dropwise. After 16 hours, the reaction was diluted with water and CHC1 3 . The layers were separated and the aqueous layer was extracted with CHCl. (3x) . The combined organic layers were dried over MgSO, , filtered and concentrated. Recrystallization (EtOH/H.O) yielded 190 mg of white crystals (30%) . J H NMR (200 MHz, CDClj) : δ 0.9 - 1.30 (m, 4H) , 1.43 (s, 9H) , 1.96- 2.10 (m, 7H) , 3.40 (brs, IH) , 3.70 (brs, IH) , 4.40 (brs, IH) , 4.40 , (brs, IH) ; MS (ES) : 257.2 (M ' +l), 242.1 (M ' - 15), 201.1 (M' - 56) . 4- (4- rans-acetamidocyclohexyl) amino-5, 6 -dimethyl -2 -phenyl- 7H- (1-phenylethyl ) pyrrolo [2,3d] pyrimidine . 4- (N-acetyl) -N- ert-butoxycarbonyl- trans- 1 , 4- cyclohexyldiamine (190 mg, 0.74 mmol), was dissolved m dichloromethane (5 mL) and diluted with TFA (6 ml) . After 16 hours, the reaction was concentrated. The crude solid, DMSC (2mL) , NaHCO, (200 mg, 2.2 mmol) and 4-chloro-5, 6-dimethyl-2 - phenyl -7H-pyrrolo [2, 3d] pyrimidine (35 mg, 0.14 mmol) were combined in a flask and heated to 130 °C. After 4.5 hours, the reaction was cooled to room temperature and diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc (3x) . The combined organic layers were dried over MgSO, , filtered and concentrated. Chromatography (silica preparatory plate; 20:1 CHCl 3 :EtOH) yielded 0.3 mg of a tan solid (1% yield). MS (ES) : 378.2 (M ' +l) . 4 - (N-methanesulfonyl) -N- ert-butoxycarbonyl- rans- 1 , 4 - cyclohexyldiamine . trans-1, 4-cyclohexyldiamine (530 mg, 2.47 mmol) was dissolved in dichloromethane (20 ml) and diluted with pyridine (233 mg, 3,0 mmol). Methanesulfonyl chloride (300 mg, 2.60 mmol) was added dropwise. After 16 hours, the reaction was diluted with water and CHC1 ; . The layers were separated and the aqueous layer was extracted with CHC1 3 (3x) . The combined organic layers were dried over MgS0 4 , filtered and concentrated, recrystallization (EtOH/H0) yielded 206 mg of white crystals (29%). 'H-NMR (200MHz, CDC1,) : δ 1.10-1.40 (m, 4H) , 1.45 (s, 9H) , 2.00-2.20 (m, 4H) , 2.98 (s, 3H) , 3.20-3.50 (brs, 2H) , 4.37 (brs, IH) ; MS (ES) 293.1 (M'+l), 278.1 (M'- 15) , 237.1 (M * -56) . 4- (4- rans-methanesulfamidocyclohexyl) amino-5, 6-dimethyl-2- phenyl-7H- (1-phenylethyl) pyrrolo [2, 3d] pyrimidine. 4- (N-sulfonyl) -N- tert-butoxycarbonyl- trans- 1, 4 - cyclohexyldiamine (206 mg, 0.71 mmol), was dissolved in dichloromethane (5ml) and diluted with TFA (6 ml) . After 16 hours, the reaction was concentrated. The crude reaction mixture, DMSO (2 ml), NaHCOJ (100 mg, l.i mmol) and 1-chloro- 5 , 6-dimethyl-2-phenyl-7H-pyrrolo [2 , 3d] pyrimidine were combined in a flask and heated to 130 °C. After 15 hours, the reaction was cooled to room temperature, and diluted with EtOAc (3x) . The combined organic layers were dried over MgS0 4 , filtered and concentrated. Chromatography (silica preparatory plate, 20:1 CHCl 3 /EtOH) yielded 2.6 mg of a tan solid (5% yield) . MS (ES) : 414.2 (M ' +l). Example 1: A solution of 4-chloro-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine (0.50 g, 1.94 mmol) and 4- rans-hydroxy cyclohexylamine (2.23 g, 19.4 mmol) in methyl sulfoxide (10.0 mL) was heated at 130°C for 5 hr. After cooling down to room temperature, water (10.0 mL) was added and the resulted aqueous solution was extracted with EtOAc (3 xlO.O mL) . The combined EtOAc solution was dried (MgS0 « ) and filtered, the filtrate was concentrated in vacuo to dryness, the residue was chromatographed on silica gel to give 0.49 g (75%) of 4- (4- rans-hydroxycyclohexyl) amino-5, 6 -dimethyl -2 -phenyl - 7H- pyrrolo [2, 3d] pyrimidine. mp 197-199°C; : H NMR (200 MHz, CDC1 3 ) δ_1.25-1.59 (m, 8H) , 2.08 (s, 3H) , 2.29 (s, 3H) , 3.68-3.79 (m, IH) , 4.32-4.38 (m, IH) , 4.88 (d, J = 8 Hz, IH) , 7.26-7.49 (m, 3H) , 8.40-8.44 (dd, J = 2.2, 8 Hz, 2H) , 10.60 (s, IH) ; MS (ES) : 337.2 (M'+l) . The following compounds were obtained in a similar manner to that of Example 1 : 4- (4- rans-hydroxycyclohexyl) amino- 6 -methyl -2 -phenyl - 1H- pyrrolo [2, 3d] pyrimidine. X H NMR (200 MHz, CDC1 3 ) δ_11.37 (s, IH, pyrrole-NH) , 8.45 (m, 2H, Ar-H), 7.55 (m, 3H, Ar-H), 6.17 (s, IH, pyrrole-H) , 4.90 (br d, IH, NH) , 4.18 ( , IH, CH-O) , 3.69 (m, IH, CH-N) , 2.40-2.20 (m, 2H) , 2.19-1.98 (m, 2H) , 2.25 (S, 3H, CH3) 1.68-1.20 (m, 4H) ; MS (ES) : 323.2 (M'+l). 4 - (4 - rans-hydroxycyclohexyl) amino-5-methyl-2-phenyl-7tf- pyrrolo [2, 3d] pyrimidine. X H NMR (200 MHz, CDC1 3 ) δ_11.37 (s, IH, pyrrole-NH) , 8.40 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 5.96 (s, IH, pyrrole-H) , 4.90 (br d, IH, NH) , 4.18 (m, IH, CK-O , 3.69 (m, IH, CH-N) , 2.38-2.20 (m, 2H) , 2.18-1.98 (m, 2H) , 2.00 (s, 3H, CH3) 1.68-1.20 (m, 4H) ; MS (ES) : 323.2 (M ' +l) . 4- (4-traπs-hydroxycyclohexyl)amino-2-phenyl-7H-pyrrolo[2, 3d] pyrimidine. mp 245.5-246.5°C; Η NMR (200MHz, CD ? OD) δ 8.33(m, 2H, Ar-H) , 7.42 (m, 3H, Ar-H) , 7.02 (d, IH, J=3.6 Hz, pyrolle-H) , 6.53 (d, IH, J=3.6 Hz, pyrolle-H) , 4.26 (m, IH, CH-O) , 3.62 (m,lH, CH-N) , 2.30-2.12 (m, 2H) , 2.12-1.96 (m, 2H) , 1.64-1.34 (m, 4H) ; MS, M+l=309.3; Anal (C,,H : .N,0) C, H, N. 4- (4- trans -hydroxycyclohexyl) amino-5 , 6 -dimethyl -2- (3- pyridyl) - 7H- yrrolo [2, 3d] pyrimidine. Η NMR (200 MHz, CDCl,) δ_1.21-1.54 (m, 8H) ; 2.28 (s, 3H) ; 2.33 (s, 3H) ; 3.70 (m, IH) , 4.31(m, IH) , 4.89 (d, IH) , 7.40 (m, IH) , 8.61 (m, 2H) , 9.64 (m, IH) ; MS (ES) : 338.2 (M ' +l) . 4 -(4 - trans -hydroxycyclohexyl ) amino-5 , 6 -dimethyl - 2 - ( 2 - f uryl ) - 7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.26- 1.64(m, 8H) , 2.22 (s, 3H) , 2.30 (s, 3H) , 3.72(m, IH) , 4.23 (m, IH) , 4.85 (d, IH) , 6.52(m, IH) , 7.12 (m, IH) , 7.53 (m, IH) , 9.28 (s, IH) ; MS (ES) : 327.2 (M'+l) . 4- (4- tran -hydroxycyclohexyl) amino-5 , 6-dimethyl-2- (3-furyl) - 7H-pyrrolo [2, 3d] pyrimidine. Ε NMR (200 MHz, CDCl,) δ 1.25- 1.63 (m, 8 H) , 2.11 (s, 3H) , 2.27 (s, 3H) , 3.71(m, IH) , 4.20 (m, IH) , 4.84 (d, IH) , 7.03 (m, IH) , 7.45(m, IH) , 8.13 (m, IH) , 10.38 (m, IH) ; MS (ES) : 327.2 (M'+l). 4 - (4 - rans -hydroxy cyclohexyl ) amino-5 , 6-dimethyl-2- cyclopentyl-7H- pyrrolo [2, 3d] pyrimidine. H NMR (200 MHz, CDCl,) δ 1.26-2.04 (m, 16 H) , 2.26 (s, 3H) , 2.27 (s, 3H) , 3.15 (m, IH) , 3.70 (m, IH) , 4.12 (m, IH) , 4.75 (d, IH) ; MS (ES) : 329.2 (M' + l) . 4- (4- rans-hydroxycyclohexyl) amino-5, 6 -dimethyl -2- (2-thιeny • -7H-pyrrolo [2, 3d] pyrimidin-4 -amine. 'H NMR (200 MHz, CDC1 3 ) δ 1.28-1.59 ( , 8H) , 2.19 (s, 3H) , 2.29 (s, 3H) , 3.74 (m, IH) , 4.19 (m, IH) , 4.84 (d, IH) , 7.09 (m, IH) , 7.34 (m, IH) , 7.85 (m, IH) , 9.02 (S, IH) ; MS (ES) : 343.2 (M ' +l). 4 - (4 - trans -hydroxy cyclohexyl ) amino-5, 6-dime thy 1-2- ( 3 - thienyl) -7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDC1 3 ) δ 1.21-1.60 (m, 8H) , 1.98 (s, 3H) , 2.23 (s, 3H) , 3.66 (m, IH) , 4.22 (m, IH) , 7.27 (m, IH) , 7.86 (m, IH) , 8.09 (m, IH) , 11.23 (s, IH) ; MS (ES) : 343.2 (M ' +l) . 4 - (4 - trans -hydroxy cyclohexyl ) amino-5, 6-dime thy 1-2- (4 - fluorophenyl) -7H- pyrrolo [2, 3d] pyrimidine. *H NMR (200 MHz, CDC1 3 ) δ 1.26- 1.66 (m, 8H) , 1.94 (s, 3H) , 2.28 (s, 3H) , 3.73 (m, IH) , 4.33 (m, IH) , 4.92 (d, IH) , 7.13 (m, 2H) , 8.41 (m, 2H) , 11.14 (s, IH) ; MS (ES) : 355.2 (M'+l) . 4 - (4 - trans -hydroxy cyclohexyl ) amino-5, 6-dime thy 1-2- ( 3 - fluorophenyl) -7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDC1 3 ) δ 1.26-1.71 (m, 8H) , 2.06 (s, 3H) , 2.30 (s, 3H) , 3.72 (m, IH) , 4.30 (m, IH) , 4.90 (d, IH) , 7.09 (m, IH) , 7.39 (m, IH) , 8.05 (m, IH) , 8.20 (m, IH) , 10.04 (s. IH) ; MS (ES) : 355.2 (M ' + l) . 4 - (4 - trans -hydroxy cyclohexyl ) amino-5, 6-dime thy 1-2- (2 - fluorophenyl) -7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDC1 3 ) δ 1.30-1.64 (m, 8H) , 2.17 (s, 3H) , 2.31 (s, 3H) , 3.73 (m, IH) , 4.24 (m, IH) , 4.82 (d, IH) , 7.28 (m, 2H) , 8.18 (m, IH) , 9.02 (m, IH) , 12.20 (s, IH) ; MS (ES) : 355.3 (M'+l) . 4- (4- rans- hydroxycyclohexyl) amino-5, 6 -dimethyl -2 -isopropyl - 7tf-pyrrolo [2, 3d] pyrimidine : H NMR (200 MHz, CDC1 3 ) δ 1.31 (d, J = 7.0 Hz, 6H) , 1.30-1.65 (m, 8H) , 2.27 (s, 3H) , 2.28 (s, 3H) , 3.01 (m, J = 7.0 Hz, IH) , 3.71 (m, IH) , 4.14 (m, IH) , 4.78 (d, IH) ; MS (ES) : 303.2. dl-4- (2- trans -hydroxy cyclohexyl ) amino-5 , 6 -dimethyl - Z - isopropyl -7H- pyrrolo [2, 3d] pyrimidine " H NMR (200 MHz, C CI3) d 1.31-1.42 (br, 4H) , 1.75-1.82 (br, 4H) , 2.02 is, 3H) , 2.29 (s, 3H) , 3.53 (m, IH) , 4.02 (m, IH) , 5.08 (d, IH) , 7.41-7.48 (m, 3H) , 8.30 (m, 2H) , 10.08 (s, IH) ; MS (ES) : 337.2 (M * -l) . 4- (3,4- rans- dihydroxycyclohexyl) amino-5, 6 -dimethyl -2 -phenyl - 7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 353.2 (M + +l) . 4- ( 3, 4 - ci s -dihydr oxy 1 cyclohexyl) amino-5, 6 -dimethyl -2 -phenyl - 7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 353.2 (M + +l) . 4- (2-acetylaminoethyl) amino-5, 6 -dimet hyl -2 -phenyl -7H- pyrrolo [2,3d] pyrimidine . mp 196-199°C; : H NMR (200 MHz, CDCl,) δ_l .72 (s, 3H) , 1.97 (s, 3H) , 2.31 (s, 3H) , 3.59 (m, 2H) , 3.96 (m, 2H) , 5.63 (br, IH) , 7.44-7.47 (m, 3H) , 8.36-8.43 (dd, J = 1 Hz, 7 Hz, 2H) , 10.76 (S, IH) ; MS (ES) : 324.5 (M ' +l) . dl-4- (2- rans-hydroxycyclopentyl) amino-5, 6 -dimethyl -2 -phenyl - 7H-pyrrolo [2 , 3d] pyrimidin . : ■ H NMR (200 MHz, CDCl,) δ_1.62 (m, 2H) , 1.79 (br, 4H) , 1.92 (S, 3H) , 2.29 (s, 3H) , 4.11 (m, IH) , 4.23 (m, IH) , 5.28 (d, IH) , 7.41-7.49 (m, 3H) , 8.22 (m, 2H) , 10.51 (s, IH) ; MS (ES) : 323.2 (M'+l) . " For preparation of 2- rans-hydroxycyclopentylamine, see PCT 9417090. dl-4- (3- rans-hydroxycyclopentyl) amino-5, 6 -dimethyl-2 -phenyl - 7H- pyrrolo [2,3d] pyrimidine . : ■ H NMR (200 MHz, CDCl,) δ_1.58-1.90 (br, 6 H, ) , 2.05 (s, 3H) , 2.29 (s, 3H) , 4.48-4.57 (tn, IH) , 4.91-5.01 (m, 2H) , 7.35-7.46 (m, 3H) , 8.42-8.47 (m, 2H) , 10.11 (s, IH) ; MS (ES) : 323.2 (M ' + l) . : For preparation of 3- rans-hydroxycyclopentylamine, see Ξ?- A-322242. dl-4- (3-cis-hydroxycyclopentyl) amino-5 , 6 -dimethyl -2 -phenyl - 7H- pyrrolo [2, 3d] pyrimidine. 1 : H NMR (200 MHz, CDCl,) δ_1.82-2.28 (br, 6H) , 2.02 (s, 3H) , 2.30 (s, 3H) , 4.53-4.60 (tn, IH) , 4.95-5.08 (m, IH) , 5.85-5.93 (d, IH) , 7.35-7.47 (m, 3H) , 8.42-8.46 (m, 2H) , 10.05 (s, IH) ; MS (ES) : 323.2 (M ' +l) . " For preparation of 3-cis-hydroxycyclopentylamine, see EP-A- 322242. 4- (3,4- trans-dihydroxycyclopentyl) amino-5, 6 -dimethyl -2 -phenyl -7H-pyrrolo [2, 3d] pyrimidine. 1 : H NMR (200 MHz, CDCl,) δ_1.92- 1.99 (br, 2H) , 2.14 (s, 3H) , 2.20 (br, 2H) , 2.30 (s, 3H) , 2.41-2.52 (br, 2H) , 4.35 (m, 2H) , 4.98 (m, 2H) , 7.38-7.47 (m, 3H) , 8.38-8.42 (m, 2H) , 9.53 (s, IH) ; MS (ES) : 339.2 (M'+l). * For preparation of 3 , 4- rans-dihydroxycyclopentylamine, see PCT 9417090. 4- (3-amino-3 -oxopropyl ) amino-5 , 6 -dimethyl -2 -phenyl -7H- pyrrolo [2 , 3d] pyrimidine . Ε NMR (200 MHz, CDCl,) δ_2.02 (s, 3H) , 2.29 (s, 3H) , 2.71 (t, 2H) , 4.18 (m, 2H) , 5.75-5.95 (m, 3H) , 7.38-7.48 (tn, 3H) , 8.37-8.41 (m, 2H) , 10.42 (s, IH) ; MS (ES): 310.1 (M'+l). 4- (3-N-cyclopropylmethylamino-3-oxopropyl) amino-5, 6-dimethyl- 2 -phenyl -7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CD,OD) δ_0.51 (q, 2H) , 0.40 (q, 2H) , 1.79-1.95 (br, IH) , 2.36 (s, 3H) , 2.40 (s, 3H) , 2.72 (t, 2H) , 2.99 (d, 2H) , 4.04 (t, 2H) , 7.58-7.62 (m, 3H) , 8.22-8.29 (m, 2H) ; MS (ES) : 364.2 (M'+l). 4- (2-amino-2-oxoethyl)amino-5,6 -dimethyl -2 -phenyl- 1H- pyrrolo [2, 3d] pyrimidine : H NMR (200 MHz, CD,OD) δ 2.31 (s, 3H) , 2.38 (s, 3H) , 4.26 (s, ' 2H), 7.36 (m, 3H) , 8.33 (m, 2H) ; MS (ES) : 396.1 (M ' +l) . 4- (2-N-methylamino-2-oxoethyl) amino-5, 6 -dimethyl -2 -pheny - 7Λ- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl:) δ_l.9? (s, 3H) , 2.17 .(s, 3H) , 2.82 (d, 3H) , 4.39 (d, 2H) , 5.76 (t, IH) , 6.71 (br, IH) , 7.41-7.48 (m, 3H) , 8.40 (m, 2H) , 10.66 is, IH) ; MS (ES) : 310.1 (M ' +l) . 4- (3- ert-butyloxyl-3-oxopropyl) amino-5, 6 -dimethyl -2 -phenyl - 7 H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ_1.45 (s, 9H) , 1.96 (s, 3H) , 2.29 (s, 3H) , 2.71 (t, 2H) , 4.01 (q, 2H) , 5.78 (t, IH) , 7.41-7.48 (m, 3H) , 8.22-8.29 (m, 2H) ; MS (ES) : 367.2 (M ' + l) . 4- (2-hydroxyethyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.92 (s, 3H) , 2.29 (s, 3H) , 3.81-3.98 (br, 4H) , 5.59 (t, IH) , 7.39- 7.48 (m, 3H) , 8.37 (m, 2H) , 10.72 (s, IH) ; MS (ES) : 283.1 (M ' + l) . 4- (3-hydroxypropyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,} δ 1.84 (m, 2H) , 1.99 (s, 3H) , 2.32 (s, 3H) , 3.62 (t, 2H) , 3.96 (m, 2H) , 3.35 (t, IH) , 7.39-7.48 (m, 3H) , 8.36 (m, 2H) , 10.27 (s, IH) ; MS (ES) : 297.2 (M ' + l) . 4 - (4-hydroxybutyl) amino-5 , 6 - dimethyl- 2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.71-1.82 (m, 4H) , 1.99 (s, 3H) , 2.31 (s, 3H) , 3.68-3.80 (m, 4H) , 5.20 (t, IH) , 7.41-7.49 (m, 3H) , 8.41(m, 2H) , 10.37 (s, IH) ; MS (ES) : 311.2 (M ' + l) . 4- (4- trans -acetylammocyclohexyl) amino-5, 6 -dimethyl -2 -phenyl - 7tf-pyrrolo [2 , 3d] pyrimidine . 4- (4- trans -methylsulfonylaminocyclohexyl) amino-5, 6 -dimethyl - 2 -phenyl - IH- pyrrolo [2,3d] pyrimidine . 4 - (2 -acetylaminoethyl ) amino-5 , 6-dimethyl -2 -phenyl - IH- 7 - ; i - phenylethyl) pyrrolo [2, 3d] pyrimidine. 4- (4- trans-hydoxycyclohexyl) amino-5, 6-dimethyl-2-phenyl-7H-1- phenylethyl) pyrrolo [2, 3d] pyrimidine . 4 - (3 -pyridylmethyl) amino-5 , 6 -dimethyl -2 -phenyl - IH- 1 - ( 1- phenylethyl) pyrrolo [2,3d] pyrimidine . 4 - (2 -methylpropyl ) amino-5 , 6 -dimethyl- 2 -phenyl - 7H- 7 - ( l - phenylethyl) pyrrolo [2, 3d] pyrimidine. Example 2 : To a stirred suspension of triphenylphosphine (0.047 g, 0.179 mmol) and benzoic acid (0.022 g, 0.179 mmol) in THF (1.0 mL) cooled to 0°C was added 4- (4- rans-hydroxycyclohexyl) amino- 5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine (0.05 g, 0.149 mmol) at 0°C. Diethyl azodicarboxylate (0.028 ml, 0.179 mmol) was then added dropwise over 10 minutes. The reaction was then allowed to warm to room temperature. After reaction was complete by TLC the reaction mixture was quenched with aqueous sodium bicarbonate (3.0 mL) . The aqueous phase was separated and extracted with ether (2 X 5.0 mL) . The organic extracts were combined, dried, and concentrated in vacuo to dryness. To the residue was added ether (2.0 mL) and hexane (5.0 mL) whereupon the bulk of the triphenylphosphine oxide was filtered off. Concentration of the filtrate gave a viscous oil which was purified by column . chromatography (hexane:ethyl acetate=4:l) to give 5.0 mg (7.6%) of 4- (4- ci s-benzoyloxycyclohexyl) amino-5 , 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 441.3 (M'+l). The reaction also produced 50.0 mg (84%) of 4- (3 -cyclohexenyl) amino-5, 6- dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 319.2 (M ' +l) . Example 3 : To a solution of 4- (4-cis-benzoyloxycyclohexyl) am o- 5 , 6 - dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine (5.0 mg, 0.0114 mmol) in ethanol (1.0 mL) was added 10 drops of 2M sodium hydroxide. After 1 hr, the reaction mixture was extracted with ethyl acetate (3 x 5.0 mL) and the organic layer was dried, filtered and concentrated in vacuo to dryness. The residue was subjected to column chromatography (hexane : ethyl acetate=4:l) to give 3.6 mg (94%) of 4-(4-c s- hydroxycyclohexyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 337.2 (M ' +l) . The following compounds were obtained in a similar manner as that of Example 3 : 4- (3-N,N-dimethyl-3-oxopropyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. "H NMR (200 MHz, CDCl,) δ 2.01 (s, 3H) , 2.31 (s, 3H) , 2.73 (t, 2H) , 2.97 (s, 6H) , 4.08 (m, 2H) , 6.09 (t, IH) , 7.41-7.48 (m, 3H) , 8.43 (m, 2H) , 10.46 (s, IH) ; MS (ES) : 338.2 (M ' + l) . 4 - (2 - f ormylaminoethyl ) amino-5, 6 -dime thy 1-2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. H NMR (200 MHz, CDCl,) δ 2.26 (s, 3H) , 2.37 (s, 3H) , 3.59-3.78 (m, 2H) , 3.88-4.01 (m, 2H) , 5.48-5.60 (m, IH) , 7.38-7.57 (m, 3H) , 8.09 (s, IH) , 8.30-8.45 (m, 2H) , 8.82 (s, IH) ; MS (ES) : 310.1 (M'+l) . 4 - (3 -acetylaminopropyl ) amino-5, 6-dime thy 1-2 - phenyl -7H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 338.2 (M'+l) . Example 4 : 4- (3- ert-butyloxy-3-oxopropyl) amino-5, 6-dimethyl -2 -pheny - IH-pyrrolo [2, 3d] pyrimidine (70.0 mg, 0.191 mmol)) was dissolved in trifluoroacetic acid:dichloromethane (1:1, 5.0 mL) . The resulting solution was stirred at room temperature for 1 hr. and then refluxed for 2 hr. After cooling down to room temperature, the mixture was concentrated in vacuo to dryness. The residue was subjected to preparative thin layer chromatography (EtOAc : hexane : AcOH=7:2.5 :0.5) to give 40.0 mg (68%) of. 4- (3-hydroxy-3- oxopropyl ) amino-5 , 6 -dimethyl-2 -phenyl - 7 H- pyrrolo [2,3d] pyrimidine. : H NMR (200 MHz, CD,OD) δ 2.32 (s, 3H) , 2.38 (s, 3H) , 2.81 (t, 2H) , 4.01 (t, 2H) , 7.55 (m, 3H) , 8.24 (m, 2H) ; MS (ES) : 311.1 (M ' +l) . The following compound was obtained in a similar manner as that of Example 4 : 4- (3-aminopropyl)amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 296.1 (M' + l), 279.1 (M * -NH 3 ) . Example 5 : 4- (3-hydroxy-3-oxopropyl) amino-5 , 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine (50.0 mg, 0.161 mmol) was dissolved in a mixture of N, N-dimethylformamide (0.50 mL) , dioxane (0.50 mL) and water(0.25 mL) . To this solution was added methylamine (0.02 mL, 40% wt in water, 0.242 mmol), triethylamine (0.085 mL) and N,N,N'N' -tetramethyl uroniu tetrafluoroborate (61.2 mg, 0.203 mmol). After stirring at room temperature for 10 min, the solution was concentrated and the residue was subjected to preparative thin layer chromatography (EtOAc) to give 35.0 mg (67%) of 4- (3-N-methyl- 3-oxopropyl) amino-5, 6 -dimethyl - 2 -phe n ' y 1 - 7 H - pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDC1 3 ) δ 1.92 (s, 3H) , 2.30 (s, 3H) , 2.65 (t, 2H) , 4.08 (t, 2H) , 5.90 (t, IH) , 6.12 (m, IH) , 7.45 (m, 3H) , 8.41 (m, 2H) , 10.68 (s, IH) ; MS (ES) : 311.1 (M ' + l) . The following compounds were obtained in a similar manner as that of Example 5 : 4- (2-cyclopropanecarbonylaminoethyl) amino-5 , 6 -dimethyl -2- phenyl-7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 350.2 (M ' +l). 4- (2-isobutyrylaminoethyl) amino-5 , 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 352.2 (M ' +l). 4- (3-propionylaminopropyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.00-1.08 (t, 3H) , 1.71-2.03 (m, 4H) , 2.08 (s, 3H) , 2.37 (s, 3H) , 3.26- 3.40 (m, 2H) , 3.79-3.96 (m, 2H) , 5.53-5.62 (m, IH) ,_6.17-6.33 (m, IH) , 7.33-7.57 (m, 3H) , 8.31-8.39 (m, 2H) , 9.69 (s, IH) ; MS (ES) : 352.2 (M ' +l) . 4- (2-methylsulfonylaminoethyl) amino-5, 6-dimethyl-2-phenyl -7H- pyrrolo [2, 3d] pyrimidine. "H NMR (200 MHz, CDC1 3 ) δ 2.18 (s, 3H) , 2.27 (s, 3H) , 2.92 (s, 3H) , 3.39-3.53 (m, 2H) , 3.71-3.88 (m, 2H) , 5.31-5.39 (m, IH) , 6.17-6.33 (m, IH) , 7.36-7.43 (m, 3H) , 8.20-8.25 (m, 2H) , 9.52 (s, IH) ; MS (ES) : 360.2 (M'+l) . Exam le : A mixture of 4-chloro-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine (0.70 g, 2.72 mmol) and 1, 2-diaminoethane (10.0 mL, 150 mmol) was refluxed under inert atmosphere for 6 hr. The excess amine was removed in vacuo, the residue was washed sequentially with ether and hexane to give 0.75 g (98%) of 4- (2-aminoethyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolof2, 3d] pyrimidine. MS (ES) ; 282.2 (M ' +l), 265.1 (M * -NH 3 ) . Example 7 : To a solution of 4- (2 -aminoethyl) amino-5, 6 -dimethyl-2 -phenyl - 7H-pyrrolo [2, 3d] pyrimidine (70.0 mg, 0.249 mmol) and triethylamine (50.4 mg, 0.498 mmol) in dichloromethane (2.0 mL) was added propionyl chloride (25.6 mg, 0.024 ml, C.2~4 mmol) at 0°C. After 1 hr, the mixture was concentrated ir. vacuo and the residue was subjected to preparative thin layer chromatography (EtOAc) to give 22,0 mg (26%) of 4- (2- propionylaminoethyl)amino-5, 6 -dimethyl -2 -phenyl -7 H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 338.2 (M ' +l) . The following compounds were obtained in a similar manner as that of Example 7 : 4 - (2-N 1 -methylureaethyl) amino-5 , 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 2.13 (s, 3H) , 2.32 (s, 3H) , 3.53 (d, 3H) , 3.55 (m, 2H) , 3.88 (m, 2H) , 4.29 (m, IH) , 5.68 (t, IH) , 5.84 (m, IH) , 7.42 (m, 3H) , 8.36 (dd, 2H) , 9.52 (s, IH) ; MS (ES) : 339.3 (M'+l) . 4 - (2-N' -ethylureaethyl) amino-5, 6 -dimethyl - 2 -phenyl - 7H- pyrrolo[ 2, 3d] pyrimidine. MS (ES) : 353.2 (M ' +l) . Example 8 : To a solution of 1- (3 -dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (41.1 mg, 0.215 mmol), dimethylamino- pyridine (2.4 mg, 0.020 mmol) and pyruvic acid (18.9 mg, 0.015 mL, 0.215 mmol) in dichloromethane (2.0 mL) was added 4- (2-aminoethyl) amino-5, 6 -dimethyl-2-phenyl -7H-pyrrolo [2, 3d] pyrimidine (55.0 mg, 0.196 mmol). The mixture was stirred at room temperature for 4 hr. Usual workup and column chromatography (EtOAc) then gave 10.0 mg (15%) of 4-(2'- pyruvylamidoethyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine.. MS (ES) : 352.2 (M'+l). Example 9 : To a solution of 4- (2-aminoethyl) amino-5, 6-dimethyl-2-phenyl- 7H-pyrrolo [2, 3d] pyrimidine (60.0 mg, 0.213 mmol) in dichloromethane (2.0 mL) was added N-trimethylsilyl isocyanate (43.3 mg, 0.051 mL, 0.320 mmol). The mixture was stirred at room temperature for 3 hr followed by addition of aqueous sodium bicarbonate. After filtration through small amount of silica gel, the filtrate was concentrated in vacua to dryness to give 9.8 mg (14%) of 4- (2-ureaethyl) amino-5 , 6- dimethyl-2-phenyl -7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 325.2 (M'+l) . The following compounds were obtained in a similar manner as that of Example 9 : dl-4- (2-acetylaminopropyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. ; H NMR (200 MHz, CDCl,) δ 1.28-1.32 (d, J=8 Hz, 3 H) , 1.66 (s, 3H) , 1.96 (s, 3H) , 2.30 (s, 3H) 3.76-3.83 (m, 2H) , 4.10-4.30 (m, IH) , 5.60-5.66 (t, J=6 Hz, IH) , 7.40-7.51(m, 3H) , 8.36-8.43 (tn, 2H) , 10.83 (s, IH) ; MS (ES) : 338.2 (M'+l) . (R) -4- (2-acetylaminopropyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine. * H NMR (200 MHz, CDC1 3 ) δ 1.31 (d, 3H) , 1.66 (s, 3H) 1.99 (s, 3H) , 2.31 (s, 3H) , 3.78-3.83 (m, 2H) , 4.17-4.22 (m, IH) , 5.67 (t, IH) , 7.38-7.5 (m, 3H) , 8.39 (m, 2H) , 10.81 (s, IH) ; MS (ES) : 338.2 (M ' +l). (R) -4 - (1 -methyl -2-acetylaminoe hyl) amino-5 , 6 -dimethyl -2 - phenyl-7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.41 (d, 3H) , 1.68 (S, 3H) , 2.21 (s, 3H) , 2.34 (s, 3H) , 3.46- 3.52 (br, m, 2H) , 4.73 (m, IH) , 5.22 (d, IH) , 7.41-7.46 (m, 3H) , 8.36-8.40 (m, 2H) , 8.93 (s, IH) ; MS (ES) : 338.2 (M'+l). (S) -4- (2-acetylaminopropyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.31 (d, 3H) , 1.66 (s, 3H) 2.26 (s, 3H) , 2.35 (s, 3H) , 3.78-3.83 (m, 2H) , 4.17-4.22 (m, IH) , 5.67 (t, IH) , 7.38-7.5 (m, 3H) , 8.39 (m, 2H) , 8.67(s, IH) ; MS (ES) : 338.2 (M ' +l). (S) -4- (1 -methyl -2-acetylaminoethyl) amino-5 , 6 -dimethyl -2- phenyl-7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ 1.41 (d, 3H) , 1.68 (s, 3H) , 2.05 (s, 3H) , 2.32 Is, 3K) , 2.46- 3.52 (m, 2H) , 4.73 (m, IH) , 5.22 (d, IH) , 7.41-7.46 (m, 2K: , 8.36-8.40 (m, 2H) , 10.13 (s, IH) ; MS (ES) : 338.2 (M " +l). Example 10: Reaction of 4-chloro-5, 6-dimethyl-2-phenyl-7K-pyrrolo [2 , 3d] pyrimidine with the mixture of dl -l-amino-2- (1 , 1-dimethyl ethoxy) carbonylamino-propane and dl -2-amino-l- (1 , 1-dimethyl ethoxy) carbonylamino-propane was run in a similar manner as that of Example 1. The reaction gave a mixture of dl-4-(l- methyl-2- (1, 1-dimethylethoxy) carbonylamino) ethylamino- 5 , 6- dimethyl-2 -phenyl-7H-pyrrolo [2, 3d] pyrimidine and dl-4- (2- methyl-2- (1, 1-dimethylethoxy) carbonylamino) ethylamino-5 , 6- dimethyl -2 -phenyl -7H-pyrrolo [2, 3d] pyrimidine which were separated by column chromatography (EtOAc :hexanes=l : 3 ) . The first fraction was dl -4- (l-methyl-2- (1, 1-dimethylethoxy) carbonylaminoe hyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine: "H NMR (200 MHz, CDCl,) δ 1.29 - 1.38 (m, 12 H) , 1.95 (s, 3H) , 2.31 (s, 3H) 3.34-3.43 (m, 2H) , 4.62-4.70 (m, IH) , 5.36-5.40 (d, J=8 Hz, IH) , 5.53 (br, IH) , 7.37-7.49(m, 3H) , 8.37-8.44(m, 2H) , 10.75 (s, IH) . MS 396.3 (M ' +l); The second fraction was dl-4- (2- (1, 1- dimethylethoxy) carbonylaminopropyl ) amino-5 , 6 -dimethyl-2 - phenyl -7H-pyrrolo [2, 3d] pyrimidine: : H NMR (200 MHz, CDCl,) δ 1.26-1.40 (m, 12 H) , 2.00 (s, 3H) , 2.31 (s, 3H) 3.60-3.90 (m, 2H) , 3.95-4.10 (m, IH) , 5.41-5.44 (d, J=6.0 Hz, IH) , 5.65(br, IH) , 7.40-7.46(m, 3H) , 8.37-8.44(m, 2H) , 10.89 (s, IH) ; MS (ES) : 396.2 (M ' +l) . The following compounds were obtained in a similar manner as that of Example 10: (S, S) -4- (2-acetylaminocyclohexyl) amino-5, 6-dimethyl 2 -phenyl- 7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ_1.43 (m, 4 H) , 1.60 (s, 3 H) , 1.83 (m, 2 H) , 2.18 (s, 3 H) , 2.30 (m, 2 H) , 2.32 (s, 3 H) , 3.73 (br, IH) , 4.25 (br, IH) , 5.29 (d, IH) , 7.43-7.48 (m, 3H) , 8.35-8.40 (m, 2H) , 9.05 (s, 1 H) . 4- (2-methyl-2-acetylaminopropyl) amino-5, 6-dimethyl-2 -phenyl - 7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ_1.51 (s, 6H) , 1.56 (S, 3H) , 2.07 (s, 3H) , 2.36 (s, 3H) , 3.76 (d, 2H) , 5.78 (t, IH) , 7.41-7.48 (m, 3H) , 7.93 (s, IH) , 8.39 (m, 2H) , 10.07 (s, IH) ; MS (ES) : 352.3 (M ' +l). ' Example 11: dl-4- (l-methyl-2- (1, 1-dimethylethoxy) carbonyl aminoethyl) amino-5, 6-dimethyl-2 -phenyl-7H-pyrrolo [2, 3d] pyrimidine (60.6 mg, 0.153 mmol) was treated with trifluoroacetic acid (0.5 mL) in dichloromethane (2.0 mL) for 14 hr. The organic solvent was removed in vacuo to dryness. The residue was dissolved in N,N-dimethylformamide (2.0 mL) and triethylamine (2.0 mL) . To the solution at 0°C was added acetic anhydride (17.2 mg, 0.016, 0.169 mmol). The resulted mixture was stirred at room temperature for 48 hr and then concentrated in vacuo to dryness. The residue was subjected to preparative thin layer chromatography (EtOAc) to give 27.0 mg (52%) of dl-4 - (1 -methyl- 2-acetylaminoethyl) amino-5 , 6 -dimethyl-2 - phenyl-7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDC1 3 ) δ 1.38-1.42 (d, J=8 Hz, 3 H) , 1.69 (s, 3H) , 2.01 (s, 3H) , 2.32 (S, 3H) 3.38-3.60 (m, 2H) , 4.65-4.80 (m, IH) , 5.23-5.26 (d, J=6 Hz, IH) , 7.40-7.51(m, 3H) , 8.37-8.43(m, 2H) , 10.44 (s, IH) ; MS (ES) : 338.2 (M ' +l) . Example 12 : (R,R) -4- (2-aminocyclohexyl) amino-5, 6 -dimethyl -2 -phenyl -7H- pyrrolo [2, 3d] pyrimidine, prepared in a similar manner as that of Example 1 from 4-chloro-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3d] pyrimidine (0.15 g, 0.583 mmol) and (IR, 2R)-(- ) -1, 2-diaminocyclohexane (0.63 g, 5.517 mmol), was treated with triethylamine (0.726 g, 7.175 mmol) and acetic anhydride (0.325 g, 3.18 mmol) in N, N-dimethylformamide (10.0 mL) at room temperature for 2 hr. After removal of solvent in vacuo, ethyl acetate (10.0 mL) and water (10.0 mL) were added to the residue. The mixture was separated and the aqueous layer was extracted with ethyl acetate (2 x 10.0 mL) . The combined ethyl acetate solution was dried (MgSO and filtered. The filtrate was concentrated in vacuo to dryness and the residue was subjected to column chromatography (EtOAc :Hexane=l : 1 ) to give 57.0 mg (26%) of (R, R) -4- (2-acetylaminocyclohexyl ) a ino- 5, 6 -dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine. * H NMR (200 MHz, CDC1 3 ) δ_1.43 (m, 4 H) , 1.60 (s, 3 H ) , 1.84 (m, 2 H) , 2.22 (s, 3 H) , 2.30 (m, 2 H) , 2.33 (s, 3 H) , 3.72 ( br, IH) , 4.24 (br, IH) , 5.29 (d, IH) , 7.43-7.48 (m, 3H) , 8.35- 8.39 (m, 2H) , 8.83 (s, 1 H) ; MS (ES) : 378.3 (M ' +l). Example 13 : To a solution of 4- (2 -hydroxyethyl) amino-5, 6-dimethyl-2- phenyl-7H-pyrrolo [2, 3d] pyrimidine (40.0 mg, 0.141 mmol) in pyridine (1.0 mL) was added acetic anhydride (0.108 g, 1.06 mmol) at 0°C. The mixture was stirred at room temperature for 4 hr and the solvent was removed in vacuo. The residue was subjected to preparative thin layer chromatography (EtOAc :hexane=l :1) to give 32.3 mg (71%) of 4- (2- acetyloxyethyl) amino-5, 6 -dimethyl-2-phenyl - 7H-pyrrolo [2, 3d] pyrimidine. : H NMR (200 MHz, CDCl,) δ_1.90 (s, 3H) , 2.08 (s, 3H) , 2.31 (s, 3H) , 4.05 (m, 2H) , 4.45 (t, 2H) , 5.42 (m, IH) , 7.41-7.49 (m, 3H) , 8.42(m, 2H) , 11.23 (s, IH) . Example 14: A solution of Fmoc-β-Ala-OH (97.4 mg, 0.313 mmol) and oxalyl chloride ( 39.7 mg, 27.3 μL, 0.313 mmol) in dichloromethane ( 4.0 mL ) with 1 drop of N,N-dimethylformamide was stirred at 0°C for 1 hr followed by addition of 4- (2-aminoethyl) amino- 5, 6-dimethyl-2-phenyl -7H-pyrrolo [2, 3d] pyrimidine (80.0 mg, 0.285 mmol ) and triethylamine (57.6 mg, 79.4 μL, 0.570 mmol) at 0°C. After 3 hr, the mixture was concentrated in vacuo and the residue was treated with the solution of 20% piperidine in N,N-dimethylforamide (2.0 mL) for 0.5 hr. After removal of the solvent in vacuo, the residue was washed with diethyl ether :hexane ( 1:5) to give 3.0 mg (3%) of 4- (6-amino-3-aza-4- oxohexyl ) amino - 5 , 6 - dime thyl - 2 - phenyl - 7H- pyrro l o [ 2 , 3 d ! pyrimidine . MS (ES) : 353 .2 ( M ' +l ) . Example 15 : A solution of 4 - (2-aminoethyl) amino-5, 6-dimethyl-2-phenyl-7H- pyrrolo [2, 3 d] pyrimidine (70.0 mg, 0.249 mmol) and succinic anhydride (27.0 mg, 0.274 mmol) in dichloromethane ( 4.0 mL ) wi t h 1 drop of N,N-dimethylformamide was stirred at room temperature for 4 hr. The reaction mixture was extracted with 20% sodium hydroxide (3 x 5.0 mL) . The aqueous solution was acidified with 3 M hydrochloride to pH = 7.0. The whole mixture was extracted with ethyl acetate (3 x 10 mL) . The combined organic solution was dried (MgSO,) and filtered. The filtrate was concentrated in vacuo to dryness to give 15.0 mg (16%) of 4- (7-hydroxy-3-aza-4, 7-dioxoheptyl) amino-5, 6- dimethyl-2-phenyl-7H-pyrrolo [2, 3d] pyrimidine. MS (ES) : 382.2 (M ' +l) . Example 16: To 10 mL of dimethylformamide (DMF) at room temperature were added 700 mg of 4 - ci s- 3 -hydroxycyclopentyl) amino-2 -phenyl- 5, 6-dimethyl- 7H-pyrrolo [2, 3d] pyrimidine followed by 455 mg of N-Boc glycine, 20 mg of N,N-dimethylaminopyridine (DMAP) , 293 mg of hydroxybenzotriazole (HOBT) and 622 mg of 1- (3- dimethylaminopropyl) -3 -ethylcarboiimide hydrochloride (EDCl) . The reaction mixture was left stirring overnight. DMF was then removed under reduced pressure and the reaction mixture was partitioned between 20mL of ethyl acetate and 50mL of water. The aqueous portion was extracted further with 2x2OmL of ethyl acetate and the combined organic portions were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification on silica gel, eluting with ethyl acetate/hexane gave 410 mg of the desired product : 4- (cis-3- (N-t-butoxycarbonyl-2-aminoacetoxy) cyclopentyl) amino-2 -phenyl-5, 6, -dimethyl -7H-pyrrolo [2, 3d] pyrimidine, MS (ES) (M'+l) =480.2. The ester was then treated with 5 mL of 20% trifluoroacetic acid in dichloromethane at room temperature, left over night and then concentrated. Tritura t ion with ethyl acetate gave 300 mg of an off wn te solid; 4- (cis-3- (2-aminoacetoxy) cyclopentyl) ammo-5 , 6 -dime hy l- 2 -phenyl-7H-pyrrolo [2, 3d] pyrimidine trifluoroacetic acid salt, MS (ES) (M * +l)=380.1. One skilled in the art will appreciate that the following compounds can be synthesized by the methods disclosed above : 4- (cis-3 -hydroxycyclopentyl) amino-5, 6 -dimethyl-2 -phenyl- 7H- pyrrolo[2,3d] pyrimidine MS (ES) (M * +l)= 323.1. 4- (cis-3- (2-aminoacetoxy) cyclopentyl) amino-5, 6 -dimethyl -2- phenyl- 7H- pyrrolo [2,3d] pyrimidinetrif luoroacetic acid salt MS (ES) (M * +l)= 380.1. 4- ( 3-acetamido ) piperidinyl-5,6-dimethyl-2-phenyl- 7H- pyrrolo [2 , 3d] pyrimidine MS (ES) (M * + l)= 364.2. 4- ( 2-N' -methylureapropyl) amino-5, 6 -dimethyl -2 -phenyl - 7H- pyrrolo[2,3d] pyrimidine, MS (ES) (M'+l) =353.4. 4- ( 2-acetamidobutyl ) amino-5, 6 -di me thyl-2-phenyl- 7H- pyrrolo[2, 3d] pyrimidine, MS (ES) (M ' + l)= 352.4. 4- ( 2-N' -methylureabutyl) amino-5, 6 -dimethyl -2 -phenyl - 7H- pyrrolo [2, 3d] pyrimidine MS (ES) (M ' + l)= 367.5 4 - ( 2-aminocyclopropylacetamidoethyl) amino-2 -phenyl- 7H- pyrrolo[2,3d] pyrimidine MS (ES) (M'+l)= 309.1. 4- ( trans -4 -hydroxycyclohexyl) amino-2- (3-chlorophenyl) -7H- pyrrolo [2, 3d] pyrimidine MS (ES) (M ' + l) =342.8. 4- ( trans -4 -hydroxycyclohexyl) amino-2- (3 -fluorophenyl) -7H- pyrroio [2,3d] pyrimidine MS (ES) (MM) =327.2. 4 - ( trans -4 -hydroxycyclohexyl ) amino-2- (4 -pyridyl ) -7H- pyrrolo [2, 3d] pyrimidine MS (ES) (M ' +l) =310.2. Example 17 Scheme IX The pyrrole nitrogen of (7) (Scheme IX) was protected with di- t-butyldicarbonate under basic conditions to yield the corresponding carbamate (22) . Radical bromination of (22) proceeded regioselectively to yield bromide (23) . In general, compound (23) served as a key electrophilic intermediate for various nucleophilic coupling partners. Displacement of the alkyl bromide with sodium phenolate trihydrate yielded compound (24) . Subsequent displacement of t he aryl chloride and removal of the t-butyl carbamate protecting group occurred in one step yielding desired compound (25) . De t ailed S ynthesis of Compounds (22) -(25) in Accordance with Scheme XX Di- -butyl dicarbonate (5.37 g, 24.6 mmol) and dimethyl aminopyridine (1.13 g, 9.2 mmol) were added to a solution containing (7) (1.50 g, 6.15 mmol) and pyridine (30 mL) . After 20 h the reaction was concentrated and the residue was partitioned between CH ; C1 : and water. The CH : C1 : layer was separated, dried over MgSO < , filtered and concentrated to yield a black solid. Flash chromatography (Si0 ; 1/9 EtOAc/Hexanes, R f 0.40) yielded 1.70 g (80%) of a white solid (22). 1 H NMR (200 MHz, CDC1 3 ) δ_8.50 (m, 2H, Ar-H), 7.45 (m, 3H, Ar-H), 6.39 (s, IH, pyrrole-H) , 2.66 (s, 3H, pyrrole- CH 3 ) , 1.76 (s, 9H, N-Bromosuccinimide (508 mg, 2.86 mmol) and AIBN (112 mg, C.55 mmol ) were added to a solution containing (22) ( 935 mg, 2.71 mmol ) and CC1 4 (50 mL) . The solution was heated to reflux. After 2 h the reaction was cooled to room temperature and concentrated in vacuo to yield a ' white solid. Flash chromatography (Si0 2 ; 1/1 CH : C1 : /Hexanes, R f 0.30) yielded 960 mg (84%)of a white solid (23). 1 H NMR (200 MHz, CDC1 3 ) δ_6.52 (m, 2H, Ar-H), 7.48 (m, 3H, Ar-H), 6.76 (s, IH, pyrrole-H) , 4 .93 (s, 2H, pyrrole- H^Br) , 1.79 (s, 9H, carbamate- CH,) ; MS, M + 1 = 423.9; Mpt = 155-157°C. Sodium phenoxide trihydrate (173 mg, 1.02 mmol) was added in one portion to a solution of bromide (23) (410 mg, 0.97 mmol) dissolved in CH : C1 : (5 mL) and DMF (10 mL) . After 2 h the reaction solution was partitioned between CH,C1 : and water. The water layer was extracted with CH : C1 ; . The combined CH ; C1 : layers were washed with water, dried over MgS0 4 , filtered and concentrated to yield a yellow solid. Flash chromatography (Si0 2 ; 1/6 EtOAc/Hexanes, R f 0.30) yielded 210 mg (50%) of a white solid (24). 1 H NMR (200 MHz, CDC1 3 ) δ_8.53 (m, 2H, Ar- H ) , 7.48 ( m, 3H, Ar-H), 7.34 (m, 2H, Ar-H), 7.03 (m, 3H, Ar- H ) , 6.83 (S, IH, pyrrole-H), 5.45 (s, 2H, ArCH : 0) , 1.76 (s, 9H, carbamate-CH,) ; MS, M * = 436.2. 57267 129 A solution containing (24) (85 mg, 0.20 mmol), N- acetylethylenediamine (201 mg, 1.95 mmol) and DMSO (3 mL) was heated to 100°C. After 1 h the temperature was raised to 130°C. After 3 h the reaction was cooled to room temperature and partitioned between EtOAc and water. The water layer was extracted with EtOAc (2x) . The combined EtOAc layers are washed with water, dried over MgSO. , filtered and concentrated. Flash chromatography (Si0 2 ; 1/10 EtOH/ CHCl, , R f 0.25) yielded 73 mg (93%)of a white foamy solid (25). 1 H NMR (200 MHz, DMSO- d6 ) δ 11.81 (br s, IH, N-H) , 8.39 (m, 2H, Ar-H), 8.03 (br t, IH, N-H), 7.57 (br t, IH, N-H), 7.20 - 7.50 ( , 5H, Ar-H), 6.89 - 7.09 (m, 3H, Ar-H), 6.59 (s, IH, pyrrole-H), 5.12 (s, 2H, ArCH,0) , 3.61 (m, 2H, NCH-) , 3.36 (m, 2H, NOT-), 1.79 (s, 3H,COCH_); MS, M+ 1 = 402.6 The following compounds were obtained in a manner similar to that of Example 17: 4 - (2-acetylaminoethyl ) amino- 6 -phenoxymethyl -2 -phenyl- 7H- pyrrolo [2, 3d] pyrimidine. mp 196-197°C; MS (ES) : 401.6 (M'+l). 4 - (2-acetylaminoethyl) amino-6- (4 -fluorophenoxy) methyl -2 phenyl-.7H-pyrrolo [2, 3d] pyrimidine. MS(ES): 420.1 (M'+l). 4 - (2 -acetylammoethyl) amino-6- (4 -chlo ophenoxy = met yl - 2 - phenyl- 7H-pyrrolo [2, 3d] pyrimidine. MS(ΞS): 436.1 (M'-l) . 4- (2-acetylaminoethyl) amino-6- (4-methoxyphenoxy) methyl -2- phenyl-7H-pyrrolo [2, 3d] pyrimidine. MS(ES): 432.1 ( '-i). 4- (2-acetylaminoethyl) amino-6- (N-pyridin-2 -one ) methy -2 - phenyl-7H-pyrrolo [2, 3d] pyrimidine. MS(ES): 403.1 (M-l). 4- (2-acetylaminoethyl) amino-6- (N-phenylamino) methy -2 -phenyl - 7H-pyrrolo [2, 3] pyrimidine. MS(ES): 400.9 (M " +l) . 4- (2-acetylaminoethyl) amino-6- (N-methyl-N-phenylammo) methyl- 2 -phenyl -7H-pyrrolo [2, 3d] pyrimidine. MS(ES): 414.3 (M ' +l). 4- (2-N' -methylureaethyl) amino-6 -phenoxymethyl-2 -phenyl - 7H- pyrrolo [2, 3d] pyrimidine. MS (ES) : 416.9 (M ' +l). Example 18: Synthesis of adenosine Antagonists. Compound 1319 and Compound 1320 (Table 13 below) can be synthesized by the general procedures herein. Compound 26 X = F Compound 1319 Compound 27 X = Cl Compound 1320 Compound 1319 (81%) Η-NMR (d 6 -DMSO) d 1.37 (m, 4H) , 1.93 (m, 2H) , 2.01 (m, 2H) , 4.11 (brs, IH) , 4.61 (d, IH, J = 4.4 Hz) , 6.59 (m, IH) , 7.09 (m, IH) , 7.21 (m, 2H) , 7.49 (dd, IH, J = 8Hz, 14Hz) , 8.03 (m, IH) , 8.18 (d, IH, J = 8 Hz) , 11.55 (brs, IH) . MS (ES) : 327.0 (M ' + l) . Coπroound 1320 (31%) MS (ES) : 343.1 ( M ' +l ) . Example 19: Synthesis of adenosine A : Antagonist. Compound 1 321 (Table 13 below) can be synthesized by 5 general procedures given below. Compo nc 1321 5 Compound 28 (10.93g, 50.76 mmol) was dissolved in DMF (67 mL) . 4-Amidinopyridine hydrochloride (8.0g, 50.76 mmol) and DBU (15.4 g, 101.5 mmol) were added sequentially and the reaction was heated to 85°C. After 22 hours, the reaction was 0 cooled to room temperature and the DMF was removed in vacuo. The dark oil was diluted with 2M HCl (80 mL) . The reaction was allowed to stand. After 2 hours, the solution was cooled to 10°C and filtered. The solid was washed with cold water and dried to yield 7.40g of a yellow solid, Compound 29 5 (69%). -H-NMR (200MHz, d^-DMSO) d 6.58 (s, IH) , 7.27 (s, IH) , 8.53 (d, 2H, J = 5.6), 9.00 (d, 2H, J = 5.2Hz), 12.35 (brs, IH) . MS (ES) : 212.8 (M'+l) . Compound 29 (7.4 mmol, 29.8 mmol) was diluted with POCl, and JO heated to 105°C. After 18 hours, the reaction is cooled to room temperature and the POCl 3 is removed in vacuo. The thick dark oil is diluted with MeOH (75mL) followed by ether (120mL) . The amorphous red solid is filtered and washed with ether to yield 3.82 g of a red solid. The crude solid is !5 approximately 80% pure and used without further purification in the next reaction. MS (ES) : 230.7 (M'+l). Compound 1321 "K-NMR (15%) (200MH, d.-DMSO) d 1.38 tm, 4H , 1.92 (brs, 2H) , 2.02 (brs, 2H) , 3.44 (brs. IH ) , 4.14 ( brs, IH) , 4.56 (d, IK, J = 4 Hz), 6.63 (m, IK; , 7.15 (m, IH ) , 7.32 (d, IH, J = 6.2 Hz), 8.20 (d, 2H, J = 4.4 Hz), 8.65 ( d, 2K, 5 J = 4.4Hz), 11.67 (brs, IH) . MS (ES): 310.2 (M ' -rlJ . Compound 1501 (Table 15 below) : H-NMR (70%) (200MHz, CD ? OD d 1.84 (s, 3H) , 3.52 (t, 2H, J = 6.0 Hz), 3.83, t, 2K, J = 6.0 Hz), 6.51 (d, IH, J = 3.4Hz), 7.06 (d, IH, J = 3.8 Hz), 7.42 10 (m, 3H) , 8.36 (m, 2H) . MS (ES) : 296.0 (M ' +l). Compound 1502 (Table 15 below) MS (ES) : 345.0 (M ' +l). Compound 1500 (Table 15 below) Ε-NMR (200MHz, CDC1 3 ) d 1.40 15 - 1.80 (m, 6H) , 1.85 - 2.10 (m, 2H) , 2.18 (s, 3H) , 2.33 (s, 3H) , 2.50 (d, 3H) , 3.90 - 4.10 (m, 2H) , 4.76 (m, IH) , 5.50 (d, IH) , 6.03 (m, IH) , 7.40 (m, 3H) , 8.37 (m, 2H) , 9.15 (brs, IH) . MS (ES) : 393.3 (M ' +l) . 20 Example 20: Synthesis of adenosine A x Antagonist. Compound 1504 (Table 15 below) can be synthesized by the general procedures given below. JU Compound 31 (200 mg, 0.47 mmol) was dissolved in DCM (4 mL) . Triethylamine (51 mg, 0.5mmol) and thiomorpholine (52 mg, O.Smmol) were added sequentially. The solution was mixed for several minutes and allowed to stand for 72 hours. The reaction was diluted with DCM and H : 0 and the layers were 35 separated. The aqueous layer was extracted with DCM. The combined DCM layers were dried over MgS0 « , filtered and concen t rated. Ethyl ether was added to the crude sample and t he resulting solid was filtered to yield lOO g cf a white solid, 32(62%). : HNMR (200MHz, CDCl,) d 1.76 (s, 9H) , 2.66 (brs, 2H) , 2.79 (brs, 2H) , 3.86 (s, 2H) , 7.46 irn, 3H! , 6.50 5 (m, 2H) . Compound 32 was combined with DMSO (3mL) and trans-4-aminocyclohexanol (144mg, 1.25 mmol) and heated to 130°C for 4 hours. The reaction was cooled to room 10 temperature, and diluted with EtOAc and H,0. The layers were separated and the aqueous layer was extracted with EtOAc (2x) . The combined organic layers were washed with H-0 and brine, dried over MgS04 , filtered and concentrated. Chromatography (silica, 8:1 CHCl3/Et0H) yields 32 mg of a tan 15 oil. Ethyl ether was added and the resulting solid was filtered to yield 5 mg of a white solid (9%) .0SIC-148265.- • K-NMR (200MHz, CD,0D) : d 1.44 (brm, 4H) , 2.03 (brm, 2H) , 2.21 (brm, 2H) , 2.70 (brm, 8H) , 3.63 (m, 4H) , 3.92 (m, IH) , 4.26 (brs, IH) , 6.42 (s, IH) , 7.42 (m, 3H) , 8.33 (m, 2H) . 20 Example 21.' Synthesis of adenosine A : Antagonist. Compound 1503 (Table 15 below) can be synthesized by the general procedures given below. The bromide, compound 31 (220 mg, 0.47 mmol) was dissolved in 1:1 DMF:Dichloromethane (5 mL) . To this was added K : CO, (71 mg, 0.52 mmol) and morpholine (0.047 mL, 0.47 mmol). The mixture was allowed to stir at room temperature overnight. Solvents were removed in vacuo and the residue was partitioned between H ; 0 and dichloromethane. The organic layer was dried with MgSO « , filtered, and concentrated to give an off white solid which upon trituration with ether/hexanes gave 175mg of a white solid, 33 (84%) . ; K-NMR (200MHz, CDCl,): ( 1.9 (9H, s) , 2.54 (4H, s) , 3.65 (4H, s), 3.85 (IK. s), 6.59 (IH, s) , 7.45 (3H, m) , 8.5 (2H, m) . Compound 33 (50 mg, 0.11 mmol) and trans-4-aminocyclohexanol (105 mg, 0.91 mmol) were taken up in DMSO (2mL) . The resultant solution was sparged with N- and then heated to lOO'C in an oil bath and stirred overnight. The crude reaction mixture was poured into water and extracted twice with ethyl acetate (50mL) . The combined organic layers were washed with H ; 0. After drying with MgSO, and filtering, the organic layer was concentrated in vacuo to give an orange solid. Chromatography (silica, 10% CH,OH in CH 2 C1 : ) yielded 15mg (33%). : H-NMR ( 200 MHz, CDCl,): ( 1.24 - 1.62 (4H, m) , 1.85 (2H, m) , 2.10 (2H, m) , 2.26 (4H, m) , 3.53 (4H, m) , 4.22 (IH, m) , 4.73 (IH, m) , 5.85 (IH, d) , 6.15 (IH, s) , 7.25 (3H, m) , 8.42 (2H, M) , 10.0 (IH, s) . MS (ES) : 408 (M * + 1). Compounds 1500, 1501, and 1502 can be synthesized using similar preparation steps of Example 20 by treating compound 32 with an appropriately substituted amine. Yeast β-Galactosidase reporter gene assays for human adenosine A x and A 2a receptor: Yeast strains (S. cerevιsιae> were transformed with human adenosine A : (A : R; CADUS strain CY12660) or human A 2a (A 2a ; CADUS strain CY8362) and the addition of a lacZ (β-Galactosidase) reporter gene to utilize as a functional readout. A complete description of the transformations is listed below (see Yeast Strains) . NΞCA (5 ' -N-ethylcarboxamidoadenosine) , a potent adenosine receptor agonist with similar affinity for A, and A 2a receptors, was used as a ligand for all assays. Test compounds were examined at 8 concentrations (0.1 - 10,000 nM) for ability to inhibit NECA-induced β-Galactosidase activity by CY12660 or CY8362. Preparation of Yeast Stock Cultures: Each of the respective yeast strains, CY12660 and CY8362, were streaked onto an LT agar plate and incubated at 30°C until colonies were observed. Yeast from these colonies were added to LT liquid (pH 6.8) and grown overnight at 30°C. Each yeast strain was then diluted to an OD 6Cr = 1.0-2.0 (approximately 1-2 X 10 " cells/ml) , as determined spectrophotometrically (Molecular Devices VMAX) . For each 6 ml of yeast liquid culture, 4 ml of 40% glycerol (1:1.5 vol:vol) was added ("yeast/glycerol stock") . From this yeast/glycerol stock, ten 1 ml aliquots were prepared and stored at -80°C until required for assay. Yeast A, R and A 2a R Assay: One vial each of CY8362 and CY12660 yeast/glycerol stock was thawed and used to inoculate Supplemented LT liquid media, pH 6.8 (92 ml LT liquid, to which is added: 5 ml of 40% glucose, 0.45 ml of IM KOH and 2.5 ml of Pipes, pH 6.8). Liquid cultures were grown 16-18 hr (overnight) at 30°C. Aliquots from overnight cultures were then diluted in LT media, containing 4U/ml adenosine deaminase (Type VI or VII from calf intestinal mucosa, Sigma), to obtain OD 0C = 0.15 (1.5 X 10 £ cells/ml) for CY8362 (A2aR) and OD« 00 = 0.50 (5X10 6 cells/ml) for CY12660 (AjR) . Assays were conducted with a final volume of 100 ul in 96- well microtiter plates, such that a final concentration of 2% DMSO was achieved in all wells. For primary screening, 1-2 concen t rations of test compounds were utilized (10 uM, lμM ) . For compound profiling, 8 concentrations were tested (10000, 1000 , 500, 100, 50, 10, 1 and 0.1 nM) . To each microtiter plate, 10 ul of 20% DMSO was added to "Control" and "Total" wells while 10 ul of Test Compound (in 20% DMSO) was added to "Unknown" wells. Subsequently, 10 ul of NECA (5 uM for A-R, 1 uM for A l 2 2a aR) were added to "Total" and "Unknown" wells; 10 uι of PBS was added to the "Control" wells. In the final addition, 80 ul of yeast strain, CY8362 or CY12660, were added to all wells. All plates were then agitated briefly (LabLine orbital shaker 2-3 min) and allowed to incubate for 4 hrs. at 30°C in a dry oven. β-Galactosidase activity can be quantitated using either colorimetric (e.g., ONPG, CPRG) , luminescent (e.g., Galacton- Star) or fluorometric substrates (e.g., FDG, Resorufin) substrates. Currently, fluorescence detection is preferred on the basis of superior signal :noise ratio, relative freedom from interference and low cost . Fluorescein digalactopyranoside (FDG, Molecular Probes or Marker Gene Technologies) , a fluorescent β-Galactosidase substrate, was added to all wells at 20 ul/well (final concentration = 80 uM) . Plates were shaken for 5-6 sec (LabLine orbital shaker) and then incubated at 37°C for 90 min (95% 0 : /5% CO : incubator) . At the end of the 90 min incubation period, β- Galactosidase activity was stopped using 20 ul/well of IM Na,C0, and all plates shaken for 5-6 sec. Plates were then agitated for 6 sec and relative fluorescence intensity determined using a fluorometer (Tecan Spectrafluor; excitation = 485 nm, emission = 535 nm) . Calculations: Relative fluorescence values for "Control" wells were interpreted as background and subtracted from "Total" and "Unknown" values . Compound profiles were analyzed via logarithmic transformation (x-axis: compound concentration) followed by one site competition curve fitting to calculate IC- values (GraphPad Prism) . Yeast strains: Saccharo yces cerevisiae strains CY12660 [far l*1 442 tbtl-1 fusl-HIS3 canl Stel4 : : trpl : :LYS2 ste3*1156 gpa l ( 4 1) -Gαi3 lys2 ura3 leu2 trpl: his3; LΞU2 PGKp- Mfα l Leader-hAlR-PH05term 2mu-orig REP3 Ampr] and CY8362 [gpalp-rGαsElOK farl*1442 tbtl-1 fusl-HIS3 canl stel4::trpl: LYS2 ste3*1156 lys2 ura3 leu2 trpl his3; LEU2 PGKp-hA2aR 2mu- ori REP3 Ampr] were developed. LT Media: LT (Leu-Trp supplemented) media is composed of lOOg DIFCO yeast nitrogen base, supplemented with the following: l.Og valine, l.Og aspartic acid, 0.75g phenylalanine, 0.9g lysine, 0.45g tyrosine, 0.45g isoleucine, 0.3g methionine, 0.6g adenine, 0.4g uracil, 0.3g serine, 0.3g proline, 0.3g cysteine, 0.3g arginine, 0.9g histidine and l.Og threonine . Construction of Yeast Strains Expressing Human A x Adenosine Receptor In this example, the construction of yeast strains expressing a human A, adenosine receptor functionally integrated into the yeast pheromone system pathway is described. I. Expression Vector Construction To construct a yeast expression vector for the human A l adenosine receptor, the A, adenosine receptor cDNA was obtained by reverse transcriptase PCR of human hippocampus mRNA using primers designed based on the published sequence of the human A : adenosine receptor and standard techniques. The PCR product was subcloned into the Ncol and Xbal sites of the yeast expression plasmid pMP15. The pMP15 plasmid was created from pLPXt as follows: The Xbal site of YEP51 (Broach, J.R. et al. (1983) "Vectors for high-level, inducible expression of cloned genes in yeast" p. 83-117 in M. Inouye (ed.), Experimental Manipulation of Gene Expression. Academic Press, New York) was eliminated by diges t ion, end-fill and religation to create YepSLNccDXba. Ano t her Xbal site was created at the BamHI site by digestion wi t h BamHI, end-fill, linker (New England Biolabs, # 1081 ) ligation, Xbal digestion and re-ligation to generate YEP5 1 NcoXt. This plasmid was digested with Esp31 and Ncol and ligated to Leu2 and PGKp fragments generated by PCR. The 2 kb Leu2 PCR product was generated by amplification from YEP51Nco using primers containing Esp31 and Bglll sites. The 660 base pair PGKp PCR product was generated by amplification from pPGK s (Kang, Y.-S. et al . (1990) Mol. Cell. Biol. l_Q:2582-2590) with PCR primers containing Bglll and Ncol sites. The resulting plasmid is called pLPX . pLPXt was modified by inserting the coding region of the a-factor pre- pro leader into the Ncol site. The prepro leader was inserted so that the Ncol cloning site was maintained at the 3' end of the leader, but not regenerated at the 5' end. In this way receptors can be cloned by digestion of the plasmid with Ncol and Xbal. The resulting plasmid is called pMP!5. The pMP15 plasmid into which was inserted the human A j adenosine receptor cDNA was designated p5095. In this vector, the receptor cDNA is fused to the 3' end of the yeast a-factor prepro leader. During protein maturation the prepro peptide sequences are cleaved to generate mature full-length receptor. This occurs during processing of the receptor through the yeast secretory pathway. This plasmid is maintained by Leu selection (i.e., growth on medium lacking leucine) . The sequence of the cloned coding region was determined and found to be equivalent to that in the published literature (GenBank accession numbers S45235 and S56143) . II. Yeast Strain Construction To create a yeast strain expressing the human A, adenosine receptor, yeast strain CY7967 was used as the starting parental strain. The genotype of CY7967 is as follows: MATα gpaD1163 gpal (41) Gαi3 farlD1442 tbt-1 FUS1-HIS3 canl stel4: :trpl: :LYS2 ste3D1156 lys2 ura3 leu2 his3 The genetic markers are reviewed below: MATa Mating type a. gpalD1163 The endogenous yeast G-protein GPAl has been deleted. gpal (41) Gαi3. gpal (41) -Gai3 was integrated into the . " . yeast genome. This chimeric Ga protein is composed of the first 41 amino acids of the endogenous yeast Ga subunit GPAl fused to the mammalian G-protein Gai3 in which the cognate N-terminal amino acids have been deleted. •p :a.rlD1442 FAR1 gene (responsible for cell cycle arrest) has been deleted (thereby preventing cell cycle arrest upon activation of the pheromone response pathway) . tbt-1 strain with high transformation efficiency by electroporation. FUS1-HIS3 a fusion between the FUS1 promoter and the HIS3 coding region (thereby creating a pheromone inducible HIS3 gene) . can 1 arginine/canavinine permease . stel4 : : trpl : :L gene disruption of STE14, a C-farnesyl YS2.... methyltransferase (thereby lowering basal signaling through the pheromone pathway) . ste3D1156 endogenous yeast STR, the a factor pheromone receptor (STE3) was disrupted. lys2 defect in 2-aminoapidate reductase, yeast need lysine to grow. ura3 defect in orotidine- 5 ' -phosphate decarboxylase, yeast need uracil to grow leu2 defect in b-isopropylmalate dehydrogenase , yeast need leucine to grow, trpl defect in phosphoribosylanthranilate, yeast need tryptophan to grow. his3 defect in imidazoleglycerolphosphate dehydrogenase, yeast need histidine to grow. Two plasmids were transformed into strain CY~9ό~ by electroporation: plasmid p5095 (encoding human A : adenosine receptor; described above) and plasmid pl584, which is a FUSl-β-galactosidase reporter gene plasmid. Plasmid pl584 was derived from plasmid pRS426 (Christianson, T.W. et al . (1992) Gene Hfi: 119-1122) . Plasmid pRS426 contains a polylinker site at nucleotides 2004-2016. A fusion between the FUS1 promoter and the β-galactosidase gene was inserted at the restriction sites Eagl and Xhol to create plasmid pl584. The pl584 plasmid is maintained by Trp selection (i.e., growth on medium lacking leucine) . The resultant strain carrying p5095 and pl584, referred to as CY12660, expresses the human A : adenosine receptor. To grow this strain in liquid or on agar plates, minimal media lacking leucine and tryptophan was used. To perform a growth assay on plates (assaying FUS1-HIS3) , the plates were at pH 6.8 and contained 0.5-2.5 mM 3 -amino-1, 2 , 4 -triazole and lacked leucine, tryptophan and histidine. As a control for specificity, a comparison with one or more other yeast-based seven transmembrane receptor screens was included in all experiments . C onstruction of Yeast Strains Expressing Human A2a Adenosine Receptor In this example, the construction of yeast strains expressing a human A2a adenosine receptor functionally integrated into the yeast pheromone system pathway is described. I. Expression Vector Construction To construct a yeast expression vector for the human A2a adenosine receptor, the human A2a receptor cDNA was obtained from Dr. Phil Murphy (NIH) . Upon receipt of this clone, the A2a receptor insert was sequenced and found to be identical to the published sequence (GenBank accession # S46950) . The receptor cDNA was excised from the plasmid by PCR with VENT polymerase and cloned into the plasmid pLPBX, which drives receptor expression by a constitutive Phosphoglycerate Kinase (PGK) promoter in yeast. The sequence of the entire insert was once again sequenced and found to be identical with the published sequence. However, by virtue of the cloning strategy employed there were three amino acids appended to the carboxy-terminus of the receptor, GlySerVal. II. Yeast Strain Construction To create a yeast strain expressing the human A2a adenosine receptor, yeast strain CY8342 was used as the starting parental strain. The genotype of CY8342 is as follows: MATa farlD1442 tbtl-1 lys2 ura3 leu2 trpl his3 fusl-HIS3 canl ste3D1156 gpaD1163 stel4 : :trpl : :LYS2 gpalp-rG αs E10K (or gpalp- rG αs D229S or gpalp-rG αs E10K+D229S) The genetic markers are as described in Example 1, except for the G-protein variation. For human A2a receptor-expression, yeast strains were utilized in which the endogenous yeast G protein GPAl had been deleted and replaced by a mammalian G αs . Three rat G αs mutants were utilized. These variants contain one or two point mutations which convert them into proteins which couple efficiently to yeast βy. They are identified as G 3 «E10K (in which the glutamic acid at position ten is replaced with lysine) , G„D229S (in which the aspartic ac d at position 229 is replaced with serine) and G„Ξ10K+D229S (which contains both point mutations) . Strain CY8342 (carrying one of the three mutant rat G as proteins) was transformed with either the parental vector pLPBX (Receptor-) or with pLPBX-A2a (Receptor * ) . A plasmid with the FUS1 promoter fused to β-galactosidase coding sequences (described in above) was added to assess the magnitude of activation of the pheromone response pathway. Functional Assay using Yeast Strains Expressing Human A : Adenosine Receptor In this example, the development of a functional screening assay in yeast for modulators of the human A : adenosine receptor is described. I . Ligands Used in Assay Adenosine, a natural agonist for this receptor, as well as two other synthetic agonists were utilized for development of this assay. Adenosine, reported to have an EC 5C of approximately 75 nM, and ( - ) -N6- (2-phenylisopropyl) -adenosine (PIA) with a reported affinity of approximately 50 nM were used in a subset of experiments. 5 ' -N-ethylcarboxamido- adenosine (NECA) was used in all growth assays. To prevent signaling due to the presence of adenosine in the growth media, adenosine deaminase (4U/ml) was added to all assays. II. Biological Response in Yeast The ability of the A, adenosine receptor to functionally couple in a heterologous yeast system was assessed by introducing the A : receptor expression vector (p5095, described above) into a series of yeast strains that expressed different G protein subunits. The majority of these transformants expressed G α subunits of the G αι or G αo subtype. Additional G α proteins were also tested for the possible identification of promiscuous receptor-Gα protein coupling. In various strains, a STE18 or a chimeric STE18- Gγ2 construct was integrated into the genome of the yeast . The yeast strains harbored a defective HIS3 gene and an integrated copy of FUS1-HIS3, thereby allowing for selection in selective media containing 3-amino-l, 2, 4-triazole (tested at 0.2, 0.5 and 1.0 mM) and lacking histidine. Transformants were isolated and monolayers were prepared on media containing 3-amino-l, 2, 4-triazole, 4 U/ml adenosine deaminase and lacking histidine. Five microliters of various concentrations of ligand (e.g., NECA at 0, 0.1, 1.0 and 10 mM) was applied. Growth was monitored for 2 days. Ligand- dependent growth responses were tested in this manner in the various yeast strains. The results are summarized in Table 1 below. The symbol (-) indicates that ligand-dependent receptor activation was not detected while (+) denotes ligand-dependent response. The term "LIRMA" indicates ligand independent receptor mediated activation. Table 3 As indicated in Table 3, the most robust signaling was found to occur in a yeast strain expressing the GPA, (41) -G αl3 chimera. III . fusl -LacZ Assay To characterize activation of the pheromone response pathway more fully, synthesis of β-galactosidase through fuslLacZ in response to agonist stimulation was measured. To perform the β-galactosidase assay, increasing concentrations of ligand were added to mid-log culture of human A λ adenosine receptor expressed in a yeast strain co-expressing a Stel8-Gγ2 chimera and GPA 4 ι-G αi . Transformants were isolated and grown overnight in the presence of histidine and 4 U/ml adenosine deaminase. After five hours of incubation with 4 U/mi adenosine deaminase and ligand, induction of β-gaiactosidase was measured using CPRG as the substrate for β-galactoside. 5 x 10 cells were used per assay. The results obtained with NECA stimulation indicated that at a NECA concentration of 10 -8 M approximately 2 -fold stimulation of β-galactosidase activity was achieved. Moreover, a stimulation index of approximately 10-fold was observed at a NECA concentration of 10 ~ M. The utility of this assay was extended by validation of the activity of antagonists on this strain. Two known adenosine antagonist, XAC and DPCPX, were tested for their ability to compete against NECA (at 5 mM) for activity in the β- galactosidase assay. In these assays, β-galactosidase induction was measured using FDG as the substrate and 1.6 x 10 cells per assay. The results indicated that both XAC and DPCPX served as potent antagonists of yeast-expressed A, adenosine receptor, with IC 50 values of 44 nM and 49 nM, respectively. In order to determine if this inhibitory effect was specific to the Ax subtype, a series of complementary experiments were performed with the yeast-based A 2a receptor assay (described in Example 4). Results obtained with the A 2a yeast-based assay indicated that XAC was a relatively effective A 2a receptor antagonist, consistent with published reports. In contrast, DPCPX was relatively inert at this receptor, as expected from published reports. IV. Radioligand Binding The A, adenosine receptor assay was further characterized by measurement of the receptor's radioligand binding parameters. Displacement binding of [ H] CPX by several adenosine receptor 146 reference compounds, XAC, DPCPX, and CGS, was analyzed using membranes prepared from yeast expressing the human A : adenosine receptor. The results with yeast membranes expressing the human A x adenosine receptor were compared to those from yeast membranes expressing the human A2a adenosine receptor or the human A3 receptor to examine the specificity of binding. To perform the assay, fifty mg of membranes were incubated with 0.4 nM [~H] CPX and increasing concentrations of adenosine receptor ligands. Incubation was in 50 mM Tris- HCl, pH 7.4, 1 mM EDTA, 10 mM MgCl 2 , 0.25 % BSA and 2 U/ml adenosine deaminase in the presence of protease inhibitors for 60 minutes at room temperature. Binding was terminated by addition of ice-cold 50 mM Tris-HCl, pH 7.4 plus 10 mM MgCl 2 , followed by rapid filtration over GF/B filters previously soaked with 0.5 % polyethyenimine, using a Packard 96-well harvester. Data were analyzed by nonlinear least square curve fitting procedure using Prism 2.01 software. The IC 50 values obtained in this experiment are summarized in Table 4, below: Table 4 These data indicate that the reference compounds have affinities consistent with those reported in the literature. The data further indicate that the yeast-based assays are of sufficient sensitivity to discriminate receptor subtype specificity. 147 Functional Assay using Yeast Strains Expressing Human A a Adenosine Receptor In this example, the development of a functional screening assay in yeast for modulators of the human A : adenosine receptor is described. I . Ligands used in Assay The natural ligand adenosine, as well as other thoroughly characterized and commercially available ligands were used for study of the human A2a receptor functionally expressed in yeast. Three ligands have been used in the establishment of this assay. They include: Ligand Re orted K λ Function Adenosine 500 nM agonist 5 ' -N-ethylcarboxamidoadenosine 10-15 nM agonist (NECA) (-)-N6-(2- phenylisopropyl) -adenosine 100-125 nM agonist (PIA) To prevent signaling due to the presence of adenosine in the growth media, adenosine deaminase (4U/ml) was added to all assays . II. Biological Response in Yeast A2a receptor agonists were tested for the capacity to stimulate the pheromone response pathway in yeast transformed with the A2a receptor expression plasmid and expressing either G αs E10K, G αs D229S or G αs E10K+D229S. The ability of ligand to stimulate the pheromone response pathway in a receptor dependent manner was indicated by an alteration in the yeast phenotype . Receptor activation modified the phenotype from histidine auxotrophy to histidine prototrophy (activation of fusl-HIS3) . Three independent transformants were isolated and grown overnight in the presence of histidine. Cells were washed to remove histidine and diluted to 2 x 10 cells/ml. 5 μl of each transformant was spotted onto nonselective media (including histidine) or selective media (1 mM AT) in the absence or presence cf 4 U/ml adenosine deaminase. Plates were grown at 30 = C for 24 hours. In the presence of histidine both Receptor * (R~) and Receptor " (R ~ ) strains were capable of growth. However, in the absence of histidine only R "*" cells grew. Since no ligand had been added to these plates two explanations were possible for this result. One possible interpretation was that the receptor bearing yeast were at a growth advantage due to Ligand Independent Receptor Mediated Activation (LIRMA) . Alternatively the yeast could have been synthesizing the ligand adenosine. To distinguish between these two possibilities, an enzyme which degrades the ligand, adenosine deaminase (ADA) , was added to the growing yeast and plates . In the presence of adenosine deaminase R cells no longer grew in the absence of histidine, indicating that the yeast were indeed synthesizing ligand. This interpretation was confirmed by an A2a growth assay in liquid. In this experiment R + yeast (a G QS E10K strain expressing the A2a receptor) were inoculated at three densities (1 x 10° cell/ml; 3 x 10 cells/ml; or 1 x 10 cells/ml) in the presence or absence of adenosine deaminase (4 U/ml) . The stringency of the assay was enhanced with increasing concentrations (0, 0.1, 0.2 or 0.4 mM)of 3-amino- 1, 2, 4-triazole (AT), a competitive antagonist of imidazoleglycerol-P dehydratase, the protein product of the HIS3 gene. In the presence of adenosine deaminase and 3- amino-1, 2, 4-triazole yeast grew less vigorously. However in the absence of 3-amino-l, 2, 4-triazole, adenosine deaminase had little effect. Thus adenosine deaminase itself had no direct effect upon the pheromone response pathway. An alternative approach to measuring growth and one that can be miniaturized for high throughput screening is an A2a receptor ligand spot assay. A G QS E10K strain expressing the A2a receptor (A2aR+) or lacking the receptor (R-) was grown overnight in the presence of histidine and 4 U/ml adenosine deaminase. Cells were washed to remove histidine and diluted t o 5 x 10° cells/ml. 1 x 10 cells were spread onto selective plates containing 4 U/ml adenosine deaminase and 0.5 or 1.0 mM 3-amino-l, 2, 4-triazole (AT) and allowed to dry for 1 hour. 5 μl of the following reagents were applied to the monolayer: 10 mM adenosine, ' 38.7 mM histidine, dimethylsulfoxide (DMSO) , 10 M PIA or 10 mM NECA. Cells were grown 24 hours at 30°C. The results showed that cells without receptor could only grow when histidine was added to the media. In contrast, R cells only grew in areas where the A2a receptor ligands PIA and NECA had been spotted. Since the plates contained adenosine deaminase, the lack of growth where adenosine had been spotted confirmed that adenosine deaminase was active. III. fusl LacZ Assay To quantitate activation of the yeast mating pathway, synthesis of β-galactosidase through fuslLacZ was measured. Yeast strains expressing G as E10K, G aS D229S or G O ..E10K+D229S were transformed with a plasmid encoding the human A2a receptor (R+) or with a plasmid lacking the receptor (R-). Transformants were isolated and grown overnight in the presence of histidine and 4 U/ml adenosine deaminase. 1 x 10 cells were diluted to 1 x 10 cells/ml and exposed to increasing concentrations of NECA for 4 hours, followed by determination of the β-galactosidase activity in the cells. The results demonstrated that essentially no β-galactosidase activity was detected in R- strains, whereas increasing amounts of β-galactosidase activity were detected in R+ strains expressing either G as E10K, G a5 D229S or G OS E10K+D229S as the concentration of NECA increased, indicating a dose dependent increase in units of β-galactosidase detected in response to exposure to increased ligand concentration. This dose dependency was only observed in cells expressing the A2a receptor. Furthermore the most potent G„ construct for the A2a receptor was G„E10K. The G„D229S construct was the second-most potent G os construct for the A2a receptor, while the G„E10K+D229S construct was the least potent of the three G as constructs tested, although even the G„Ξ10K»D225≤ construct stimulated readily detectable amounts of β- galactosidase activity. For a further description of the assays identified, see U.S. Application Serial No. 09/088985, entitled "Functional Expression of Adenosine Receptors in Yeast", filed June 2, 1998 (Attorney Docket No. CPI-093) , the entire contents of which are hereby incorporated herein by reference . Pharmacological Characterization of the Human Adenosine Receptor Subtypes Material and Methods Ma terials . [ H] -DPCPX [Cyclopentyl-1 , 3-dipropylxantine, 8- [dipropyl-2,3- 3 H(N) ] (120.0 Ci/mmol) ; [ 3 H] -CGS 21680, [carboxyethyl- 3 H (N) ] (30 Ci/mmol) and [ : "l] -AB-MECA ([ 125I]-4-Aminobenzyl-5 ' -N-Methylcarboxamideoadenosine) (2,200 Ci/mmol) were purchased from New England Nuclear (Boston, MA). XAC (Xantine amine congener); NECA (5'-N- Ethylcarboxamidoadenosine) ; and IB-MECA from Research Biochemicals International (RBI, Natick, MA). The Adenosine Deaminase and Complete protease inhibitor cocktail tablets were purchased from Boehringer Mannheim Corp. (Indianapolis, IN) . Membranes from HEK-293 cells stably expressing the human Adenosine 2a [RB-HA2a] ,- Adenosine 2b [RB-HA2b] or Adenosine 3 [RB-HA3] receptor subtypes, respectively were purchased from Receptor Biology (Beltsville, MD) . Cell culture reagents were from Life Technologies (Grand Island, NY) except for serum that was from Hyclone (Logan, UT) . Yeast strains : Saccharo yces cerevisiae strains CY12660 [farl* ' l442 tbtl-1 fusl-HIS3 canl Stel4 : : trpl : :LYS2 Ste3*1156 gpal (41) -Gαi3 lys2 ura3 leu2 trpl: his3; LEU2 PGKp- MfαlLeader-hAlR-PH05term 2mu-orig REP3 Ampr] and CY8362 [gpalp-rGαsElOK farl*1442 tbtl-1 fusl-HIS3 canl stel4::trρl: LYS2 ste3*1156 lys2 ura3 leu2 trpl his3; LEU2 PGKp-hA2aR 2mu- ori REP3 Ampr] were developed as described above . Yeast cul ture : Transformed yeast were grown in Leu-Trp [LT. 1 media (pH 5.4) supplemented with 2% glucose. For the preparation of membranes 250 ml of LT medium were inoculated with start titer of 1-2 x 10 cells/ml from a 30 ml overnight culture and incubated at 30 C under permanent oxygenation by rotation. After 16 h growth the cells were harvested by centrifugation and membranes were prepared as described below. Mammalian Tissue Cul ture -. The HEK-293 cells stably expressed human Adenosine 2a receptor subtype (Cadus clone # 5) were grown in Dulbeco"s minimal essential media (DMEM) supplemented with 10% fetal bovine serum and IX penicillin/streptomycin under selective pressure using 500 mg/ml G418 antibiotic, at 37°C in a humidified 5% C0 2 atmosphere . Yeast Cell Membrane Preparations : 250 ml cultures were harvested after overnight incubation by centrifugation at 2,000 x g in a Sorvall RT6000 centrifuge. Cells were washed in ice-cold water, centrifuged at 4°C and the pellet was resuspended in 10 ml ice-cold lysis buffer [5 mM Tris-HCl, pH 7.5; 5 mM EDTA; and 5 mM EGTA] supplemented with Protease inhibitor cocktail tablets (1 tablet per 25 ml buffer) . Glass beads (17 g; Mesh 400-600; Sigma) were added to the suspension and the cells were broken by vigorous vortexing at 4°C for 5 min. The homogenate was diluted with additional 30 ml lysis buffer plus protease inhibitors and centrifuged at 3,000 x g for 5 min. Subsequently the membranes were peleted at 36,000 x g (Sorvall RC5B, type SS34 rotor) for 45 min. The resulting membrane pellet was resuspended in 5 ml membrane buffer [50 mM Tris-HCl, pH 7.5; 0.6 mM EDTA; and 5 mM MgCl 2 ] supplemented with Protease inhibitor cocktail tablets (1 tablet per 50 ml buffer) and stored at -80 °C for further experiments. Mammalian Cell Membrane Prepara tions : HEK-293 cell membranes were prepared as described previously (Duzic E et ai . Biol . Chem. , 267, 9844 -9851 , 1992) , Briefly, cells were washed with PBS and harvested with a rubber policeman. Cells were pelted at 4°C 200 x g in a Sorvall RT6000 centrifuge. The pellet was resuspended in 5 ml/dish of lysis buffer at 4 C C (5 mM Tris-HCl, pH 7.5; 5 mM EDTA; 5 mM EGTA; 0.1 mM Phenylmethylsulfonyl fluoride, 10 mg/ml pepstatin A; and 10 mg/ml aprotinin) and homogenized in a Dounce homogenizer. The cell lysate was then centrifuged at 36,000 x g (Sorvall RC5B, type SS34 rotor) for 45 min and the pellet resuspended in 5 ml membrane buffer [50 mM Tris-HCl, pH 7.5; 0.6 mM EDTA; 5 mM MgCl 2 ; 0.1 mM Phenylmethylsulfonyl fluoride, 10 mg/ml pepstatin A; and 10 mg/ml aprotinin) and stored at -80 °C for further experiments . The Bio-Rad protein assay kits, based on the Bradford dye- binding procedure, (Bradford, M. : Anal. Biochem. 72:248 (1976) ) were used to determine total protein concentration in yeast and mammalian membranes. Adenosine 1 receptor subtype saturation and competi tion radioligand binding: Saturation and competition binding on membranes from yeast cell transformed with human A x receptor subtype were carried out using antagonist [ H] DPCPX as a radioactive ligand. Membranes was diluted in binding buffer [50 mM Tris-HCl, pH 7.4; containing 10 mM MgCl 2 ; 1.0 mM EDTA; 0.25% BSA; 2 U/ml adenosine deaminase and 1 protease inhibitor cocktail tablet/50 ml] at concentrations of 1.0 mg/ml . In saturation binding membranes (50 μg/well) were incubate with increasing concentrations of [ H] DPCPX (0.05 - 25 nM) in a final volume of 100 μl of binding buffer at 25°C for 1 hr in the absence and presence of 10 μM unlabeled XAC in a 96-well microtiter plate. In competition binding membranes (50 μg/well) were incubate with [~H] DPCPX (1.0 nM) in a final volume of 100 ml of binding buffer at 25°C for 1 hr in the absence and presence of 10 μM unlabeled XAC or increasing concentrations of competing compounds in a 96-well microtiter plate. Adenosine 2a receptor subtype competi tion radiol igand binding: Competition binding on membranes from HΞK293 cell stably expressing the human A2a receptor subtype were carried out using agonist [ H] CGS-21680 as a radioactive ligand. Membranes was diluted in binding buffer [50 mM Tris-HCl, pH 7.4; containing 10 mM MgCl 2 ; 1.0 mM EDTA; 0.25% BSA; 2 U/ml adenosine deaminase and 1 protease inhibitor cocktail tablet/50 ml] at concentrations of 0.2 mg/ml. Membranes (10 μg/well) were incubate with [ 3 H] CGS-21680 (100 nM) in a final volume of 100 ml of binding buffer at 25°C for 1 hr in the absence and presence of 50 μM unlabeled NECA or increasing concentrations of competing compounds in a 96-well microtiter plate . Adenosine 3 receptor competi tion radioligand binding: Competition binding on membranes from HEK293 cell stably expressing the human A3 receptor subtype were carried out using agonist [ 125I] AB-MECA as a radioactive ligand. Membranes was diluted in binding buffer [50 mM Tris-HCl, pH 7.4; containing 10 mM MgCl 2 ; 1.0 mM EDTA; 0.25% BSA; 2 U/ml adenosine deaminase and 1 protease inhibitor cocktail tablet/50 ml] at concentrations of 0.2 mg/ml. Membranes (10 μg/well) were incubate with [ I] AB-MECA (0.75 nM) in a final volume of 100 μl of binding buffer at 25°C for 1 hr in the absence and presence of 10 μM unlabeled IB-MECA or increasing concentrations of competing compounds in a 96-well microtiter plate. At the end of the incubation, the A 1# A 2a and A 3 receptor subtypes radioligand binding assays was terminated by the addition of ice-cold 50 mM Tris-HCl (pH 7.4) buffer supplemented with 10 mM MgCl 2 , followed by rapid filtration over glass fiber filters (96-well GF/B UniFilters, Packard: previously presoaked in 0.5% polyethylenimine in a Filtermate 196 cell harvester (Packard) . The filter plates were dried coated with 50 μl /well scintillation fluid (MicrcScint-20, Packard) and counted in a TopCount (Packard) . Assays were performed in triplicate. Non-specific binding was 5.6 * 0.5%, 10.8 + 1.4% and 15.1 + 2.6% of the total binding in a AIR, A2aR and A3R binding assay, respectively. Adenosine 2b receptor subtype competi tion radioligand binding: Competition binding on membranes from HEK293 cell stably expressing the human A2b receptor subtype were carried out using Ai receptor antagonist [ H] DPCPX as a radioactive ligand. Membranes was diluted in binding buffer [10 mM Hepes- KOH, pH 7.4; containing 1.0 mM EDTA; 0.1 mM Benzamidine and 2 U/ml adenosine deaminase] at concentrations of 0.3 mg/ml. Membranes (15 μg/well) were incubate with [ H] DPCPX (15 nM) in . a final volume of 100 μl of binding buffer at 25°C for 1 hr in the absence and presence of 10 μM unlabeled XAC or increasing concentrations of competing compounds in a 96-well microtiter plate. At the end of the incubation, the assay was terminated by the addition of ice-cold 10 mM Hepes-KOH (pH 7.4) buffer followed by rapid filtration over glass fiber filters (96-well GF/C UniFilters, Packard) previously presoaked in 0.5% polyethylenimine in a Filtermate 196 cell harvester (Packard) . The filter plates were dried coated with 50 μl/well scintillation fluid (MicroScint-20, Packard) and counted in a TopCount (Packard) . Assays were performed in triplicate. Non-specific binding was 14.3 + 2.3% of the total binding. Specific binding of [ 3 H] DPCPX; [ 3 H] CGS-21680 and [ 125 I] AB- MECA was defined as the difference between the total binding and non-specific binding. Percent inhibition of the compounds was calculated against total binding. Competition data were analyzed by iterative curve fitting to a one site model, and K values were calculated from IC 50 values (Cheng and Prusof, Biochem. Pharmacol. 22, 3099-3109, 1973) using the GraphPad Priz 2. 01 software. Results A primary function of certain cell surface receptors is to recognize appropriate ligands. Accordingly, we determined ligand binding affinities to establish the functional integrity of the Adenosine 1 receptor subtype expressed m yeast. Crude membranes prepared from Saccharomyces cerevisiae transformed with human Adenosine l receptor subtype construct exhibited specific saturable binding of [ H] DPCPX with a K D of 4.0 + 0.19 nM. The K D and B max value were calculated from the saturation isotherm and Scatchard transformation of the data indicated a single class of binding sites. The densities of adenosine binding sites in the yeast membrane preparations were estimated to 716.8 + 43.4 fmol/mg membrane protein. The pharmacological subtype characteristics of the recombinant yeast cells transformed with human A : receptor subtype were investigated with subtype selective adenosine ligands (XAC, DPCPX; CGS-15943; Compound 600; Compound 1002; NECA, (R)-PIA; IB-MECA and Alloxazine) that competed with [ 3 H] DPCPX in the expected rank order. Displacement curves recorded with these compounds show the typical steepness with all the ligands, and the data for each of the ligands could be modeled by a one-site fit. The apparent dissociation constants estimated for the individual compound from the curves (Table 5) are consistent with value published for the receptor obtained from other sources. Table 5 Ki values for membranes from yeast cells transformed with human A α receptor subtype Ligands K χ (nM) XAC 5.5 DPCPX 7.1 CGS-1594 10.8 NECA 179.6 (R)-PIA 56.3 IB-MECA 606.5 Alloxazine 894.1 Compound 600 13.9 Compound 1002 9.8 Tables 6 through 12 demonstrate the efficacy and structure activity profiles of deazapurines of the invention. Tables 13 and 14 demonstrate selectivity can be achieved for human adenosine receptor sites by modulation of the functionality about the deazapurine structure. Table 14 also demonstrates the surprising discovery that the compounds set forth therein have subnanomolar activity and higher selectivity for the A 3b receptor as compared to the compounds in Table 13. TABLE 6 Effect of Ng-Substituen: TABLE 7 Effect of C->-Substituent TABLE S Effect of PviTole Rine Subsuiuem Me Me 8451 Me / \ / 806 Me Me so: Me' TABLE 9 TABLE 10 Effect ofN^-Substiiuent :ft3-i ii Effect of g-Subsutuen: TABLE 12 'Retro-Amide" Anaioεues TABLE 13 Profile of Selective Adenosine Antagonists R, is 3-chlorophcnyl;' R, is 4-pyndyl; ' % activity :2> 10 μM Table 14: Profile of Selective A 2b Antagonists Compound XR, Binding Data K t (nM) 1400 -O-Ph Me 41.7 21 10.3 14.6 1401 -0-Ph(p)F Me 33 58 8.8 18 1402 -0-Ph(p)Cl Me 825 591 22 60 1403 -N-pyridin- Me 60 41 18 48 2-one 1404 -NH-Ph Me 49 31 4.6 57 TABLE 15 . Adenosine A Receptor Selective Compounds * at least 10 times more selective than other three subtv es . Pages 176-201 relate to compounds specific to the A-. receptor Summary of the Invention The present invention is also based on compounds which selectively bind to adenosine A 2a receptor, thereby treating a di-sease associated with A2a adenosine receptor in a subject by administering to the subject a therapeutically effective amount of such compounds. The disease to be treated are associated with, for example, a central nervous system disorder, a cardiovascular disorder, a renal disorder, an inflammatory disorder, a gastrointestinal disorder, an eye disorder, an allergic disorder or a respiratory disorder. This invention also features a compounc having the structure: :vι; wherein NR : R : is a substituted or unsuostituted 4-8 membered ring; wherein Ar is a substituted or unsubstituted four to six membered ring; wherein R; is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is - C(Ra) (Rs)XRt, wherein X is 0, S, or NR-., wherein Rr and R are each independently H or alkyl, wherein Rε and R- are each independently alkyl or cycloalkyl, or Re, RT and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members . wherein R : is wherein R5 is H, alkyl, substituted alkyl, or cycloalkyl; with the proviso that NRiR: is not 3-acetamιdo piperadino, 3- hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3- aminocarbonylmethyl, or pyrrolidino; with the proviso that NR.R: is 3-hydroxymethyl piperadino only when Ar is 4-pyrιdyl. This invention also features a method for inhibiting the activity of an A 2a adenosine receptor in a cell, which comprises contacting said cell with the above-mentioned compounds . This invention -also provides a compound having the structure: (vι; wherein NR,R. is a substituted or unsubstituted A -i membered ring; wherein Ar is a substituted or unsubstituted four to six membered ring; wherein R4 is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Rs) (Rg)XRέ, wherein X is 0, S, or NR7, wherein Re and Rs are each independently H or alkyl, wherein Re and RT are each independently alkyl or cycloalkyl, or Re, R? and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members. wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; with the proviso that NR1R2 is not 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl, or pyrrolidino; with the proviso that NR1R2 is 3-hydroxymethyl piperadino only when Ar is 4-pyridyl. In one embodiment of the compound, Ar is a substituted or unsubstituted four to six membered ring, phenyl, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1,2,4- tria∑ole, pyridine, 2 ( IH) -pyridone, ( IH) -pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, IH-indole, indoline, benzopyrazole, 1, 3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido [2 , 3-b] pyrazine, pyrido[3,4- bjpyrazine, pyrido [3, 2-c] pyridazine, purido [ 3, 4-b] -pyridine, lH-pyrazole [3, 4-d] pyrimidine, pteridine, 2 ( IH) -quinolone, 1 (2H) -isoquinolone, 1 , 4-benzisoxazine , benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide , quinoxaline-N-oxide, quinazoline-N-oxide, benzoxazine, phthalazine, cinnoline, or having a structure: wherein Y is carbon or nitrogen; wherein R3 is H, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, halogen, methoxy, methyl amino, methyl thio; In another embodiment of the compound, the compound has the structure : wherein m is 1 or 2; wherein RA and RB are each independently be H, -OH, -CH2OH, -CH,CH 2 0H, -C(=0)NH 2 , a heteroatom, or -C (=0) NR,R,' ; wherein R 3 is aryl, substituted aryl, or heteroaryl; wherein R 3 ' is alkyl, or XR 3 " , wherein X is O, or N and R" is substituted alkyl or aryl. In another embodiment of the compound, R1R2N is (D) -2- aminocarbonyl pyrrolidino, (D) -2-hydroxymethyl pyrrolidino, (D) -2-hydroxymethyl- rans-4-hydroxy pyrrolidino, piperazino, or 3-hydroxymethyl piperadino. In another embodiment of the compound, the compound has the structure : wherein m is 0, 1, 2, or 3; wherein Y is 0, S, or NR, wherein R is RA or RB; wherein RA and RB are each independently be H, - OH, -CH20H, -CH 2 CH ; 0H, -C(=0)NH2, a heteroatom, or -C(=0)NR 3 R ; wherein R 3 is aryl, substituted aryl, or heteroaryl; wherein R 3 ' is alkyl, or XR 3 " , wherein X is O, or N and R" is substituted alkyl or aryl. In another embodiment of the compound, the compound has the structure : (Compound 1600! In another embodiment of the compound, the compound has the structure : [Compound 1601; In another embodiment of the compound, the compound has the structure : (Compound 1602; In another embodiment of the compound, the compound has the structure : [Compound 1603; In another embodiment of the compound, the compound has the structure : (Compound 1604 In another embodiment of the compound, the compound has the structure : (Compound 1605) In another embodiment of the compound, the compound has the structure : (Compound 1606) In another embodiment of the compound, the compound has the structure : (Compound 1607) In yet another embodiment of the compound, the compound has the structure : In a further embodiment of the compound, the compound has the structure : This invention further provides a compound having the structure (V) : (V) wherein R is H, or methyl. In one embodiment of the compound V, the compound has the structure : (Compound 1608 In another embodiment of the compound V, the compound has tne structure : This invention also provides a method for treating a disease associated with A2a adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of compounds IV, or V. In one embodiment of the method, the compound treats said diseases by stimulating adenylate cyclase. In another embodiment of the method, the subject is a mammal In another embodiment of the method, the mammal is a human. In another embodiment of the method, said A2a adenosine receptor is associated with Parkinson's disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia . Diseases associated with adenosine Al, A2a, A2b and A3 receptors are disclosed in WO 99/06053 and WO-09822465, WO-09705138, WO- 09511681, WO-09733879, JP-09291089, F T/US98/16053 and U.S. Patent No. 5,516,894, the entire content of which are fully incorporate herein by reference. This invention also provides a water-soluble prodrug of compounds IV, or V; wherein said water-soluble prodrug that is metabolized in vivo to produce an active drug which selectively inhibit A2a adenosine receptor. In one embodiment of the prodrug, said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. This invention also provides a pharmaceutical composition comprising the prodrug and a pharmaceutically acceptable carrier. This invention also provides a method for inhibiting the activity of an A2a adenosine receptor in a cell, which comprises contacting said cell with compounds IV, or V. In one embodiment of the method, the compound is an antagonist of said A2a adenosine receptor. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. This invention also provides a method for treating a gastrointestinal disorder in an subject, comprising administering to the an effective amount of compounds IV, or V. In one embodiment of the method, said disorder is diarrhea. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of A2a adenosine receptors. This invention further provides a method for treating respiratory disorder in a subject, comprising administering to the subject an effective amount of compounds IV, or V. In one embodiment of the method, said disorder is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In another embodiment of the method, the subject is a human. In another embodiment of the method, said compound is an antagonist of A2a adenosine receptors. This invention also provides a method for treating damage to the eye of a subject which comprises administering to said subject an effective amount of compounds IV, or V. In one embodiment of the method, said damage comprises retinal or optic nerve head damage. In another embodiment of the method, said damage is acute or chronic . In another embodiment of the method, said damage is the result of glaucoma, edema, ischemia, hypoxia or trauma. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound s an antagonist of A2a adenosine receptors. This invention also provide a pharmaceutical composition comprising a therapeutically effective amount of compounds IV, or V and a pharmaceutically acceptable carrier. In one embodiment of the pharmaceut cal composition, said therapeutically effective amount is effective to treat Parkinson' s disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a surgic l irrigating solution. This invention also provides a combination therapy for Parkinson's disease comprising compounds IV and V, and any of the dopamine enhancers. This invention further provides a combinational therapy for cancer comprising compounds IV and V, and any of the cytotoxic agents. This invention further provides a combinational therapy for glaucoma, comprising compounds IV or V, and a prostaglandin agonist, a muscrinic agonist, or a b-2 antagonist. This invention also provides a packaged pharmaceutical composition for treating a disease associated with A2a adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of compounds IV, or V; and (b) instructions for using said compound fcr treating said disease in a subject. This invention also provide a method of preparing compound IV, comprising the steps of reacting to provide wherein P is a removable protecting group: treating the product of step a) under clization conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the chlorinated product of step c) with NHR1R2 to provide wherein NRιR ; is a substituted or unsubstituted 4-8 membered ring; wherein Ar is a substituted or unsubstituted four to six membered ring; wherein R< is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Re) (R«)XRc, wherein X is O, S, or NR , wherein Rt and R ° are each independently H or alkyl, wherein R, and R- are each independently alkyl or cycloalkyl, or Ro, R- and the nitrogen together form a substituted or unsubstituted ring of between 4 and 7 members. wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; with the proviso that NR1R2 is not 3-acetamιdo piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-amιnocarbonylmethyl, or pyrrolidino; with the proviso that NR3.R2 is 3-hydroxymethyl piperadino only when Ar is 4-pyrιdyl. This invention further provides a method of preparing compound V, comprising the steps of reacting to provide wherein P is a removable protecting group; treating the product of step a) under cyclization conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the chlorinated product of step c) first with dimethylamine and formaldehyde, then with N-methyl benzylamine and finally witli NH2R1 to provide wherein Ri is acetomido ethyl; wherein Ar is 4-pyrιdyl; wherein R is H, or methyl; wherein Rs is N-methyl-N-benzyl ammomethyl . As used herein, "A compound is A 2a selective." means that a compound has a binding constant to adenosine 2a receptor of at least five time higher then that to adenosine A , A 2b , or A 3 . The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy in hurrans . This invention will be better understood from the Experimental Details which follow. However, one skilled in the art will readily appreciate that the specifi - methods and results discussed are merely illustrative of the invention as described more fully in the claims which follow thereafter. Example 22: Synthesis of Adenosine A 2a Antagonists, compounds 1601, 1602, and 1603. Compound 27 1 Compound 26 (10.93g, 50.76 mmol) was dissolved in DMF (67 mL) . 4-Amidinopyridine hydrochloride (8.0g, 50.76 mmol) and DBU (15.4 g, 101.5 mmol) were added sequentially and the reaction was heated to 85°C. After 22 hours, the reaction was cooled to room temperature and the DMF was removed in vacuo. The dark oil was diluted with 2M HCl (80 mL) . The reaction was allowed to stand. After 2 hours, the solution was cooled to 10°C and filtered. The solid was washed with cold water and dried to yield 7.40g of a yellow solid, compound 27 (69%). X H-NMR (200MHz, d 6 -DMS0) d 6.58 (s, IH) , 7.27 (s, IH) , 8.53 (d, 2H, J = 5.6), 9.00 (d, 2H, J = 5.2Hz), 12.35 (brs, IH) . MS (ES) : 212.8 (M * +l) . Compound 27 (7.4 mmol, 29.8 mmol) was diluted with P0C1 3 and heated to 105°C. After 18 hours, the reaction is cooled to room temperature and the P0C1 3 is removed in vacuo. The thick dark oil is diluted with MeOH (75mL) followed by ether (120mL) . The amorphous red solid is filtered and washed with ether to yield 3.82 g of a red solid. The crude solid, compound 28, is approximately 80% pure and used without further purification in the next reaction. 'H-NMR (200MHz, d 6 -DMSO) d 6.58 (s, IH) , 7.27 (s, IH), 8.53 (d, 2H, J = 5.6), 9.00 (d, 2H, J = 5.2Hz), 12.35 (brs, IH) . MS (ES) : 212.8 (M + +l). Compound 1601: DMSO (5 mL) and D-prolinol (500mg, 4.94 mmol) were added to compound 28 (500mg, 2.1 " mmol) was added. The reaction was heated to 120°C. After 18 hours, The reaction was cooled to room temperature and diluted with EtOAc and H 2 0. The layers were separated and the aqueous layer was extracted with EtOAc (2x) . The combined organic layers were washed with H 2 0 (2x) , brine, dried over MgS0 4 , filtered and concentrated to yield 200mg of a tan solid. The solid was recrystallized from EtOAc to yield 82 mg of a tan solid (13%) . "H-NMR (200 MHz, d 6 -DMS0) d 2.05 (m, 4H) , 3.43 (m, IH) , 3.70 - 4.00 (m, 3H) , 4.50 (brs, IH) , 4.92 (brs, IH) , 6.62 (m, IH) , 7.22 (m, IH), 8.22 (d, 2H, J = 6.0 Hz), 6.64 (d, 2H, J = 6.2 Hz), MS (ES): 296.0 (M τ +1), mp = 210 - 220 D C (decomp.). Compound 1602: Chromatography (silica, 9:1 CHC13/Me0H) yielded 10 mg of a tan solid (2%). 'H-NMR (d -DMSO) d 2.00 - 2.50 (m, 4H), 4.05 ( , IH) , 4.21 (m, IH), 6.71 (d, IH, J = 3.2 Hz), 7.18 (d, IH, J = 3.2 Hz), 8.37 (d, 2H, J = 4.8 Hz), 8.56 (d, 2H, J = 5 .0 Hz). MS (ES) : 309.1 (M + +l). Compound 1603. Chromatography (silica, 20:1 Hexanes /EtOAc) yielded 135 mg of a tan solid (53%). H-NMR (d c -DMSO) d 2.00 (m, 4H), 3.43 (brs, IH), 3.74 (brs, 2H) , 3.87 (brs, IH) , 4.49 (brs, IH) , 4.93 (m, IH) , 6.56 (m, IH) , 7.12 (m, IH) , 7.40 (m, 3H) , 8.34 (m, 2H) , 11.62 (brs, IH) . MS (ES) : 295.1 (M τ +1). Compound 1605. Into a 50mL RBF 60mg of 2- ( 4 ' -pyridyl ) -4- Chloropyrimidmopyrrole HCl salt was dissolved in 2mL anhydrous DMSO. 3- (R) -Hydroy-(D) -prolinol TFA salt (380mg) and 500mg sodium bicarbonate were added thereto. The mixture was then flashed with nitrogen gas for 5mm and heated to 130 r C. After 2 hours, the reaction was cooled to room temperature and the DMSO was removed in vacuo. The residue was partitioned between EtOAc (15mL) and saturated sodium bicarbonate aqueous solution (15mL). The organic layer was separated and washed with brine (15mL) and dried over Na 2 S0 4 . After rsmoval of solvent, the crude product was purified by preparative TLC (CH 2 Cl 2 /Me0H = 95/5) to yield 35 mg (50%). -H-NMR (200MHz, CDCl,) ( 2.3-2.5 (IH), 3.4-3.8 (3H), 4.4-4.6 (2H) , 6.4 (IH); 7.1 (IH); 8.2 (d, 2H); 8.7 (d, 2H) ; 11.0 (IH). MS (ES): 312 (M+1). Example 23 : Synthesis of Adenosine A 2a Antagonist , compound 1606 . Compound 28 (200mg) was treated with DMF (30mL), (, (-dimethylglycine methyl ester (73mg HCl salt in 2mL water) and 500mg sodium bicarbonate. After 18 hours, the DMF was removed in vacuo. The residue was partitioned between EtOAc (30mL) and saturated sodium bicarbonate aqueous solution (15mL). The organic layer was washed with brine (15mL), dried over sodium sulfate, filtered and concentrated. Chromatography (silica, 10:4 hexanes/EtOAc) yielded 150mg of pure product, compound 29 (69%). X H-NMR (200MHz, CDC1 3 ) , ( 1.4 (s, 6H) , 3.8 (s, 3H) ; 3.9 (s, 2H) ; 6.4 (s, IH) ; 7.4-7.5 (m, 3H) ; 8.4 (m, 2H); 9.8 (s, IH) . Compound 1606: Procedure is the same as Compound 1605 (72%) . H-NMR (200MHz, CDC1 3 ), ( 1.3 (s, 6H), 1.7-1.9 (m, 2H) ; 2.05-2.30 (m, 2H) ; 3.6-4.1 (m, 11H); 4.80-4.95 (m, IH) ; 6.4 (s, IH) ; 7.4-7.6 (m, 3H); 8.3-8.4 (d, J = 8.5 Hz, 2H) , 10 (s, IH) . MS (ES): 424.0 (M + +l) . The following compounds can be synthesized in the same manner. Compound 1600: (51%). MS (ES): 326.0 (M * +l). Compound 1607: X H-NMR (200MHz, CDCl,) , ( 1.40 - 1.80 (m, 5H) , 2.80 - 3.50 (m, 3H), 4.60 - 4.80 (m, 3H) , 6.66 (d, IH, J = 6.2Hz) , 7.26 (m, IH) , 8.21 (d, 2H, J = 6.3Hz) , 8.65 (d, 2H, J = 5.8Hz), 11.90 (s, IH) . MS (ES) : 310.1 (M ' +l) . Compound 1608: (64%) . H-NMR (200MHz, d f -DMSO) , ( 1.75 (s, 3H) , 2.11 (s, 3H) , 2.29 (s, 3H) , 3.56 (m, 6H) , 7.23 - 7.41 (m, 5H) , 8.00 (brs, IH), 8.23 (d, 2H, J = 6.0Hz) , 8.63 (d, 2H, J = 5.4 Hz) , 8.82 (brs, IH) , 11.56 (brs, IH) . MS (ES) : 444.0 (M * +l) . Compound 1604: *H-NMR (200MHz, CD 3 OD) ( 3.40 (m, 4H) , 4.29 (m, 4H) , 6.99 (s, IH) , 7.5 - 7.2 (m, 3H) , 7.90 (d, 2H) , 8.39 (d, 2H) , 8.61 (d, 2H) . MS (ES) : 357.0 (M + +1) . TABLE 16. Adenosine A 2a Receptor Selective Compounds * at least 5 times more selective than other three subtypes Pages 202-256 relate to compounds spec fic to the A 3 receptor Summary of the Invention The present invention is also based on compounds which selectively bind to adenosine A 3 receptor, thereby treating a disease associated with A 3 adenosine receptor in a subject by administering to the subject a therapeutically effective amount of such compounds. The disease to be treated are associated with, for example, asthma, hypersens tivity, rhinitis, hay fever, serum sickness, allergic vasculitis, atopic dermantitis, dermantitis, psorasis, eczema, ldiopathic pulmonary fibrosis, eosinophillic chlorecystitis, chronic airway inflammation, hypereosinophilic syndromes, eosinophilic gastroenteritis, edema, urticaria, eosinophilic myocardial disease, episodic angioedema with eosinophilia, inflammatory bowel disease, ulcerative colitis, allergic granulomatosis , carcinomatosis , eosinophilic granuloma, familial histiocytosis , hypertension, mast cell degranulation, tumor, caroiac hypoxia, cerebral ischemia, diuresis, renal failure, neurological disorder, mental disorder, cognitive disorder, myocardial ischemia, bronchoconstriction, arthritis, autoimmune disease, Crohn' s disease, Grave's disease, diabetes, multiple sclerosis, anaemia, psoriasis, fertility disorders, lupus erthyematosus, reperfusion injury, brain arteriole diameter, the release of allergic mediators, scleroderma, stroke, global ischemia, central nervous system disorder, cardiovascular disorder, renal disorder, inflammatory disorder, gastrointestinal disorder, eye disorder, allergic disorder, respiratory disorder, or immunological disorder. This invention also features a compound having the structure: wherein Ri is H and R2 is cyclopropyl methylamino carbonylethyl, cis-3-hydroxy cyclopentyl, acetamido butyl, methylamino carbonylamino butyl, ethylamino carbonylamino propyl, methylamino carbonylamino propyl, 2-acetyl amino- 3-methyl butyl, N, N-diethylamino carbonylamino ethyl, thioacetamido ethyl, 3-amino acetyloxy cyclopentyl, 3- hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2- imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl, 1- aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2- imidazolyl ethyl, acetamido ethyl, 1- (R) -phenyl-2- hydroxyethyl, N-methylaminocarbonyl pyridyl-2- methyl, or Ri, R2 and the nitrogen together are 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino. wherein R3 is a substituted or unsubstituted four to six menbered ring, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1 , 2, 4-triazole, pyridine, 2(1H)- pyridone, 4 ( IH) -pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, IH-indole, indoline, benzopyrazole, 1, 3-ben∑odιoxole, benzoxazole, purine, coumarin, cnroione, quinolme, tetrahydroquinoline, isoquinoline, benzimidazole, qumazolme, pyrido [2, 3-b] pyrazine, pyrido [ 3, 4-b] pyrazine, pyrido [3, 2-c] pyridazine, purido [3, 4-b] -pyridine, 1H- pyrazole [3, 4-d] pyrimidine, pteπαme, 2 ( IH) -qumolone, 1 (2H) -isoquinolone, 1 , 4-benzιsoxazme, benzothiazole, quinoxaline, quinolme-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, qumazolme-N-oxide, benzoxazine, phthalazme, or cinnol e. wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein Rβ is H, alkyl, substituted alkyl, aryl, or substituted aryl. This invention also features a method for inhibiting the activity of an A 3 adenosine receptor in a cell, which comprises contacting said cell with the above-mentioned compounds. typical practice and is known to those skilled in the art. Typical synthetic schemes for the preparation of deazapurine intermediates of the invention are outlined below in Scheme I. This invention also provides a method of preparing compound IV, comprising the steps of reacting to provide wherein P is a removable protecting group; treating the product of step a) under cycli7ation conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the chlorinated product of step c) with NHR1R2 to provide wherein Ri is H and R2 is cyclopropyl methylamino carbonylethyl, cis-3-hydroxy cyclopentyl, acetamido butyl, methylamino carbonylamino butyl, ethylamino carbonylamino propyl, methylamino carbonylamino propyl, 2-acetyl amino- 3-methyl butyl, N, N-diethylamino carbonylamino ethyl, thioacetamido ethyl, 3-amino acetyloxy cyclopentyl, 3- hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2- imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl, 1- aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2- imidazolyl ethyl, acetamido ethyl, 1- (R) -phenyl-2- hydroxyethyl, N-methylaminocarbonyl pyridyl-2- methyl, or Ri, R2 and the nitrogen together are 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino. wherein R3 is a substituted or unsubstituted four to six membered ring; wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein "ftε is H, alkyl, substituted alkyl, aryl, or substituted aryl. This invention also provides a method of preparing compound of V, comprising the steps of reacting to provide wherein P is a removable protecting group; treating the product of step a) under cyclization conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the chlorinated product of step c) with NH2CH2(CH2)mCH2NHC(=0)Rl to provide wherein m is 0, 1, or 2; wherein Ri is cyclopropyl methyl, methyl, methylamino, or aminomethyl; wherein R2 is aryl, substituted aryl, heteroaryl; wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein Re is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(R9) (Rιo)NR7Re, wherein R9 and Ric are each H or alkyl, wherein R7 and Rs are each alkyl or cycloalkyl, or RT, Rs and the nitrogen together form a ring system of between 4 and 7 members . This invention further provided a method of preparing compound VI, comprising reacting to provide wherein P is a removable protecting group: b) treating the product of step a) under cyclization conditions to provide c) treating the product of step b) under suitable conditions to provide d) treating the c to provide wherein R2 is unsubstituted aryl wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein Re H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Rsf) (RioJNR-Rβ, wherein R9 and Ri are each H or alkyl, wherein R7 and Re are each alkyl cr cycloalkyl, or R- , Rf and the nitrogen together form a ring system of between 4 and 7 members. This invention also provides a compound having the structure: IV wherein Ri is H and R2 is cyclopropyl methylamino carbonylethyl, cis-3-hydroxy cyclopentyl, acetamido butyl, methylamino carbonylamino butyl, ethylamino carbonylamino propyl, methylamino carbonylamino propyl, 2-acetyl amino- 3-methyl butyl, N, N-diethylamino carbonylamino ethyl, thioacetamido ethyl, 3-arnino acetyloxy cyclopentyl, 3- hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2- imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl , 1- aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2- imidazolyl ethyl, acetamido ethyl, 1- (R) -phenyl-2- hydroxyethyl, N-methylaminocarbonyl pyridyl-2- methyl, or Ri, R2 and the nitrogen together are 3-acetamido piperadino, 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3-aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino. wherein R3 is a substituted or unsubstituted benzene, pyrrole, thiophene, furan, thiazole, imidazole, pyrazole, 1, 2 , 4-triazole, pyridine, 2 ( IH) -pyridone, 4 ( IH) -pyridone, pyrazine, pyrimidine, pyridazine, isothiazole, isoxazole, oxazole, tetrazole, naphthalene, tetralin, naphthyridine, benzofuran, benzothiophene, indole, 2, 3-dihydroindole, IH- indole, indoline, benzopyrazole, 1, 3-benzodioxole, benzoxazole, purine, coumarin, chromone, quinoline, tetrahydroquinoline, isoquinoline, benzimidazole, quinazoline, pyrido [2, 3-b] pyrazine, pyrido [3, 4-b] pyrazine, pyrido [ 3, 2-c] pyridazine, purido [ 3, 4-b] -pyridine, 1H- pyrazole [ 3, 4-d] pyrimidine, pteridine, 2 ( IH) -quinolone, 1 (2H) -isoquinolone, 1, 4-benzιsoxazine, benzothiazole, quinoxaline, quinoline-N-oxide, isoquinoline-N-oxide, quinoxaline-N-oxide, quinazoline-N-oxide, benzoxazine, phthalazine, or cinnoline. wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein Re is H, alkyl, substituted alkyl, aryl, or substituted aryl . In one embodiment of the compound, the compound has the structure : In another embodiment of the compound, R3 is phenyl. In another embodiment of the compound, Rs is hydrogen or methyl . In another embodiment of the compound, Re is hydrogen, methyl, phenyl, 3-chlorophenyloxy methyl, or trans-2- phenylamino methyl pyrrolidino methyl. This invention further provides a compound having the structure : wherein m is 0, 1, or 2; wherein Ri is cyclopropyl methyl, methyl, methylamino, or aminomethyl; wherein R2 is aryl, substituted aryl, or heteroaryl; wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein Re is H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein said substituted alkyl is -C(Rs) (Rιo)NRιRι, wherein R.= and Ro are each H or alkyl, wherein RT and Rs are each alkyl or cycloalkyl, or R^, Rf and the nitrogen together form a ring system of between 4 and 7 members. In one embodiment of compound V, m is 0 and R2 is phenyl. In another embodiment of compound V, m is 1 and R2 is phenyl. In another embodiment of compound V, m is 2 and R2 is phenyl . In another embodiment of compound V, R: and Re are methyl. In another embodiment of compound V, Rs and Rε are methyl. In another embodiment of compound V, Rs and Rβ are methyl. In another embodiment of compound V, the compound has the structure: (Compound 1316; In another embodiment of compound V, the compound has the structure : (Compound 1311; In another embodiment of compound V, the compound has the structure : (Compound 1202 ] In another embodiment of compound V, the compound has the structure : (Compound 1310; In another embodiment of compound V, the compound has the structure : (Compound 1312; This invention further provides a compound having the structure : HO. (Compound 609( This invention also provides a compound having the structure VI wherein R2 is unsubstituted aryl wherein Rs is H, alkyl, substituted alkyl, or cycloalkyl; wherein Re H, alkyl, substituted alkyl, aryl, arylalkyl, amino, substituted aryl, wherein s.id substituted alkyl is -C(R&) (Rιo)NR7Rs, wherein R9 and Rr are each H or alkyl, wherein R and Rs are each alkyl or cycloalkyl, or R7, Rs and the nitrogen together form a ring system of between 4 and 7 members. In one embodiment of compound VI, the compound has the structure : (Compound 1309) In one embodiment of compound 1309, the compound has t he structure : In another embodiment of compound 1309, the compound has the structure : This invention also provides a compound having the structure: VII wherein R : is 3-hydroxy cyclopentyl ethylamino carbonylamino propyl, N, N-diethylamino carbonylamino ethyl, thioacetamido ethyl, 3-amino acetyloxy cyclopentyl, 3-hydroxy cyclopentyl, 2-pyrrolyl carbonyl aminoethyl, 2- imidazolidinone ethyl, l-aminocarbonyl-2-methyl propyl, 1- aminocarbonyl-2-phenyl ethyl, 3-hydroxy azetidino, 2- imidazolyl ethyl, acetamido ethyl, 1- (R) -phenyl-2- hydroxyethyl , or N-methylaminocarbonyl pyridyl-2- methyl; wherein R 3 and R 4 are independently H, substituted or unsubstituted alkyl, or aryl. In one embodiment of the compound, the compound has the structure : (Compound 1700; In another embodiment of the compound, the compound has the structure : (Compound 1701) In another embodiment of the compound, the compound has the structure : (Compound 1702; In another embodiment of the compound, the compound has the structure : (Compound 1704 In another embodiment of the compound, the compound has the structure : (Compound 1705; In another embodiment of the compound, the compound has the structure : (Compound 1706; In another embodiment of the compound, the compound has the structure : HO , In another embodiment of the compound, the compound has the structure : HQ, In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : (Compound 1707) In another embodiment of the compound, the compound has the structure : (Compound 1708 In another embodiment of the compound, the compound has the structure : (Compound 1709; In another embodiment of the compound, the compound has the structure : (Compound 1710; In another embodiment of the compound, the compound has the structure : (Compound 1712) In another embodiment of the compound, the compound has the structure : (Compound 1713; In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : (Compound 1714) In another embodiment of the compound, the compound has the structure: In another embodiment of the compound, the compound has the structure : (Compound 1715; In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : This invention also provides a compound having the structure: wherein Ri, R and the nitrogen together are 3-hydroxy pyrrolidino, 3-methyloxy carbonylmethyl pyrrolidino, 3- aminocarbonylmethyl pyrrolidino, or 3-hydroxymethyl piperadino; wherein R 3 and R 4 are independently H, substituted or unsubstituted alkyl, or aryl. In one embodiment of the compound, the compound has the structure : (Compound 1711) In another embodiment of the compound, the compound has the structure : (Compound 1703) In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : (Compound 1716; In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : (Compound 1717 In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : (Compound 1718) In another embodiment of the compound, the compound has the structure : In another embodiment of the compound, the compound has the structure : This invention also provides a method for treating a disease associated with A3 adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of any of the compounds IV, V, VI, VI, or VIII. In one embodiment of the method, the subject is a mammal. In another embodiment of the method, the mammal is a human. In another embodiment of the method, said A3 adenosine receptor is associated with a central nervous system disorder, a cardiovascular disorder, asthma, hypersensitivity, rhinitis, hay fever, serum sickness, allergic vasculitis, atopic dermantitis, dermantitis, psorasis, eczema, ldiopathic pulmonary fibrosis, eosinophillic chlorecystitis, chronic airway inflammation, hypereosmophilic syndromes, eosinophilic gastroenteritis, edema, urticaria, eosinophilic myocardial disease, episodic angioedema with eosmophilia, inflammatory bowel disease, ulcerative colitis, allergic granulomatosis , carcinomatosis, eosinophilic granuloma, familial histiocytosis, hypertension, mast cell degranulation, tumor, cardiac hypoxia, cerebral ischemia, diuresis, renal failure, neurological disorder, mental disorder, cognitive disorder, myocardial ischemia, bronchoconstriction, arthrit.s, autoimmune disease, Crohn's disease, Grave's disease, diabetes, multiple sclerosis, anaemia, psoriasis, fertility disorders, lupus erthyematosus, reperfusion injury, brain arteriole diameter, the release of allergic mediators, scleroderma, stroke, global ischemia, central nervous system disorder, cardiovascular disorder, renal disorder, inflammatory disorder, gastrointestinal disorder, eye disorder, allergic disorder, respiratory disorder, or immunological disorder. Diseases associated with adenosine Al, A2a, A2b and A3 receptors are disclosed in WO 99/06053 and WO-09822465, WO-09705138, WO- 09511681, WO-09733879, JP-09291089, PCT/US98/16053 and U.S. Patent No. 5,516,894, the entire content of which are fully incorporate herein by reference. This invention also provides a water-soluble prodrug of any of the compounds IV, V, VI, VII, or VIII; wherein said water- soluble prodrug that is metabolized in vivo to an active drug which selectively inhibit A3 adenosine receptor. In one embodiment of the prodrug, said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. This invention also provides a pharmaceutical composition comprising the prodrug and a pharmaceutically acceptable carrier . This invention also provides a method for inhibiting the activity of an A3 adenosine receptor in a cell, which comprises contacting said cell with any of the compounds IV, V, VI, VII, or VIII. In one embodiment of the method, the compound is an antagonist of said A3 adenosine receptor. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. This invention also provides a method for treating a gastrointestinal disorder in an subject, comprising administering to the an effective amount of any of the compounds IV, V, VI, VII, or VIII. In one embodiment of the method, said disorder is diarrhea. In another embodiment of the method, t^e subject is a human. In another embodiment of the method, the compound is an antagonist of A3 adenosine receptors. This invention further provides a method for treating respiratory disorder in a subject, comprising administering to the subject an effective amount of any of the compounds IV, V, VI, VII, or VIII. In one embodiment of the method, said disorder is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In another embodiment of the method, the subject is a human. In another embodiment of the method, said compound is an antagonist of A3 adenosine receptors. This invention also provides a method for treating damage to the eye of a subject which comprises administering to said subject an effective amount of any of tne compounds IV, V, VI, VII, or VIII. In one embodiment of the method, said damage comprises retinal or optic nerve head damage. In another embodiment of the method, said damage is acute or chronic . In another embodiment of the method, said damage is the result of glaucoma, edema, ischemia, hypoxia or trauma. In another embodiment of the method, the subject is a human. In another embodiment of the method, the compound is an antagonist of A3 adenosine receptors. This invention also provide a pharmaceutical composition comprising a therapeutically effective amount of any of the compounds IV, V, VI, VII, or VIII and a pharmaceutically acceptable carrier. In one embodiment of the pharmaceutical composition, said therapeutically effective amount is effective to treat a respiratory disorder or a gastrointestinal disorder. In another embodiment of the pharmaceutical composition, said gastrointestinal disorder is diarrhea. In another embodiment of the pharmaceutical composition, said respiratory disorder is asthma, allergic rhinitis, or chronic obstructive pulmonary disease. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an ophthalmic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a systemic formulation. In another embodiment of the pharmaceutical composition, said pharmaceutical composition is a surgical irrigating solution. This inventio also provides a packaged pharmaceutical composition for treating a disease associated with A3 adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of any of the compounds IV, V, VI, VII, or VIII; and (b) instructions for using said compound for treating said disease in a subject. Compounds represented by the formula IV, V, VI, VII, and VIII can be synthesized by the Schemes I-IX. As used herein, "A compound is A 3 se. ective." means that a compound has a binding constant to adenosine A3 receptor of at least ten time higher then that to adenosine A ϊ r A 2a , or A 2b . The invention is further illustrated by the following examples which in no way should be construed as being further limiting. The contents of all references, pending patent applications and published patent applications, cited throughout this application, including those referenced in the background section, are hereby incorporated by reference. It should be understood that the models used throughout the examples are accepted models and that the demonstration of efficacy in these models is predictive of efficacy humans. A skilled artisan will know that metabolism of the compounds disclosed herein a subject produces certain biologically active metabolites which can serve as crugs . This invention will be better understood from the Experimental Details which follow. However, one s :illed in the art will readily appreciate that the specific methods and results discussed are merely illustrative of the invention as described more fully in the claims which follow thereafter. Example 24 : Adenosine A 3 Antagonist Experimentals Compound 1700 (Table 17 below): MS (ES): 366.1 (M'+l). Compound 1710 (Table 17 below): MS (ES, : 381.1 (M'+l Compound 1316 (Table 17 below): MS (ES): 353.2 (M ' +l). Compound 1703 (Table 17 below): MS (ES): 357.1 (M'+l). Compound 1719 (Table 17 below): X H-NMR (200MHz, d fc -DMSO) ( 1.75 (m, 2H) , 3.11 (m, 2H) , 3.35 (s, 3H) , 3.59 (m, 2H) , 5.72 (m, IH) , 5.96 ( , IH) , 6.55 (s, IH) , 7.15 (s, IH) , 7.49 (m, 2H) , 8.32 (m, 2H) . Compound 1704 (Table 17 below): MS (ES): 367.0 (M'+l). Compound 1706 (Table 17 below): X H-NMR (200MHz, CDC1 3 ) d 1.22 (m, 2H) , 1.60-2.40 (m, 4H) , 4.53 (m, IH) , 4.94 (m, IH) , 5.70 (d, IH, J = 8.2 Hz), 6.35 (d, IH, J = 2.8 Hz), 6.97 (d, IH, J = 2.0 Hz), 7.50 (m, 3H) , 8.40 (m, 2H) , 10.83 (brs, IH) . Compound 1707 (Table 17 below): MS(ES): 347.0 (M'+l). Compound 1708 (Table 17 below): MS (ES) 399.0 (M+l). Compound 1709 (Table 17 below): MS (ES) 385.9 (M ' +l). Compound 1710 (Table 17 below): MS (ES) 434.0 (M'+l). Compound 1711 (Table 17 below): : H-NMR (200MHz, CD,OD) d 3.95 (d, 2H, J = 5.8Hz), 4.23 - 4.31 (m, 2H) , 4.53 (t, 2H, J = 8.8Hz), 6.30 (d, IH, J = 3.0Hz), 6.98 (d, IH, J = 3.0Hz), 7.45 - 7.48 (m, 3H) , 7.83 - 8.42 (m, 2H) , 9.70 (brs, IH) . MS (ES): 281.1 (M + +l) . OSIC-148313 : H-NMR (200MHz, CD 3 0D) d 3.02 (m, 2H) , 3.92 (m, 2H) , 5.09 (2, 2H), 6.53 (s, IH) , 6.90-7.04 (br s, IH) , 6.92 (m, 2H) , 7.02 (m, IH) , 7.21 (dd, IH, J = 8.2Hz) , 7.40 (m, 3H) , 7.50-7.80 (br s, IH), 8.33 (m, 2H) . MS (ES) : 445.1 (M'+l) . Compound 1713 (Table 17 below) : -H-NMR (200MHz, CDC1 3 ) d 1.65-1.80(m, 7H) , 1.88-2.00(m, IH) , 2.10 - 2.40 (m, IH) , 2.70-3.05 (m, 3H) , 3.09-3.14 (m, 2H), 3.16-3.38 (m, IH) , 3.45 (d, IH, J = 14Hz), 3.53-3.60 (m, 2H) , 2.84-3.92 (m, 2H) , 3.97 (d, IH, J = 14Hz), 5.55 (t, IH, J = 5.8Hz), 6.17 (s, IH) , 6.55-6.59 (m, 2H) , 6.64-6.71 (m, IH) , 7.11-7.19 (m, 2H) , 7.43-7.46 (m, 3H), 8.38-8.42 (m, 2H) , MS (ES): 484.0 (M + +l). Compound 1714 (Table 17 below): MS (ES): 471.0 (M + +l). Compound 1715 (Table 17 below): MS (ES): 505.0 (M'+l). Compound 1716 (Table 17 below): " 'H-NMR (200MHz, CD,OD) d 1.65 (m, IH) , 2.18 (m, IH) , 2.49 (br d, 2H, J = 6.2Hz), 2.64 (m, IH), 3.38 (m, IH) , 3.69 (s, 3H) , 3.72 (m, IH) , 3.93 (m, IH) , 4.10 (m, IH), 5.06 (2, 2H) , 6.58 (s, IH) , 6.92 (m, 2H) , 7.02 (m, IH), 7.23 (dd, IH, J = 8.1Hz), 7.39 (m, 3H) , 8.32 (m, 2H) . MS (ES) : 477.1 (M ' + l) . Compound 1717 (Table 17 below) : : H-NMR (200MHz, CD OD) d 1.69 (m, IH), 2.26 (m, IH) , 2.42 (d, 2H, J = 7.4Hz) , 2.72 (m, IH) , 3.53 (m, IH) , 3.83 (m, IH) , 4.02 (m, IH) , 4.14 (dd, IH, J = 10.6, 7.0Hz) , 5.14 (2, 2H) , 6.69 (s, IH) , 6.96 (m, 2H) , 7.06 (m, IH) , 7.25 (dd, IH, J = 8.0Hz) , 7.39 ( , 3H) , 8.35 (m, 2H) . MS (ES) : 462.2 (M ' +l) . Compound 1718 (Table 17 below) : L H-NMR (200MHz, CD 3 OD) d 1.40 - 2.00 (m, 5H) , 3.52 (d, 2H, 7.6Hz) , 3.80 - 4.00 (m, IH) , 4.00 - 4.20 (m, 3H) , 4.50 ( , 2H) , 6.36 - 6.50 (m, 2H) , 6.54 (s, IH) , 6.84 - 6.92 (m, IH) , 7.05 (t, IH, J = 8.2Hz) , 7.30 - 7.45 (m, 3H) , 8.24 (d, 2H, J = 9.8Hz) . MS (ES) : 449.0 (M'+l) . TABLE 17. Adenosine A 3 Receptor Selective Compounds * at least 10 times more selective than other three subtypes This invention provides a compound having the structure : 1505 This invention also provides a compound having the structure 1506 This invention further provides a compound having the structure : 1507 This invention also provides a compound having the structure: 1508 This invention further provides a compound having the structure: 1509 This invention also provides a compound having the structure 1510 This invention also provides a compound having the structure 1511 This invention further provides a compound having the structure : 1512 This invention also provides a compound having the structure 1513 This invention further provides a compound having the structure : OH 1514 This invention further provides a compound having the structure : OH 1515 This invention also provides a compound having the structure: OH 1516 OH 1517 This invention further provides a compound having the structure : 1518 This invention also provides a compound having the structure 1519 This invention further provides a compound having the structure : OH 1520 In a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520. In a further embodiment the invention provides the above method, wherein the subject is a mammal. In a further embodiment the invention provides the above method, wherein the mammal is a human. In a further embodiment the invention provides the above method, wherein said Ai adenosine receptor is associated with cognitive disease, renal failure, cardiac arrhythmias, respiratory epithelia, transmitter release, sedation, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstriction, neutropil chemotaxis, reflux condition, or ulcerative condition. In a further embodiment the invention provides a water-soluble prodrug of compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, wherein the water-soluble prodrug is metabolized in vivo to produce an active drug which selectively inhibits Ai adenosine receptor. In a further embodiment the invention provides, wherein said prodrug is metabolized in vivo by esterase catalyzed hydrolysis . In a further embodiment the invention provides a pharmaceutical composition comprising the above prodrug and a pharmaceutically acceptable carrier. In a further embodiment the invention provides a method for inhibiting the activity of an Ai adenosine receptor in a cell, which comprises contacting the cell with compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520. In a further embodiment the invention provides the above method for inhibiting the activity of an Ai adenosine receptor in a cell, wherein the compound is an antagonist of the Ai adenosine receptor. In a further embodiment the invention provides the above method for inhibiting the activity of an Ai adenosine receptor in a cell, wherein the cell is human cell. In a further embodiment the invention provides the above method for inhibiting the activity of an Ai adenosine receptor in a human cell, wherein the compound is an antagonist of Ai adenosine receptors. In a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, wherein said disease is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. In a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, wherein said disease is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder and wherein the subject is a human. In a further embodiment the invention provides a method for treating the above disease, wherein said compound is an antagonist of Ai adenosine receptors. In a further embodiment the invention provides a combination therapy for asthma, comprising the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, and a steroid, β2 agonist, glucocorticoid, lucotriene antagonist, or anticolinergic agonist. In a further embodiment the invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, and a pharmaceutically acceptable carrier. In a further embodiment the invention provides a method for treating a respiratory disorder with the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520, wherein said respiratory disorder is asthma, allergic rhinitis, or chronic obstructive pulmonary disease . In a further embodiment the invention provides the above pharmaceutical composition (s) , wherein said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. In a further embodiment the invention provides the above pharmaceutical composition (s) , wherein said pharmaceutical composition is a systemic formulation. In a further embodiment the invention provides the above pharmaceutical composition (s) , wherein said pharmaceutical composition is a surgical irrigating solution. In a further embodiment the invention provides a packaged pharmaceutical composition for treating a disease associated with Ai adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520; and (b) instructions for using said compound for treating said disease in a subject. In a further embodiment the invention provides a pharmaceutically acceptable salt of the compound 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, or 1520. In a further embodiment the invention provides the above pharmaceutically acceptable salt, wherein the pharmaceutically acceptable salt of the compound 1509, 1511, 1515, 1518, or 1519 contains a cation selected from the group consisting of sodium, calcium and ammonium. In yet a further embodiment the invention provides a method for treating a disease associated with Ai adenosine receptor in a subject, wherein the Ai adenosine receptor is associated with congestive heart failure. Exemplificat on Example 21: Synthesis of 1- [ 6- (4-Hydroxy-4-phenyl-pιperidm-l- yl-methyl) -2-phenyl-7H-pyrrolo [2, 3-d] pyπmιdιn-4-yl] - pyrrolidme-2-carboxylιc acid amide (1505) . Compound 1505 was synthesized in a manner similar to that of Example 17 using synthesis scheme IX with L-prolmeamide and 4- phenyl-pιperιdιn-4-ol to obtain: 1505 π -H-NMR (d 6 -DMS0) d 1.53 (s, IH) , 1.60 ;s, IH) , 1.84-2.30 (m, 6H), 2.66 (m, 2H) , 3.60 (s, 2H) , 3.88 (m, IH; 4.02 m, IH) , 4.66 (d, IH, J = 6.8Hz), 4.73 (s, IH) , 6.44 (s, IH) , 6.94 (s, IH) , 7.12 - 7.50 (m, 10H) , 8.35 ( , 2H) , 11.6 (brs, IH) ; MS (ES) : 305.1 (M'+l) ; mp = 234-235°C. Example 22: Synthesis of [N- (2-Phenyl-7H-pyrroIo [2, 3-d] pyπmιdιn-4-yl) (L) -prol amide (1506) Compound 1506 was synthesized using synthesis scheme VII with L-prolmeamide to obtain: -H-NMR (DMSO-d 5 ) d 2.05 (m, 4H) , 3.85 m, IH) , 4.05 ( , IH) , 4.70 (d, IH, J=8.0Hz) , 6.58 (brs, IH) , 6.95 (brs, IH) , 7.15 (d, IH, J=3.4Hz) , 7.40 (m, 3H) , 7.50 (brs, IH) , 8.40 (m, 2H) , 11.6 (brs, IH) ; MS (ES) : 308.3 (M ' +l) . mp= 236-238°C. Example 23: Synthesis of [N- (2-phenyl-6-methoxymethyl-7H- pyrrolo[2, 3-d]pyrιmιdm-4-yl) - (L) -prolmamide ( 1507 ) Compound 1507 was synthesized using precursor compound 23 of synthesis scheme IX to obtain: Bromide 23 (4.23g, lO ol) is dissolved in anhydrous methanol (60mL) and DCM (120mL) and treated AgOCCF- unαer N- at rt for lh. The solid is removed by filtration and washed with DCM (2x20mL) . The filtrate is concentrated in va cuo . Tne residue is redissolved DCM (80mL) . The resulted solution is tnen washed with saturated NaHCO, solution and brine, dried over MgSO,, filtered and concentrated to give 3.71g (4, 99%) off white solid. -NMR (CDCl;) d 1.75 (s, 9H), 3.51 (s, 3H) , 4.83 (s, 2H), 6.70 (s, IH) , 7.47 (m, 3H) , 8.52 ( , 2H). Aryl chloride 4 (2.448g, 6.55mmol), DMSO (15mL), L-prolineamide (4.0g, 35.0mmol) and NaHC0 3 (2.9g) are combined and heated to 120°C under nitrogen. After 4h, the reaction is cooled to room temperature and diluted with water (60ml) . The resulted slurry is extracted with DCM (lOx). The combined organic layers are washed with saturated NaHCO ^ solution and brine, dried over MgS0 4 , filtered and concentrated to give 2.48g brown solid. Pure product (1.86g, 81%) is obtained after flash column as white solid. White crystals are gotten from THF/hexane. M.p. = 213- 215°C. H-NMR (CDC1 3 ) d 2.15 (m, 3H), 2.52 (m, IH) , 3.26 (s, 3H; 3.92 ra, IH! 4.10 m. IH) , 4.42 (s, 2H) , 5.08 (d, IH, J=8.2Hz), 5.49 (brs, IH) , 6.48 (s, IH) , 7.08 (brs, IH) , 7.42 (m, 3H) , 8.38 (m, 2H) , 9.78 (brs, IH) ; MS (ES): 352.2 (M + +l). Example 24: Synthesis of 4-Hydroxy-l- (2-phenyl-7H-pyrrolo [2 , 3- d] pyrιmιdm-4-yl] lie acid amide (1508) Compound 1508 was obtained with synthesis scheme VII usinσ cis- hydroxy prolineamide to obtain: H-NMR (d 6 -DMS0) d 1.90 (m, IH) , 3.85 (d, IH, J = 9.2Hz), 4.08 (m, IH), 4.37 (s, IH) , 4.67 (dd, IH, J = 8.8, 4.0Hz), 5.30 (s, IH), 6.55 (s, IH), 7.15 (s, 2H), 7.37 (m, 3H), 7.64 (s, IH), 8.37 (m, 2H), 11.65 (brs, IH) ; MS (ES): 324.2 (M'+l); mp = 268- 271°C. Example 25: Synthesis of 3- [4- ( (S) -2-Carbamoyl-pyrrolodιn-l- yl ) -2-phenyl-7H-pyrrolo [2 , 3-d] pyrιmιdm-6-yl] -propionic acid (1509) Compound 1509 was obtained using precursor compound 23 of synthesis scheme IX to obtain: The tert-butoxycarbonyl protected aryl bromide 23 (4.0g, 9.5mmol), dry DMSO (25ml), NaH : P0, (454mg, 3.79mmol) and Na . HPO ., (1.62g, 11.4mmol) were combined and heated to 50-C under argon for approximately 3.5h. The mixture was then poured into water (200ml) and extracted with three 100ml portions of EtOAc. The combined organic layers were thoroughly washed with water, brine, dried over MgSO.., filtered and concentrated to give a yellow solid which was purified by triturating with ethanol. to give 1.55g of a pale yellow solid (7) . The mother liquor was purified by flash chromatography (10% EtOAc in hexane) to give an additional 454mg (60%). H-NMR (CDCl,) d 1.77 (s, 9H) , 7.25 (s, IH) , 7.48 ( , 3H) , 8.52 (m, 2H) 10.39 (s, IH) ; m.p.= 156°C (dec) . Aldehyde 7 (600mg, 1.7mmol) was dissolved in dry THF (20ml) and cooled to 0°C under argon. To this was added a 0°C solution of ( tert-butoxycarbonylmethylene) -triphenylphosphorane (694mg, 1.8mmol) in 10ml of dry THF dropwise through a cannula. After 3h the mixture was concentrated and purified by triturating with ethanol to give 565mg (73%) of a white solid (8) . : HNMR (CDC1 3 ) d 1.58 (s, 9H), 1.79 (s, 9H) , 5.46 (d, IH), 6.95 (s, IH) , 7.48 (m, 3H) , 8.09 (d, IH), 8.56 ,m, 2H) . A solution of compound 8 (565mg 1.2mmol) in 5ml THF was diluted to 100ml with EtOAc. After adding 600mg of catalyst (5% wt Pd, 50% H-O) and purging with argon, the mixture was hydrogenated under atmospheric pressure. After 8h the mixture was filtered, concentrated and purified with flash chromatography (10% EtOAc in hexane) to isolate 200mg (35%) of 9 as a clear oil that crystallized upon standing. : HNMR (CDCl ) d 1.42 (s, 9H) , 1.75 (s, 9H) , 2.65 (t, 2H) , 3.32 (t, 2H) , 6.41 (s, IH) 7.45 (m, 3H) , 8.51 (m, 2H) . Aryl chloride 9 (200mg, 0.44mmol), DMSO (10ml) and L- prolinamide (440mg, 4.4mmol) were combined and heated to 85°C under argon. After 14 hours the mixture is cooled to room temperature and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer washed with EtOAc (3x) . The combined organic layers were thoroughly washed with water (3x), brine, dried over MgS0 4 , filtered and concentrated to give 10 as a yellow film which was purified by flash chromatography (2.5% MeOH in CH_,C1 : ,) . 185mg (97%). MS (ES) : 435.8 (M'+l) . HCl, dioxane Ester 10 (30mg, mmol) in 5ml dioxane was hydrolyzed by adding 0.5ml concentrated HCl. After 3 hours the mixture was concentrated in vacuo and recrystalized in EtOH/ EtOAc to obtain 1509 as a white solid (20mg, 61%) . MS (ES) : 380 (M'+l) . Example 26: Synthesis of [N- (2-phenyl-6-aminocarbonyl methoxymethyl-7if-pyrrolo [2 , 3-d] pyrimidin-4 -yl ) - (L) -prolinamide (1510) Compound 1510 was obtained using precursor compound 23 of synthesis scheme IX to obtain: Bromide 23 (1.27g, 3mmol) and molecular sieve (5g) are stirred in anhydrous methyl glycolate (5.8g, δOmmol) and DCM (40mL) . The solution is treated with AgOTf under N 2 and allowed to stir for 3h. The solid is removed by filtration and washed with DCM (2x20mL) . The filtrate is concentrated z n vacuo . The residue is redissolved in DCM (80mL) . The resulted solution is then washed with water, saturated NaHCO, solution and brine, dried over MgS0 4 , filtered and concentrated to give 1.35g (99%) off white solid (12). : H-NMR (CDC1 3 ) d 1.75 (s, 9H., 3.80 (s, 3H), 5.0 (s, 2H), 6.78 (s, IH), 7.47 (m, 3H) , 8.52 (m, 2H). Aryl chloride 12 (177mg, 0.41mmol), DMSO (lOmL), L-prolinamide (466mg, 4mmol) and NaHC0 3 (500mg) are combined and heated to 120°C under nitrogen. After 4h, the reaction is cooled to room temperature and diluted with water (60ml) . The resulted slurry is extracted with DCM (5x30mL). The combined organic layers are washed with saturated NaHCO, solution and brine, dried over MgS0 4 , filtered and concentrated to give brown solid. Pure product (154mg, 92%) is obtained after flash column as white solid (13). ÷H-NMR (CDC1 3 ) d 2.15 (m, 3H), 2.52 (m, IH) , 3.55 (s, 3H), 4.58 (s, 2H), 5.08 (s, IH, ), 5.85 (brs, IH) , 6.48 (s, IH), 7.08 (brs, IH) , 7.42 (m, 3H), 8.40 (m, 2H), 10.58 (brs, IH) ; MS (ES) : 410.1 (M ' +l) . Methyl ester 13 (124mg, 0.3mmol) is dissolved in HOCH, (15mL). Ammonia is bubbled through the solution for 0.5h. The reaction mixture is then stirred for another 3h at rt . After removal of solvent lilmg of a white solid (1510, 93%) is obtained. H-NMR (CDCl,) d 1.82 (m, 3H) , 2.20 (m, IH) , 2.80 (m, IH) , 3.10 (m, IH), 3.63 (dd, 2H, 3.87 (m, IH), 4.07 (m, IH), 4.97 (m, IH), 5.96 (m, 2H) , 6.35 (s, IH), 6.86 (brs, IH) , 7.11 (brs, IH), 7.37 (m, 3H) , 8.28 (m, 2H), 11.46 (brs, IH) ; MS (ES) : 394.8 (M ' +l) . Example 27: Synthesis of [4- (2-Carbamoylpyrrolιdιn-l-yl ) -2- phenyl-7H-pyrrolo [2, 3-d] pyrιmιdme-6-carboxylιc acid] (1511) Compound 1511 was synthesized using precursor compound 15 of synthesis scheme VII to obtain: To a suspension of sodium hydride (780mg of a 60% o l suspension, 19.5mmol) m dry DMF (20mL) , cooleα by an ice/water bath, under nitrogen, is added a solution of the pyrrolopyrimidine 15 (2.00g, 7.52mmol) m DMF iO_nL) over 5 mm. After 15 min, benzenesulfonyl chloride (1.2mL, 9.40mmol) is added, then tne cooling bath is removed. After 4n, the reaction mixture is poured into a mixture of ice and sat. NaHCO sol., the precipitated solid is filtered off and triturated with acetone (3 ) and methanol (2 ), yielding 2.37g of a beige solid. This solid (16) contains approx. 10mol-% DMF (based on that 83% yield) and can be used m the next step; a pure sample can be obtained by chromatography on silica gel using acetone as eluent. -H-NMR (CDC1 3 ) : d 6.70 (d, J = 4.2Hz, IH) , 7.47-7.68 (m, 6H) , 7.76 (d, J = 4.2Hz, IH), 8.24-8.32 (m, 2H), 8.48-8.56 (m, 2H) ; IR (solid) : n = 3146 cm ' , 1585, 1539, 1506, 1450, 1417, 1386, 1370, 1186, 1176, 1154, llll, 1015, 919, 726, 683, 616, 607; MS (ES): 372/370 (MH ) ; Tip = 226-227 °C. To a solution of the Λ/-sulfonyl compound 16 (337mg, 0.911mmol) in dry THF (34mL) , cooled by dry ice/acetone, is added LDA-THF (l.OmL, 1.5M solution cyclohexane, 1.5mmol). After 45mιn, carbon dioxide is bubbled into the solution for 5mm, then the cooling bath is removed. When the solution has reached ambient temp., the solvents are evaporated, yielding 398mg of the salt 17, containing 0.5 equiv. of ( iPr ) 2 NCO_Lι, as yellow solid. The salt is used without purification in the next step. H-NMR ( D, - DMSO): d = 6.44 (s, IH) , 7.50-7.75 (m, 6H), 8.33-8.40 (m, 2H), 8.53 (dd, J= 8.0, 1.6Hz, 2H) . A solution of the lithium salt 17 (50mg) and L-prolmamide (122mg, 1.07mmol) DMSO (1.5mL) is heated under nitrogen to 80 °C for 15.5h. 4% aq. acetic acid (lOmL) is added to the cooled solution, and the mixture is extracted with EtOAc (5 ' 10mL). The combined organic layers are washed with 4% aq. acetic acid (lOmL), water (lOmL) and brine (lOmL) and are dried over MgS04. Filtration and concentration gives 4 Omg of 18 as a yellowish solid, which is used without purification m the next step. H-NMR (CD,0D) : d = 1.95-2.36 (m, 4H), 3.85-3.95 (m, IH), 3.95-4.17 (m, IH), 4.72 (brs, IH), 7.14 (s, IH), 7.35-7.45 (m, 3H), 7.45-7.70 (m, 3H), 8.33-8.50 (m, 4H). A solution of sodium hydroxide m metnanol (1.5mL, 5M, 7.5mmol ) is added to a solution of the pyrrolopyrimidine 18 (40mg, O.Oδlmmol) m methanol (2mL) . After 2h, the pH is adjusted to 5, most of the methanol is evaporated, tie mixture is extracted with EtOAc (5 lOmL) , the combined organic layers are washed with brine and dried over MgS0 4 . Filtr a tion and concentration yields 24mg of a pale yellow solid, which is triturated with toluene/EtOAc/MeOri to yield 15.6mg (55%) cf the acid 1511 as slightly yellowish solid. : H-NMR (CD OD) : d = 2.05-2.20 (m, 4H), 3.95-4.10 (m, IH) , 4.15-4.25 (m, IH), 4.85 (brs, IH), 7.14 (s, IH) , 7.35-7.42 (m, 3H) , 8.38-8.45 (m, 2H) ; IR (solid): n = 3192 cm '1 , 2964, 2923, 2877, 1682, 1614, 1567, 1531, 1454, 1374, 1352, 1295, 1262, 1190, 974, 754, 700; MS (ES): 352 (M'+l); m.p. = 220 °C (decomp. / . Example 28: Synthesis of 1- ( 6-methyl-2-phenyl-7H-pyrrolo [2 , 3- d] pyrιmιdme-4-yl ) - (S) -pyrrolιdme-2 -carboxylic acid amide (1512) Compound 1512 was synthesized by the following steps: Aryl chloride 20 (3g, 10.7 mmol), DMSO (50ml) and (S)- prolmamide were combined and heated to 85°C under argon. After stirring overnight (14hrs), the mixture was cooled to room temperature and poured into 800ml of water. This was extracteα with three 200ml portions of EtOAc. Tne combined organic layers were thoroughly washed with water [ 3 x 300 ml), crme, αrieα over MgSO,, filtered and concentrated to give a dark brown solid. The solid was recrystallized twice from EtO^c to yield 1.95g (57%) of a tan solid (1512). HNMR (DMSO-d c ) d 1.8-2.2 (m, 4H) , 2.3 (s, 3H) , 3.8 (m, IH), 4.0 (m, IH) , 4.6 (d, IH) 6.2 (s, IH), 6.9 (s, IH) , 7.2 (m, 3H) , 7.3 (s, IH), 8.4 (m, 2H), 11.5 (s, IH) ; MS (ES) : 322 (M ' +l) Example 29: Synthesis of 1- [ 6- (2-Hydroxy-ethoxymetnyl ) -2-phenyl-7H-pyrrolo[2,3-d] pyrιmιdm-4-yl] -pyrrolιdιne-2-carb oxylic acid amide (1513) Compound 1513 was synthesized in a manner similar to that of Example 17 using synthesis scheme IX with L-prolineamide and ethane-1, 2-dιol to obtain: 1513 MS (ES) : 382 (M'+l ' Example 30: Synthesis of 4- ( 6-Imιdazol-l-ylmethyl- 2-phenyl-7H-pyrroιo[2, 3-d] pyrιmιdm-4-ylamιno) -cyclohexanol (1514) . Compound 1514 was synthesized in a manner similar to that of Example 17 using synthesis scheme IX with N-6 ammo cyclohexanol and imidazole to obtain: OH 1514 MS (ES; 389 (M ' +l Example 31: Synthesis of 4- ( 4-Hydroxy-cyclohexylammo) -2-phenyl-7H-pyrrolo [2 , 3-d] pyrιmιdιne-6-carboxylιc acid (1515) Compound 1515 was synthesized in a manner similar to that of Example 27 using synthesis scheme IX with N-6 am o cyclohexanol to obtain: OH 1515 MS (ES) : 353 (M'+i; Example 32: Synthesis of 4- [ 6- (2-Hydroxy-ethoxymethyl ) -2-phenyl-7H-pyrrolo[2,3-d] pyrimidm-4-ylamιno] -cyclohexanol (1516) Compound 1516 was synthesized in a manner similar to that of Compound 1513 using synthesis scheme IX with N-6 amino cyclohexanol to obtain: OH 1516 MS (ES) : 383 (M ' +l) Example 33: Synthesis of 4- ( 4-Hydroxy-cyclohexylammo) -2-phenyl-7H-pyrrolo [2 , 3-d] pyrιmιdme-6-carboxylιc acid methyl ester (1517) A solution of the lithium salt 17 (O.lSmmol) in dry DMF (4mL) is stirred with methyl iodide (O.lmL, i.6mmol) at 20 °C under argon for 3h. DMF is evaporated, and aqueous ammonium chloride solution is added (15mL). The mixture is extracted with EtOAc (3 ' 15mL), the combined organic layers are washed with water (2'10mL) and brine (lOmL) and are dried over MgSO„ . Filtration and concentration gives 21mg (38%) of the methyl ester 22. A solution of the methyl ester 22 (24.5mg, 0.057mmol) and & - traπs-aminocyclohexanol (66mg, 0.57mmol) m DMSO (1.5mL) is heated under nitrogen to 80 °C for 5t , then the heating is stopped, and stirring at 20 °C is continued for 13.5n. 4% aq. acetic acid (lOmL) is added to the cooled solution, and the mixture is extracted with EtOAc (3 ' 10mL) . The combined organic layers are washed with 4% aq. acetic acid (lOmL), water (lOmL) 2N NaOH (lOmL), water (lOmL), and brine (lOmL) and are dried over MgSO,. To a solution of the crude material obtained after filtration and concentration (IH NMR indicates about 50% removal of the benzenesulfonyl group) _n THF (2mL) is added a solution of NaOH m MeOH ( 0.5mL of 5κ solution, 2.5mmol) at ambient temperature. After 20mm, water and sat. NaHCO- solution (5mL each) are added, and the mixture is extracted with EtOAc (4 15mL) . The combined organic layers are washed with 2N NaOH (lOmL), water (lOmL), and brine (lOmL) and are dried over MgSO,.. Chromatography of the crude material obtained after filtration and concentration on silica gel, eluting with hexanes/EtOAc 1:1 © 1:2 yields 8.6mg (4l%) of 1517 as a white solid, mp. 225-227 °C. X H-NMR (CD 3 OD) : d = 1.38-1.62 (m, 4H) , 1.95-2.10 (m, 2H), 2.10-2.25 (m, 2H) , 3.55-3.70 (m, IH), 3.91 (s, 3H), 4.20-4.35 (m, IH) , 7.32 (s, lri) , 7.35-7.47 (m, 3H) , 8.35-8.42 (m, 2H) ; IR (solid): n = 3352 cm " , 3064, 2935, 2860, 1701, 1605, 1588, 1574, 1534, 1447, 1386, 1333, 1263, 1206, 1164, 1074, 938, 756, 705; MS (ES): 367 (MH ' ). Example 34: Synthesis of [4- (2-Carbamoyl-pyrrolιαm-l-yl ) -2 -phenyl -7H-pyrrolo [2, 3-d] ρyπmιdιn-6-ylmethoxy] -acetic acid methyl ester (1518) Compound 1518 was synthesized m a manner similar to example 26 using precursor compound 12 to obtain: 1518 MS (ES) : 410 (M'+l Example 35: Synthesis of [ 4- (2-Carbamoyl-pyrrolιdιn-l-yl ) -2-phenyl-7H-pyrrolo [2, 3-d] pyrιmιdιn-6-ylmethoxy] -acetic acid (1519) Compound 1519 was synthesized in a manner similar to compound 1518 wherein the methyl ester group was hydrolized with a base to obtain: h- 1519 MS : 396 (M * +i; 15 Example - "* : Synthesis of 4- ( 4-Hydroxy-cyclohexylamino) -2- phenyl-7H- 'trolo [2, 3-d] pyrimidine-6-carboxylic acid amide (1520) 23 1520 20 Gaseous ammonia is condensed into a solution of tne pyrrolopyrimidine 23 (7.8mg, 0.021mmol) m methanol ( 6mL) , cooled by dry ice/acetone, until a total volume of 12mL is reached. After stirring for lOd at 20 °C, tne solvents are evaporated, and the residue is purified by preparative TLC on silica gel, eluting with 5% MeOH m CH : C1 2 . The material thus obtained is triturated with ether to yield 6.5mg (88%) of the amide 1520 as white solid, mp . 210-220 °C (decomp.). H-NMR (CD : OD) : d = 1.40-1.60 (m, 4H) , 2.00-2.15 (m, 2H) , 2.15-2.25 (m, 2H), 3.55-3.70 (m, IH) , 4.20-4.35 (rr, IH) , 7.16 (s, IH) , 7.35-7.47 (m, 3H) , 8.34-8.40 (m, 2H) ; IR (solid) : n = 3358 cm ' , 3064, 3025, 2964, 2924, 2853, 1652, 1593, 1539, 1493, 1452, 1374, 1326, 1251, 1197, 1113, 1074, 1028, 751, 699; MS (ES): 352 ( H ~ ) . Activity of Compounds Adenosine 1 (A : ) receptor subtype saturation and competition radio ligand binding were carried out for compounds 1505, 1506, 1507, 1508, 1509, 1510, 1511, 1512, 1513, 1514, 1516, 1517, 1518, 1519, and 1520 as described herein and inter alia , on pages 152-153 of this specification. All of the above- referenced compounds equaled or surpassed the A, receptor binding affinity of reference compounds 1318 or 1319 as described herein and, in ter al ia , m Table 13, on page 171 of the specification. The water solubilities of the above compounds listed in Table 18 are expected to be better than reference compounds 1318 or 1319 due to tneir cLogP values, which were calculated using the computer program CS ChemDraw, ChemDraw Ultra ver. 6.0 ©1999 as provided by CambridgeSoft Corporation, 100 Cambridge Park Drive, Cambridge, MA 02140. The compounds specific to the A : receptor listed m Table 18 had lower cLogP values, between about 1.5 to about 3.4, as compared to reference compounds 1318 or 1319 with a cLogP value about 3.8. It was not predicted that the more polar A : receptor compounds listed in Table 18 having lower cLogP values than the reference compounds 1318 or 1319 would still retain the potency and A : receptor binding selectivity as compared to those reference compounds. Table 18 10 15 20 25 Pages 288-293 relate to additional coπpounds specific to A receptor This invention provides a compound having the structure: 1609 This invention also provides a compound having the structure 1610 In a further embodiment the invention provides a method for treating a disease associated with A2a adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of compounds 1609 or 1610. The invention also provides the above method, wherein the subject is a mammal. The invention further provides the above method, wherein the mammal is a human. The invention also provides the method for treating a disease associated with A2a adenosine receptor in a subject, wherein the A 2a adenosine receptor is associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, senile dementia, or Parkinson's disease. The invention provides the above method, wherein the compound treats the diseases by stimulating adenylate cyclase. The invention also provides a water-soluble prodrug of the compound 1609 or 1610, wherein the water-soluble prodrug is metabolized in vivo to an active drug to selectively inhibit an A 2a adenosine receptor. The invention also provides a water-soluble prodrug of the compound 1609 or 1610, wherein the prodrug is metabolized in vivo by esterase catalyzed hydrolysis. The invention also provides a pharmaceutical composition comprising the water-soluble prodrug of the compound 1609 or 1610, and a pharmaceutically acceptable carrier. The invention also provides a method for inhibiting the activity of an A 2a adenosine receptor in a cell, which comprises contacting the cell with compound 1609 or 1610. The invention also provides a method for inhibiting the activity of an A 2a adenosine receptor in a cell, which comprises contacting the cell with compound 1609 or 1610, wherein the compound is an antagonist of said A 2a adenosine receptor. The invention also provides the above method, wherein the cell is a human cell. The invention also provides the above method, wherein the cell is a human cell and the compound is an antagonist of A, a adenosine receptors. The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of the compound 1609 or 1610 and a pharmaceutically acceptable carrier. The invention also provides the above pharmaceutical composition, wherein the therapeutically effective amount is effective to treat Parkinson's disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is an ophthalmic formulation. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is a systemic formulation. The invention also provides the above pharmaceutical composition, wherein the pharmaceutical composition is a surgical irrigating solution. The invention also provides a combination therapy for Parkinson's disease, comprising the compounds 1609 or 1610, and any of the dopamine enhancers . The invention also provides a combination therapy for cancer, comprising the compound 1609 or 1610, and any of the cytotoxic agents . The invention also provides a combination therapy for glaucoma, comprising the compound 1609 or 1610, and a prostaglandin agonist, a muscrinic agonist, or a β-2 antagonist. The invention also provides a packaged pharmaceutical composition for treating a disease associated with A 2a adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound 1609 or 1610; and (b) instructions for using the compound for treating said disease in a subject. Exemplification Example 41: Synthesis of 1- ( 6-Phenyl-2-pyridin-4-yl- 7H- pyrrolo[2,3-d] pyrimidin-4-yl] -pyrrolidine-2-carboxylic acid amide (1609) . Compound 1609 was synthesized by reacting L-prolinamide with the appropriate chloride intermediate described in synthesis scheme II on page 82 to obtain: 1609 Η-NMR (d 6 -DMSO) d 1.95-2.15 (m, 4H) , 4.00 (brs, IH) , 4.15 (brs, IH) , 4.72 (brs, IH) , 6.90 (brs, IH) , 7.19 (brs, IH) , 7.30 (t, IH, J = 7.0Hz), 7.44 (t, 2H, J = 7.0Hz) , 7.59 (s, IH) , 7.92 (brs, 2H) , 8.26 (d,2H, J = 6.2Hz) , 8.65 (d, 2H, J = 6.2Hz) ; MS (ES) : 384.9 (M ' + l) ; Mpt = 280-316°C (decomp.) . Example 42: Synthesis of 1- [ 6- ( 3-Methoxy-phenyl ) -2-pyrιαιr--- yl- 7#-pyrrolo [2, 3-d] pyrιmιdm-4 -yl ] acid amide (1610) . Compound 1610 was synthesized by reacting L-prolmamide with the appropriate chloride intermediate described m synthesis scheme II on page 82 to obtain: 1610 H-NMR (d 6 -DMSO) d 2.07(m,4H) , 3.85(s,3H) , 4.02(m,lH) , 4.17(m,lH) , 4.75 (m,lH), 6.89(m,lH) , 7.00(s,lH) , 7.23(s,lH) , 7.35 (t, IH, J=8.2Hz) , 7.53(s,2H) , 7.60(s,iH), 8.28 (d, 2H, J=5.8Hz ) , 8.67 (d,2H, J=5.8Hz) , 12.37 (s, IH) ; MS (ES) : 415.0 (M'+l) . Activity of Compounds Adenosine 2a (A 2 receptor subtype competition radio ligand binding were carried out for compounds 1609 and 1610 as described herein and ter alia, on page 153 of this specification. Compounds 1609 and 1610 were found have A 2a receptor binding affinity and selectivity. Pages 294-300 relate to additional compounds specific to A. receptor This invention also provides a compound having the structure: 1720 In a further embodiment the invention provides a method for inhibiting the activity of an A3 adenosine receptor in a cell, which comprises contacting the cell with the compound 1720. In a further embodiment the invention provides a method for inhibiting the activity of an A3 adenosine receptor in a cell, wherein the compound is an antagonist of the A 3 adenosine receptor. In a further embodiment the invention provides the above method for inhibiting the activity of an A3 adenosine receptor in a cell, wherein the cell is human cell. In a further embodiment the invention provides the above method for inhibiting the activity of an A3 adenosine receptor in a cell, wherein the cell is a human cell and wherein the compound is an antagonist of A3 adenosine receptors. In a further embodiment the invention provides a method of treating damage to the eye of a subject which comprises administering to the subject a composition comprising a therapeutically effective amount of the compound 1720. In a further embodiment the invention provides the above method, wherein the damage comprises retinal or optic nerve head damage. In a further embodiment the invention provides a therapy for glaucoma, comprising administering to a subject a therapeutically effective amount of the compound 1720. In a further embodiment the invention provides a therapy for glaucoma comprising one or more adenosine receptor antagonists, preferably comprising an adenosine receptor A3 antagonist (preferably an N-6 substituted 7-deazapurme, most preferably [2-(3ff-Imιdazol-4-yl)-ethyl]-(2-phenyl-7H-pyrrolo[2,3- d] pyrιmιdm-4-yl ) -amme) . In an alternative embodiment the invention provides a combination therapy for glaucoma comprising an adenosine receptor A3 antagonist (preferably an N-6 substituted 7- deazapur e, most preferably [2- (3H-Imj.dazol-4-yl ) -ethyl] - (2- phenyl-7ff-pyrrolo [2, 3-d] pyrιmιdm-4-yl ) -amine) ) and one or more other compounds selected from the group consisting of beta adrenoceptor antagonists (i.e. beta adrenergic antagonists or b-blockers) (e.g. timolol maleate, betaxolol, carteolol, levobunolol, metipranolol, L-653328 (tne acetate ester of L- 652698), beta 1 adrenoceptor antagonists), alpha-2 adrenoceptor agonists (e.g. aplaclonidme, bπmonidine, AGN-195795, AGN- 190837 (an analog of Bay-a-6781 ) ) , carbonic anhydrase inhibitors (brmzolamide, dorzolamide, MK-927 (an inhibitor of the human carbonic anhydrase II isoenzyme), inhibitors of carbonic anhydrase IV isoenzyme), cholmergic agonists (e.g. muscarinic cholmergic agonists, carbachol, pilocarpme HCl, pilocarpme nitrate, pilocarpme, pilocarpme prodrugs (e.g. DD-22A) ) , prostaglandms and prostaglandm receptor agonists (e.g. latanoprost, unoprostone isopropyl, PGF2 alpha agonists, prostanoid-selective FP receptor agonists, PG agonists such as the hypotensive prostamides) , angiotensm converting enzyme (ACE) inhibitors (e.g. Spirapril, spiraprilat ) , AMPA receptor antagonists, 5-HT agonists (e.g. a selective 5-HT 1A receptor agonist such as MKC-242 ( 5-3- [ ( (2S) -1 , 4-benzodιoxan-2- ylmethyl ) ammo] propoxy-1, 3-benxodιoxole HCl), angiogenesis inhibitors (e.g. the steroid anecortave), NMDA antagonists (e.g. HU-211, memantme, the cannabmoid NMDA-receptor agonist dexanabmol, prodrugs and analogs of dexanabmol, NR2B- selective antagonists (e.g. eliprodil (SL-82.0715) ) , renin inhibitors (e.g. CGP-38560, SR-43845), cannabmoid receptor agonists (e.g. tetrahydrocannabmol (THC) and THC analogs, selective CB2 cannabmoid receptor agonists (e.g. L-768242, L- 759787), compounds such as anandamide that bind to both brain- specific CB1 receptors and peripheral CB2 receptors), angiotensm receptor antagonists (e.g., angiotensm II receptor antagonists (e.g. CS-088), selective angiotens II AT-I receptor antagonists, such as losartan potassxum , hydrochlorothiazide (HCTZ), somatostatm agonists (e.g. the non-peptide somatostatm agonist NNC-26-9100), glucocorticoxd antagonists, mast cell degranulation inhibitors (e.g. nedocromil), alpha-adrenergic receptor blockers (e.g. dapiprazole, alpha-2 adrenoceptor antagonists, alpha 1 adrenoceptor antagonists (e.g. ounazosm) ) , alpha-2 adrenoceptor antagonists, thromboxane A2 mimetics, protein kinase inhibitors (e.g. H7), prostaglandin F derivatives (e.g. S-1033), prostaglandιn-2 alpha antagonists (e.g. PhXA-34), dopamine Dl and 5-HT2 agonists ( fenoldopam) , nitπc-oxide- releasmg agents (e.g. NCX-904 or NCX-905, nitπc-oxide- releasmg derivatives of timolol), 5-hT 2 antagonists (e.g. sarpogrelate) , NMDA antagonists (e.g. prodrugs and analogs of dexanabmol), alpha 1 adrenoceptor antagonists (e.g. bunazosm), cyclooxygenase inhibitors (e.g. diclofenac, or the non-steroidal compound nepafenac) , inosine, dopamine D2 receptor and alpha 2 adrenoceptor agonists (e.g. talipexole) , dopamine Dl receptor antagonist and D2 receptor agonists (e.g. SDZ-GLC-756) , vasopressin receptor antagonists (e.g. vasopressm V2 receptor antagonists (e.g. SR-121463)), endothelm antagonists (e.g. TBC-2576), 1- ( 3-hydroxy-2- phosphonylmethoxypropyl cytosine (HPMPC) and related analogs and prodrugs, thyroid hormone receptor ligands (e.g. KB- 130015), muscannic Ml agonists, NMDΛ-receptor antagonists (e.g. the cannabmoid NMDA-receptor antagonist dexanabmol) , PG agonists such as the hypotensive lipids, prostamides, sodium channel blockers, NMDA antagonists, mixed-action ion channel blockers, beta adrenoceptor antagonist and PGF2 alpha agonist combinations (e.g. latanoprost and timolol), cyclase activators (e.g. atrial natriuretic _>eptιde (ANP) or non- peptide mimetics, inhibitors of ANP neutral endopeptidase, nitrovasodilators (e.g. nitroglycerin, hydralazme, sodium nitroprusside) , endothelm receptor modulators (e.g. ET-1 or non-peptide mimetics, sarafotoxin-Sδc) , etnacrynic acid, other phenoxyacetic acid analogs (e.g. mdacrmone, ticrynafen) , actm disrupters (e.g. latrunculin) , calcium channel blockers (e.g. verapamil, nifedipine, brovmcanme, mvaldipine) and neuroprotective agents. A combination therapy for glaucoma, comprising the compound of 1702, and one or more compounds selected from the group consisting of beta adrenoceptor antagonists, alpha-2 adrenoceptor agonists, carbonic anhydrase inhibitors, cholmergic agonists and prostaglandm receptor agonists. In a further embodiment the invention provides a pharmaceutical composition comprising a therapeutically effective amount of the compound 1720 and a pharmaceutically acceptable carrier. In a further embodiment the invention provides a packaged pharmaceutical composition for treating a disease associated with A3 adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound 1720; and (b) instructions for using said compound for treating said disease in a subject. In a further embodiment the invention provides a method of making a composition which comprises the compound 1720, the method comprising admixing the compound 1702 with a suitable carrier. In a further embodiment the invention provides a pharmaceutically acceptable salt of compound 1720, wherein the pharmaceutically acceptable salt contains an anion selected from the group consisting of maleic, fumaric, tartaric, acetate, phosphate and mesylate. Exemplification Example 43: Synthesis of [2- (3H-Imidazol-4-yl ) -ethyl] - (2- phenyl-7f-pyrrolo [2, 3-dj pyrimidin-4 -yl) -amine (1720) Compound 1720 was synthesized using precursor compound 1 of synthesis scheme VII to obtain: Aryl chloride 1 (400mg, 1.50mmol), DMSO (lOmL) and histamme (1.67g, 15.0mmol) are combined and heated to 120°C under nitrogen. After 6.5h, the reaction is cooled to room temperature and partitioned between EtOAc and water. The layers are separated and the aqueous layer is extracted with EtOAc (3x). The combined organic layers are washed with brine (2x), dried over MgS0 4 , filtered and concentrated to yield 494mg of a brown solid. The solid is washec with cold MeOH and recrystallized from MeOH to yield 197mg (43%) of an off white solid (1720). 'H-NMR (CD,OD) d 3.05 (t, 2H, J = 7.0Hz), 3.94 (t, 2H, J = 7.0Hz), 6.50 (d, IH, J = 3.5Hz), 6.88 (brs, IH) , 7.04 (d, IH, J = 3.5Hz), 7.42 (m, 3H) , 7.57 (s, IH) , 8.34 (m, 2H) ; MS (ES) : 305.1 (M+l); Mpt = 234-235 c C. Activity of Compounds Adenosine 3 (A 3 ) receptor competition radio ligand binding was carried out for compound 1720 as described herein and in ter al ia , on pages 153-154 of this specification. Compound 1720 was found to have an A- receptor binding affinity greater than 10 times that of reference compound 1308 as described herein and, in ter alia , m Table 13, on page 169 of the specification. Incorporation by Reference All patents, published patent applications and other references disclosed herein are hereby expressly -incorporated herein by reference. Equivalents Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, many equivalents to specific embodiments of the invention described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims. This invention further provides compounds having the formula: XI wherein R X NR 2 together form a ring having the structure R 5 is H, or substituted or unsubstituted alkyl or alkylaryl .

Claims: What is claimed is 1. A compound having the structure : wherein RjNR 2 together form a ring having the structure R 5 is H, or substituted or unsubstituted alkyl or alkylaryl . The compound of claim 1, having the structure: 3. The compound of claim 1, having the structure The compound of claim 1, having the structure 5. The compound of claim 1, having the structure The compound of claim 1, having the structure: 7. The compound of claim 1, having the structure The compound of claim 1, having the structure 9. The compound of claim 1, having the structure: 10. The compound of claim 1, having the structure 11. The compound of claim 1, having the structure 12. The compound of claim 1, having the structure: 13. The compound of claim 1, having the structure 14. The compound of claim 1 , having the structure: 15. The compound of claim 1, having the structure: 16. The compound of claim 1, having the structure 17. The compound of claim 1, having the structure 18. A method for treating a disease associated with Ai adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1. 19. The method of claim 18, wherein the subject is a mammal . 20. The method of claim 19, wherein the mammal is a human. 21. The method of claim 18, wherein said Ai adenosine receptor is associated with cognitive disease, renal failure, cardiac arrhythmias, respiratory epithelia, transmitter release, sedation, vasoconstriction, bradycardia, negative cardiac inotropy and dromotropy, branchoconstriction, neutropil chemotaxis, reflux condition, or ulcerative condition. 22. A water-soluble prodrug of the compounds of claim 1, wherein the water-soluble prodrug is metabolized in vivo to produce an active drug which selectively inhibits Ai adenosine receptor. 23. The prodrug of claim 22, wherein said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. 24. A pharmaceutical composition comprising the prodrug of claim 22 and a pharmaceutically acceptable carrier. 25. A method for inhibiting the activity of an Ai adenosine receptor in a cell, which comprises contacting the cell with a compound of claim 1. 26. The method of claim 25, wherein the compound is an antagonist of the Ai adenosine receptor. 27. The method of claim 25, wherein the cell is human cell. 28. The method of claim 27, wherein the compound is an antagonist of Ai adenosine receptors. 29. The method of claim 18, wherein said disease is asthma, chronic obstructive pulmonary disease, allergic rhinitis, or an upper respiratory disorder. 30. The method of claim 29, wherein the subject is a human. 31. The method of claim 30, wherein said compound is an antagonist of Ai adenosine receptors. 32. A combination therapy for asthma, comprising the compound of claim 1, and a steroid, β2 agonist, glucocort icoid, lucotriene antagonist, or anticolinergic agonist. 33. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1, and a pharmaceutically acceptable carrier. 34. The method of claim 29, wherein said respiratory disorder is asthma, allergic rhinitis, or chronic obstructive pulmonary disease. 35. The pharmaceutical composition of claim 33, wherein said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. 36. The pharmaceutical composition of claim 33, wherein said pharmaceutical composition is a systemic formulation. 37. The pharmaceutical composition of claim 33, wherein said pharmaceutical composition is a surgical irrigating solution. 38. A packaged pharmaceutical composition for treating a disease associated with Ai adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound of claim 1; and (b) instructions for using said compound for treating said disease in a subject. 39. A pharmaceutically acceptable salt of the compound of claim 1. 40. The pharmaceutically acceptable salt of claim 39, wherein the pharmaceutically acceptable salt of the compound of claims 6, 8, 12, 15, or 16 contains a cation selected from the group consisting of sodium, calcium and ammonium. 41. The method of claim 18, wherein the Ai adenosine receptor is associated with congestive heart failure. 42. A compound having the structure 43. A compound having the structure: 44. A method for treating a disease associated with A2a adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 42 or 43. 45. The method of claim 44, wherein the subject is a mammal . 46. The method of claim 45, wherein the mammal is a human. 47. The method of claim 46, wherein said A 2a adenosine receptor is associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, senile dementia, or Parkinson's disease. 48. The method of claim 44, wherein the compound treats said diseases by stimulating adenylate cyclase. 49. A water-soluble prodrug of the compound of claim 42 or 43, wherein said water-soluble prodrug that is metabolized in vivo to an active drug which selectively inhibit A 2a adenosine receptor. 50. The prodrug of claim 49, wherein said prodrug is metabolized in vivo by esterase catalyzed hydrolysis. 51. A pharmaceutical composition comprising the prodrug of claim 49 and a pharmaceutically acceptable carrier. 52. A method for inhibiting the activity of an A 2a adenosine receptor in a cell, which comprises contacting said cell with a compound of claims 42 or 43. 53. The method of claim 52, wherein the compound is an antagonist of said A 2a adenosine receptor. 54. The method of claim 53, wherein the cell is a human cell. 55. The method of claim 53, wherein the compound is an antagonist of A 2a adenosine receptors. 56. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claims 42 or 43 and a pharmaceutically acceptable carrier. 57. The pharmaceutical composition of claim 56, wherein said therapeutically effective amount is effective to treat Parkinson's disease and diseases associated with locomotor activity, vasodilation, platelet inhibition, neutrophil superoxide generation, cognitive disorder, or senile dementia. 58. The pharmaceutical composition of claim 56, wherein said pharmaceutical composition is an ophthalmic formulation. 59. The pharmaceutical composition of claim 56, wherein said pharmaceutical composition is an periocular, retrobulbar or intraocular injection formulation. 60. The pharmaceutical composition of claim 56, wherein said pharmaceutical composition is a systemic formulation. 61. The pharmaceutical composition of claim 56, wherein said pharmaceutical composition is a surgical irrigating solution. 62. A combination therapy for Parkinson's disease, comprising the compounds of claim 42 or 43, and any of the dopamine enhancers . 63. A combinational therapy for cancer, comprising the compound of claim 42 or 43, and any of the cytotoxic agents . 64. A combinational therapy for glaucoma, comprising the compound of claim 42 or 43, and a prostaglandin agonist, a muscrinic agonist, or a β-2 antagonist. 65. A packaged pharmaceutical composition for treating a disease associated with A 2a adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound of claim 42 or 43; and (b) instructions for using said compound for treating said disease in a subject. 66. A pharmaceutically acceptable salt of the compound of claim 42 or 43. 67. The pharmaceutically acceptable salt of claim 66, wherein the pharmaceutically acceptable salt of the compound of claim 41 or 42 contains anion selected from the group consisting of maleic, fumaric, tartaric, acetate, phosphate and mesylate. 68. A compound having the structure: 69. A method for inhibiting the activity of an A3 adenosine receptor in a cell, which comprises contacting the cell with a compound of claim 68. 70. The method of claim 69, wherein the compound is an antagonist of the 3 adenosine receptor. 71. The method of claim 69, wherein the cell is human cell. 72. The method of claim 71, wherein the compound is an antagonist of A3 adenosine receptors. 73. A method of treating damage to the eye of a subject which comprises administering to the subject a composition comprising a therapeutically effective amount of the compound of claim 68. 74. The method of claim 73, wherein the damage comprises retinal or optic nerve head damage. 75. A therapy for glaucoma, comprising administering to a subject a therapeutically effective amount of the compound of claim 68. 76. A combination therapy for glaucoma, comprising the compound of claim 68, and one or more compounds selected from the group consisting of beta adrenoceptor antagonists, alpha-2 adrenoceptor agonists, carbonic anhydrase inhibitors, cholinergic agonists, prostaglandins and prostaglandin receptor agonists, angiotensin converting enzyme (ACE) inhibitors, AMPA receptor antagonists, 5-HT agonists, angiogenesis inhibitors, NMDA antagonists, renin inhibitors, cannabinoid receptor agonists, angiotensin receptor antagonists, hydrochlorothiazide (HCTZ), somatostatin agonists , glucocorticoid antagonists, mast cell degranulation inhibitors, alpha-adrenergic receptor blockers, alpha-2 adrenoceptor antagonists, thromboxane A2 mimetics, protein kinase inhibitors, prostaglandin F derivatives, prostaglandin-2 alpha antagonists, dopamine Dl and 5-HT2 agonists, nitric-oxide-releasing agents, 5-HT 2 antagonists, cyclooxygenase inhibitors, inosine, dopamine D2 receptor and alpha 2 adrenoceptor agonists, dopamine Dl receptor antagonist and D2 receptor agonists, vasopressin receptor antagonists, endothelin antagonists, 1 - ( 3 - hydr oxy- 2 - phosphonylmethoxypropyl) cytosine (HPMPC) and related analogs and prodrugs, thyroid hormone receptor ligands, muscarinic Ml agonists, sodium channel blockers, mixed- action ion channel blockers, beta adrenoceptor antagonist and PGF2 alpha agonist combinations, guanylate cyclase activators, nitrovasodilators , endothelin receptor modulators, ethacrynic acid, other phenoxyacetic acid analogs, actin disrupters, calcium channel blockers and neuroprotective agents. 77. A combination therapy for glaucoma, comprising the compound of claim 68, and one or more compounds selected from the group consisting of beta adrenoceptor antagonists, alpha-2 adrenoceptor agonists, carbonic anhydrase inhibitors, cholinergic agonists and prostaglandin receptor agonists. 78. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 68 and a pharmaceutically acceptable carrier. 79. A packaged pharmaceutical composition for treating a disease associated with A3 adenosine receptor in a subject, comprising: (a) a container holding a therapeutically effective amount of the compound of claim 68; and (b) instructions for using said compound for treating said disease in a subject. 80. A method of making a composition which comprises the compound of claim 68, the method comprising admixing the compound of claim 68 with a suitable carrier. 81. A pharmaceutically acceptable salt of the compound of claim 68. 82. The pharmaceutically acceptable salt of claim 81, wherein the pharmaceutically acceptable salt contains an anion selected from the group consisting of maleic, fumaric, tartaric, acetate, phosphate and mesylate.

Inventors: CASTELHANO ARLINDO L, MCKIBBEN BRYAN, WITTER DAVID J, CASTELHANO, ARLINDO, L., MCKIBBEN, BRYAN, WITTER, DAVID, J.
Applicants: OSI PHARM INC, OSI PHARMACEUTICALS, INC.
Application year: 2001
Main classification: C07D487
IPC codes: A61K9, A61K31, A61K45, A61P5, A61P7, A61P9, A61P11, A61P13, A61P25, A61P27, A61P29, A61P37, A61P39, A61P43, C07D487