MXPA06002223A

MXPA06002223A - Substituted 8-heteroaryl xanthines

Info

Publication number: MXPA06002223A
Application number: MXPA/A/2006/002223A
Authority: MX
Inventors: Wang Guoquan; M Rieger Jayson; D Thompson Robert
Original assignee: Adenosine Therapeutics Llc; M Rieger Jayson; D Thompson Robert; Wang Guoquan
Priority date: 2003-08-25
Filing date: 2006-02-24
Publication date: 2007-04-20

Abstract

The present invention provides compounds and pharmaceutical compositions that are selective antagonists of A2B adenosine receptors (ARs). These compounds and compositions are useful as pharmaceutical agents.

Description

XANTINAS 8-HETEROARILO SUBSTITUTE FIELD OF THE INVENTION The present invention relates to compounds and pharmaceutical compositions that are selective antagonists of A2B adenosine (ARs) receptors. These compounds and compositions are useful as pharmaceutical agents.

BACKGROUND OF THE INVENTION The alkylxanthine theophylline (compound A) an antagonist Weak non-selective adenosine (See Linden, J., et al., Cardiovascular Biology of Purines, eds. G. Burnstoc, et al., 1998, p. 1-20) is therapeutically useful for the treatment of asthma. However, its use is associated with undesirable side effects, such as insomnia and diuresis. In recent years, the use of theophylline as a bronchodilator for the relief of asthma has been supplanted by drugs of other classes, namely, selective β2-adrenergic agonists, corticosteroids, and recently leukotriene antagonists. These compounds also have limitations, therefore, the development of a drug of the theophylline type with reduced side effects remains desirable. It has been recognized that theophylline and its closely related caffeine analog block endogenous adenosine by acting as a local modulator of adenosine receptors in the brain and in other organs at therapeutically useful doses. Adenosine activates four subtypes of adenosine receptors coupled to the G protein (ARs), A | / A2A / A2B / A3. Enprophyllin, (compound B), is another example of a xanthine which has been reported to block adenosine A2B receptors and is used to treat asthma. However, this compound only weakly blocks the adenosine A,, A2A and A3 receptors. It has also been shown by LaNoue eí al. (U.S. Patent No. 6,060,481) that selective A2B adenosine antagonists are useful for improving insulin sensitivity in a patient. Therapeutic concentrations of theophylline or enprolifein have been reported to block human A2B receptors, and it has been suggested that selective antagonists for this subtype may have potential use as antiasthmatic agents. (See Feoktistov, I., et al., Pharmacol Rev. 1997. 49, 381-402, and Robeva, AS., Et al., Drug Dev. Res. 1996, 39, 243-252). The enprofilina has a value Kl, declared of 7μ and is something selective in the union to the ARs A2B human. (See Robeva, AS., At .. Drug Dev. Res. 1996, 39, 243-252 and Linden, J., et al., Mol.Pharmacol., 1999, 56, 705-713). A2B ARs are expressed in some mast cells, such as the BR line of canine mastocytoma cells, which appear to be responsible for triggering acute Ca2 + mobilization and degranulation. (See Auchampach, J.A. et al., Mol.Pharmacol., 1997, 52, 846-860 and Forsyth, P., et al., Inflamm. Res. 1999, 48, 301-307). The Ars A2B also trigger the mobilization of Ca2 +, and participate in a delayed release of IL8 from human HMC-1 mast cells. Other functions associated with AR A2B are the control of cell development and gene expression (see Neary, J., et al., Trends Neurosci 1996, 19, 1 3-1 8) vasodilatation of endothelial dependence (See Martin, PL., Et al., J. Pharmacol. Exp. Ther 1993, 265. 248-253), and fluid secretion from the intestinal epithelium. (See Strohmeier, GR., Et al., J Biol. Chem. 1995, 270. 2387-2394). It has also been reported that adenosine acting through ARs A2B stimulates chloride permeability in cells expressing the transport regulator of cystic fibrosis. (See Clancy, J. P., et al., Am. J Physiol. 1999, 276. C361 -0369) Recently, Linden went to. (U.S. Patent No. 6. 545.002) have described a new group of compounds and pharmaceutical compositions that are selective antagonists of adenosine A2B receptors (ARs). Although selective probes of the adenosine receptor subtype are available for A1 f A2A, and A3 ARs, only a few selective antagonists and no selective agonists for the A2B receptor are known. Therefore, there continues to be a continuing need for compounds that are selective antagonists of the A2B receptor.

BRIEF DESCRIPTION OF THE INVENTION The present invention provides compounds that act as antagonists of adenosine A2B receptors. Accordingly, the present invention provides a compound of formula wherein: R is hydrogen, (C5) alkyl, haloalkyl (C3-C5) alkenyl or (C3-C5) alkynyl; R1 and R2 are independently hydrogen, alkyl (Cr C8), alkenyl (C3-C8), alkynyl (C3-C8), alkoxy (C ^ Cs), cycloalkyl (C3-C8), cycloalkylocyls-CsJalkyloylC ^ Ca) -, heterocycle (C4-C10), heterocycle (C4-C10) alkyl (C1-C8) -, aryl (C6-C10), aryl (C6-C? O) alkyl (C1-C8) -, heteroaryl (C5-C10), or heteroaryl (C5-C? o) alkyl (C? -8) -; X is a 5-10 membered heteroaryl ring having a nitrogen atom and which is optionally interrupted with 1, 2, or 3 non-peroxy oxy (-O-), thio (-S-), sulfinyl (-SO) groups -), sulfonyl (-S (O) z-) or amine -N (R9) -; Z is -OR3, -SR3, halo, S (O) mNR4R5, -NR4R5, or heterocycle (C4-C? O) wherein the heterocycle is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano. nitro, -ORa, -SRa, alkyl (d-Cß), aryl (Cß-C10), -O-aryl (C6-C10), hydroxyalkyl (C? -Cβ), RbRcNalkyl (C1-C8), haloalkyl (d-C8) ), - NR Rc, C (O) Ra, -COORa, and -C (O) NRbRc each Z1 is independently alkyl (d-C8), alkenyl (C2-C8), (C2-C8) alkynyl, -OR6, -SR6 > halo, R6Oalkyl (d-C8), R7R8Nalkyl (d-C8), haloacyl (d-Cß), -NR7R8, R7R8Nalkyl (d-Cß). -C (O) R6, COOR6 and -C (O) NR7R8 R3 is (d-C8) alkyl, (C3-C8) alkenyl, (C3-C8) alkynyl, (C3-C8) aryl, (C6-C10) aryl ) (C 1 -C 8) -alkyl, (C 5 -C 10) heteroaryl, β-β-arylalkyl-Cι-JalkyloylC ^Cβ), -C (O) R 6, or -C (O) NR 7 R 8; R4 and R5 are independently hydrogen, (d-C8) alkyl, (C3-Ca) alkenyl, (C3-C8) alkynyl, (d-C8) alkoxy, (C3-C8) cycloalkyl, (C3-C8) cycloalkyl, alkyl ( C1-C8) -, polycycloalkyl (C6-C18), polycycloalkyl (C6-C18) alkyl (d-C8) -, heterocycle, heterocycle (C3-C10) alkyl (d-C8) -, -NR7R8, aryl (C6-C10), aryl-C9-dC-C8-alkyl) -alkyl-, (C5-C10) heteroaryl, (C5-C6) heteroaryl (C1-C8) -alkyl, - (C2-C4-Y) q- (CH2) 2-4X1, -C (O) R6, -CO2R6, -C (O) NR7R8, or -S (O) 2 -NR7R8 or R4 and R5 together with the atoms to which they are attached form a mono ring -, bicyclic- or saturated or partially unsaturated aromatic having 3, 4, 5, 6, 7, or 8, atoms in the ring and optionally comprising 1, 2, 3, or 4 heteroatoms selected from non-peroxide oxy (-O -), thio (-S-), sulfinyl (-SO-), sulfonyl (-S (O) 2-) and amine -N (R9) - in the ring, where the ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa , -SRa, (C6-d0) aryl, - Oaplo (C6, -C10), hydroxyalkyl (dd), RbRcNalkyl (d-C8), haloalky (d-C8), NRbRc, -C (O) Ra, -COOR3 , and C (O) NR R °; X1 is -OR6, -C (O) R6, -CO2R6 or -NR7R8; and Y is oxy (-O-), thio (-S-), sulfinyl (-SO-). suifonyl (-S (O) 2-) and amine -N (R9) -; wherein the alkyl, alkenyl, cycloalkyl, alkynyl, aryl, heterocycle, or heteroaryl groups of the groups R1, R2, R3, R4 and R5 are optionally substituted with one or more substituents independently selected from halo, cyano, nitro, -ORa, - SRa, aryl (C6-C? O), -O-aryl (C6-C10), hydroxyalkyl (d-C8), RbR ° Nalkyl (d-C8), haloalkyl (d-C8), NR Rc, -C (O) Ra, -COORa, and C (C) NRbRc; where R6 is hydrogen, alkyl (d-C8), RaOaquiIo (C1-C8), RbRcNalkyl (C1-C8), haloalkyl (d-C8), heterocycle (C3-C10), heterocycle (C3-C10) alkyl (C1- C8) -, aryl (C6-C10), aryl (C6-C? O) alkyl (d-C8) -, heteroaryl (C-C10), heteroaryl (C4-C10) alkyl (C1-C8) -; wherein the heterocycle, heteroaryl or aryl are optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-C8), R RcNalkyl (d-C8), haloalkyl (d-C8), NRbRc, -C (O) Ra, -COORa, and -C (O) NRbRc; where R7, R8 and R9 are independently hydrogen, (C? -C8) alkyl, RaOalkyl (d-C?), R R Nalkyl (d-C8), haloalkyl (C? -C8), (C3-C10) heterocycle, (C6-C10) aryl, (C6-C10) aryl (C1-C8) alkyl, (C4-C10) heteroaryl; -COORa, or C (O) Ra, or C (O) NRbRc where the heterocycle, heteroaryl or aryl are optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, -SRa, aryl (C6-C10), -Oaryl (Ce-C? 0), hydroxyalkyl (d-C8), RbRcNalkyl (d-Cß), haloalkyl (d-C8), NRbRc, -C (O) Ra, -COORa, and C (O) NRbRc: or R7 and R8 together with the atoms to which they are attached form a mono-, bicyclic- or saturated or partially unsaturated aromatic ring having 3, 4, 5, 6, 7, or 8, atoms in the ring optionally the ring has from 4 to eight ring atoms and optionally comprises 1, 2, 3, or 4 heteroatoms selected from non-peroxide oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (-S (O) 2-) or amine N (R ) - in the ring: Ra is hydrogen, or alkyl (d-C6); Rb and R ° are each hydrogen, alkyl (d-C6), alkoxy (C? -C6), cycloalkyl (C3-C8), alkylthio (C? -C6), aryl (C6-C10), aryl (C6-) C10) (C 1 -C 6) alkyl, heteroaryl, or heteroarylalkyl (C 6 -C 6); or Rb and R ° together with the nitrogen to which they are attached form a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, or thiomorpholinyl ring; where n is 0, 1, 2, 3. 4, 5, 6, 7, or 8; m is 1 or 2; and q is 1, 2, 3, or 4; or a pharmaceutically acceptable salt thereof. The invention also provides pharmaceutically acceptable salts of a compound of formula (I). The invention also provides a pharmaceutical composition comprising a compound of formula 1, or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable diluent or carrier. Additionally, the invention provides a therapeutic method for preventing or treating a pathological disorder or symptom in a mammal, such as a human being where the activity, i.e. hyper activity, of adenosine A2B receptors is involved in one or more symptoms of the pathology and antagonism (ie blocking) of its activity is desired to improve said symptoms. Such diseases or disorders include, but are not limited to, asthma, allergies, allergic diseases (for example allergic rhinitis or sinusitis), autoimmune diseases (for example lupus), diarrheal diseases, insulin resistance, diabetes, prevention of degranulation of mast cells associated with ischemic / reperfusion injury, heart attacks, inhibition of angiogenesis in neoplastic tissues, and inhibition of angiogenesis in diabetic retinopathies or in hyperbaric retinopathies induced by oxygen. The invention also includes a method for the treatment of asthma, diarrheal diseases, insulin resistance, diabetes, inhibition of angiogenesis in neoplastic tissues, and inhibition of angiogenesis in diabetic retinopathies or in oxygen-induced hyperbaric retinopathies in a mammal ( example, a human) comprising administering to the mammal in need of such therapy, an effective amount of at least one compound of formula I or pharmaceutically acceptable salts thereof. The invention provides a compound of formula I for use in medical therapy, preferably for use in the treatment of diseases or disorders associated with altered activity or activation of the A2B receptor, including asthma, diarrheal diseases, insulin resistance, diabetes, ischemic / reperfusion pressures, inhibition of angiogenesis in neoplastic tissues and inhibition of angiogenesis in diabetic retinopathies or in oxygen-induced hyperbaric retinopathies. The invention also provides the use of a compound of formula I for the manufacture of a medicament for the treatment of a disorder or pathological symptom in a mammal, such as a human being, that are associated with the activity or altered activation of the A2B receptor, which include the diseases or pathologies mentioned above. The invention also includes a method comprising contacting a compound of the formula I, which optionally has a radioactive isotope (radionuclide), such as, for example, tritium, radioactive iodine (eg, 125l for binding assays or 123l for Spectral imaging) and the like, with target sites of the adenosine A2B receptor comprising said receptors, in vivo or in vitro, so as to bind to said receptors. Cell membranes comprising attached adenosine A2B receptor sites can be used to measure the selectivity of test compounds for adenosine receptor subtypes or can be used as a tool to identify potential therapeutic agents for the treatment of diseases or disorders associated with the intermediation of the A2B receptor, by contacting these agents with said radioligands and receptors, and measuring the degree of displacement of the radioligand and / or binding of the agent.

DETAILED DESCRIPTION OF THE INVENTION Applicants have discovered that the compounds of the invention having the formula I may be useful for the treatment of diseases or disorders associated with the activity or altered activation of the A2B receptor. The following definitions are used, unless otherwise described: halo is fluorine, chlorine, bromine, or iodine. Alkyl, alkoxy, alkenyl, alkynyl, etc. denote both straight and branched groups; but the reference to an individual radical such as propyl "covers only straight chain, and a branched chain isomer such as" isopropyl "is specifically mentioned.When the alkyl may be partially unsaturated, the alkyl chain may comprise one or more ( for example 1, 2, 3, or 4) double or triple bonds in the chain. "Aryl" denotes a phenyl radical or an ortho-fused bicyclic carbocyclic radical having approximately nine to ten ring atoms in which at least one of the rings is aromatic. "Arylalkyl" or "(C6-C10) aryl (C1-C8) alkyl-" refers to a group of the formula arylalkyl (C? -C8) -, where aryl and alkyl (C? -C8) are as defined herein. "Heterocycle" encompasses a cyclic radical attached or linked through an atom of a carbon or nitrogen ring of a monocyclic, fused bicyclic, or bridged, saturated or unsaturated bicyclic ring system, containing 5-10 atoms in the ring, and preferent from 5-6 atoms in the ring, which consists of carbon and one, two, three or four heteroatoms, each selected from the group consisting of non-peroxide oxy (-O-), thio (-S-) groups, sulfinyl (-SO-), sulfonyl (-S (O) 2-), amine -N (R9) -, or -N =, where R9 is as defined herein, and optionally contains 1 -3 double bonds ( for example, -CH = CH- or -CH = N-). Heterocycle includes, for example, tetrahydrofuryl, dihydrofuryl, tetrahydroimidazolyl, azanorbornyl, pyrrolidyl, piperidyl, piperizyl, morpholinyl, azepinyl, 1,3-diazepinyl, 1,3-benzodiazepinyl, 1,4-diazepinyl, 1,4-benzodiazepinyl, 1, 5-diazepinyl, 1, 5-benzodiazepine and the like. "Heteroaryl" embraces a radical linked through a ring atom of a monocyclic aromatic ring containing 5-10 atoms in the ring, preferably from 5-6 ring atoms, consisting of carbon and one, two, three or four heteroatoms each selected from the group consisting of non-peroxide groups oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (-S (O) 2-) or amine (-N) (R9) -), where R9 is as defined herein. Preferred heteroaryl groups include, midazolyl, triazolyl, triazinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridinyl, pyrimidinyl, indolyl, isoquinolyl, quinolyl, and the like. As recognized by those skilled in the art, the imidazole ring of the compounds of the present invention may exist in tautomeric forms or, as tautomers, and therefore is also included within the scope of the invention. The tautomeric isomers are represented as structures (la) and (I b): When a compound (1) is named or referenced, for example, it is understood for the purposes of the present application, that the tautomers (la) and (Ib) are also encompassed. Similarly, when reference is made to compound (la), it is understood for the purposes of the present application that tautomers (I) and (Ib) are also encompassed. The same happens for the reference to the tautomer (Ib). "Optional" or "optional" means that the subsequently described event or condition may occur but does not necessarily occur, and that the description includes cases in which the event or condition occurs and cases in which it does not occur. For example, "optionally substituted" means that the aforementioned substituent may be present but need not be present, and that the description includes situations in which the aforementioned substituent is included and situations in which the aforementioned substituent is not included. The term includes, "for example", "such as", and the like are used illustratively and do not limit the present invention The indefinite articles "a" and "an" and mean "at least one" or "one or more" when used in this application, including the claims, unless specifically indicated otherwise, Those skilled in the art will appreciate that the compounds of the invention having a chiral center may exist and may be isolated in the optically active and racemic forms.Some compounds may exhibit polymorphism. It should be understood that the present invention encompasses any racemic, optically active, polymorphic, or stereoisomeric form or mixtures thereof of a compound of the invention, which possesses the useful properties described herein, the manner of preparing these forms optically being known in the art. active (for example, by resolution of the racemic form by recrystallization techniques, by synthesis from optically active starting materials, by chiral synthesis or by chromatographic separation using a chiral stationary phase) and how to determine, for example, activity antitumor, herbicidal activity or other therapeutic activity using the conventional tests described herein or using other similar tests that are well known in the art. The specific and preferred values listed below for the radicals, substituents and ranges are given for illustrative purposes only; they do not exclude other defined values or other values within the ranges defined for radicals and substituents. Specifically, alkyl (C? -C8) can be methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, rt-butyl, n-pentyl, isopentyl, 3-pentyl, n- hexyl. n-heptyl, n-octyl or branched (C3-C8) alkyl; (C2-C8) alkenyl may be vinyl, 1-propenyl, 2-propenyl (aryl), 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 1-hexenyl. 2-hexenyl, 3-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl or the branched (C3-C8) alkenyl; (C3-C8) alkenyl can be 2-propenyl (allyl), 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl, 3-heptenyl , 2-octenyl, 3-octenyl, 4-octenyl, or branched (C3-C8) alkenyl, (C2-C8) alkynyl can be ethynyl, 1-propynyl, 2-propynyl (propargyl), 1-butynyl, 2- butynyl, 3-butynyl, 1 -pentinyl, 2-pentynyl, 3-pentynyl, 1-hexyl, 2-hexynyl, 3-hexynyl, 1 -heptinyl, 2-heptynyl, 3-heptynyl, 1-octyl, 2-octynyl, 3-octynyl, 4-octynyl, or branched (C3-C8) alkynyl; (C3-C8) alkynyl can be 2-propynyl (propargyl), 2-butynyl, 3-butynyl, 1 -pentinyl, 2-pentynyl, 3-pentynyl, 1-hexyl, 2-hexynyl, 3-hexynyl, 1-heptinyl . 2-heptinyl, 3-heptinyl, 1-octinyl, 2-octynyl. 3-octynyl, 4- octynyl, or branched (C3-C8) alkynyl; Alkoxy (d-C8) can be methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy. iso-butoxy, sec-butoxy, io-butoxy, pentoxy, 3-pentoxy, n-hexyloxy, n-heptylioxy, n-octyloxy, or branched (C3-C8) alkoxy; haloalkyl (d-C8) can be iodomethyl, bromomethyl, chloromethyl, fluoromethyl, trifluoromethyl, 2-chloroethyl, 2-bromoethyl, 2-fluoroethyl, 3-fIuorpropyl, 2,2,2-trifluoroethyl, pentafluoroethyl, or halo (C3-C8) branched; (C3-C8) cycloalkyl may be cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; (C3-C8) cycloalkyl (d-C8) alkyl- may be cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl ,. 2-cyclopropylethyl, 2-cyclobutylethyl, 2-cyclopentyethyl or 2-cyclohexylethyl; aryl (C6-do) can be phenyl, indenyl or naphthyl: heterocycle can be tetrahydrofuryl, dihydrofuryl, tetrahydroimidazolyl, azanorbornyl, pyrrolidyl, piperidyl, piperizyl, morpholinyl, azepinyl, 1,3-diazepinyl, 1,3-benzodiazepinyl, 1,4 -diazepinyl 1,4-benzodiazepinyl, 1,5-diazepinyl, or 1,5-benzodiazepine. Arylalkyl can be phenylethyl, benzyl, 2-phenylpropyl, 3-phenylpropyl, 2-naphthylmethyl or 3-naphthylmethyl; and heteroaryl may be imidazolyl, triazolyl, triazinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridyl, pyrimidinyl, indolyl, isoquinolyl, quinolyl, or an oxide thereof. The alkyl groups (d-C8) can be methyl, ethyl, propyl, butyl, pentyl, hexyl, hepty, and octyl; the alkenyl groups are ethenyl, propenyl, butenyl, pentenyl, and hexenyl.

Specific cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Specific cycloalkylalkyl groups are cyclopropylmethyl, cyclobutylmethyl, cyclopropylethyl, cyclopentylmethyl, cyclohexylmethyl, 2-cyclopentylethyl, and 2-cyclohexylethyl. Specific aryl groups are phenyl, indenyl or naphthyl. Specific arylalkyl groups are benzyl and 2-phenylethyl. Specific haloalkyl groups are bromoethyl, chloroethyl, fluoroethyl, trifluoromethyl, 2,2,2-trifluoroethyl or 3-fluorophenyl. A specific value for R is hydrogen, methyl, ethyl, allyl, propargyl, / '-propyl, n-propyl, n-butyl, i-butyl or haloalkyl (d-d). Another specific value for R is hydrogen, methyl, ethyl, -CH2-CH2-CI, -CH2-CH2-Br, or -CH2-CH2-CH2-F. A specific value for R is hydrogen. A specific value for R1 is hydrogen, alkyl (d-C4), alkenyl (C1-C4), alkynyl (C3-C4), phenyl, or phenylalkyl (C? -C4). Another specific value for R1 is (C3-C6) cycloalkyl and (C3-C6) cycloalkyl (d-C4) - alkyl. Another specific value for R1 is cyclopropyl or cyclopropylmethyl. Another specific value for R1 is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-butyl, i-butyl, phenyl, phenethyl, or benzyl. Another specific value for R1 is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, or (methoxyphenyl) ethyl. Another specific value for R1 is ethyl, n-propyl or allyl. A specific value for R2 is hydrogen, (C1-C4) alkyl, (C3-C) alkenyl, (C3-C4) alkynyl, phenyl, or phenylalkyl (C3-C4). Another specific value for R2 is (C3-C6) cycloalkyl and (C3-C6) cycloalkyl (C1-C4) alkyl-. Another specific value for R2 is cyclopropyl or cyclopropimethyl. Another specific value for R2 is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-butyl, i-butyl, phenyl, phenethyl, or benzyl. Another specific value for R2 is hydrogen, methyl, ethyl, allyl, propargyl, n-propyl, n-propyl, or (methoxyphenyl) ethyl. Another specific value for R2 is ethyl, n-propyl or allyl. A specific value for X is imidazolyl, triazolyl, triazinyl, oxazolyl, isoxazoium, thiazolyl. isothiazolyl, thiodiazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridinyl, pyrimidinyl, indolyl, isoquiriolyl, or quinolyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, cyano, nitro, alkyl (d- C8), -ORa, -SRa, aryl (Ce-do), -O-aryl (C6-C10), hydroxyalkyl (d-C8), RbRcNalkio (d-C8), haloalkyl (d-C8), -NRbRc, -C (O) Ra, -COORa, and C (O) NRbRc. Another specific value for X is 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, silt, nitro, alkyl (d-Cß), -ORa, -SRa. aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (Ci-Cß), RbRcNalkyl (d-Cß), haloalkyl (d-C8), NRbRc, C (O) Ra, -COORa, and -C (O) NRbRc. A specific value for -X (Z1) n-Z is a group that has the formula Another specific value for -X (Z1) n-Z is a group that has the formula: Another specific value for -X (Z1) n-Z is a group of the formula: Another specific value for -X (Z1) n-Z is a group that has the following order: Another specific value for Z is -OH, -Oalkyl (C? -C4). Oaryl (d-Cio), -O-aryl (C6-C? 0) alkyl (C? -C4), NR4R5, F, Cl, Br, or I. Another specific value for Z is -NR4R5. Another specific value for Z is 0- (CH2) q - ^ - COOH -N'R i (CH2CH20) q-CH2CH2OH R 'Rβ ~ N -FT (CH2GH20) q-CH2CHzNH2, or < CH2CH2O) q-CH2CH2-C0OH A specific value for R 4 is hydrogen, (C 1 -C 6) alkyl, (C 3 -C 6) cycloalkyl, (C 3 -C 6) cycloalkyl (C 1 -C 4) alkyl, (C 3 -C 6) heterocycle, aryl (C 6 -C 6) ? 0), aryl (C6-C? 0) alkyl (C -C) -, heteroaryl (C5-Cß) or heteroaryl (C5-C6) alkyl (C1-C4) -, -S (O2) N H2, - C (O) R6, -CO2R6, or -C (0) NR6R7. Another specific value for R4 is hydrogen, alkyl (d-C4), hydroxyalkyl (C2-C4), cycloalkyl (C3-C6), aryl (C6-C? 0), aralkyl (C7-C? 0), heteroaryl (C5-Cß), - (CH2-CH2-O) q- (CH2-CH2-O) -Ra, - (CH2-CH2-O) q- (CH2-CH2) -COORa, -NRaRb, - NR7R8, -C (O) R6, -CO2R6 or -C (O) NR7R8. Another specific value for R 4 is hydrogen, methyl, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxyethyl, diethoxyethyl, methylbenzyl, aminomethyl, benzyl, methoxybenzyl, methoxyphenethyl, furylmethyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O ) R6, -CO2R6, or -C (O) NHR7. Another specific value for R is methyl, ethyl, cyclopropyl, cyclopropylmethyl. -C (O) R6, -CO2R6, or -C (O) NHR7. A specific value for R5 is hydrogen, (C? -C6) alkyl, (C3-C6) cycloalkyl, (C3-C6) cycloalkyl (C1-C4) alkyl, heterocycle (C3-C6), aryl (C6-C10), aryl (C6-C10) alkyl (C1-C4) -) heteroaryl (C5-C6), or heteroaryl (C5-C6) alkyl (d-C4) -, - S (O2) NH2, -C (O) R6, -CO2R6, or -C (O) NR6R7. Another specific value for R5 is hydrogen, alkyl (d-C4), hydroxyalkyl (C2-C4), cycloalkyl (C3-C6), aryl (C6-C10), aralkyl (C7-C? 0), heteroaryl (C5-C6), - (CH2-CH2-O) q (CH2CH2) -ORa, - (CH2CH2-O) q (CH2-CH2) -COORa, - (CH2CH2-O) ) q (CH2-CH2) -NRaRb, -NR7R8, -C (O) R6, -CO2R6, or -C (O) NR7R8. Another specific value for R5 is hydrogen, methyl, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxyethyl, diethoxyethyl, methylbenzyl aminomethylbenzyl, methoxybenzyl, methoxyphenethyl, furylmethyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O) R6, -CO2R6, or -C (O) NHR7. Another specific value for R5 is methyl, ethyl, cyclopropyl, cyclopropylmethyl -C (O) R6, -CO2R6, or -C (O) NHR7. A specific value for R4 and R5 taken together with the nitrogen to which they are attached is a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, or thiomorpholinyl ring, each optionally substituted with 1, 2, 3, or 4 independently selected substituents between halo, cyano, nitro, -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-C8), RbRcNalkyl (d-C8), haloa-alkyl (d-C8), - NRbRc, -C (O) Ra, -COORa, and -C (O) N RbRc. A specific value for R6 is alkyl (d-C6), cycloalkyl (C3-C6), cycloalkyl (C3-C6) alkyl (C? -C4) -, heterocycle (C-C6), aryl (d-Cio), aryl (C6-C? 0) (C? -C4) alkyl- (C5-C6) heteroaryl, or (C5-C6) heteroaryl (C? -C4) -alkyl, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, cyano, nitro, alkyl (d-Cß), -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C? o), hydroxyalkyl (C? -C?), RbRcNalkyl (C ? -Cβ), haloalkyl (d-C8), NRbRc, -C (O) Ra, -COORa, and C (O) NR Rc. A specific value for R6 is aryl (C6-C? 0), heteroaryl (d-d), each optionally substituted with 1, 2, or 3 substituents independently selected from halo, cyano, nitro, alkyl (d-Cß), haloalkyl (C? -8), -COORa, and C (O) NRbRc. A specific value for R6 is pyridyl, optionally substituted with F, Cl, Br. I CF3, cyano, nitro, COORa, or -CONHRa. Another specific value for the compound is that in which R is hydrogen, methyl, or ethyl; R1 and R2 are independently methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, cyclopropyl, cyclopropylmethyl, n-butyl, X is 3-pyridyl substituted at the 6-position with Z, where Z is a heterocycle (C-) C10) or -NR4R5, R4 is methyl, ethyl, cyclopropyl, cyclopropylmethyl and is R5 -C (O) R6, where R6 heteroaryl optionally substituted with 1. 2 or 3 substituents independently selected from halo, cyano, nitro, haloalkyl (d-Cß), -C (O) Ra, -COORa, and -C (O) NRbR °, and where Ra, Rb and Rc are independently hydrogen, methyl, ethyl, propyl, isopropyl, or cyclopropyl. The compounds of the invention can have the formula: ASPECTS OF THE INVENTION The present invention provides a compound of formula I: wherein: R is hydrogen, (C1-C5) alkyl, haloalkyl (C? -8), alkenyl (C5-C5), or alkynyl (C3-C5) ); R 1 and R 2 are independently hydrogen, (C 1 -C 8) alkyl, (C 3 -C 8) alkenyl, (C 3 -C 8) alkynyl, (C 1 -C 8) alkoxy, (C 3 -C 8) cycloalkyl, (C 3 -C 8) cycloalkyl (d-C8) -, heterocycle (C4-C? 0), heterocycle (C4-C? 0) alkyl (d-C8) -, aryl (C6-C? 0), aryl (C6-C? 0) alkyl (C? -C8) -, heteroaryl (C5-C10), or heteroaryl (C5-do) alkyl (d-C8) -; X is a 5-10 membered heterocarbyl ring having a nitrogen atom and which is optionally interrupted with 1, 2, or 3 non-peroxide groups oxy (-O-), thio (-S-), sulfinyl (-SO-) 2, sulfonyl (-S (O) 2-) or amine -N (R 9) -; Z is -OR3, -SR3, halo, -S (O) m-NR4R5, -NR4R5, or a heterocycle (C4-C? 0) wherein the heterocycle is optionally substituted with 1, 2, 3, or 4 independently selected substituents between halo, cyano, nitro, -ORa, -SRa, alkyl (C? -8), aryl (C-do), -O-aryl (C-C10), hydroxyalkyl (d-C8) or, RbRcNalkyl (d-C8) , haloalkyl (d-C8), NRbR °, -C (O) Ra, -COORa, and -C (O) NRbRc; each Z1 is independently alkyl (C? -C8), alkenyl (C2-C8), (C2-C8) alkynyl, -OR6, -SR6, halo, R6Oalkyl (dd), R7R8Nalkyl (d-Cß) or, haloalkyl (d-Cß), -NR7R8, R7R8Nalkyl (d- C8) , -C (O) R6. -COOR6, and -C (O) NR7R8 R3 is (d-C8) alkyl, (C3-C8) alkenyl, (C3-C8) alkynyl, (C6-C10) aryl, (C6-C10) alkyl (C? -C8) -, (C5-C10) heteroaryl, (C5-C10) heteroaryl (C? -C) -, -C (O) R6, or -C (O) NR7R8; R4 and R5 are independently hydrogen, (C-C8) alkyl, (C3-C8) alkenyl, (C3-C8) alkynyl, alkoxy (dd), (C3-C8) cycloalkyl, (C3-C8) cycloalkyl (C8) alkyl ) -, polycycloalkyl (C6-C? 8), polycycloalkyl (C6-C? 8) alky (Ci-Cß) -, heterocycle (C3-d0), heterocycle (C3-C10) alkyl (C? -8) -, -NR7R8, aryl (Cß-C10), aryl (C6-C or) alkyl (Ci-Cß) -, heteroaryl (C5-C10), heteroaryl (C5-C10) alkyl (C? -8) -, (C2-) C4-Y) q (CH2) 2-4X1, -C (O) R6, -CO2R6. -C (O) NR7R8, or -S (O) 2-NR7R8 or R4 and R5 together with the atoms to which they are attached form a mono-, bicyclic or aromatic saturated or partially unsaturated ring having 3.5-4. 6, 7, or 8, atoms in the ring and optionally comprising 1, 2, 3, or 4 heteroatoms selected from non-peroxide oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (-S (O) 2-) and amine -N (R9) - in the ring, and wherein the ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa , -SRa, aryl (Cß-C10), -O-aryl (C6-C10), hydroxyalkyl (d-C8), R RcNalkyl (d-Cß), haloalkyl (d-Cß). NRbR °, -C (O) Ra, -COORa, and -C (C) NRbRc; X1 is -OR6, -C (O) R6, -CO2R6, or NR7R8 and Y is oxy (-O-), a (-S-), sulfinyl (-SO-), sulfonyl (-S (O) 2- ) and amine -N (R9) -; wherein the alkyl, alkenyl, cycloalkyl, alkynyl, aryl, heterocycle or heteroaryl groups of R1, R2, R3, R4 and R5 are optionally substituted with or more substituents independently selected from halo, silt, nitro, -ORa, -SRa, aryl ( Ce-do), -Oaryl (Cß-C? O), hydroxalkyl (C? -C8), RbRcNalkyl (Ci- C8), haloalkyl (d-CB), NR Rc, -C (O) Ra, -COORa, and -C (O) NRbRc. where R6 is hydrogen, (C? -C8) alkyl, RaOalkyl (d- C8), RbRcNalkyl C8), haloacyl (d-C8), heterocycle (C3-C10), heterocycle (C3-C? 0) alkyl (dd) ) -, aryl (C6-C10), aryl (C6-C? 0) alkyl (d-CB) -, heteroaryl (C4-C10), heteroaryl (C4-C? 0) to alkyl (C? -8) -; wherein the heterocycle, heteroaryl or aryl are optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, -SRa, aryl (C6-C10), -Oaryl (d-Cio), hydroxyalkyl (d-C8), R RcNalkyl (d-C8), haloalkyl (d-Cß), NRbRc, -C (O) Ra, -COORa, and -C (O) NRbRc; where R7, R8 and R9 are independently hydrogen, (d-C8) alkyl, RaOalkyl (C? -8), RbRcNalkyl (C? -8), haloalkyl (C? -8), heterocycle (C3-C10), aryl ( C6-C? 0), aryl (C6-C10) alkyl (d-C8) -, heteroaryl (C4-C10); -COORa, -C (O) Ra, or -C (O) NRbRc where the heterocycle, heteroanyl or aryl are optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, - SRa, aryl (C6-C10), -Oaryl (C? -C8), hydroxalkyl (d-C8), RbRcNalkyl (C1-C8), haloalkyl (C? -8), NRRc, -C (O) Ra, -COORa, and -C (O) NRbRc; or R7 and R8 together with the atoms to which they are attached form a mono-, bicyclic- or saturated or partially unsaturated aromatic ring having 3, 4, 5, 6, 7, or 8 ring atoms where the ring optionally has 4 to 8 atoms in the ring optionally comprises 1, 2, 3, or 4 heteroatoms selected from non-peroxide oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonyl (-S (O 2-) or amine N (Rb) in the ring; Ra is hydrogen, or alkyl (d-C6); Rb and Rc are each independently hydrogen, alkyl (d-C6), akoxy (C6-6), cycloalkyl (dd), alkylthio (d-C6), aryl (C6-C10), aryl (C6- or C) alkyl (Ci-Ce) -, heteroaryl, or heteroarylalkyl (C? -C6) -; or Rb and R ° together with the nitrogen to which they are attached form a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, mortolinyl, or thiomorpholinyl ring; and where n is 0, 1, 2, 3,4, 5, 6, 7, or 8; m is 1, or 2; and q is 1 2, 3, or 4; Or a pharmaceutically acceptable salt thereof. In one aspect of the invention, R is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-butyl, i-butyl or haloalkyl (01 -04). In another aspect, R is hydrogen, methyl, ethyl, -CH2-CH2-CI, -CH2-CH2-Br, or -CH2-CH2-CH2-F. In one variation, R is hydrogen. In one aspect of the invention, the above compound is provided in which R1 is hydrogen, (C? -C) alkyl, (C3-C4) alkenyl, (C3-C) alkynyl, phenyl, or phenylalkyl (C? -C ). In another aspect, R1 is (C3-C6) cycloalkyl and (C3-C6) cycloalkyl (C? -C) alkyl. In one variation, R1 is cyclopropyl or cyclopropylmethyl. In another variation, R1 is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-butyl, n-butyl, phenyl, phenethyl, benzyl, or (methoxy-ethyl) ethyl. In a further variation, R 1 is ethyl, n-propyium or allyl. In one aspect of the invention, the above compound is provided wherein it is hydrogen, (C? -C4) alkyl, (C3-C) alkenyl, (C3-C4) alkynyl, phenyl, phenylalkyl (C? -C4), or (methoxyphenyl) ethyl, In one variation, R2 is (C3-C6) cycloalkyl or (C3-C6) cycloalkyl (C? -C4) alkyl. In another variation, R2 is cyclopropyl or cyclopropylmethyl. In another variation, R2 is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-butyl, i-butyl, phenyl, phenethyl, or benzyl. In a further variation, R2 is ethyl, n-propyl or allyl. In one aspect of the invention, the above compound is provided in which Z is -OH. -Oalkyl (C1-C4), -Oaryl (C6-C10). - Oaryl (C6-C? O) alkyl (d-C4), -NR4R5, F, Cl, Br, or I. In another aspect of the invention, the above compound is provided in which R 4 is hydrogen, (C 1 -C 6) alkyl, (C 3 -C 6) cycloalkyl, (C 3 -C 6) cycloalkyl (C 1 -C 4) alkyl, (C 3) heterocycle -C6), aryl (Cedo), aryl (C6-C? O) alkyl (C? -C4) -, heteroaryl (C5-C6), or heteroaryl (C5-C6) alkyI (C? -C4), -S (O2) NH2, -C (O) R6, -CO2R6, or -C (O) NR6R7. In one variation, R 4 is hydrogen, (C 1 -C 4) alkyl, hydroxy (C 2 -C), cyclo (C 3 -C 6) alkyl, aryl (C 6 -C 0), aralkyl (C 7 -C 7), heteroaryl ( C5-C6), (-CH2CH2O) q (CH2CH2) -ORa, (CH2CH2O) q (CH2CH2) -COORa, - (CH2CH2O) q (CH2CH2) NRaR, -NR7R8, -C (O) R6, -CO2R6, or -C (O) NR7R8. In another variation, R 4 is hydrogen, meter, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxyethyl, diethoxyethyl, methylbenzyl, aminomethylbenzyl, methoxybenzyl, methoxyphenethyl, furylmethyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O) R 6 , -CO2R6, or -C (O) NHR7. In a further variation, R 4 is methyl, ethyl, cyclopropyl, cyclopropylmethyl, -C (O) R 6, -CO 2 R 6, or -C (O) NHR 7. In one aspect of the invention, the above compound is provided in which R5 is hydrogen, (d-C6) alkyl, (C3-C6) cycloalkyl, (C3-C6) cycloalkyl (C1-C4) alkoxy, (C3-) heterocycle C6), aryl (C6-C10), aryl (C6-C? O) (C1-C4) alkyl-, heteroaryl (C5-C6), or heteroaryl (C5-C6) alkyl (d-C4), -S ( O2) NH2, -C (O) R6, -CO2R6, or -C (O) NR6R7. In one variation, R 5 is hydrogen, (C 1 -C 4) alkyl, (C 2 -C 4) hydroxyalkyl, (C 3 -C 6) cycloalkyl, (C 6 -C 0) aryl, (C 7 -C 6) aralkyl (C 5) aralkyl -C6), - (CH2CH2O) q (CH2CH2) -ORa, (CH2CH2-O) q- (CH2CH2) -COORa, - (CH2-CH2-O) q - (CH2CH2) NRaRb, -NR7R8. -C (O) R6, - CO2R6, or -C (O) NR7R8. In another variation, R5 is hydrogen, methyl, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxyethyl, diethoxyethyl, methylbenzyl, aminomethylbenzyl, methoxybenzyl, methoxyphenethyl, furylmethyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O) R6 , -CO2R6, or -C (O) NHR7. In another variation, R5 is methyl, ethyl, cyclopropyl, cyclopropylmethyl. -C (O) R6, -CO2R6, or -C (O) NHR7. In one aspect of the invention, the above compound is provided in which R 4 and R 5 taken together with the nitrogen to which they are attached are a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazinyl, morpholinyl, or thiomorpholinyl ring, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, -SRa, aryl (C6-C? 0), -O-aryl (C6-C? 0), hydroxyalkyl (d-C8), R RcNalkyl (d-C8), haloalkyl (d-C8), NRbRc, -C (O) Ra, -COORa, and -C (O) NR Rc. In another aspect of the invention, the above compound is provided wherein it is alkyl (C? -C6), cycloalkyl (C3-C6), cycloalkyl (C3-C6) alkyl (d-C4), heterocycle (C3-C6) , aryl (C6-C10), aryl (C6-C? o) alkyl (C? -C4) -, heteroaryl (C5-C6), or heteroaryl (C5-C6) alkyl (C1-C4), each of the which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, cyano, nitro, alkyl (d-C8), -ORa, -SRa, aryl (C6-C? 0), -O-aryl (C6-C10) , hydroxyalkyl (d-C8), R RcNalkyl (C? -8), haloalkyl (d-Cß), NR Rc, -C (O) Ra, -COORa, and C (O) NRbRc. In one variation, R6 is aryl (C6-C? O), heteroaryl (05-06), each of which is optionally substituted with 1, 2, or 3 substituents independently selected from halo, cyano, nitro, alkyl (C ? -C8), haloalkyl (d-C8), -COORa, and C (O) NRbRc. In another variation. R6 is pyridyl, optionally substituted with F, Cl, Br, I, CF3, cyano, nitro, -COORa, or -CONHR3. Another specific value for the compound is that in which R is hydrogen, methyl, or ethyl; R1 and R2 are independently methyl, ethyl, allyl, proparyl, i-propyl, n-propyl, cyclopropyl, cyclopropylmethyl, or n-butyl; X is 3-pyridyl substituted at the 6-position with Z, where Z is a heterocycle (C -C?) Or -NR R5, R4 is methyl, ethyl, cyclopropyl, cyclopropylmethyl and is -C (O) R6, where a heteroaryl optionally substituted with 1 2 or 3 substituents independently selected from halo, cyano, nitro, haloalkyl (C, -C8), -C (O) Ra, -COORa, and C (O) NRbRc, and wherein Ra, R and Rc are independently hydrogen, methyl, ethyl, propyl, isopropyl, or cyclopropyl. In another aspect of the invention, the above compound is provided in which R is hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-butyl, i-butyl or haloalkyl (C1-C4); and R1 and R2 are independently hydrogen, methyl, ethyl, allyl, propargyl, i-propyl. n-propyl, cyclopropyl, cyclopropylmethyl, n-butyl, i-butyl, phenyl, phenethyl, or benzyl. In one variation, R is hydrogen, methyl, ethyl, -CHo-CHz-CI, -CH2-CH2-Br, or -CH2-CH2-CH2-F; and R1 and R2 are independently hydrogen, methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, cyclopropyl, cyclopropylmethyl, or (methoxyphenyl) ethyl. In one aspect of the invention, the above compound is provided in which X is imidazolyl, triazolyl, triazinyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl, pyrrolyl, pyrazinyl, tetrazolyl, pyridinyl, pyrimidinyl, indolyl, isoquinolyl, or quinolyl, each optionally substituted with 1, 2, or 3 substituents independently selected from halo, cyano, nitro, alkyl (dd), -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-C8), RbRcNalkyl (d-C8), haloalkyl (d-C8), NRbRc, -C (O) Ra, - COOR3, and -C (O) NRbRc. In a variation of the above. X is 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl, each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, cyano, nitro, alkyl (C? -8), -ORa , -SR3, aryl (Cβ-do), -O-aryl (Cβ-C ?o), hydroxyalkyl (d-C8), RbRcNalkyl (d-Cβ), haloalkyl (d-C8), -NR R °, -C ( O) Ra, -COOR3, and C (O) NRbRc. In another variation, -X (Z) nZ has the formula: In another variation, -X (Z1) n-Z has the formula In one aspect of the invention, the above compound is provided in which Z is -OH, -Oalkyl (d-C4), -OC (O) NR7R8, alkyl (dd), -NR4R5, F, Cl, Br, or I, where R4 and are independently hydrogen, alkyl (Ci-d), cycloalkyl (C3-C6), heterocycle (C3-C6), aryl (d-do), aralkyl (C7-C12), heteroaryl (C5-C6) , or heteroaryl (C5-C6) alkyl (d-C4), -S (O2) NH2, -C (O) R6, -CO2R6. or -C (O) NR6R7. In one variation, Z is -NR4R5. In one aspect of the invention, the above compound is provided in which R4 and R5 together with the nitrogen to which they are attached form a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, or thiomorpholinyl ring, where the ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C? o), hydroxyalkyl (C? -8), RbRcNalkyl (Ci-Cß), haloalkion (d-C8), NRbRc, C (O) Ra, -COORa and-C (O) NRbRc. In a variation of the foregoing, R 4 and R 5 are independently hydrogen, (C 1 -C 4) alkyl, hydroxy (C 2 -C 4) alkyl, (C 3 -C 6) cycloalkyl, (C 6 -C 6) aryl, aralkyl (C -C) 0), heteroaryl (Cs-Ce), - (CH2-CH2-O) q- (CH2-CH2) -ORa, (CH2CH2O) q (CH2CH2) -COOR3, - (CH2-CH2-O) q- ( CH2-CH2) NR3Rb, -NR7R8, -C (O) R6, -CO2R6, or-C (O) NR7R8. In another variation, R 4 and R 5 are independently hydrogen, methyl, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxyethyl, diethoxyethyl. methylbenzyl, aminomethylbenzyl, methoxybenzyl, methoxyphenethyl, furylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O) R6, -CO2R6, or -C (O) NHR7. In a further variation, R6 is methyl, methoxy, or pyridyl, and R7 is phenyl, fluorophenyl, or methoxyphenyl. In one aspect of the invention, the above compound is provided, wherein R is hydrogen, methyl, or ethyl; R1 and R2 are independently methyl, ethyl, allyl, propargyl, i-propyl, n-propyl, cyclopropyl, cyclopropylmethyl, n-butyl, i-butyl; and Z is a heterocycle (C-C10) in which the heterocycle is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, nitro, -ORa, -SR3, aryl (C6-C? ), -Aryl (C6-C? O), hydroxyalkyl (d-C8) RbRcNalkyl (d-C8), haloalkyl (C? -8), NRbRc, -C (O) R3, -COORa, and-C (O ) NRbR °. In one aspect of the invention, the above compound is provided in which Z is selected from the group consisting of: p?; M? P-x-0 (CH2) q-C00H 0- (C &0 0 COOH, N Ü. '' 4 - N-N ß (CH2CH2?) A -CH2CH20H 4 R8, (CH2CH20) q-CH2CH2NH2, or In a variation of the above, -X (Z1) n-Z is selected from the group consisting of: In another variation, R1 and R2 are n-propyl; R is hydrogen and n is zero. In one aspect of the invention, the above compound is provided in which -X (Z1) n -Z is selected from the group consisting of: In one aspect of the invention, the compound selected from the group consisting of: 1,3-Dipropyl-8- (6-chloro-3-pyridyl) xanthine; 1-Propyl-3-propargyl-8- (6-chloro-3-pyridyl) xanthine; 1, 3-DipropyI-8- (6-ethylamine-3-pyridyl) xanthine: 1,3-Dipropyl (-8- (6- (2-hydroxyethyl) amino-3-pyridyl) xanthine; 1,3-Dipropyl- 8- [6- (4-acetylpiperazinyl) -3-pyridyl] xanthine 1,3-Dipropyl-8- [6- (benzylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (1 -piperidin-yl) -3-pyrid i Ixanxanthi, 1,3-Dipropyl-8- (6-pyrrolidinylpyrid-3-yl) xanthine; 1,3-Dipropyl-8- (6- [4-methyl (perhydro-1) , 4-diazepin-1 -ii)] - 3-pyridyljxanthine; 1,3-Dipropyl-8- (6-methylamino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (4-methoxybenzylamine) 3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (3-methylpiperidin) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (2-hydroxypropyl) amino-3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (2,2-dimethoxyethyl) amino-3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (1-hydroxy-2-propyl) amino-3-pyridyl-xanthine; 1,3-Dipropyl-8- (6-morpholino-3-pyridyl) xanthine; 1,3-Dipropyl-8- (6-dimethylamino-3-pyridyl) xanthine; 1,3-Dipropyl-8 - [[6- (2-hydroxyethoxy) ethylamino] -3-pyridyljxanthine; 1,3-Dipropyl-8- (6-piperazino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (2-hydroxy-2-phenylethyl) amino-3-pyridyl-xanthine; 1,3-Dipropyl-8- [6- (4-aminomethyl-amino) -3-pyridyl-xanthine; 1,3-Dipropyl-8- (6-phenylamino-3-pyridyl) xanthine: 1,3-dipropyl-8- (6-cyclopropylamino-3-pyridyl) xanthine; 1,3-dipropyl-8-. {6} - (6-pyridylmethylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- (6- (4-methylpiperazino) -3-pindyl) xanthine; 1,3-Dipropyl-8- [6- (3- pyridylmethylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (2-methylbenzylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- [2- (3,4 -methoxyphenyl) ethylamino] -3-pyridyljxanthine 1,3-Dipropyl-8- [6 - [(N-propylcarbamoyl), methyl ami no] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (3-pentylamino) -3-pyridyl] xanthine 1,3-Dipropyl-8- [6- (2,2-diphenylethylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- [2- (1-ethylpyrrolidinomethylamine)] - 3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (3-methoxybenzylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6 - [(N-phenylcarbamoyl) methylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (furfurylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- [2- (4-methoxyphenyl) ethylamino] -3-pyridyl-xanthine; 1,3-Dipropyl-8- [6- (2-methoxybenzamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (propylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (cyclopentylamino) -3-pyridyl]] xanthine; 1,3-Dipropyl-8- [6- (cyclohexylamino) -3-pyridyl] xanthine, 1,3-Dipropyl-7-ethyl-8- (6-chloro-3-pyridyl) xanthine; 1, 3-Dipropyl-7- (3-fluoropopil-8- (6-chloro-3-pyridyl) xanthine; 1,3-DipropyI-7-methyl-8- (6-cyrano-3-pyridyl) xanthine; , 3-Dipropyl-7 (2-bromoethyl) -8- (6-chloro-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (2-thiophenmethylamino) -3-pyridyl] xanthine; 3-Dipropyl-8- [6 - [(N- (4-methoxyphenylcarbamoyl) methylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine: 1, 3-Di pro pil-8- [6 - [(N- (4-f luo rof enylcarbamoyl) methylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N-isonicotinoylmethyl] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N-methoxycarbonylmethylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N-phenylcarbamoyl, N- (2-phenylcarbamoyloxyethyl) amino] -3-pyridyl) xanthine; 1, 3-Dipropyl-8-. { 6- [4- (N-phenylcarbamoyl)] piperazino-3-pyridyl} xanthine; 1, 3-Dipropyl-8-. { 6- [4- (N-isonicotinoyl)] piperazino-3-pyridyljxanthine; 1-Propyl-3- (4-methoxyphenyl) ethyl-8- (6-chloro-3-pyridyl) xanthine; 1-Propyl-3- (methoxy-phenylethyl) -8- (6-piperazino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (4-pyridylamino) -3-pyridyl] xanthine; 1, 3-Dipropyl-8- [6- [4- (N-nicotinoyl)] plperazino-3-pyridyljxanthine; 1,3-Dipropyl-8- [6- (hexahydro-1,4-diazepin-1-yl) -3-pyridyl] xanthine; 1,3-Diethyl-8- (6-chloro-3-pyridyl) xanthine; 1,3-Dethyl-8- (6-piperazino-3-pyridyl) xanthine; 1, 3-Diethyl-8- [6-. { (N-phenylcarbamoyl) methylamino] -3-pyridyl) xanthine; 1,3-Diethyl-8- [6- [N-nicotinoylethylamino] -3-pyridyl) xanthine; 1,3-Dethyl-8- (6-methylamino-3-pyridyl) xanthine; 1,3-Diethyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine; 1, 3-Diethyl-8- [6. { N-nicotinoylcyclopropylamino] -3-pyridyl) xanthine; 1,3-Dicyclopropylmethyl-8- (6-methylaminopyridin-3-yl) xanthine; 1-Propargyl-3-methyl-8- (6-methylamino-3-pyridyl) xanthine; 8 [6- (2,5-diaza-bicyclo [2.2.2] oct-2-yl) -pyridin-3-yl] -1- 3-dipropyl-3,7-dihydroporine-2,6-dione; 1,3-Dicyclopropylmethyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine 1,3-Dicyclopropylmethyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine; 1,3-Diallyl-8- (6-methylamino-3-pyridyl) xanthine 1-Chlopropylmethii-3-ethyl-8- (6-methylaminopyridin-3-yl) xanthine; 1,3-Diethyl-8- [6- (2-pyridylmethylamino) -3-pyridyl] xanthine; 1,3-Diethyl-8- [6- (3-pyridyl-methylamino) -3-pyridyl] -xanthine; 1, 3-Diethyl-8- [6- (3-methoxybenzylamino) -3-pyridyl] xanthine 1,3-DipropyI-8- [6-. { 2- (3-pyridyl) -ethylamino] -3-pyridyl] xanthine; 1, 3-Detll-8- [6- [2- (3-pyridyl) -ethylamino] -3-pyridyl] xanthine; 1, 3-Dipropyl-8-. { 6- [2- (2-pyridyl) -ethylamino] -3-pyridyl] xanthine; 1,3-Diethyl-8- [6- [2- (2-pyridyl) -ethylamino] -3-pyridyl] xanthine; 1,3-Diethyl-8- (6-pyrrolidinylpyrid-3-yl) xanthine; 1, 3-Diethyl-8- [6- [2- (1-pyrrolidinyl) -ethylamino] -3-pyridi] xanthine: 1,3-Dipropyl-8- (6- (2-methoxyethyl) amino-3-pyridyl ) xanthine; 1,3-Dipropyl-8- (6- (2-acetylaminoeti) amino-3-pyridyl) xanthine; 1,3-Diethyl-8 ~ (6-bromo-3-pyridyl) xanthine; 1, 3-Dipropyl-8-. { 6- [4- (2-pyridyl) -piperazino] -3-pyridyl} xanthine; 1, 3-Diethyl] -8-. { 6- [4- (2-pyridyl) -piperazino] -3-pyridyl} xanthine; 1,3-Diethyl-8- [6- (trans-2,5-dimethyl-piperazino) -3-pyridyl-xanthine; 1, 3-Dipropyl-8-. { 6- [4- (2-pyrimidiI) -piperazino] -3-pyridylxanthine; 1, 3-Diethyl-8-. { 6- [4- (2-pyrimidinyl) -piperazino] -3-pyridinyl} xanthine; 1,3-Diethyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine; 1-Propargyl, 3-methyl-8- (6-bromo-3-pyridyl) xanthine; 1, 3-Diethyl-8- [6-. { N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine; 1-Propargyl, 3-methyl-8- (6- (2-methoxyethyl) -3-pyridyl) xanthine 1,3-Diethyl-8- [6-. { N-isonicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine; 1 - (5- (1, 3-Diethyl-2,3,67-tetrahydro-2,6-dioxo-1 H -purin-8-yl) pyridin-2-yl) -1 - (2-methoxyethyl) - 3- (pyridin-4-yl) urea; 1,3-Dimethyl-8- (6-bromo-3-pyridyl) xanthine; 1,3-Dimethyl-8- (6-methylamino-3-pyridyl) xanthine; 1,3-Dimethyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine; 1-Propargyl, 3-methyl-8- [6- [N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine; 1-Propargyl, 3-methyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- (2,6-dichloro-3-pyridyl) xanthine; 1,3-Dipropyl-8- (2,6-Dimethylamino-3-pyridyl) xanthine; 1,3-Dipropyl -8- (2,6-di (2-methoxyethyl) -3-pyridyl) xanthine; 1,3-Dipropyl-8- [2,6-di [N-nicotinoylmethylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [2,6-di [N-nicotinoyl, N-methoxyethyl] -3-pyridyl) xanthine; 1,3-Diethyl-8- [6- [N- (2-pyrazinecarbonyl) methylamino] -3-pyridyl) xanthine; 1,3-Diethyl-8- [6- [N- (isoxazole-5-carbonyl) methylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N- (2-pyrazinecarbonyl) methylamino) -3-pyridyl) xanthine; 1, 3-Dipropyl-8- [6-. { N- (isoxazole-5-carbonyl) methylamino] -3-pyridyl) xanthine; 1, 3-Dípropyl-8- [6- [N- (5-methylisoxazole] -3-yl-3-carbonyl) methylam] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N- (2-chloro-6-methoxypyridinyl-4-carbonyl), N-methylamino] -3-pyridyl) xanthine; 1, 3-Dipropyl-8- [6- [N- (isonicotinoyl N-oxide), N-methylamino} -3-pyridyl) xanthine: 1-Propyl-3- (4-methoxyphenyl) ethyl-8- (6-methylamino-3-pyridyl) xanthine; 1, 3-Diethyl-8- [6- [N- (isonicotinoyl N-oxide), N-methylamino] -3-pyridyl) -xanthine: 1,3-diallyl-8- (6-chloro-3-pyridyl) ) xanthine; 1-propyl-3- (4-methoxyphenyl) ethyl-8- [6- (N-nicotinoylmethylamino) -pyridyl] xanthine; 1-propyl-3- (4-methoxyphenyl) ethyl-8- [6- (N- (6-chloronicotinoyl) methylamino) -3-pyridyl] xanthine; 1,3-diallyl-8- [6- (N-nicotinoylmethylamino) -3-pyridyl] xanthine; 1,3-diallyl-8- [6- (N- (6-chloronicotinoyl]) methylamino) -3-pyridyljxanthine; 1,3-Dipropyl-8- [6- (N- [6- (trifluoromethyl) nicotinoyl] methylamino) -3-pyridyl] xanthine 1,3-diethyl-8- [6- (2-hydroxy-5-methyl) benzaldehydehydrazono] -3-pyridyl} xanthine; 1-Cyclopropyl-3-propyl-8- [6- (N- [6- (trifluoromethyl) nicotinoyl] methylamino) -3-pyridyl] xanthine 1,3-diethyl-8- [6- (bromopyridine-3-carbaldehydehydrazono] -3- pyridyl] xanthine 1-cyclopropylo-3-ethyl-8- (6-methylamino-3-pyridyl) xanthine; 1-cyclopropyl-3-propyI-8- (6-methylamino-3-pyridyl) xanthine: 1 - Propyl-3-cyclopropyl-8- (6-methylamino-3-pyridyl) xanthine; 1-Cyclopropyl-3-propyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine: 1-Cyclopropyl] - 3-propyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine; 1,3-Diethyl-8- [6- (N- (6-chloronicotinoyl) methylamino) -3-pyridyljxanthine; 1,3-Dipropyl-8- (2-c! Gold-6-methoxyethylamino-4-pyridyl) xanthine; 1,3-Dipropyl -8- (2-chloro-6-methylamino-4-pyridyl) xanthine; 1,3-Dipropyl-8- [2- [N-nicotinoyl, N- (2-methoxyethyl) amino] -6-chloro-4-pyridyl) -xanthine; 1,3-Dipropyl-8- [2- [N-nicotinoyl, N-methylamino] -6-chloro-4-pyridyl) xanthine; 1 -Cyclopropyl-3-propyl-8- [6- [N- (6-chloronicotinoyl) methylamino} -3-pyridyl) xanthine; 1-Ethyl-3-cyclopropyl-8- (6-methylamino-3-pyridyl) xanthine; 1-Ethyl-3-cyclopropyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine; 1,3-Diethyl-8- [6-hydrazin-3-pyridyl] xanthine; 1,3-Diethyl-8- [6- (cyclopropylamino) -3-pyridyl] xanthine; 1, 3-Diethyl-8-. { 6- (cyclopropylmethylamino) -3-pyridyl] xanthine; N '- [5- (1, 3-Diethyl-2,6-dioxo-2,3,6,7-tetrahydro-1 H-purin-8-yl) -pyridin-2-yl] -hydrazide; N- [5- (1, 3-diethyl-2,6-dioxo-2,3,6,7-tetrahydro-1 H -purin-8-yl) -pyridin-2-yl] -N'- (pyridine -3-carbonii) -hydrazide; 1,3-Diethyl-8- [6- (ethylamino) -3-pyridyl] xanthine; 1, 3-Diethyl-8- [6- [N-nicotinoylcyclopropylmethyl] amino] -3-pridyl) xanthine; and 1-Cyclopropylmethyl-3-ethyl-8- [6- [N- (6-chloronicotinoyl) methylamino] -3-pyridyl) xanthine; or a pharmaceutically acceptable salt, optionally in the form of a single stereoisomer or a mixture of stereosomers thereof. In one aspect of the invention, there is provided a pharmaceutical composition comprising: (a) a therapeutically effective amount of a compound described above, and (b) a pharmaceutically acceptable excipient. In another aspect, a pharmaceutical composition is provided comprising: (a) a therapeutically effective amount of a compound of the foregoing; and (b) a pharmaceutically acceptable excipient. In one aspect of the invention, there is provided a therapeutic method for preventing or treating a pathological disorder or symptom in a mammal, in which the activity of the adenosine A2B receptors is involved and antagonism of its action is desired, which comprises administering to the mammal an effective amount of a compound of the present invention. In another aspect of the invention, there is provided a method for the treatment of asthma, allergies, allergic diseases or an autoimmune disease comprising administering an effective amount of a compound of the present invention to a mammal in need of such treatment. In a further aspect of the invention, a method is provided for the treatment of diarrheal diseases, insulin resistance, diabetes, cancer, ischemia / reperfusion injury, diabetic retinopathy or oxygen-induced hyperbaric retinopathy, which comprises administering an effective amount of a compound of the present invention or a pharmaceutically acceptable salt thereof to a mammal in need of such treatment. In a further aspect of the invention there is provided a therapeutic method for preventing or treating pathological disorders or symptoms in a mammal, in which it is involved in the activity of the adenosine A2B receptors and antagonism of its action, which comprises administering a mammal, is desired. an effective amount of a compound of the present invention. In another aspect of the invention, the compound of the present invention is provided for use in medical therapy. In another aspect, there is provided a use of a compound of the invention, for the manufacture of a medicament, which is useful for the treatment of a disease in a mammal, such as a human being. It will be understood that any aspect or feature of the present invention, whether characterized as preferred or not characterized in a preferred manner, may be combined with any other aspect or feature of the invention, whether said other feature is characterized in the manner preferred or not is characterized in the preferred form. For example, an aspect or characteristic described as being preferred, for example a particular R group, or a group R 1 specific for a particular compound of the formula (for example, in which R 1 is hydrogen, (C 1 -C 5) alkyl, haloalkyl (C? -C8), (C3-C5) alkenyl or (C3-C5) alkynyl, can be combined with any other group such as R2, X, Z, Z1 etc ... to form a compound of the invention having a Different combination of substituents without deviating from the present invention Additional compounds useful for the practice of the invention are described in the following table: Table 1: Activity of A2B Antagonists Ra R R -X (Z1) n -Z tA2B K, Comp 1 2 (n) P P r r x and +++ Propargyl M a P H XH +++ P H -0-O P H -0-0 P H -O-O, ++++ P H - - +++ P H ~? X i? P H o? Ú - (*) OH ++++ OO ++++ - *, Me 'v_ / NI -O / > 0"* -o ^ and \ .M X Ra -x. { z1) "- z tA2B K, Comp (nM) < Xb yyX > -? X P P P CH r r 3- -? - a Ra "X (Z1) p-Z tA2B K, Comp (nM) < XP Ra -X. { Z1) "- Z tA2B K, Comp (nM) = N t t - - * OH E E 3 t t \ f -NH Me E E t t H -t * -y * K * Me > t t x > Ra R -X (Z1) n -Z tA2B K, Comp 1 2 R (nM) Propargyl M H e -CK.

Alilo Alilo -O 't? Me E E t t -OHÍ Q o 92 H r < X? - mo 03 1 1 9 o-oo H 3 3 Ql. l »1 ^" ~ 0 ~ H 3 3 +++, and-X J J e H > -NH d d Ot } 0 o-o H 3 3 and z dtuoo z-u (tz) x- y y ey fr9 - Ra 9. R -X. { Z1) "- Z tA2B K, 1 Comp 2 R (nM) M Propargyl H 1 e ~ 0 ~ Br OMe M Propargyl H ~ ~ NH 3 e M M H 7 e e -CK. +++ a P P u _ 02 r r -Cl Ra -X (Z1) "- Z tA2B K, Comp (nM) 09 -. 09 -ypy P P O-? 10 r r 11 Ra -x. { z1) "- z tA2B K, Comp (nM) 93 xx-y -} i oe 3 3 62 02 82 "K J LZ Y 1 J E2 .xr iXX 3 3 = / O -O and 22 (WU) duioo 'W azVÍ z-u (pz) x- y y ey - 89 Ra R R -X (Z1) "- Z tA2B K¡ Comp 1 2 (nM) 6 t 7 t \ / ~ "- NI E E 8 t t Ra -X (Z1)" - z tA2B K, Comp (nM) XXm 39 O- ^ 40 H - 41 -0- _ 43 H Note: + Ki < 10000 nM, ++: Ki < 5000 nM, +++: K¡ < 500 nM, ++++: Ki < 100 nM.

Synthesis of the compounds of Formula Compounds of Formula IA can be prepared by the methods described in P. J. Scammells, et al., J. Med. Chem. 37, 2704-2712 (1994). A diamino-1,3-disubstituted uracil is acylated with 6-chloronicotinoyl chloride in pyridine at 5 ° C to provide the compounds of Formula (5a). The resulting amide (5a) is cyclized by reflux in an aqueous solution of sodium hydroxide to provide compound IA. The 6-chloronicotinoyl chloride is prepared by refluxing 6-hydroxynicotinic acid in thionyl chloride using DMF as catalyst as shown in Reaction Scheme 1. Compound IA can be alkylated with alkyl bromide or iodide to provide compounds of Formula IB. Compounds IA or IB react with substituted amine at 50-16 ° C in a tube under pressure to provide the compounds of Formula IC Compounds of Formula IC in which R 4 is hydrogen can react with socianate or with acyl chloride to provide the compounds of Formula I in which R4 is -C (O) NHR7 (ID) or C (O) R6 (IE), respectively REACTION SCHEME I (Formula I in which X = 3-plridyl, R4 = -C (0) R ") The compounds of the invention in which Z is -NR4R5 and R4 and R5 together with the atoms to which they are attached form a ring containing an NH group, for example IC, or IA1, can be prepared by reaction of the compound with a isocyanate or an acyl chloride to provide compounds having the Formula IF and IG, as shown in Scheme 2, below: REACTION SCHEME 2 SCHEME 3 shows that compound IA can react with hydrazine or substituted hydrazine at 1 00-160 ° C to provide the compounds of Formula IA2. Compounds of Formula IA2 in which R8 is hydrogen can react with acyl chloride to provide the compounds of Formula IH and IJ. Compound IA can also react with ketone or aldehyde to provide the compound of Formula IL.

REACTION SCHEME 3 The following abbreviations have been employed here: [125] ABA [125l]? / 6- (4-aminobenzyl) -adenosine 125l-ABOPX 125l-3- (4-amino-3-Yodobenzyl) -8-oxyacetate-1-propyl -xanthin AR adenosine receptor • CGS 21680 2- [4 - [(2-carboxyethyl) phenyl] ethyl-amino] -5N -? / - ethylcarbamoyl adenosine CPX 8-cyclopentyl-1,3-Dipropylxanthine DMEM medium eagle modified with Dulbecco DMF N, N-dimethyltrimamide DMSO dimethylsulfoxide EDTA ethylenediamine tetraacetate HEK cells human embryonic kidney cells Ki, equilibrium inhibition constant ECA 5 '- (? / - ethylcarbamoyl) adenosine R-PA ft- / V6-phenylpropyladenosine TEA triethylamine TLC thin layer chromatography ZM 241385 4- (2- [7-amino-2- { FuriI.} { 1, 2,4.} Triazolo. {2,3-a.} {1, 3.5.} Triazin-5-ylaminoeityl) phenol In cases where the compounds are sufficiently basic or acidic to form stable non-toxic base or acid salts, it may be appropriate for the administration of the of salts. Examples of pharmaceutically acceptable salts are the acid addition salts formed with acids that form an acceptable physiological anion, for example, tosylate, methanesulfonate, acetate, citrate, malonate, tartrate, succinate, benzoate, ascorbate, ketoglutarate, and α-glycerophosphate . Suitable inorganic salts can also be formed, including hydrochloride, sulfate, nitrate, bicarbonate and carbonate salts. The pharmaceutically acceptable salts can be obtained using conventional procedures well known in the art, for example reaction of a sufficiently basic compound such as an amine with an appropriate acid that provides a physiologically acceptable anion. Alkali metal salts (eg, sodium, potassium or lithium salts) or alkaline earth metals (eg calcium) and carboxylic acids can also be prepared. Those skilled in the art will appreciate that the compounds of the invention having a chiral center may exist and may be isolated in the optimally active and racemic forms. Some compounds may exhibit polymorphism. It should be understood that the present invention encompasses any racemic, optically active, polymorphic or stereisomeric form or mixtures thereof: of a compound of the invention, which possesses the useful properties described herein, the form of preparing the forms optically being known in the art. active (for example by resolution of the racemic form by recrystallization techniques, by synthesis from optically active starting materials, by chiral synthesis or by chromatographic separation using a chiral stationary phase). It is also conventional to determine adenosine A2B antagonism activity using the conventional tests described herein or using other similar tests that are well known in the art. The compounds of Formula I can be formulated in the form of pharmaceutical compositions and can be administered to a mammalian host, such as a human patient, in a variety of ways adapted to the chosen route of administration, ie orally or parenterally, via the intravenous, intramuscular, local, by inhalation or subcutaneously. Examples of pharmaceutical compositions are those described in "Remington: The Science and Practice of Pharmacy", A. Gennaro, ed. , 20th edition, Lippincott, Williams &; Wiikins, Philadelphia, PA. Therefore, the present compounds can be administered systemically, for example, orally, in combination with a pharmaceutically acceptable carrier such as an inert diluent or an edible assimilable carrier. They can be wrapped in gelatin capsules of hard or soft shell, they can be compressed in the form of tablets or they can be incorporated directly with the patient's diet food. For oral therapeutic administration, the active compound can be combined with one or more excipients and can be used in the form of nugible tablets, buccal tablets, slow-dissolving circular pills, capsules, elixiris, suspensions, syrups, wafers and the like. Said compositions and preparations should contain at least 0.1% active compound. The percentage of the compositions and preparations can vary, of course and conveniently can be between about 2 to about 60% of the weight of a given unit dosage form. The amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained. Tablets, slow-dissolving circular pills, pills, capsules, and the like may also contain the following: binders such as tragacanth gum, acacia gum , corn starch or gelatin; excipients tajes as dicalcium phosphate; a disintegrating agent such as corn starch, potato starch, alginic acid and the like; an ubricant such as magnesium stearate; and a sweetening agent such as sucrose, fructose, lactose or aspartame or a flavoring agent such as pepermin, sorghum oil or cherry flavoring may be added. When the unit dosage form is a capsule, it may contain in addition to the materials of the preceding type, a liquid carrier such as a vegetable oil or a polyethylene glycol. Various other materials may be present as coatings or may be otherwise modified to physical form of the solid unit dosage form. For example tablets, pills or capsules can be coated with gelatin, wax, lacquer or sugar and the like. A syrup or elixir may contain the active compound, sucrose or fructose as a sweetening agent, methyl and propylparabens as preservatives, a dye and a flavoring such as cherry or orange flavor. Naturally any material used in the preparation in any unit dosage form should be employed in pharmaceutically acceptable and substantially non-toxic amounts. In addition, the active compound can be incorporated into devices and sustained release preparations. The active compound can also be administered Intravenously or intraperitoneally by infusion or injection. The solutions of the active compound or its salts can be prepared in water, optionally in admixture with a non-toxic surfactant. Dispersions can also be prepared in glycerol, liquid polyethylene glycols, triacetin, and mixtures thereof and in oil. Under normal conditions of storage and use, these preparations contain a preservative to prevent the development of microorganisms. The pharmaceutical dosage forms suitable for injection or infusion may include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient, which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions, optionally encapsulated in liposomes. In all cases, the final dosage form should be sterile as fluid and stable under the conditions of manufacture and storage. The liquid carrier or vehicle can be a solvent or a liquid dispersion medium comprising, for example, water, ethanol, a polyol (for example glycerol, propylene glycol, liquid polyethylene glycols and the like), vegetable oils, non-toxic glyceryl esters and appropriate mixtures thereof. The proper fluidity can be maintained, for example, by the formation of liposomes, by the maintenance of the required particle size in the case of dispersions or by the use of surfactants. The prevention of the action of microorganisms can be effected by various antibacterial and antifungal agents, for example parabens, chlorobutanol, phenol, sorbic acid, imimerosal and the like.

In many cases it will be preferable to include isoonic agents for example sugars, buffers or partner chloride. The prolonged absorption of the injectable compositions can be effected by the use in the compositions of agents that delay absorption, for example aluminum monostearate and gelatin. Sterile injectable solutions are prepared by incorporating the active compound in the required amount in an appropriate solvent with several of the other ingredients enumerated above, as required, followed by filter sterilization. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze drying techniques, which provide a powder of the active ingredient plus an additional desired ingredient present in the solutions filirado in sterile form. For local administration, the present compounds can be applied purely that is when they are liquid. However, it will generally be convenient to administer them to the skin in the form of compositions or formulations, in combination with an acceptable dermaphological portion which may be a solid or a liquid. Useful solid carriers include finely divided solids such as calcium, clay, microcrystalline cellulose, silica, alumina and the like. Useful liquid carriers include water, alcohols or glycols or water-alcohol / glycol mixtures, in which the compounds can be dissolved or dispersed at effective levels, optionally with the aid of non-toxic surfactants. Additional coadjuvants can be added as fragrances and additional antimicrobial agents to opfimize the properties for a finished use. The resulting liquid compositions can be applied from absorbent pads, used to impregnate bandages and other bandages or to spray them over the affected area using aerosol or pump type sprayers. Thichans, such as synnemic polymers, fatty acids, fatty acid esters and esters, fatty alcohols, modified celluloses or modified mineral materials can also be used with liquid carriers to form disseminated passages, gels, ointments, soaps and the like to be applied directly on the skin of the patient. Examples of useful dermaological compositions which can be used for administering the compounds of Formula I to the skin are known in the maigery; for example, see Jacquet ef al. (Pateníe de EE. No. 4,608,392), Geria (Paíente de USA UU No. 4,992,478), Smifh et al. (US Pact No. 4,559, 157) and Wortzman (U.S. Pat. No. 4,820,508). Useful doses of the compounds of Formula I can be determined by comparing their activity in vitro, and the activity in vivo in animal models. Methods for extrapolation of effective doses in mice and other animals to humans are known in the art; for example, see the Patenfe of EE. UU No. 4,938,949. In general, the concentration of the compounds of Formula I in a liquid composition, as a lotion, will be about 0.1-25% by weight, preferably about 0.5-1.0% by weight. The concentration in a semi-solid or solid composition such as a gel or a powder will be about 0.1-5% by weight, preferably about 0.5-2.5% by weight. The amount of compound or salt or derivative of the same acid required to be used in the process will vary not only according to the selected salt but also to the route of administration, the nature of the transient that was used, and the age and condition. of the patient and finally will be at the discretion of the clinician or attending physician. In general, however, an appropriate dose will be within the range of from about 1.0 to about 100 mg / kg, preferably from about 10 to about 75 mg / kg of body weight per day, more preferably 5 to about 20 mg per day. kilogram of body weight of the patient who receives it. The compound can conveniently be administered in a unit dosage form; for example, tablets, oblong tablets, etc., containing 4 to 400 mg, preferably 10 to 200 mg, more preferably, 20 to 1000 mg of active ingredient per unit dosage form. Ideally, the active ingredient should be administered so as to achieve peak active compound concentrations in the plasma, from about 0.02 to about 20 μM. preferably about 0.1 to 10 μM, more preferably, about 0.5 to about 5 μM. These concentrations can be obtained for example by intravenous injection of a solution of 0.005 to 0.5% of the active ingredient, or they can be administered orally in the form of a bolus containing approximately 4 to 400 mg of the active ingredient. The compounds of the invention can be administered by inhalation from an inhaler, insufflator, atomizer or pressurized pack or other aerosol spray release means. The pressurized packages may comprise an appropriate propellant such as carbon dioxide or appropriate gas. In the case of a pressurized aerosol, the dosage unit can be determined by providing a value to release a dosed amount. Inhalers, insufflators, atomizers have been fully described in the pharmaceutical reference books such as in Remington's Pharmaceutical Sciences Volumes 1 6 (1980) or 18 (1 990) Mack Publishing Co. The desired dose can be conveniently presented in a single dose or in divided doses administered at appropriate doses, for example, in two, four or more sub-doses per day. The sub-dose itself may be further divided, for example, into a number of freely spaced discrete administrations; such as multiple inhalations from an insufflator or by applying a plurality of drops to the eyes. All patents, patent applications, books and literature cited in the specification are hereby incorporated by reference in their entirety. In the case of any inconsistency, the present description shall prevail including any of the definitions thereof. The invention has been described with reference to various specific and preferred embodiments and techniques. However, it should be understood that many variations and modifications may be made always within the spirit and scope of the invention. The invention will now be illustrated by the following non-limiting examples.

EXAMPLES Pharmacology. The ability of the compounds of the invention to act as aniagonyses of A2B adenosine receptors can be determined using pharmacological models that are well known in the maigery or using test procedures which will be described briefly. The cDNA of the rat A2B receptor was subcloned into the pDoubleTrouble expression plasmid using the techniques described by Robeva, A. et al. , Biochem. Pharmacoi , 51, 545-555 (1996). The plasmid was amplified in competent JM1 09 cells and plasmid DNA was isolated using Wizard Megaprep columns (Promega Corporation, Madison, Wl). A2B adenosine receptors were introduced into HEK-293 cells by Lipofectin alfa as described by Felgner, P. L. ef al, Proc. Nati Acad. Sci. USA. 84. 7413-7417 (1987). Cell culture HEK cells were cultured under humidified atmosphere at 5% CO2 / 95% O2 at a temperature of 37 ° C. Colonies were selected for cell development at 0.6 mg / ml of G418. The transfected cells were maintained in DMEM supplemented with a mixture of Hams F12 (1/1) nutrients, 10% newborn calf serum, 2 mM glutamine, and containing 50 l U / mL penicillin, 50 mg / mL streptomycin, and 0.2 mg / mL Geneticin (0418, Boehringer Mannheim). The cells were grown in round plates with a diameter of 10 cm and subcultured when they developed to confluence (approximately after 72 hours). Adhesion studies to radioligand In A2B receptors: confluent monolayers of cells HEK-A2B were washed with PBS followed by Regulator A cooled with ice (10 mM HEPES, 10 mM EDTA, pH 7.4) with protease inhibitors (1.0 μg / mL benzamidine, 1000 μM phenylmetanesulfonyl fluoride, and 2 pg / mL of each of aprotinin, pepsphatin and leupepinine). The cells were homogenized in a Polytron (Brinkmann) for 20 s, centrifuged at 30,000 x g, and the granulate was washed twice with HE buffer (10 mM HEPES, 1 mM EDTA, pH 7.4 with protease inhibitors). The final granulate was resuspended in HE buffer, supplemented with 10% sucrose and frozen in aliquots at -80 ° C. For binding tests, the membranes were thawed and diluted 5-10 with HE until a final protein concentration of approximately 1 mg / mL. To remove the concentrations of prophene, membranes and models of bovine serum albumin were dissolved in 0.2% NaOH / 0.01% SDS and the protein was determined using fluorescamine fluorescence. Stowell, 0. P. ef al. , Anal. Biochem .. 85, 572-580 (1978). Saturation binding assays for A2B adenosine receptors in rats were carried out with [3 H] ZM214,385 (17 Ci / mmol, Tocris Cookson, Bristol UK) (Ji, X. ef al., Druq Design Discov. 16, 216-226 (1999)) or 125 I-ABOPX (2200 Ci / mmol). To prepare 125l-ABOPX, 10 μL of 1 mM ABOPX in methanol / 1 M NaOH (20: 1) was added to 50 μL of 100 mM phosphate buffer at pH 7.3. 1 or 2 mCi of Na 25l was added, followed by 10 L of 1 mg / mL of chloroamine-T in water. After incubation, for 20 minutes at ambient temperature, 50 μL of 10 mg / mL of Na-melabisulfite in water was added to quench the reaction. The reaction mixture was applied to a C18 HPLC column, eluting with a mixture of methanol and 5 mM phosphate at pH 6.0. After 5 minutes at 35% methanol, the concentration of meianol escalated to 100% in 15 minutes. Unreacted ABOPX eluted in 1 1 -12 min. 125l-ABDPX was eluted at 18-19 minutuses with a yield of 50-60% with respect to initial 125 l. In equilibrium adhesion assays the ratio of l2r l / 125l-ABOPX was 1 0-20 / 1. The radioligand binding experiments were carried out in triplicate with 20-25 μg of membrane protein in a total volume of 0.1 ml of HE buffer supplemented with 1 U / ml adenosine deaminase and 5 mM MgCl2. The incubation time was 3 hours at 21 ° C. The specific binding was measured in the presence of 100 μM of ÑECA. Competing experiments were carried out using 0.6 nM of 125 I-ABOPX. The membranes were filtered on Whatman GF / C filters using a Brandel cell harvester (Gaithersburg, MD) and washed repeatedly for 1 to 5-20 seconds with an ice-cold buffer (10 mM Tris, 1 mM MgCl 2, pH 7.4). The Bmax and KD values were calculated using the Marquardf minimal nonlinear square inertification for the single site binding models. Marquardt, D. M., J. Soc. Indusí. Appl. Math .. 1 1. 431 -441, 21 (1963). The K values for different compounds were derived from the Cl50 values as described. J., Cycl. Nucí Res. 8, 163-172 (1982). Data from the replication experiments are tabulated as averages ± SEM. In other Adenosine receptors: [3H] CPX. Bruns, R. F. ef al. , NaunvnScbmiedeberq's Arch. Pharmacol. 335. 59-63 (1987). 125 I-ZM241385 and 125 I-ABA were used in the radioligand binding assays to the membranes derived from the HEK-293 cells expressing the rat recombinant ARs A-, A2A and A3, respectively. [3H] R -? / 6-phenylpropyladenosine linkage.

Schwabe, U. et al, Naunvn-Schmiedeberg's Arch. Pharmacol .. 313. 179-187 (1 980). ([3H] R-PIA, Amersham, Chicago, I L) to receptors Ai of cerebral cortical membranes of rat and [3H] CGS 21680, Jarvis, M. F. et al. , J. Pharmacol. Exp. Therap. , 251. 888-893 (1989). (Dupont NEN, Boston, MA) to A2A receptors of rat striatal membranes was carried out in the manner described. Adenosine deaminase (3 units / ml) was present during the preparation of the brain membranes, in a pre-incubation for 30 minutes at 30 ° C, and during incubation with the radioligands. All the non-radioactive compounds were initially dissolved in DMSO, and diluted with buffer to the final concentration, where the amount of DMSO never exceeded 2%. Incubations were determined by rapid filtration on Whatman GF / B filters using a Brandell cell harvester (Brandeli, Saitbersburg, MD). The tubes were rinsed several times with 3 ml of regulator each time. At least six different concentrations of the competitor were left, covering three orders of magnitude appropriately adjusted for the Cl50 of each compound. The values of the Clso, calculated with the non-linear regression method implemented in (Graph-Pad Prism, San Diego, CA), were converted to the apparent K, values as described. Linden, J., J. Cycl. Nucí Res. 8: 163-172 (1982). The Hill coefficients of the compounds tested were in the range of 0.8 to 1.1. Functional Assay: HEK-A2B cells from a confluent T75 flask were rinsed with phosphate-buffered saline (PBS) of Ca 2+ -free Dulbecco and Mg 2+ and then incubated in Ca 2+ -free HBSS and Mg 2+ - with 005% trypsin and 053 mM EDTA, until the cells were detached. Cells were rinsed twice by centrifugation at 250 xg in PBS and resuspended in 10 ml of HBSS composed of 137 mM NaCl, 5 mM KCF, 0.9 mM MgSO4, 1.4 mM CaCl2, 3 mM NaHCO3, 0.6 mM Na2HPO4, 0.4 mM KH3PO, 5.6 mM glucose, and 10 mM HEPES, pH 7.4 and the indo-1 M fluorescent dye (5 μM), sensitive to Ca2 +, at 37 ° C for 60 min. The cells were rinsed once and resuspended in 25 ml of dye-free HBSS, topped with 1 U / ml adenosine deaminase and maintained at ambient temperature. Adenosine receptor antagonists prepared as 100X charges in DMSO or vehicle were added, and the cells were transferred to a 37 ° C bath for 2 min. Then the cells (1 million in 2 ml) were transferred to a cube with fixed agitation at 37 ° C in a specilufluorimeter Aminco SLM 8000 (SML instrumenis, Urbana IL). The indo-1 fluorescence ratios obtained at 400 and 485 nm (excitation, 332 nm) were recorded using an aperture with a width of 4 nm. ÑECA was added after an equilibrium period of 100s. Accumulation of Cyclic AMP One generation of cyclic AMP was filtered in regulator DMEM / HEPES (DMEM containing 50 mM HEPES, pH 7.4, 37 ° C).

Each of the receptacles of the cells was read twice with DMEM / HEPES regulator, and then 1 00 μL of adenosine deaminase (final concentration 10 iU / ml) and 100 μL of solutions of rolipram and cilostamide (each in one) were added. final concentration of 10μM), followed by 50μL of the test compound (appropriate concentration) or regulator. After 15 minutes, the incubation was terminated at 37 ° C by removing the medium and 200 μL of 0.1 M HCl was added. Extracts of acid were stored at -20 ° C until the test. The amounts of cyclic AMP were deferred following a protocol that used a cAMP (PKA) binding protein [van der Wenden et al. , 1995], with the following minor modifications. The assay regulator consisted of 150 mM K2HPO4 / l 0 mM EDTA / 0.2% BSA FV at pH 7.5. Samples (20 ml) were incubated for 90 minutes at 0 ° C. Incubations were filtered on glass microfiber filters GF / C in a Brandel M-24 Cell Harvester. The filters were further rinsed four times with 2 ml 150 mM of K2HPO4 / 10 mM EDTA (pH 7.5, 4 ° C). Perforated filters were counted in a Packard Emulsifier Safe scintillation fluid 2 hours after being removed. The available data of the affinity test for the compounds of the invention are reported in Table 1. The data reported for the term A2B constitute the displacement level of the binding of [125l] ABOPX specific to the rat A2B receptors (rA2B) expressed in HEK-293 cells. Synthesis and Characterization Nuclear magnetic resonance spectroscopy was carried out on a Varian-300 MHz spectrometer and the spectra were taken in DMSO-dβ or CDCI3. Unless indicated, chemical changes are expressed as ppm downfield from tetramethylsilane or the related ppm of DMSO (2.5 ppm). A mass spectrometer was performed by electroshock ionization (ESI) with a ThermoEinnigan LCQ mass spectrometer. All xanin derivatives were homogeneous as verified using TLC (silica gel 60 F254, 0.25 mm, supported on aluminum, EM Science, Sibbstown, NJ) and HPLC (Shimadzu) using a 5 micron analytical column Varian 018 ( 4.6 mm x 150 mm) in a linear gradient in a solvent solvent system, at a flow rate of 1 ml / min. The solvent system used was MeOH (0.1% formic acid) H2O (0.1% formic acid). Peaks were detected by UV absorption at 232 nm and 254 nm. It was shown that the NMR and mass specimens matched the assigned structure. Example 1. General Procedure Preparation of 6-chloronicotinoyl chloride: 6-Hydroxynicotinic acid (1444 g, 10.4 mmol) was suspended in thionyl chloride (8 ml). DMF (0.50 ml) was added. The mixture was refluxed for 2 hours. After allowing the reaction to cool, the thionyl chloride was extracted with a stream of nitrogen, and the residue was dried under vacuum overnight and used directly for the next step. Preparation of 1,3-Dipropyl-8- (6-chloro-3-pyridyl) xanthine (1): 6-Chloronicotinoyl chloride prepared from 6-hydroxynicotinic acid (1.44 g, 10.4 mmol) was added dropwise. ), in CH2CI2 (20 ml) to a solution of 5,6-diamino-1,3-dipropyluracil (1.81 g, 8 mmol) in dry pyridine (8.2 ml), maintained at 5 ° C. The reaction was heated to ambient temperature and stirred for an additional 3 hours. Water (50 ml) was added to quench the reaction. The solvent was evaporated to provide a dark colored oil. The oil was refluxed for 2 hours in 2N NaDH (20 ml). After cooling, the pH was carefully adjusted to 7 with concentrated HCl. A solid formed and was collected and washed with water (20 ml), ether (20 ml) and chloroform (20 ml) to obtain a whitish solid (1.9 g). The product was used in the following step without further purification. General procedures for the reaction of 1,3-Dipropyl-8- (6-chloro-3-pyridyl) xanthine (1) with substituted amines. Compound 1 (40 mg, 0.15 mmol) and the corresponding substituted amine (0.5 ml or 0.5 g) were placed in a tube under pressure. (Etanor, 4 ml, was added as a solvent if the melting point of the amine was above 80 ° C). The pressure tube was flushed with argon, sealed and stirred at 160 ° C for 48-60 hours. After cooling, ether (10 ml) was added. The resulting solid was collected and purified by column of silica gel or preparative TLC (Solvenie A: CH2C12: MeOH = 20: 1 to 1: 1 or Solvent B: CH2Cl2: MeOH TEA = 20: 1: 0.1 to 4: 1 : 0.1). General procedures for the preparation of urea compounds: The substituted amino pyridyl compound (IC) (10 mg) in dry THF (5 ml) was suspended in a tube under pressure. Isocyanate (0.25 ml) was added. The mixture was stirred at 90 ° C for 48 hours. After cooling, the solvent was evaporated. The residue was purified by preparative TLC (CH2Cl2 MeOH 1 1: 1). General procedures for the preparation of amide compounds: The substituted pyridyl amino compound (15 mg) and the desired acid chloride (4-6 equivalents) were suspended in dry DMF (2 ml). Pyridine (0.1 - 0.1 5 ml) was added to the mixture. The mixture was stirred at room temperature for 24 hours. Solvent was extracted and the residue was purified by column of silica gel or by preparative TLC (CH2CI2: MeOH = 1: 1 or Ethyl Acetone: Hexane: MeOH = 15: 85: 5) Preparation of 13-Diethyl-8 - [6-hydrazino-3-pyridyljxanitine (138): Compound 1 (500 mg, 1.44 mmoles) and hydrazine (4 ml) were placed in a pressure tube. Aeolol (30 ml) was added. The pressure tube was flushed with argon, sealed and stirred at 100-1 60 ° C for 10-16 hours. After cooling, the resulting solid was collected and washed with methanol and ether to provide compound 138 (40 mg). The product was used for the next step without further purification. General procedures for the preparation of the compounds of the Formula IL: Compound 138 (31.5 mg, 0.1 mmol) was suspended in acetic acid (5 ml) in a pressure tube. Aldehyde or ceione (0.12 mmol) was added. The pressure tube was flushed with argon, sealed and stirred at 100-160 ° C for 2-10 hours. After cooling, the resulting solid was collected and purified by silica gel column or by preparative TLC (CH2Cl2 MeOH = 20: 1 to 10: 1) to provide the compound of Formula IL.

EXAMPLES The following compunds of the invention were prepared using the procedures described below. Compound 1: 1,3-Dipropyl-8- (6-chloro-3-pyridyl) xanthine 1H NMR (DMSO, dβ): d 0.89 (m, 6H), 1.59 (m, 2H), 1.73 (m, 2H) , 3.88 (t 2H, J = 7.2Hz), 4.00 (t, 2H, J = 7.2Hz), 7.68 (d, 1H, J = 8.4Hz), 8.50 (dd, 1H, J, = 2.4 Hz, J2 = 8.4Hz), 9.07 (d, 1H, J = 2.4Hz). MS: m / z 348 (M + H) +. Compound 2: 1-Propyl-3-propargyl-8- (6-chloro-3-pyridyl) xanthine MS: m / z 316 (M + H) +. Compound 3: 1,3-Dipropyl-8- (6-ethylamino-3-pyridyl) xanthine 1H NMR (DMSO, d6): d 0.89 (m, 6H), 1.14 (t, 3H, J = 7.2 Hz), 1.56 (m, 2H), 1.72 (m, 2H), 3.33 (m, 2H), 3.84 (t 2H, J 7.2 Hz), 3.99 (1. 2H, J = 7.2 Hz), 6.52 (d. , 1H, J 8.7 Hz), 7.09 (1, 1H), 8.00 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7Hz), 8.72 (d, 1H, = 2.4Hz).

MS: m / z 357 (M.H). Compound 4: 1,3-Dipropyl-8- (6- (2-hydroxyethyl) amino-3-pyridyl) xanthine 1H NMR (DMSO, d6): d 0.88 (m, 6H), 1.57 (m, 2H) , 1.71 (m, 2H), 3.36 (m, 2H). 3.53 (m, 2H), 3.85 (t, 2H, J = 7.2 Hz), 3.99 (t, 2H, J = 7.2 Hz), 4.73 (t, 1H, 5.4 Hz), 6.57 (d, 1H, J = 8.7 Hz), 7.11 (t, 1H), 7.99 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7 Hz), 8.70 (d, 1H, J = 2.4 Hz). MS: m / z 373 (M + H). Compound 5: 1,3-Dipropyl-8- [6- (4-acetylpiperazinyl) -3-pyridyljxanthine H NMR (DMSO, d6): d 0.84 (m, 6H), 1.52 (m, 2H), 1.68 (m, 2H), 2.00 (s, 3H), 3.52 (m, 8H), 3.81 (t, 2H, J = 7.2 Hz), 3.96 (t, 2H, J = 7.2 Hz), 6.92 (d, 1H, J = 8.7 Hz), 8.14 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7 Hz), 8.79 (d, 1H, J = 2.4 Hz). MS: m / z 440 (M + H) +. Compound 6: 1,3-Dipropyl-8- [6- (benzylamino) -3-pyridyljxanthine 1H NMR (DMSO, d6): d 0.87 (, 6H), 1.54 (m, 2H), 1.71 (m, 2H), 3.84 (t, 2H, J = 7.2 Hz), 3.98 (t 2H, J = 7.2 Hz), 4.54 (d, 2H, J = 6.5 Hz), 6.61 (d, 1H, J = 8.7 Hz), 7.22 (m, 1H), 7.31 (m, 4H), 7.66 (t, 1H, J = 6.0 Hz), 8.02 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7 Hz), 8.71 (d, 1H, J = 2.4 Hz). MS: m / z 419 (M + H) +. Compound 7: 1,3-Dipropyl-8- [6- (1-piperidinyl) -3-pyridyl] xanthine? NMR (DM80, dβ): d 30.88 (m, 6H), 1.63 (m, 10H), 3.61 (i, 4H, J = 5.7 Hz), 3.85 (t, 2H, J = 7.2 Hz), 4.00 (f, 2H, J = 7.2 Hz), 6.91 (d, 1H, J = 9.0 Hz), 8.12 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0 Hz), 8.79 (d, 1H, J = 2.4Hz). MS: m / z 397 (M + H) +. Compound 8: 1,3-Dipropyl-8- (6-pyrrolidinylpyrid-3-yl) xanthine? NMR (DM80, dβ): d 0.88 (m, 6H), 1.55 (m, 2H), 1.73 (m, 2H), 1.95 (m, 4H), 3.43 (m, 4H) , 3.85 (t, 2H, J = 7.5 Hz), 4.00 (t, 2H, J = 7.5 Hz), 6.54 (d, 1H, J = 9.0 Hz), 8 , 12 (dd, 1H, J, = 2.4 Hz, J2 = 9.0 Hz), 8.79 (d, 1H, J = 2.4 Hz). MS: m / z 383 (M + H) +. Compound 9: 1,3-Dipropyl-8-. { 6- [4-methyl (perhydro-14-diazepin-1-yl)] - 3-pyridyl} xanthine? NMR (DMSO, dβ): d 0.88 (m, 6H), 1.56 (m, 2H), 1.72. (m, 2H), 1.88 (m, 2H), 2.47 (m, 5H), 2.60 (m 2H), 3.64 (t, 2H, J =, 0 Hz), 3.77 (m , 2H). 3.85 (t, 2H. = 7.2 Hz), 3.99 (t, 2H, J = 7.2 Hz), 6.73 (d, 1H, J = 9.0 Hz), 8.12 (dd, 1, J? =, 4 Hz, J2 = 9.0 Hz), 8.78 (d, 1H, J = 2.4 Hz). MS: mz 426 (M + 2). Compound 10: 1,3-Dipropyl-8- (6-methylamin-3-pyridyl) xanthine? NMR (DMSO, dβ): d 0.88 (m, 6H), 1.56 (m, 2H), 1.72. (m, 2H), 2.81 (d, 3H, J = 4.5 Hz), 3.85 (t, 2H, J = 7.5 Hz), 3.99 (t, 2H, J = 7.5 Hz) ), 6.52 (d, 1HL J = 8.7 Hz), 7.08 (q, 1H, J = 4.5 Hz), 8.01 (dd, 1H, i = 2.4 Hz. J2 = 8.7 Hz), 8.73 (d, 1H, J = 2.4 Hz). EM. m / z 343 (M + H) +. Compound 11: 1,3-Dipropyl-8- [6- (4-methoxybenzylamino) -3-pyridi!) Xanthine NMR (DMSO, d6): d 087 (m.6H), 1.59 (m, 2H), 1.71 (m, 2H), 3.71 (s, 3H), 387 (t, 2H, J = 7.2 Hz), 3.98 (t, 2H, J = 7.2 Hz)! 4.45 (d, 2H, J = 6.3Hz), 6.58 (d, 1H, J = 9.0 Hz), 6.87 (d, 2H, J = 8.7Hz), 7.25 ( d, 2H, J = 8.7Hz), 7.60 (f, 1H), 8.01 (dd.1H, J? = 2.4Hz, J2 = 9.0Hz), 8.71 (d, 1H J = 2.4Hz). MS: m / z 449 (M + H) +. Compound 12: 1,3-Dipropyl-8- [6- (3-methylpiperidin) -3-pyridyljxanthine? NMR (DM30, d6): d 0.88 (m, 9H), 1.14 (m, 1H), 1.40-1.80 (m, 8H), 2.55 (dt, 1H, J1 = 2.1Hz, J2 = 10.5Hz), 2.86 (dt, 1H, J? = 2.1Hz, J2 = 10.5Hz), 3.85 (t, 2H, J = 7.5Hz), 4.00 (t, 2H, J = 7.5Hz), 4. 30 (d, 2H, J = 13.5Hz), 6.92 (d, 1H, J = 9.0Hz), 8.10 (dd, 1H J? = 2.4 Hz, J2 = 9.0Hz), 8.79 (d, 1H, J = 2.4Hz). MS: m / z 411 (M + H) +. Compound 13: 1,3-Dipropyl-8- [6- (2-hydroxypropyl) amino-3-pyridyl] xanthine? NMR (DMSO, d6): d 0.87 (m, 6H), 1.08 (d, 3H, J = 6.0Hz), 1.56 (m, 2H), 1.72 (m, 2H), 3.26 (m, 2H), 3.77 (m, 1H), 3.85 (t, 2H, J = 7.5Hz), 3.99 (t, 2H, J = 7.5Hz), 4.76 (d, 1H, J = 4.5Hz), 6.60 (d, 1H, J = 9.0 Hz), 7.10 (t, 1H, J = 6.0Hz), 7.99 (dd, 1H, Ji = 2.4Hz, J2 = 9.0Hz), 8.69 (d, 1H, J = 2.4Hz).

MS: m / z 387 (M + H) +. Compound 14: 1,3-Dipropyl-8- [6- (2,2-dimethoxyethyl) amino-3-pyridyl] xanthine NMR (DM30, dβ): d 0.88 (m, 6H), 1.56 (m, 2H), 1.72 (m, 2H), 3.29 (s, 6H), 3.45 (i, 2H, J = 5.7Hz), 3.85 (1, 2H, J = 7.5Hz), 3.99 (f, 2H, J = 7.5Hz), 4.49 (1, 1H, J = 5.4 Hz), 6.62 (d, 1H, J = 9.0 Hz), 7.19 (t, 1H, J = 5.7 Hz), 8.00 (dd, 1H, J, = 2.4 Hz, J2 = 9.0 Hz), 8.71 (d, 1H, J = 2.4Hz). MS: m / z 417 (M + H) +. Compound 15: 1,3-Dipropyl-8- [6- (1-hydroxy-2-propyl) amino-3-pyridyl] xanthine? NMR (DMSO, dβ): d 0.88 (m, 6H), 1.12 (d, 3H, J = 6.6Hz), 1.56 (m, 2H), 1.74 (m, 2H), 3.27 (m, 2H), 3.46 (m, 1H), 3.85 (1, 2H, J = 7.2Hz) .3.98 (t, 2H, J = 7.2Hz), 4.74 (t, 1H, J = 5.4Hz), 6.56 (d, 1H, J = 9.0 Hz), 6.90 (d , 1H, J = 7.5 Hz), 7.98 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz), 8.69 (d, 1H, J = 2.4Hz). MS: m / z 387 (M + H) +. Compound 16: 1,3-Dipropyl-8- (6-morpholin-3-pyridyl) xanthine NMR (DMSO, d6): d 0.87 (m.6H), 1.57 (m, 2H), 1.73 (m, 2H), 3.55 (m, 4H), 3.69 (m, 4H), 3.85 (t, 2H, J = 7.2Hz), 3.99 (t, 2H, J = 7.2Hz), 6.94 (d, 1H, J = 9.0 Hz), 8.17 (dd, 1H, J? = 2.4 Hz, J2 = 9.0Hz), 8.83 (d, 1H, J = 2.4Hz). MS: m / z 399 (M + H) +.

Compound 17: 1,3-Dipropyl-8- (6-dimethylamino-3-pyridyl) xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.55 (m, 2H), 1.75 (m, 2H), 3.09 (s, 6H), 3.85 (t, 2H, J = 7.2Hz), 3.99 (t, 2H, J = 7.2Hz), 6.73 (d, 1H, J = 9.0 Hz), 8.13 (dd, 1H, J ? = 2.4 Hz, J2 = 9.0 Hz), 8.80 (d, 1H, J = 2.4Hz). MS: m / z 357 (M + H) +. Compound 18: 1,3-Dipropyl-8- (6- (2-hydroxyethoxy) ethylamino] -3-pyridyl] xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.57 (m, 2H), 1.72 (m, 2H), 3.49 (m, 8H), 3.85 (t, 2H, J = 7.5Hz), 3.99 (t, 2H, J = 7.5Hz), 4.59 (t, 1H, J = 5.4Hz), 6.58 (d, 1H, J = 9.0 HZ), 7.15 (t, 1H), 8.00 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0Hz), 8.71 (d, 1H, J = 2.4Hz), 13.42 (s, 1H). MS: m / z 417 (M + H) +. Compound 19: 1,3-Dipropyl-8- (6-piperazin-3-pyridyl) xanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 m, 2H), 1.72 (m, 2H), 2.78 (m, 4H), 3.52 (m, 4H). 3.85 (t, 2H, J = 7.5 Hz), 3.99 (t, 2H, J = 7.5Hz), 6.88 (d, 1H, J = 9.0Hz), 8.13 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz). 8.80 (d, 1H, J = 2.4Hz). MS: m / z 398 (M + H) +. Compound 20: 1,3-Dipropyl-8- [6- (2-hydroxy-2-phenylethyl) amino-3-pyridyl] xanthine 1H NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m, 2H). 1.72 (m, 2H), 3.32 (m, 1H), 3.55 (m, 4H), 3.85 (t, 2H, J = 7.2Hz), 3.99 (t, 2H, J = 7.2Hz), 4.76 (m, 1H ), 5.55 (d, 1H, J = 4.5Hz), 6.63 (d, 1H, J = 8.7Hz), 7.20-7.40 (m, 6H), 8.00 (dd, 1H, J0 = 2.4 Hz, J2 = 8.7 Hz) ), 8.72 (d, 1H, J = 2.4Hz), 13.42 (s, 1H). MS: m / z 449 (M + H) +. Compound 21: 1,3-Dipropyl-8- [6- (4-aminomethylbenzylamino) ~ 3-pyridyl] xanthine NMR (DMSO, d6): d 0.86 (m, 6H), 1.55 (m, 2H), 1.71 (m, 2H), 3.72 (s, 2H), 3.84 (i, 2H, J = 7.2Hz), 3.97 (f, 2H, J = 7.2Hz), 4. 50 (d, 1H, J = 6.0Hz), 6.57 (d, 1H, J = 9.0 Hz), 7.27 (s, 4H), 7.54 (i, 1H, J = 6.0 Hz), 8.00 (dd, 1H, J ? = 2.4 Hz, J2 = 9.0 Hz), 8.68 (d, 1H, J = 2.4Hz). MS: m / z448 (M + H) +. Compound 22: 1,3-Dipropyl-8- (6-phenylamino-3-pyridyljxanthine 1H NMR (DMSO, d6): d 0.88 (m, 6H), 1.55 (m, 2H), 1.76 (m, 2H), 3.86 (t, 2H, J = 7.5Hz), 4.01 (t, 2H, J = 7.5Hz), 6.93 (m, 2H), 7.29 (t, 2H, J = 7.8Hz), 7.68 (d, 2H, J = 7.8Hz), 8.19 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz), 8.87 (d, 1H, J = 2.4Hz), 9.45 (s, 1H) MS: m / z405 (M + H) +. Compound 23: 1,3-Dipropyl-8- (6-cyclopropylamino-3-pyridyljxanthine? NMR (DMSO, d6): d 0.44 (m, 2H), 0.72 (m, 2H), 0.87 (m, 6H), 1.56 (m, 2H), 1.72 (m, 2H), 2.58 (, 1H), 3.85 (i, 2H, J = 7.5Hz), 3.99 (i, 2H, J = 7.5Hz), 6.66 (d, 1H. = 9.0 Hz) 7.36 (d, 1H, J = 2.7Hz), 8.10 (dd, 1H, J? = 2.4 Hz, J2 = 9.0Hz), 8.74 (d, 1H, J = 2.4Hz) EM. 369 (M + H) + Compound 24: 1,3-Dipropyl-8- [6- (6-pyridylmethylamino) -3-pyridyl] xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 ( m, 2H), 1.72 (m, 2H), 3.84 (t, 2H, J = 7.2Hz), 3.98 (t, 2H, J = 7.2Hz), 4.62 (d, 2H, J = 6.0Hz), 6.67 (d, 1H, J = 8.7Hz), 7.25 (m, 2H), 7.73 (m, 2 HO, 8.04 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7Hz), 8.51 (d, 1H, J = 4.8H), 8.69 (d, 1H, J = 2.4Hz). MS m / z 420 (M + H) +. Compound 25: 1,3-Dipropyl-8- (6- (4-methylpiperazino) -3-pyridyl) xanthine? NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m, 2H), 1.72 (m, 2H), 2.21 (s, 3H), 2.38 (t, 4H, J = 4.8Hz), 3.59 ( 1, 4H, J = 4.8Hz), 3.85 (,, 2H, J = 7.5Hz), 4.00 (,, 2H, J = 7.5Hz), 6.93 (d, 1H, J = 9.0 Hz), 8.15 (dd , 1H, J? = 2.4 Hz. J2 = 9.0 Hz), 8.81 (d, 1H, J = 2.4Hz) MS: m / z 412 (M + H) +. Compound 26: 1,3-Dipropyl-8- (6- (3-pyridylmethylamino) -3-pyridyl] xanthine? NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m, 2H), 1.71 ( , 2H), 3.84 (f, 2H, J = 7.5Hz), 3.98 (1, 2H, J = 7.5Hz), 4.56 (d, 2H, J = 5.7 Hz), 6.63 (d, 1H, J = 8.7Hz), 7.33 (dd, 1H, J? = 4.5 Hz, J2 = 7.8Hz), 7. 71 (m, 2H), 8.04 (dd, 1H, J? = 2.4 Hz, J2 = 8.7Hz), 8.43 (dd, 1H, J? = 1.8Hz, J2 = 4.5Hz), 8.55 (d, 1H, J = 1.8Hz), 8.71 (d, 1H, J = 2.4Hz). MS: m / z 420 (M + H) +. Compound 27: 1, 3-Dipropyl-8- [6- (2-methylbenzylamino) -3-pyridyljxanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m, 2H), 1.72 (m, 2H), 2.31 (s, 3H), 3.85 (t, 2H, J = 7.2Hz), 3.99 (t, 2H, J = 7.2Hz), 4. 50 (d, 2H, J = 5.4 Hz), 6.62 (d, 1H, J = 8.7Hz), 7.10-7.25 (m, 4H), 7.51 (1, 1H, J = 5.4Hz), 8.01 (dd, 1H , J? = 2.4 Hz, J2 = 8.7 Hz), 8.72 (d, 1H, J = 2.4Hz). MS: m / z 433 (M + H) +. Compound 28: 1,3-Dipropyl-8- [6- [2- (3,4-dimethoxyphenyl) eti-amino] -3-pyridyl] xanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m , 2H), 1.72 (m, 2H), 2.77 (1, 2H, J = 7.5Hz), 3.49 (m, 2H), 3.70 (s, 3H), 3.73 (s, 3H), 3.85 (t, 2H, J = 7.5Hz ), 3.99 (f, 2H, J = 7.5Hz), 6.55 (d, 1H, J = 9.0Hz), 6.74 (dd, 1H, J? = 1.8Hz, J2 = 8.4Hz), 6.85 (m, 2H) , 7.17 (í, 1H, J = 5.4Hz), 8.01 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz), 8.73 (d, 1H, J = 2.4Hz). MS: m / z 493 (M + H) +. Compound 29: 1,3-Dipropyl-8- [6 - ((N-propylcarbamoyl), methylamino] -3-pyridyl) xanthine? NMR (DMSO, d6): d 0.88 (m, 9H), 1.54 (m, 4H). 1.72 (m, 2H), 3.17 (m, 2H), 3.30 (d, 3H, J = 5.4Hz), 3.86 (1, 2H, J = 7.5Hz), 4.01 (i, 2H, J = 7.5Hz) , 7.43 (d, 1H, J = 9.0 Hz), 8.01 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz), 8.99 (d, 1H, J = 2.4Hz), 9.29 (f, 1H, 5.4Hz) MS: m / z 428 (M + H) +. Compound 30: 1,3-Dipropyl-8- [6- (3-pentylamino) -3-pyridyl} xanthine? NMR (DM30, d6) d 0.88 (m, 12H), 1.37-1.65 (m, 6H), 1.72 (m, 2H), 3.84 (m, 3H), 3.98 (i, 2H, J = 7.2Hz), 6.54 (d, 1H, J = 8.7Hz), 6.90 (d, 1H, J = 8.4Hz), 7.96 (dd, 1H, J1 = 2.4 Hz, J2 = 8.7Hz), 8.67 (d, 1H, J = 2.4Hz). MS: m / z 399 (M + H) +. Compound 31: 1,3-Dipropyl-8- [6- (2,2-diphenylethylamino) -3-pyridyl] xanthine 1H NMR (DMSO, d6): d 0.86 (m, 6H), 1.54 (m, 2H), 1.72 (m, 2H), 3.82-4.00 (m, 6H), 4.36 (t, 1H, J = 7.5Hz), 6.53 (d, 1H, J = 9.0Hz), 7.15-7.34 (m, 11H), 7.97 (dd, 1H, J? = 2.4 Hz, J2 = 9.0Hz), 8.75 (d, 1H, J = 2.4Hz). MS: m / z 509 (M + H) +. Compound 32: 1,3-Dipropyl-8- [6- [2-. { 1- ethylpyrrolidinomethylamino)] - 3-pyridyljxanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.04 (t, 2H, J = 7.2 Hz), 1.50-1.86 (m, 8H), 2.12 (m, 1H), 2.25 (m, 1H), 2.58 (m, 1H), 2.86 (m, 1H), 3.09 (m, 2H), 3.51 (m, 1H), 3.84 (t, 2H, J = 7.5Hz), 3.99 (t, 2H, J = 7.5Hz), 6.60 (d, 1H, J = 9.0 Hz), 6.98 (br , 1H), 7.99 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz), 8.70 (d, 1H, J = 2.4Hz). MS: m / z 440 (M + H) +. Compound 33: 1,3-Dipropyl-8- [6- (3-methoxybenzylamino) -3-pyridyl] xanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.54 (m, 2H), 1.72 (, 2H), 3.71 (s, 3H), 3.85 (t, 2H, J = 7.8Hz), 3.99 (1.2H, J = 7.8Hz), 4.51 (d, 2H, J = 6.0Hz), 6.61 (d , 1H, J = 9.0 Hz), 6.70-6.91 (m, 3H), 7.22 (t, 1H, J = 7.5Hz), 7.64 (t, 1H, J = 6.0Hz), 8.02 (dd, 1H, J ? = 2.4 Hz, J2 = 9.0 Hz), 8.71 (d, 1H, J = 2.4Hz). MS: m / z 449 (M + H) +. Compound 34: 13-Dipropyl-8- [6 - [(N-phenylcarbamoyl) methylamino] -3-pyridyl) xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.57 (m, 2H), 1.75 (m, 2H), 3.44 (s, 3H), 3.86 (t, 2H, J = 7.5Hz), 4.02 (t, 2H, J = 7.5Hz), 7. 04 (í, 1H, J = 7.2Hz), 7.32 (í, 2H, J = 7.5Hz), 7.48 (d, 1H, J = 9.0Hz), 7. 60 (, 3H), 8.47 (dd, 1H, J, = 2.4 Hz, J2 = 9.0 Hz), 9.12 (d, 1H, J = 2.4Hz). MS: m / z 462 (M + H) +. Compound 35: 1,3-Dipropyl-8- [6- (furfurylamino) -3-pyridyljxanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.57 (m, 2H), 1.73 (m, 2H), 3.87 (t, 2H, J = 7.5Hz), 3.99 (t, 2H, J = 7.5Hz), 4.52 (d, 2H, J = 5.7 Hz), 6.27 (d, 1H, J = 3.0 Hz), 6.38 (m, 1H), 6.3 (d, 1H, J = 9.0 Hz), 7. 56 (m, 2H), 8.03 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0 Hz), 8.73 (d, 1H, J = 2.4 Hz). MS: m / z 409 (M + H) +. Compound 36: 1,3-Dipropyl-8- [6- [2- (4-methoxyphenyl) et.lamino] -3-pyridyl] xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 (m, 2H). 1.72 (m.2H), 2.77 (t, 2H, J = 7.5 Hz), 3.47 (q, 2H, f = 7.5 Hz), 3.71 (s, 3H), 3. 85 (t, 2H, J = 7.2Hz), 3.99 (f, 2H, J = 7.2 Hz), 6.55 (d, 1H, J = 9.0 Hz), 6.85 (d, 2H, J = 3.4 Hz), 7.16 ( d, 2H, J = 8.4 Hz), 8.00 (dd, 1H, J? = 2.4 Hz, J2 = 9.0 Hz), 8.73 (d, 1H, J = 2.4Hz) MS: m / z 463 (M + H) +. Compound 37: 1,3-Dipropyl-8- [6- (2-methoxybenzylamino) -3-pyridyl] xanthine NMR (DMSO, dβ): d 0.86 (m, 6H), 1.56 (m, 2H), 1.71 (m, 2H), 3.82 (s, 3H), 3.87 (t, 2H, J = 7.2Hz), 3.98 (t, 2H, J = 7.2 Hz), 4.48 (d, 2H, J = 6.0 Hz), 6.62 (d, 1H, J = 9.0 Hz), 6.87 (t, 1H, J = 7.2Hz), 6.98 (d, 1H, J = 7.5Hz), 7.20 (m, 2H), 7.46 (í, 1H, J = 6.0 Hz), 7.99 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0 Hz), 8.70 (d, 1H, J = 2.4Hz). MS: m / z 449 (M + H) +. Compound 38: 1,3-Dipropyl-8- [6- (propylamino) -3-pyridyljxanthine 1H NMR (DMSO, d6): d 0.88 (m, 9H), 1.53 (m, 4H), 1.72 (m, 2H) , 3.24 (q, 2H, J = 6.3Hz), 3.85 (t, 2H, J = 7.5Hz), 3.98 (t, 2H, J = 7.5Hz), 6.53 (d, 1H, J = 8.7Hz), 7.13 (t, 1H, J = 5.7 Hz), 7.99 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7Hz), 8.70 (d, 1H, J = 2.4Hz). MS: m / z 371 (M + H) +. Compound 39: 1,3-Dipropyl-8- [6- (cyclopentylamino) -3-pyridyljxanthine? NMR (DMSO, dβ): d 0.88 (m, 6H), 1.40-1.75 (m, 10H), 1. 72 (m, 2H), 3.84 (t, 2H, J = 7.2Hz), 3.99 (t, 2H, J = 7.2Hz), 4.17 (m, 1H), 6.52 (d, 1H, J = 8.7Hz) , 7.10 (d, 1H, J = 6.6 Hz), 7.99 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7Hz), 8.70 (d, 1H, J = 2.4Hz). MS: m / z 397 (M + H) +.

Compound 40: 1,3-Dipropyl-8- [6- (cyclohexylamino) -3-pyridyljxanthine? NMR (DMSO, d6): d 0.88 (m, 6H), 1.13-1.91 (m, 14H), 1.72 (m, 2H), 3.76 (m, 1H), 3.84 (t, 2H, J = 7.5Hz), 3.98 (i, 2H, J = 7.5Hz), 6.52 (d, 1H, J = 9.0 Hz) 7.00 (d, 1H, J = 7.8 Hz), 7.97 (dd, 1H, J? = 2.4 Hz, J2 = 9.0Hz), 8.69 (d, 1H, J = 2.4Hz) MS: m / z 411 (M + H) +. Compound 41: 1,3-Dipropyl-7-ethyl-8- (6-chloro-3-pyridyl) xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.33 (1, 3h, J = 7.2 Hz), 1.59 (m, 2H), 1.73 (m, 2H), 3.87 (1, 2H, J = 1, 5Hz), 3.99 (t, 2H, J = 7.5Hz), 7.74 (d, 1H, J = 8.4Hz), 8.19 (dd, 1H, Ji = 2.4 Hz, J2 = 8.4Hz), 8.74 (d, 1H, J = 2.4Hz). MS: m / z 376 (M + H). Compound 42: 13-Dipropyl-7- (3-fluoropropyl-8- (6-chloro-3-pyridyl) xanthine? NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 (m, 2H), 1.72 (m, 2H), 2.09 (m, 1H) 2.18 (m, 1H), 3.89 (1, 2H, J = 7.5Hz), 3.98 (1, 2H, J = 7.5Hz), 4.29 (t, 1H, J = 5.4 Hz), 4.43 (m, 3H), 7.75 (dd, 1H, Ji = 0.6Hz, J2 = 8.4Hz), 8.19 (dd, 1H, J? = 2.4 Hz, J2 = 8.4HZ), 8.74 (dd, 1H, J? = 0.6Hz, J2 = 2.4Hz), MS: m / z 408 (M + H) +. Compound 43: 1,3-Dipropyl-7-methyl-8- (6-chloro-3-pyridyl) xanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m, 2H), 1.72 (m , 2H), 3.86 (t, 2H, J = 7.5Hz), 3.99 (t, 2H, J = 7.5Hz), 4.01 (s, 3H), 7.74 (d, 1H, J = 8.4Hz), 8.26 (dd) , 1H, Ji = 2.4 Hz, J2 = 8.4Hz), 8.82 (d, 1H J = 2.4Hz), MS: m / z 362 (M + H) +. Compound 44: 1,3-Dipropyl-7 (2-bromoethyl) -8- (6-chloro-3-pyridyl) xanthine NMR (DMSO, dβ): d 0.88 (m, 6H), 1.59 (m, 2H), 1.72 (m, 2H), 3.85 (m, 4H), 3.99 (t, 2H, J = 7.5Hz), 4.66 (t, 2H, J = 6.0Hz), 7.76 (d, 1H, J = 8.4Hz), 8.21 (dd, 1H, J? = 2.7 Hz, J2 = 8.1Hz), 8.76 (d, 1H, J = 2.7Hz). MS: m / z 456 (M + H) +. Compound 45: 13-Dipropyl-8- [6- (2-thiophenmethylamino) -3-pyridyljxanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 (m, 2H), 1.72 (m, 2H), 3.85 (t, 2H, J = 7.5Hz), 3.99 (t, 2H, J = 7.5Hz), 4.70 (d, 2H, J = 6.0Hz), 6.60 (d, 1H, J = 8.7 Hz), 6.94- 7.03 (m, 2H), 7.35 (dd, 1H, J? = 1.5Hz, J2 = 5.1Hz), 7.70 (t, 1H, J = 6.0Hz), 8.04 (dd, 1H, J? = 2.4 Hz, J2 = 8.1Hz), 8.75 (d, 1H, J = 2.4Hz). MS: m / z 425 (M + H) +. Compound 46: 1,3-Dipropyl-8- [6 - [(N- (4-methoxyphenylcarbamoyl) methylamino] -3-pyridyl) xanthine? NMR (DMSO, d6): d 0.89 (m, 6H), 1.56 (m, 2H), 1.73 (m, 2H), 3.43 (s, 3H), 3.73 (s, 3H), 3.87 (i, 2H, J = 7.2Hz), 4.02 (t, 2H, J = 7.2Hz), 6.89 (dd, 2H, J = 6.9Hz), 7.48 (m, 3H), 8.47 (dd, 1H, J, = 2.4 Hz, J2 = 9.0Hz), 9.11 (d, 1H, J = 2.4Hz).

MS: m / z 492 (M + H) +. Compound 47: 1,3-Dipropyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine? NMR (DMSO, d6): d 0.87 (m, 6H), 1.57 (m, 2H), 1.73 (m, 2H), 3.49 (s, 3H), 3.86 (t, 2H, J = 7.2Hz), 3.99 (í, 2H, J = 7.2Hz), 7.35 (dd, 1H, J? = 7.8Hz, J2 = 7.8 Hz), 7.41 (d, 1H, J = 8.4Hz), 7.71 (di, 1H, J, = 1.5 Hz, J2 = 8.4Hz), 8.32 (dd, 1H, Ji = 2.4 Hz, J2 = 8.4Hz), 8.46 (d, 1H, J = 2.1), 8.54 (dd, 1H, J1 = 2.1Hz, J2 = 4.8Hz), 8.98 (d, 1H, J = 2.4 Hz) . MS m / z 448 (M + H) +. Compound 48: 1,3-Dipropyl-8- [6 - [(N- (4-fluorophenylcarbamoyl) methylamino] -3-pyridyl) xanthine NMR (DMSO, dβ): d 0.88 (m, 6H), 1.57 (m, 2H), 1.75 (m, 2H), 3.44 (s, 3H), 3.88 (t, 2H, J = 7.5Hz), 4.03 (f, 2H, J = 7.5Hz), 7.15 (i, 2H, J = 8.7 Hz), 7.49 (d, 1H, J = 9.0Hz), 7.62 (m, 2H), 8.47 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0Hz), 9.12 (d, 1H, J = 2.4Hz) . MS m / z 480 (M + H) +. Compound 49: 1,3-Dipropyl-8- [6- [N-isonicotinoylmethylamino] -3-pyridyl) xanthine NMR (DMSO, dβ): d 0.88 (m, 6H), 1.57 (m, 2H), 1.75 (m , 2H), 3.47 (s, 3H), 3.85 (í, 2H, J = 7.5Hz), 3.99 (í, 2H, J = 7.5Hz), 7.26 (d, 2H, J = 5.4Hz), 7.46 (d , 1H, J = 8.7Hz), 8.34 (dd, 1H, J? = 2.4 Hz, J2 = 8.7Hz), 8.54 (d, 2H, J = 5.4Hz), 8.96 (d, 1H, J = 2.4 Hz). EM. m / z 448 (M + H) +. Compound 50: 1,3-Dipropyl-8- [6- [N-methoxycarbonylmethylamino] -3-pyridyl) xanthine MS: m / z 401 (M + H) +. Compound 51: 1,3-Dipropyl-8- [6- [N -phenylcarbamoyl, N- (2-phenylacarbamoyloxyethyl) amino] -3-pyridyl) xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.57 (m, 2H), 1.75 (m, 2H), 3.87 (t, 2H, J = 7.5Hz), 4.03 (t, 2H, J = 7.5Hz), 4.34 (m, 4H), 6.92-7.57 (m, 11H), 8.44 (dd, 1H, J -, = 2.4 Hz, J2 = 8.7Hz), 9.12 (d, 1H, J = 2.4Hz), 9.58 (s (br), 1H). MS: m / z 611 (M + H) +. Compound 52: 1,3-Dipropyl-8-. { 6- [4- (N-Phenylcarbamoyl)] piperazino-3-pyridyl} xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 (m, 2H), 1.73 (m, 2H), 3.57 (m, 4H), 3.67 (m, 4H), 3.86 (t, 2H, J = 7.2Hz), 4.01 (t, 2H, J = 7.2Hz), 6.93 (t, 1H, J = 7.5 Hz), 6.99 (d, 1H, J = 9.0 Hz), 7.23 (t, 2H, J = 7.8Hz), 7.46 (d, 2H, J = 7.8Hz), 8.19 (dd, 1H, J? = 2.4Hz, J2 = 9.0Hz), 8.61 (s, 1H), 8.85 (d, 1H, J = 2.4Hz). MS: m / z 517 (M + H) +. Compound 53: 1,3-Dipropyl-8-. { 6- [4- (N-isonicotinoyl)] piperazino-3-pyridyl} xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 (m, 2H), 1.73 (m, 2H), 3.38 (m, 2H), 3.64 (m, 2H), 3.75 (m, 4H) , 3.86 (t, 2H, J = 7.2Hz), 4.00 (t, 2H, J = 7.2Hz), 6.96 (d, 1H, J = 9.0 Hz), 7.44 (d, 2H, J = 5.1Hz), 8.19 (dd, 1H, J? = 2.4 Hz, J2 = 9.0Hz), 8.69 (d, 2H, J = 5.1Hz), 8. 84 (d, 1H, J = 2.4Hz). MS: m / z 503 (M + H) +.

Compound 54: 1-propyl-3- (4-methoxyphenyl) ethyl-8- (6-chloro-3-pyridyl) xanthine? NMR (DMSO, d6): d 0.84 (t, 3H, J = 7.2Hz), 1.53 (m, 2H), 2.93 (,, 2H, J = 7.2Hz), 3.67 (s, 3H), 3.83 (t, 2H, J = 7.2Hz), 4.20 (,, 2H, J = 7.2Hz), 6.81 (d, 2H, J = 8.1Hz), 7.12 (d, 2H, J = 8.1Hz), 7.68 (d, 1H, J = 8.4Hz), 8.44 (dd, 1H, J? = 2.4 Hz, J2 = 8.4Hz), 8.98 (d, 1H, J = 2.4 Hz). MS: m / z 440 (M + H) +. Compound 55: 1-Propyl-3- (methoxyphenylethyl) -8- (6-piperazino-3-pyridyl) xanthine NMR (DMSO, d6): d 0.84 (m, 3H), 1.52 (m, 2H), 3.38 (m, 2H), 2.77 (m, 4H), 2.94 (t, 2H, J = 7.5Hz), 3.51 (m, 4H), 3.69 (s, 1H), 3.83 (í, 2H, J = 7.5Hz), 4.20 (t, 2H, J = 7.5Hz), 6.83 (d, 2H, J = 8.4 Hz), 6.89 (d, 1H, J = 9.0 Hz), 7.14 (d, 2H, J = 8.4 Hz), 8.14 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0 Hz), 8.82 (d, 1H, J = 2.4Hz). MS: m / z 490 (M + H) +. Compound 56: 13-Dipropyl-8- [6- (4-pyridylamino) -3-pyridyljxanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 (m, 2H), 1.74 (m, 2H), 3.87 (t, 2H, J = 7.5Hz), 4.03 (t, 2H, J = 7.5Hz), 6.30 (d, 2H, J = 7.8Hz), 7.94 (d, 1H, J = 8.7Hz), 8.53 ( d, 1H, J = 7.8Hz), 8.60 (dd, 1H, Ji = 2.4 Hz, J2 = 8.7Hz), 9.17 (d, 1H, J = 2.4 Hz). MS: m / z 407 (M + 2) +. Compound 57: 1,3-Dipropyl-8-. { 6- [4- (N-nicotinoyl)] piperazino-3-pyridyl) xanthine NMR (DMSO, d6): d 0.88 (m, 6H), 1.56 (m, 2H), 1.74 (m, 2H), 3.46-3.83 (m, 8H), 3.88 (t, 2H, J = 7.5Hz), 4.00 (t, 2H, J = 7.5Hz), 6.96 (d, 1H, J = 9.0 Hz), 7.50 (dd, 1H J? = 7.8 Hz. J2 = 7.8Hz), 7. 89 (d, J = 7.5Hz), 8.19 (dd, 1H, J? = 2.4 Hz, J2 = 9.0Hz), 8.66 (m, 2H). 8.84 (d, 1H, J = 2.4 Hz). MS: m / z 503 (M + H) +. Compound 58: 1,3-Dipropyl-8- [6- (hexahydro-1,4-diazaepin-1-yl) -3-pyridyl] xanthine NMR (DMSO, d6): d 0.87 (m, 6H), 1.56 ( m, 2H), 1.74 (m, 4H), 2.66 (t, 2H, J = 5.4Hz), 2.86 (f, 2H, J = 5.4Hz), 3.68 (m, 4H), 3.85 (f, 2H, J = 7.5Hz), 3.99 (í, 2H, J = 7.5Hz), 6.72 (d, 1H, J = 9.0 Hz), 8.10 (dd, 1H, Ji = 2.4 Hz, J2 = 9.0Hz), 8.77 (d, 1H, J = 2.4 Hz). MS: m / z 412 (M + H) +. Compound 59: 13-Diethyl-S- (6-chloro-3-pyridyl) xanthine? NMR (DMSO, d6): d 1.14 (t, 3H, J = 6.9Hz), 1.26 (t, 3H, J = 6.9Hz), 3.94 (q, 2H, J = 6.9Hz), 4.09 (q, 2H, J = 6.9Hz), 7.68 (d, 1H, J = 8.4Hz), 8.46 (dd, 1H, J? = 2.4 Hz, J2 = 8.4Hz), 9.07 (d, 1H, J = 2.4 Hz). MS: m / z 320 (M + H) +. Compound 60: 1,3-Diethyl-8- (6-piperazino-3-pyridyl) xanthine MS: m / z 370 (M + H) +. Compound 61: 1,3-Diethyl-8- (6 - [(N-phenylcarbamoyl) methylamino] -3-pyridyl) xanthine MS: m / z 434 (M + H) +. Compound 62: 1,3-Diethyl-8- [6- [N-nicotinoylethylamino] -3-pyridyl) xanthine MS: m / z 434 (M + H) +. Compound 63: 13-Diethyl-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 315 (M + H) +. Compound 64: 1, 3-Diethyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine MS: m / z 420 (M + H) +. Compound 65: 1, 3-Dimethyl-8- [6- [N-nicotinoylcyclopropylamino] -3-pyridyl) xanthine MS: m / z 446 (M + H) +. Compound 66: 1, 3-Dicyclopropylmethyl-8 ~ (6-ethylaminopyridin-3-yl) xanthine MS: m / z 367 (M + H) +. Compound 67: 1-Propargyl-3-methyl-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 31 1 (M + H) +. Compound 68: 8- [6- (25-diaza-bicyclo [2.2.2] oct-2-yl) -pyridyl-3-yl} -13-Dipropyl-3,7-dihydro-purine-2,6-dione MS: m / z 41 0 (M + H) +. Compound 69: 1, 3-Dicyclopropylmethyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine MS: m / z 472 (M + H) +. Compound 70: 1, 3-Dicyclopropiimethyl-8- [6- [N-nicotinoylethylamino] -3-pyridyl) xanthine MS: m / z 486 (M + H) +. Compound 71: 1, 3-Diallyl-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 339 (M + H) +. Compound 72: l-Clopropylmethyl-3-ethyl-8- (6-methylaminopyridin-3-yl) xanthine MS: m / z 342 (M + H) +. Compound 73: 13-Diethyl-8- [6- (2-pyridylmethylamino) -3-pyridyljxanthin MS: m / z 392 (M + H) +. Compound 74: 1, 3-Diethyl-8- [6- (3-pyridylmethylamino) -3-pyridyljxanthine MS: m / z 392 (M + H) +. Compound 75: 1, 3-Diethyl-8- [6- (3-methoxybenzylamino) -3-pyridyljxanthine MS: m / z 421 (M + H) +. Compound 76: 1, 3-Dipropyl-8- [6- [2- (3-pyridyl) -ethylamino] -3-pyridyl] xanthine MS: m / z 434 (M + H) +. Compound 77: 1, 3-Diethyl-8- [6- [2- (3-pyridyl) -ethylamino] -3-pyridyl] xanthine MS: m / z 406 (M + H) +. Compound 78: 1, 3-Dipropyl-8- [6- [2- (2-pyridyl) -ethylamino] -3-pyridyl] xanthine MS: m / z 434 (M + H) +.

Compound 79: 1, 3-Diethyl-8- [6- [2- (2-pyridyl) -ethylamino] -3-pyridyljxanthin MS m / z 406 (M + H) +. Compound 80: 1, 3-Diethyl-8- (6-pyrrolidinylpyridyl-3-yl) xanthine MS: m / z 355 (M + H) +. Compound 81: 1, 3-Diethyl-8- [6- [2- (1-pyrrolidinyl) -ethylamino] -3-pyridyl] xanthine MS m / z 398 (M + H) +. Compound 82: 1, 3-Dipropyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine MS: m / z 387 (M + H) +. Compound 83: 1, 3-Dipropyl-8- (6- (2-acetylaminoethyl) amino-3-pyridyl) xanthine MS: m / z 414 (M + H) +. Compound 84: 13-Diethyl-8- (6-bromo-3-pyridyl) xanthine MS: miz 364 (M + H) +. Compound 85: 1, 3-Dipropyl-8-. { 6- [4- (2-pyridyl) -piperazino-3-pyridyl} xanthine MS: m / z 475 (M + H) +. Compound 86: 1, 3-Diethyl-8-. { 6- [4- (2-pyridii) -piperazino] -3-pyridyl) xanthine MS: m / z 447 (M + H) +. Compound 87: 1, 3-Diethyl-8- [6- (trans-2,5-dimethylpiperazino) -3-pyridyl] xanthine MS: m / z 398 (M + H) +. Compound 88: 1, 3-Dipropyl-8-. { 6- [4- (2-pyrimidinyl) -piperazino] -3-pyridyl) xanthine MS m / z 476 (M + H) +. Compound 89: 1, 3-Diethyl-8-. { 6- [4- (2-pyrimidyl) -piperazino] -3-pyridyl} xanthine MS: m / z 448 (M + H) +. Compound 90: 1, 3-Diethyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine MS: m / z 359 (M + H) +. Compound 91: 1-Propargyl, 3-methyl-8- (6-Bromo-3-pyridyl) xanthine MS: m / z 360 (M + H) +. Compound 92: 1, 3-Diethyl-8- [6- [N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine MS: m / z 464 (M + H) +. Compound 93: 1-Propargyl, 3-methyl-8- (6- (2-methoxyethyl) -3-pyridyl) xanthine MS: m / z 355 (M + H) +. Compound 94: 1, 3-Diethyl-8- [6- [N-isonicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine MS: m / z 464 (M + H) +. Compound 95: 1- (5- (1, 3-Diethyl-2,3,6,7-tetrahydro-2,6-dioxo-1 H -purin-8-yl) pyridin-2-yl) -1 - ( 2-methoxyethyl) -3- (pyridin-4-yl) urea MS: m / z 479 (M + H) +.

Compound 96: 1, 3-Dimethyl-8- (6-bromo-3-pyridyl) xanthine MS: m / z 460 (M + H) +. Compound 97: 1, 3-Dimethyl-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 287 (M + H) +. Compound 98: 1, 3-Dimethyl-8- [6- [N-nicotinoylmethylamino) -3-pyridyl) xanthine MS: m / z 392 (M + H) +. Compound 99: 1, 3-Dipropii-8- [6- [N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine MS: m / z 492 (M + H) +. Compound 100: 1-Propargyl, 3-methyl-8- [6- [N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine MS: m / z 359 (M + H) +. Compound 101: 1-Propargyl, 3-methyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine MS: m / z 416 (M + H) +. Compound 102: 1, 3-Dipropyl-8- (2,6-dichloro-3-pyridyl) xanthine MS: m / z 382 (M + H) +. Compound 103: 1, 3-Dipropyl-8- (2,6-dimethylamino-3-pyridyl) xanthine MS: m / z 372 (M + H) +. Compound 104: 1, 3-Dipropyl -8- (2,6-di (2-methoxyethyl) -3-pyridyl) xanthine MS: m / z 460 (M + H) +. Compound 105: 1, 3-Dipropyl-8- [2,6-di [N-nicotinoylmethylamino} -3- pyridyl) xanthine MS: m / z 582 (M + H) +. Compound 106: 1, 3-Dipropyl-8- [2,6-cii [N-nicotinoyl, N-methoxyethyl] -3-pyridyl) xanthine MS: m / z 670 (M + H) +. Compound 107: 1, 3-Diethyl-8- [6- [N- (2-pyrazinecarbonyl) methylamino] -3-pyridyl) xanthine MS: m / z 421 (M + H) +. Compound 108: 1, 3-Diethyl-8- [6- [N- (isoxazole-5-carbonyl) methylamino] 3-pyridyl) xanthine MS: m / z 410 (M + H) +. Compound 109: 1, 3-Dipropyl-8- [6- [N- (2-pyrazinecarbonyl) methylamino] -3-pyridyl) xanthine MS: m / z 449 (M + H) +. Compound 1 10: 1, 3-Dipropyl-8- [6- [N- (isoxazole-5-carbonyl) methylamino] 3-pyridyl) xanthine MS: m / z 438 (M + H) +. Compound 1 1 1: 1, 3-Dipropyl-8- [6- [N- (5-methylisoxazol-3-yl-3-carbonyl) methylamino] -3-pyridyl) xanthine MS: m / z 452 (M + H ) + Compound 112: 1, 3-Dipropyl-8- [6- [N- (2-chloro-6-methoxypyridinyl-4-carbonyl), N-methylamino] -3-pyridyl) xanthine MS: m / z 512 (M + H) +.

Compound 1 13: 1, 3-Dipropyl-8- [6- [N- (lsonicotinoyl N-oxide), N-methylamino] -3-pyridyl) xanthine MS m / z 464 (M + H) +. Compound 1 14: 1-propyl-344-methoxypheni) etiI-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 435 (M + H) +. Compound 115: 1, 3-Diethyl-8- [6- [N- (lsonicotinoyl N-oxide), N-methylamino] -3-pyridyl) xanthine MS: m / z 436 (M + H) +. Compound 116: 1, 3-Diallyl-8- (6-chloro-3-pyridyl) xanthine MS: m / z 344 (M + H) +. Compound 1 17: 1-propyl-3- (4-methoxyphenyl) ethyl-8- [6- (N-nicotinoylmethylamino) -3-pyridyl] xanthine MS: m / z 540 (M + H) +. Compound 118: 1-propyl-3- (4-methoxyphenyl) ethyl-8- [6- (N- (6-chloronicotinoyl) methylamino) -3-pyridyl] xanthine MS: m / z 574 (M + H) +. Compound 119: 1, 3-Diallyl-8- [6- (N-nicotinoylmethylamino) -3-pyridyl] xanthine MS: m / z 444 (M + H) +. Compound 120: 1, 3-Diallyl-8- [6- (N- (6-chloronicotinoylmethylamino) -3-pyridyl] xanthine MS: m / z 478 (M + H) + Compound 121: 1,3-Dipropyl- 8- [6- (N- [6- (trifluoromethyl) nicotinoyl] methylamino) -3-pyridyl] xanthine MS: m / z 516 (M + H) + Compound 122: 1,3-diethyl-8- (6 - (2-hydroxy-5-methyl) benzaldehydehydrazono] -3-pyridylJxanthine MS: m / z 434 (M + H) + Compound 123: 1-Cyclopropyl-3-propyl-8- [6- (N- [ 6- (trifluoromethyl) nicotinoyl] methylamino) -3-pyridyl] xanthine MS is m / z 446, Compound 124: 1, 3-diethyl-8- [6- (bromopyridin-3-carbaldehydehydrazino] -3-pyridyl] xanthine EM : m / 483 (M + H) + Compound 125: 1-Cyclopropyl-3-ethyl-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 327 (M + H) + Compound 126: 1 Cyclopropyl-3-propyl-8- (6-methyl-3-pyridyl) xanthine MS: m / z 341 (M + H) + Compound 127: 1-Propyl-3-cyclopropyl-8- (6- methylamino-3-pyridyl) xanthine MS: m / z 341 (M + H) + Compound 128: 1-Cyclopropyl-3-propyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine MS: m / z 385 (M + H) +. Compound 129: 1-Cyclopropyl-3-p ropil -8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanthine MS: mz 446 (M + H) +.

Compound 130: 1,3-Diethyl-8- [6- (N- (6-chloronicotinoyl) methylamino) -3-pyridyl-xanthine-Mxm-fz 454 (M - + - H ^ Compound 131: 1,3-Dipropyl-8 - (2-Chloro-6-methoxyethylamino-4-pyridyl) xanthine MS: m / z 421 (M + H) + Compound 132: 1,3-Dipropyl-8- (2-chloro-6-methylamino-4-) pyridyl) xanthine MS m / z 377 (M + H) + Compound 133: 1,3-Dipropyl-8- [2- [N-nicotinoyl, N- (2-methoxyethi) amino] -6-chloro-4 -pyridyl) xanthine MS: m / z 527 (M + H) +. Compound 134: 1, 3-Dipropyl-8- [2- [N-nicotinoii, N-methylamino] -6-chloro-4-pyridyl) xanthine MS: m / z 482 (M + H) +. Compound 135: 1-Cyclopropyl-3-propyl-8- [6- [N- (6-chloronicotinoyl) methylamino] -3-pyridi1) xanthine MS: m / z 480 (M + H) +. Compound 136: 1 -EtI-3-cyclopropyl-8- (6-methylamino-3-pyridyl) xanthine MS: m / z 327 (M + H) +. Compound 137: 1-Ethyl-3-cyclopropyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine MS: m / z 371 (M + H) +.

Compound 138: 1, 3-Diethyl-8- [6-hydrazino-3-pyridyljxanthine MS: m / z 316 (M + H) +. Compound 139: 1, 3-Diethyl-8- [6- (cyclopropylamino) -3-pyridyljxanthine MS: m / z 341 (M + H) +. Compound 140: 1, 3-Diethyl-8- [6- (cyclopropylmethylamino) -3-pyridyl] xanthine MS: m / z 355 (M + H) +. Compound 141: N '- [5- (1, 3-Diethyl-2,6-dioxo-2,3,6,7-tetrahydro-1 H-purin-d-i1) -pyridin-2-yl] -hydrazide MS: m / z 421 (M + H) +. Compound 142: N- [5- (1,3-Dethyl-2,6-d-oxo-2, 3,6,7-tetrahydro-1 H -purin-d-yl) -pyridin-2-i ] -N - (pyridine -3-carboni1) -hydrazide MS: m / z 526 (M + H) +. Compound 143: 1, 3-Diethyl-8- [6- (ethylamino) -3-pyridyljxanthine MS: m / z 329 (M + H) +. Compound 144: 1, 3-Diethii-d- [6- [N-nicotinoylcyclopropylmethylamino] -3-pyridyl) xanthine MS: m / z 460 (M + H) +. Compound 145: 1-Cyclopropylmethyl-3-Ethyl-d- [6- [N- (6-chloronicotinoyl) methylamino] -3-pyridyl) xanthine MS: m / z 480 (M + H) +.

Claims

CLAIMS 1. A compound of the formula I:

wherein: R is hydrogen, (C1-C5) alkyl, haloalkyl (C? -8), (C3-C5) alkenyl or (C3-C5) alkynyl; R1 and R2 are independently hydrogen, alkyl (d-C8), alkenyl (C3-C8), alkynyl (C3-C8), alkoxy (C? -8), cycloalkyl (C3-C8), cycloalkyl (C3-C8) alkyl (C? -C8) -, heterocycle (C4-C? 0), heterocycle (C4-C10) alkyl (C? -C8) -, aryl (C6-C0), aryl (C6-C? O) alkyl ( C? -C8) -, heteroaryl (C5-C10), or heteroaryl (C5-CioJalkyloid-Cs) -; X is a 5-10 membered heteroaryl ring having a niologen atom and which is optionally interrupted with 1, 2, or 3 non-peroxide oxy (-O-), thio (-S-), sulfinyl (-SO) groups -), sulfonyl (-S (O) 2-) or amine -N (R9) -; Z is -OR3, -SR3, halo, S (O) mNR4R5, -NR4R5, or heterocycle

(C4-C1 0) wherein the heterocycle is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano. nitro, -ORa, -SRa, alkyl (C? -Cβ), aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (C, -C8), haloalkyl Ci-Cs), -NRbRc, C ( O) Ra, -COORa, and -C (O) NRbRc each Z1 is independently alkyl (C -? - C8), alkenyl (C2-C8), alkynyl (C2-C8), -OR6, -SR6, halo, RβOalkyl d-Cß), R7R8Nalkyl (C1-C8), haloacyl (d-C8), -NR7R8, R7R8Nalkyl (C, -C8). -C (O) R6, COOR6 and -C (O) NR7R8 R3 is (d-C8) alkyl, (C3-C8) alkenyl, (C3-C8) alkynyl, (C3-C8) aryl, (C6-do) aryl ) alkyl (C? -C8) -, heteroaryl (C5-C10), heteroarylC-C ^ Jalkyloid-Cg) -, -C (O) R6, or -C (O) NR7R8; R4 and R5 are independently hydrogen, alkyl (d-C8), alkenyl (C3-C8), alkynyl (C3-C8), alkoxy (d-C8), cycloalkyl (C3-C8), cycloalkyl (C3-C8) alkyl ( d-C8) -, polycycloalkyl (C6-C? 8), polycycloalkyl (C6-C18) alkyl (C? -8) -, heyerocycle, heterocycle (C3-C10) alkyl (d-C8) -, -NR7R8 , aryl (C6-C10), aryl (C6-C10) alkyl (C1-C8) alkyl-, heleroaryl (C5-C10), heteroaryl-doCalkyloid-Cs) -, - (C2-C4-Y) q- (CH2 ) 2-4X-C (O) R6, -CO2R6, -C (O) NR7R8, or -S (O) 2-NR7R8 or R4 and R5 together with the atoms to which they are attached form a mono- ring, bicyclic- or saturated or partially unsaturated aromatic having 3, 4, 5, 6, 7, or 8, atoms in the ring and optionally comprising 1, 2, 3, or 4 hetero-atoms selected from non-peroxide oxy (-O-) , thio (-S-), sulfinyl (-SO-), sulfonyl (-S (O) 2-) and amine -N (R9) - in the ring, where the ring is optionally substituted with 1, 2, 3, or 4 substitutes independently selected enfre halo, cyano, ni, -ORa, -SRa, (Cß-C10) aryl, -Oaryl (C6, -C10), hydroxyalkyl (d-C8), RbRcNalkyl (C? -C8), haloalkyl (d-C8), NRbRc, -C (O) Ra, -COORa, and C (O) NRbRc;

X1 is -OR6, -C (O) R6, -CO2R6 or -NR7R8; and Y is oxy (-O-), thio (-S-), sulfinyl (-SO-). suifonyl (-S (O) 2-) and amine -N (R9) -; wherein the alkyl, alkenyl, cycloalkyl, alkynyl, aryl, heterocycle, or heteroaryl groups of the groups R1, R2, R3, R4, and R5 are optionally susiiuted with one or more unsubstituted subsitutes selected from halo, cyano, nitro, -ORa, - SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-C8), RbRcNalkyl (d-C8), haloalkyl (d-C8), NR Rc, -C (O) Ra, - COORa, and C (C) NRbR °; where R6 is hydrogen, alkyl (d-C8), RaOacyl (C1-C8),

RbRcNalkyl (d-C8), haloalkyl (d-C8), heterocycle (C3-C10), heterocyclic-CioHalkyloxyCi-Cs) -, aryl (C6-C0), aryl (C6- C10) alkyl (C-, -C8) -, heeroaryl (C4-C10), heeroaryl (C4-C10) alkyl (C1-C8) -; wherein the heterocycle, heteroaryl or aryl are optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, cyano, kidney, -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-C8), RbRcNalkyl (C1-C8), haloalkyl (d-C8), NRRc, -C (O) Ra, -COORa, and -C (O) NRbRc; where R7, R8 and R9 are independently hydrogen, alkyl (d-C8), RaOalkyl (d-C8), RbR ° Nalkyl (d-C8), haloalkyl (C? -8), heterocycle (C3-C10), aryl ( C6-C10), aryl (C6-C10) alkyl (C1-C8) -, heteroaryl (C4-C10); -COORa, or C (O) Ra, or C (O) NRbRc where the heyerocycle, heeroaryl or aryl is optionally subsituted with 1, 2, 3, or 4 selected independently selected halogen, cyano, ni, -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-Cß), R RcNalkyl (d- Cß), haloalkyl (d-C8), NRbR °, -C (O) Ra, - COORa, and C (O) NRbRc: or R7 and R8 conjunctly with the atoms to which they are attached form a mono-, bicyclic ring - or saturated or partially unsaturated aromatic having 3, 4, 5, 6, 7, or 8, atoms in the ring optionally the ring has 4 to 8 asbestos in the ring and optionally comprises 1, 2, 3, or 4 hetero-atoms selected from non-peroxide oxy (-O-), thio (-S-), sulfinyl (-SO-), sulfonium (-S (O) 2-) or amine N (R) - in the ring: Ra is hydrogen , or alkyl (d-C6); Rb and Rc are each hydrogen, alkyl (d-C6), alkoxy (d-C6), cycloalkyl (C3-C8), alkylthio (d-C6), aryl (C6-C10), aryloylCβ-dc alkyl-Cß) -, heteroaryl, or heteroarylalkyl (d-C6) -; or Rb and Rc together with the nifrogen to which they are attached form a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, or thiomorpholinyl ring; where n is 0, 1, 2, 3. 4, 5, 6, 7, or 8; m is 1 or 2; and q is 1,

2, 3, or 4; or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1, wherein R is hydrogen, methyl, ethyl, ary, propargyl, i-propyl, n-propyl, n-butyl, i-butyl or haloalkyl (d-C).
3. The compound of claim 1, wherein R is hydrogen, methyl, ethyl, -CH2-CH2-CI, -CH2-CH2-Br, or -CH2-CH2-CH2-F.
4. The compound of claim 1, wherein R is hydrogen.

5. The compound of claim 1 or claim 2, wherein R 1 is hydrogen, (C 1 -C 4) alkyl, (C 3 -C 4) alkenyl, (C 3 -C 4) alkynyl, phenyl or phenyl (C 1 -C) alkyl. 6. The compound of claim 1, wherein R1 is (C3-C6) cycloalkyl and (C3-C6) cycloalkyl (C-C4) - alkyl. 7. The compound of claim 1, wherein R1 is cyclopropyl or cyclopropylmethyl. 8. The compound of claim 1, wherein R1 is hydrogen, methyl, ethyl, aryl, propargyl, i-propyl, n-propyl, n-butyl, -butyl, phenyl, phenelyl, benzyl, or (methoxyphenyl) ethyl . 9. The compound of claim 1, wherein R1 is ethyl, n-propyl or allyl. The compound of claim 1, wherein R 2 is hydrogen, (C 1 -C 4) alkyl, (C 3 -C 4) alkenyl, (C 3 -C 4) alkynyl, phenyl, phenylalkyl (d-C 4), or (methoxyphenyl) ethyl . 1 . The compound of claim 1, wherein R2 is (C3-C6) cycloalkyl or (C3-C6) cycloalkyl (C1-C4) alkyl 12. The compound of claim 1, wherein R2 is cyclopropyl or cyclopropylmethyl. The compound of claim 1 wherein R2 is hydrogen, me yl, efil, allyl, propargyl, i-propyl, n-propyl, n-butyl, i-butyl, phenyl, phenethyl or benzyl. The compound of claim 1, wherein R2 is ethyl, n-propyl or allyl.

15. The compound of claim 1, claim 9, or claim 14, wherein Z is -OH, -alkyl (C-C4), -O-aryl (C6-C10), -O-aryl (C6-C10) -alkyl (C1-C4) , -NR4R5, F, Cl, Br, or I. The compound of claim 1, wherein R 4 is hydrogen, (d-C6) alkyl, (C3-C6) cycloalkyl, (C3-C6) cycloalkyl (C? -C4) -, (C3-C6) heterocycle ), aryl (C6-C10), aryl (C6-C10) alkyl (C? -C4) -, heteroaryl (C5-C6) or heteroaryl (C5-C6) alky (C1-C4) -, -S (O2) NH2, -C (O) R6, -CO2R6, or -C (O) 2NR6R7. 17. The compound of claim 1, wherein R4 is hydrogen, (d-C4) alkyl, hydroxyalkyl (dC), (C3-C6) cycloalkyl, (C6-C10) aryl, (C7-C? 0) aralkyl, heeroaryl (C5-C6), (CH2CH2O) q (CH2CH2) COORa, -NR7R8, -C (O) R6, -CO2R6, or -C (O) NR7R8. 18. The compound of the claim wherein R4 is hydrogen, methyl, ethyl, propyl, penlyl, hydroxy, hydroxypropyl, ethoxy, ethoxy, methyl-benzyl. aminomethylbenzyl, meioxybenzyl, mefoxifeneyl, furylmethyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O) R6 -CO2R6, -C (O) NHR7. 9. The compound of claim 1, wherein R4 is methyl, ethyl, cyclopropyl, cyclopropylmethyl, -C (O) R6, -CO2R6, or -C (O) NHR7. The compound of claim 1, wherein R5 is hydrogen, alkyl (d-Cß), cycloalkyl (C3-C6), cycloalkyl (C3-C6) alkyl (C1-C4) -, heterocycle (C3-C6), aryl (C6-C10), aryl (C6-C10) alkyl (C? -C4) -, heeroaryl (C5-C6), heteroaryl (5-C6) alkyl (d-C4) -, -S (O2) NH2, -C (O) R6, -CO2R6, or -C (O) NR6R7.

twenty-one . The compound of claim 1, wherein R5 is hydrogen, (C-C4) alkyl, hydroxy (C2-C) hydroxy, (C3-C6) cycloalkyl, (C6-C10) aryl, (C7-C10) aralkyl. Heteroaryl (C5-C6), (CH2CH2O) qCH2CH2) -ORa, (CH2CH2O) qCH2CH2) -COORa, (CH2CH2O) qCH2CH2) - -N RaRb, -NR7R8, -C (O) R6, -CO2R6, or - C ( O) NR7R8. 22. The compound of claim 1, wherein R5 is hydrogen, methyl, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxy, ethoxy, methyl-benzyl, amino-benzyl, methoxy-benzyl, methoxy-pheneyl, furyl-methyl, cyclopentyl, cyclohexyl, thiophenyl, -C ( O) R6, -CO2R6, or -C (O) NHR7. 23. The compound of claim 1, wherein R5 is methyl, ethyl, cyclopropyl, cyclopropylmethyl, -C (O) R6, -CO2R6, or -C (O) NHR7. 24. The compound of claim 1, wherein R4 and

R5 taken jointly with the niologen to which they are attached are a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, or thiomorpholinyl ring each optionally susfused with 1, 2, 3, or 4 subsitutes independently selected from halo, cyano, nitro, -ORa, -SRa, aryl (C6-C10), -aryl (C6-C10) hydroxyalkyl (d-C8), R RcNalkyl (d-C8), haloalkyl (d-C8), NRbRc, -C (O ) Ra, -COORa and O (C) NRbRc. 25. The compound of claim 1, wherein R6 is (d-C6) alkyl, (C3-C6) cycloalkyl, (C3-C6) cycloalkyl (C1-C4) alkyl, (C3-C6) heterocycle, aryl ( C6-C10), aryl (C6-C10) to [quilo (C? -C4) -, heeroaryl (C5-C6), or heteroaryl (C5-C6) alkalo (C? -C4) -, each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, cyano, nitro, alkyl (d-Cß), -ORa, -SRa, aryl (C6-C10), -O-aryl (C6-C10), hydroxyalkyl (d-Cß), RbR ° Nalkyl (d-C8), haloalkyl (d-C8), NR Rc, -C (O) Ra, -COORa, and -C (O) NRbRc. 26. The compound of claim 1, wherein R6 is aryl (Cβ-do) heyaroaryl (C5-C6), each optionally substituted with 1 2, or 3 substituents independently selected from halo, cyano, nifro, alkyl (C). ? -C8), haloalkyl (C? -C8), -COORa, and C (O) NRbRc. 27. The compound of claim 1, wherein R6 is pyridyl, optionally substituted with F, Cl, Br, I, CF3, cyano, nitro, COORa, or -CONHR3. 28. The compound of claim 1, wherein: R is hydrogen, meiyl or ethyl; R1 and R2 are independently methyl, ethyl, allyl, propargyl, propyl, n-propyl, cyclopropyl, cyclopropylmethyl or n-buyl; and X is 3-pyridyl substituted at the 6-position with Z, where 7 is a heterocycle (C4-C10) or NR R5, where R4 is methyloxy, cyclopropyl, cyclopropylmethyl and R5 is -C (O) R6 where R6 is optionally substituted heteroaryl with 1 2 or 3 independently selected halo, cyano, nitro, haloalkyl (d-C8), -C (O) Ra, -COORa, and -C (O) NRbRc, and wherein Ra, Rb and Rc are independently hydrogen, methyl, ethyl, self, isopropyl or cyclopropyl. 29. The compound of claim 1, wherein R1 and R2 are independently hydrogen, (C1-C) alkyl, (C3-C4) alkenyl, (C3-C4) alkynyl, phenyl, or phenyl (C1-C) alkyl. 30. The compound of claim 1, wherein R is hydrogen, me yl, ethyl, allyl, propargyl, i-propyl, n-propyl, n-buyl, i-buyl or haloalkyl (C? -C4); R1 and R2 and are independently hydrogen, methyl, ethyl, aryl, propargyl, propyl, n-propyl, cyclopropyl, cyclopropylmethyl, n-butyl, i-butyl, phenyl, phenethyl or benzyl. 31 The compound of claim 1, wherein R is hydrogen, mephyl, efyl, -CH2-CH2-CI, -CH2-CH2-Br, or -CH2-CH2-CH2-F; and R1 and R2 are independently hydrogen, methyl, ethyl, aryl, propargyl, -propyl, n-propyl, cyclopropyl, cyclopropylmethyl or (methoxyphenyl) ethyl. 32. The compound of claim 1 or claim 29, wherein X is imidazolyl, triazolyl, triazinyl, oxazoyl, isoxazoyl, thiazolyl, isoiazolyl, thiodiazolyl, pyrrolyl, pyrazinyl, pyridinyl, pyrimidinyl, indolyl, isoquinolyl, or quinolyl. , each of which is optionally substituted with 1, 2, or 3 independently selected substituents on halo, cyano, ni, alkyl (d-Cß), -ORa, -SRa, aryl (Cß-C10), -Oaryl (Cedo) ), hydroxylalkyl (d-C8), RbRcN alkyl (C? -8), haloalkyl (d-Cß), NRbRc, C (O) Ra, -COORa and -C (O) NRbRc.

33. The compound of claim 1 or claim 29, wherein X is 2-pyridinyl, 3-pyridinyl or 4-pyridinyl, each optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halo, cyano, nitro, (d-C8) alkyl, -ORa, -SRa, aryl (C6-C10), -Oaryl (Cedo), hydroxyalkyl (d-C8), RR ° N alkyl (d-C8), haloalkyl (d-C8) ), NR R °, -C (O) Ra, -COORa and -C (O) NRbRc. 34. The compound of claim 33, wherein - X (Z1) n-Z has the formula:

35. The compound of claim 34, wherein X (Z) n-Z has the formula

36. The compound of claim 1, wherein Z is

-OH, -Oalkyl (d-C4), -OC (O) NR7R8, alkyl (dd), -NR4R5, F, Cl, Br, or I, wherein R4 and are independently hydrogen, alkyl (Ci- C6), (C3-C6) cycloalkyl, (C3-C6) heteroaryl, (C6-C10) aryl, (C7-C12) aralkyl, (C5-C6) heyaroaryl, or (C5-Ce) heteroaryl (d-C4) alkyl, - S (O2) NH2, -C (O) R6, -CO2R6, or -C (O) NR6R7. 37. The compound of claim 1 or claim 29, wherein Z is -NR4R5. 38. The compound of claim 1, wherein R4 and R5 together with the nitrogen to which they are attached form a pyrrolidyl, piperidyl, piperazinyl, azepinyl, diazepinyl, morpholinyl, or thiomorpholino ring, wherein the ring is optionally substituted with 1, 2. , 3, or 4 substituents independently selected from halo, cyano, niatro, -ORa, aryl (C6-C10), -aryl (C6-C10), hydroxyalkyl (d-C8), RbRcNalkyl (d-C8), haloalkyl ( d-C8), NRbRc, -C (O) Ra, -COORa, and C (O) NRbRc. 39. The compound of claim 1, wherein R4 and R5 are independently hydrogen, (C-C4) alkyl, hydroxyalkyl

(C2-C4), cycloalkyl (C3-C6), aryl (C6-C10), aralkyl (C7-C-? 0), heferoaryl (C5-C6), - (CH2-CH2-O) q- (CH2- CH2) -ORa,

(CH2CH2O) q (CH2CH2) -COORa, (CH2CH2O) q (CH2CH2) NRaR, -NR7R8, -C (O) R6, -CO2R6, or -C (O) NR7R8. 40. The compound of claim 1, wherein R4 and

R5 are independently hydrogen, methyl, ethyl, propyl, pentyl, hydroxyethyl, hydroxypropyl, ethoxyethyl, diefoxethyl, meilbenzyl, aminomethylbenzyl, meioxybenzyl, meiopheneyl, furylmethyl, cyclopentyl, cyclohexyl, thiophenyl, -C (O) R6, -CO2R6, or -C (O) NHR7.

41 The compound of claim 1, wherein R6 is meityl, meioxy, or pyridyl, and R7 is phenyl, fluorophenyl or methoxyphenyl. 42. The compound of claim 1, wherein: R is hydrogen, methyl, ethyl; R 1 and R 2 are independently meily, ethyl, alkyl, propargyl, propyl, n-propyl, cyclopropyl, cyclopropylmethyl, n-buyl, i-buyl and Z is a (C 4 -C 0) heterocycle wherein the heterocycle is optionally substituted with , 2, 3 or 4 selected independent subsitutes on halo, cyano, nifro, aryl (C6-C? O), -O-aryl (C-C10), hydroxyalkyl (d-C8), RbR ° Nalkyl (d-C8), haloalkyl (d-C8),

NRbRc, -C (O) Ra, -COORa, and C (O) NRbRc. 43. The compound of claim 1, wherein Z is selected from the group consisting of:

-N-R4 ^ ~ "(CH2CH20) q-CH2CH2NH2., Or (CH2CH2O) q-CH2CH2-C00H

44. The compound of claim 1 or claim 29, wherein -X (Z1) n -Z is selected from the group consisting of:

45. The compound of claim 1, wherein R1 and R2 are n-propyl; R is hydrogen and n is zero. 46. The compound of claim 1, wherein -X (Z1) n -Z is selected from the group consisting of:

47. The compound of claim 1 which is: 1,3-Dipropyl-8- (6-chloro-3-pyridyl) xanine; 1,3-Dipropyl-8- (6-eylamino-3-pyridyl) xanine; 1, 3-Dipropii-8- (6- (2-hydroxyethyl) amino-3-pipdyl) xanthine; 1, 3-Dipropyl-8- (6- (4-acetylpiperazinyl) -3-pyridyl] xanthine: 1,3-Dipropyl-8- (6-pyrrolidinylpyrid-3-yl) xanthine; 1,3-Dipropyl-8- (6-methylamino-3-pyridyl) xanthine 1,3-D-propyl-8-. {6- (2-hydroxypropyl) amino-3-pyridyl] xanthine;

1,3-Dipropyl-8- [6- (22-dimethyloxy-yl) amino-3-pyridyl] xanine; 1, 3-Dipropyl-8 - [[6- (2-hydroxy-eneyl) -ylamino] -3-pyridyl-xanine and 1,3-Dipropyl-8- [6- [N-nicoyinoylethylamino] -3-pyridyl) xanine; or a pharmaceutically acceptable salt thereof. 48. The compound of claim 1, which is: 1,3-Dieyyl-8- [6-. { N-nicotinoylethylamino] -3-pyridyl) xanthine; 1,3-Diethyl-8- [6- [N-nicotinoylmethylamino-3-pyridyl] xanthine; 8- [6- (2, 5-diaza-bicyclo { 2.2.2] oct-2-yl) -pyridin-3-yl] -1, 3- Dipropyl-3,7-dihydro-purine-26- Mrs; 1,3-Dipropyl-8- (6- (2-acetylaminoethyl) amino-3-pyridyl) xanthine; 1 - (5- (1, 3-Dieyyl-2,3,6,7-teirahydro-2,6-dioxo-1 H -purin-8-yl) pyridin-2-yl) -1 - (2-methoxyethyl) ) -3- (pyridin-4-yl) urea; 1,3-Dimethyl-8- (6-meylamino-3-pyridyl) xanthine 1-propargyl, 3-mephyl-8-. { 6- [N-nicotinoylmethylamino] -3-pyridyl) xanine; 1,3-Diethyl-8- [6- [N- (isoxazole-5-carbonyl) methylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N- (2-pyrazinecarbonyl) methylamino] -3-pridyl) xanthine; 1,3-Dipropyl-8- [6- [N- (isoxazole-5-carbonyl) methylamino] -3-pyridyl) xanthine 1-Cyclopropyl-3-propyl-8-. { 6- [N-nicotinoylmethylamino} -3-pyridyl) xanine; and 1,3-Dephy-8- [6- [N-nicoyinoylcyclopropylmethylamino] -3-pyridyl) xanine or a pharmaceuically acceptable salt thereof. 49. A compound of claim 1, selected from the group consisting of: 1,3-diazepin-1-yl)] - 3-pyridyl} xanine; 1,3-Dipropyl-8- [6- (1-hydroxy-2-propyl) amino-3-pyridyl-xanthine; 1,3-Dipropyl-8- (6-morpholino-3-pyridyl) xanthine 1,3-Dipropyl-8- (6-dimethylamino-3-pyridyl) xanthine; 1,3-Dipropyl-8- (6-piperazino-3-pyridyl) xanthine; 1, 3-Dipropyl-8- [6- (4-aminomefilbenzylamino) -3-pyridyljxanine; 1,3-D-propyl-8- (6-cyclopropylamino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- { N-isonicoylinylmethylamino] -3-pyridyl) xanthine; and 1,3-Dipropyl-8- [6- (hexahydro-1,4-diazepin-yl) -3-pyridyljxanine; or a pharmaceutically acceptable salt thereof. 50. A compound of claim 1 selected from the group consisting of: 1,3-Dicyclopropimethyl-8- [6- [N-n-cofinoylmethyllamino] -3-pyridyl) xanthine; 1,3-Dicyclopropylmethyl-8- [6- [N-nicotinoylethylamino] -3-pyridyl) xanthine;

1,3-Diethyl-8- [6- (2-pyridylmethylamino) -3-pyridyl] xanine; 1, 3-Diethyl-8-. { 6- (3-pyridylmethyliamino) -3-pyridyl] xanthine 1,3-Diethyl-8- [6- (3-meiaxybenzylamino) -3-pyridyl] xanthine; 1, 3-Dipropyl-8-. { 6- [2- (2-pyridyl) -yrylamino] -3-pyridyl] xanthine; 1,3-Dethyl-8- (6- [2- (1-pyrrolidinyl) -erylamino] -3-pyridyl] xanine

1, 3-Dipropyl-8-. { 6- [N- (5-methylisoxazol-3-yl-3-carbonyl) meylamino] -3-pyridyl) xanthine; and 1,3-Diethy1-8- [6- (N- (6-chloronicotinoyl) -methylamino) -3-pyridyl-xanthine or a pharmaceutically acceptable salt thereof. 51 A compound of claim 1, selected from the group consisting of: 1,3-Dipropyl-8- (6-cyrano-3-pyridyl) xanthine; 1-Propyl-3-propargyl-8- (6-chloro-3-pyridyl) xanthine; 1,3-Dipropyl-8- (6-ethylamino-3-pyridyl) xanphan; 1,3-Dipropyl-8- (6- (2-hydroxyethyl) amino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (4-acetylpiperazinyl) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (benzylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (1-piperidinyl) -3-pyridyl] xanthine; 1,3-Dipropyl-8- (6-pyrrolidinylpyrid-3-yl) xanthine; 1, 3-Dipropyl-8-. { 6- [4-methyl (perhydro-1,4-diazepin-1-yl)] - 3-pyridyl} xanthine; 1,3-Dipropyl-8- (6-methylamino-3-pyridyl) xanine; 1,3-Dipropyl-8- [6- (4-methoxybenzylamino) -3-pyridyl] xanthine, 1,3-Dipropyl-8- [6- (3-methylpiperidino) -3-pyridyl] xanine;

1,3-Dipropyl-8- [6- (2-hydroxypropyl) amino-3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (2,2-dimethoxy-eyl) amino-3-pyridyl] xanine; 1, 3-Dipropyl-8- [6- (1-hydroxy-2-propyl) amino-3-pyridyl] xanine

1, 3-Dipropyl-8- (6-morpholino-3-pyridyl) xanthine 1,3-Dipropyl-8- (6-dimethylamino-3-pyridyl) xanthine 1,3-Dipropyl-8 - [[6- (2 -hydroxyeoyl) eylamino-3-pyridyl] xanine; 1,3-Dipropyl-8- (6-piperazino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (2-hydroxy-2-phenylethyl) amino-3-pyridyljxanine; 1, 3-Dipropyl-8- [6- (4-aminomethylbenzylamino) -3-pyridyljxanthine 1,3-Dipropyl-8- (6-phenylamino-3-pyridyl] xanthine 1,3-Dipropril-8- (6-cyclopropylamino -3-pyridyl] xanthine 1,3-Dipropyl-8- [6- (6-pyridylmethylamino) -3-pyridyl] xanthine 1,3-D-propyl-8- (6- (4-methylpiperazino) -3-pyridyl ) xanthine; 1,3-Dipropyl-6- (6- (3-pyridylmethylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (2-meilybenzylamino) -3-pyridyl] xanine; 1,3-Dipropyl-8- [6- [2- (3,4-dimethoxyphenyl) ethylamino] -3-pyridyljxanthine 1,3-Dipropyl-8- [6 - [(N-propylcarbamoyl) methylamino] -3-pyridyl ) xanthine; 1,3-Dipropril-8- [6- (3-pentylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (2,2-diphenylethylamino) -3-pyridyl] xanine; 1, 3-Dipropyl-8- [6- [2- (1-ethylpyrrolidinomethylamino)] - 3-pyridyljxanfin; 1,3-Dipropril-8- [6- (3-meioxybenzylamino) -3-pyridyl] xanthine; , 3-Dipropyl-8- [6 - [(N-methylcarbamoyl) methylamino] -3-pyridyl) xanthine, 1,3-Dipropyl-8- [6- (furfurialmino) -3-pyridyl] xanthine 1, 3- Dipropyl-8- [6- [2- (4-mefoxiphenyl) eilamin or] -3- pyridyl] xanthine; 1, 3-Dipropyl-8- [6- (2-mefoxibenzylamino) -3-pyridyl] xanthine 1,3-Dipropyl-8- [6- (propylamino) -3-pyridyl] xanthine: 1,3-Dipropyl-8 - [6- (cyclopentylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- (cyclohexylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-7-ethyl-8- (6-chloro-3-pyridyl) xanthine; 1,3-Dipropyl-7- (3-fluoropropyl-8- (6-chloro-3-pyridyl) xanthine 1,3-Dipropyl-7-meityl-8- (6-chloro-3-pyridyl) xanthine; 3-Dipropyl-7 (2-bromoethyl) -8- (6-chloro-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- (2-thiophenemethylamino) -3-pyridyl] xanthine; -D-propyl-8- [6 - [(N- (4-meioxy-3-enylcarbamoyl) methylamido] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N-nicotinoylmethylamino] -3-pyridyl ) xanthine; 1, 3-Dipropyl-8- [6 - [(N- (4-fluorophenylcarbamoyl) methylamino] -3-pyridyl) xanthine 1,3-Dipropyl-8- [6- [N-isonicotinoylmethylamino] -3-pyridyl) xanine; 1, 3-Dipropyl-8- [6- [N-meioxycarbonylmethylamino] -3-pyridyl) xanin: 1,3-Dipropyl-8- [6- [N-phenylcarbamoyl, N- (2-phenylcarbamoyloxyethyl) amino] -3 -pyridyl) xanine; 1, 3-Dipropyl-8-. { 6- [4- (N-Phenylcarbamoyl)] piperazino-3-pyridyl} xanlina; 1, 3-Dipropyl-8-. { 6- [4- (N-isonicotinoyl)] piperazino-3-pyridyljxanfin; 1-propyl-3- (4-methoxyphenyl) ethyl-8- (6-chloro-3-pyridyl) xanthine; 1-Propyl-3- (methoxyphenylethyl) -8- (6-piperazino-3-pyridyl) xanthine: 1,3-Dipropyl-8- [6- (4-pyridylamino) -3-pyridyl] xanthine; 1, 3-Dipropyl-8-. { 6- [4-N-nicotinoyl)] piperazino-3-pyridyl} 1,3-Dipropyl-8- [6- (hexahydro-1,4-diazepin-1-yl) -3-pyridyl] xanine; 1,3-Diethyl-8- (6-chloro-3-pyridyl) xanthine; 1,3-Dieyyl-8- (6-piperazino-3-pyridyl) xanthine; 1, 3-Diethyl-8-. { 6 - [(N-Phenylcarbamoyl) methylamino] -3-pyridyl) xanthine: 1,3-D-beyl-8- [6- [N-nicotinoynylamino] -3-pyridyl) xanthine 1,3-Diethyld-8 - (6-meitylamino-3-pyridyl) xanine; 1, 3-Dieyyl-8- [6- [N-nicoiinoylmethylamino] -3-pyridyl) xanin: 1,3-Diethyl-8- [6- [N-nicotinoylcyclopropylamino] -3-pyridyl) xanthine 1,3-Dicyclopropylmethyl -8- (6-methylaminopyridin-3-yl) xanine; 1-Propargyl-3-methyl-8- (6-meylamino-3-pyridyl) xanthine; 8- [6- (2,5-diaza-bicyclo [2.2.2] oci-2-yl) -pyridin-3-yl} -1, 3- dipropyl-3,7-dihydro-purine-2,6-dione; 1,3-Dicyclopropylmethyl-8- [6- [N-nicotynoylmethylamino] -3-pyridyl) xanine; 1, 3-Dicyclopropylmeiyl-8- [6- [N-n-colin oilmef Mam ino] -3-pyridyl) xanthine, 1,3-diallyl-8- (6-methylamino-3-pyridyl]) xanthine; 1-Cyclopropyl methyl-3-yl-8- (6-methylaminopyridin-3-yl) xanine; 1,3-Diefyl-8- [6- (2-pyridylmethylamino) -3-pyridyl] xanine; 1,3-Diethyl-8- [6- (3-pyridylmethylamino) -3-pyridyl] xanine; 1,3-Diethyl-8- [6- (3-meioxybenzylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- [6- [2- (3-pyridyl) -ethylamino} -3-pyridyl] xanthine; 1,3-Diethyl-8- [6- [2- (3-pyridyl) -ephilamino] -3-pyridyl] xanthine; 1, 3-Dipropyl-8- [6- [2- (2-pyridyl) -ethylamino] 3-pyridyl] xanthine 1,3-Diethyl-8- [6- [2- (2-pyridylethylamino] -3 -pyridyl] xanthine; 1,3-Diethynyl-8- (6-pyrrolidinopyrid-3-yl] xanthine; 1,3-Diethynyl-8- [6- [2- (1-pyrrolidinyl) -yrylamino] -3-pyridyl ] xanthine, 1,3-Dipropyl-8- (6- (2-meioxyethyl) amino-3-pyridyl) xanthine; 1,3-Dipropyl-8- (6- (2-acetylaminoethyl) amino-3 -pyridyl) xanthine 1,3-Diethyl-8- (6-bromo-3-pyridyl) xanthine; 1,3-Dipropyl-8-. {6- [4- (2-pyridyl) -piperazino] -3- pyridyl) xanthine; 1,3-Diethy1-8- {6- [4- (2-pyridyl) -piperazino] -3-pyridyl} xanine; 1,3-Diethyl-8- [6- (trans) -2,5-dimethylpiperazino) -3-pyridyl] xanine;

1, 3-Dipropyl-8-. { 6- [4- (2-pyrimidinyl) -piperazino] -3-pyridyl} xanthine, 1, 3-Dieyyl-8-. { 6- [4- (2-pyrimidinyl) -piperazino] -3-pyridyl} xanin 1, 3-Dieyyl-8- (6- (2-methoxyethyl) amino-3-pyridyl) xanthine; 1-Propargyl, 3-methyl-8- (6-Bromo-3-pyridyl) xanine; 1,3-Diethyl-8- [6- [N-nicofinoyl, N- (2-methoxy-ethyl) amino] -3-pyridyl) xanthine; 1-Propagyl, 3-meityl-8- (6- (2-methoxy-yl) -3-pyridyl) xanthine, 1,3-Diethy1-8- [6- [N-isonicotinoyl, N- (2-meioxyethyl) amino] -3-pyridyl) xanthine; 1 - (5- (1, 3-Dieyyl-2,3,6,7-eeryhydro-2,6-dioxo-1 H -purin-8-yl) pyridin-2-yl) -1 - (2-meityl) ) -3- (pyridin-4-yl) urea 1,3-Dimethyl-8- (6-bromo-3-pyridyl) xanthine; 1,3-Dimethyl-8- (6-mephi-amino-3-pyridyl) xanthine; 1,3-Dimethyl-S- [6- [N-nicotinoylmethylamino] -3-pyridyl] xanthine; 1,3-Dipropyl-S- [6- [N-nicotinoyl, N- (2-methoxy-eyl) aminoyl-3-pyridyl) xanthine; 1 -Propargyl, 3-methyl-8- [6- [N-nicotinoyl, N- (2-methoxyethyl) amino] -3-pyridyl) xanthine; 1-Propargyl, 3-methyl-8- [6- [N-nicoininoylmethylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- (2,6-dichloro-3-pyridyl) xanine; 1,3-Dipropyl-8- (2,6-dimethylamino-3-pyridyl) xanthine) 1,3-Dipropyl-8- (2,6-di (2-methoxyethyl) -3-pyridyl) xanthine;

1,3-Dipropyl-8- [2,6-di [N-nieothinoylmethylamino] -3-pyridyl) xanine; 1,3-Dipropyl-8- [2,6-di [N-nicoininoyl, N-methoxy-yl] -3-pyridyl) xanthine; 1, 3-Diethyl-8- [6- [N- (2-pyrazinecarbonyl) meilylamino] -3-pyridyl) xanine; 1,3-Diethyl-8- [6- [N- (isoxazole-5-carbonyl) meylamino] -3-pyridyl) xanthine; 1,3-Dipropyl-8- [6- [N- (2-pyrazinecarbonyl) methylamino] -3-pyridyl) xanine; 1,3-Dipropyl-8- [6- [N- (isoxazole-5-carbonyl) -methylamino-3-pyridyl) xanthine; 1,3-Dipropyl-8- [6 [N- (5-methylisoxazol-3-yl-3-carbonyl) meylamino] -3-pyridyl) xanthine; 1, 3-D [propyl [-8- [6-. { N- (2-chloro-6-meioxypyridinyl-4-carbonyl),

N-meitylamino] -3-pyridyl) xanthine 1,3-Dipropyl-8- [6- [N- (N-lsonicotinoyl oxide), N-methylamino-3-pyridyl) xanthine: 1-propyl-3- (4 -methoxyphenyl]) ethyl-8- (6-meitylamino-3-pyridyl) xanine; 1, 3-Diefyl-8- [6- [N- (N-lsonicoyinoyl) oxide, N-methy [amino] -3-pyridyl) xanine; 1,3-Diallyl-8- (6-chloro-3-pyridyl) xanin-1-propyl-3- (4-mexoxyphenyl) ethyl-8- [6- (N-nicoininoylmethylamino) -3-pyridyl] xanine;

1 - . 1-propyl-3- (4-mexoxyphenyl) ethyl-8-. { 6- (N- (6-chloronicotinoyl) -methylamino) -3-pyridyl] xanin: 1,3-diallyl-8- [6- (N-nicholinoylmethylamino) -3-pyridyl] xanthine; 1,3-diallyl [-8- [6- (N- (6-chloroniconicotinoyl) methylamino) -3-pyridyl] xanine; 1, 3-Dipropyl-8- [6- (N- [6- (trifluoromethyl) nicoyinoyl] methylamino) -3-pyridyl] xanthine 1,3-Dieyyl-8- [6- (2-hydroxy-5-methyl) benzaldehydehydrazono] -3- pyridyl] xanine; 1, 3-Diethyl-8- [6- (bromopyridine-3-carbaldehydohydrazone.) - 3-pyridyl] xanthine 1-Cyclopropyl-3-ethyl-8- (6-methylamino-3-pyridyl) xanine 1 - Cyclopropyl-3-propyl-8- (6-meitylamino-3-pyridyl) xanine; 1-Propyl-3-cyclopropyl-8- (6-methylamino-3-pyridyl) xanphan; 1-cyclopropyl-3 propyl-8- (6- (2-mefoxiefil) amino-3-pyridyl) xanine.1-Cyclopropyl-3-propyI-8- [6- [N-nicotinoylmethylamino] -3-pyridyl) xanine, 1,3-Diethyl -8- [6- (N- (6-chloronicoyinoyl) meylamino) -3-pyridyl] xanthine; 1,3-Dipropyl-8- (2-chloro-6-meioxyethylamino-4-pyridyl) xanthine 1,3-Dipropyl-8- (2-chloro-6-methylamino-4-pyridyl) xanine; 1, 3-Dipropyl-8- [2- [N-nicotinoyl, N- (2-meioxyethyl) amino] -6-chloro-4-pyridyl) xanthine, 1,3-Dipropyl-8- [2- [N- nicotinoyl, N-methylamino] -6-chloro-4-pyridyl) xanin: 1-Cyclopropyl-3-propyl-8- [6- [N- (6-chloronicoyinoyl) methylamino] -3-pyridyl) xanine, 1-Eile -3-cyclopropyl-8- (6-methylamino-3-pyridyl) xanine; 1-Ethyl-3-cyclopropyl-8- (6- (2-meioxyethyl) amino-3-pyridyl) xanthine; 1, 3-Dieyil-8-. { 6-hydrazine-3-pyridyl] xanine; 1,3-Diethyl-8- [6- (cyclopropylamino) -3-pyridyl] xanine; 1,3-Diethyl-8- [6- (cyclopropylmethyl) amino) -3-pyridyl] xanthine; N- [5- (1, 3-diethyl-2,6-dioxo-2,3,6,7-tetrahydro-1 H -purin-8-yl) -pyridin-2-yl] -hydrazide; N- [5- (1, 3-diethyl-2,6-dioxo-2,3,6,7-tetrahydro-1 H -purin-8-yl) -pyridin-2-yl] -N- (p. Ridn-3-carbonyl) -hydrazide; 1,3-Diethyl-8- [6- (erylamino) -3-pyridyl] xanthine; 1,3-Diethyl-8- [6- [N-nicotinoylcyclopropylmethylamino] -3-pyridyl) xanine; and 1-Cyclopropylmethyl-3-ethyl-8-. { 6- [N- (6-chloronicoyinoyl) mephilaminoyl-3-pyridyl) xanine; or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or a mixture of stereoisomers thereof. 52. A pharmaceutical composition comprising: (a) an idraeuically effective amount of a compound of claim 1; and (b) a pharmaceutically acceptable excipient. 53. A pharmaceutical composition comprising: (a) a therapeutically effective amount of a compound of claim 51; and (b) a pharmaceutically acceptable excipient. 54. A therapeutic method for the prevention or treatment of a pathological symptom or disorder in a mammal, where the activity of receptors adenosine A2B is involved if the action is desired, which comprises administering to the mammal an effective amount of a compound of claim 1. 55. A method for the eradication of asthma, allergies, allergic diseases or an autoimmune disease comprising administering an effective amount of a compound of claim 1 to a mammal in need of such treatment. 56. A method for the treatment of diarrheal diseases, insulin resistance, diabetes, cancer, ischemia / reperfusion injury, diabetic retinopathy or oxygen-induced hyperbaric retinopathy, which comprises administering an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof to a mammal in need of such treatment. 57. A method for the prevention or treatment of a pathological symptom or disorder in a mammal, wherein the activity of adenosine AaB receptors is involved, and antagonism of its action is desired which comprises administering to a mammal an effective amount of a The compound of claim 1. 58. The compound of claim 1, for use in medicinal therapy. 59. The use of a compound of claim 1 for the manufacture of a useful medicament for the delivery of a disease in a mammal, such as a human being.