MXPA01010001A

MXPA01010001A - Purine derivatives having phosphodiesterase iv inhibition activity

Info

Publication number: MXPA01010001A
Application number: MXPA/A/2001/010001A
Authority: MX
Inventors: David Cavalla; Mark Chasin; Peter Hofer; Andre Gehrig; Peter Wintergest
Original assignee: David Cavalla; Mark Chasin; Euroceltique Sa; Andre Gehrig; Peter Hofer; Peter Wintergest
Priority date: 1999-04-02
Filing date: 2001-10-02
Publication date: 2002-05-09

Abstract

Disclosed are compounds of formula (I), wherein R3, R6a, R6b and R8 are substituted as disclosed herein. The compounds are effective in effecting PDE IV inhibition in patients in need thereof.

Description

P RINE DERIVATIVES C N CTIVID PHOSPHODIESTERASE IV BACKGROUND OF THE INVENTION Asthma is a complex disease involving the concerted actions of multiple inflammatory and immunological cells, spasmogens, inflammatory mediators, cytokines and growth factors. In recent practice there have been four major classes of compounds used in the treatment of asthma, specifically bronchodilators (ie, β-adrenoceptor agonists), anti-inflammatory agents (ie, corticosteroids), prophylactic anti-allergic agents (ie , cromilina sodium) and xanthines (ie, theophylline), which apparently have both bronchodilator and anti-inflammatory activity. Theophylline has been an especially preferred drug for the treatment of asthma. Although it has been used for its direct bronchodilator action, it is currently thought that the therapeutic value of theophylline also comes from the anti-inflammatory activity. Its mechanism of action remains unclear. However, it is thought that several of its cellular activities are important in its activity as anti-asthmatic, including the inhibition of cyclic nucleotide phosphodiesterase, the antagonism of adenosine receptors, stimulation of catecholamine release and its ability to increase the amount and activity of suppressor T lymphocytes. Although all this may contribute to its activity, only PDE inhibition can explain both anti-inflammatory and bronchodilator components. However, it is known that theophylline has a narrow therapeutic index and a wide range of undesirable side effects that are considered problematic. Of the aforementioned activities, the activity of theophylline to inhibit the cyclic nucleotide phosphodiesterase has recently received considerable attention. Cyclic nucleotide phosphodiesterases (PDEs) have received considerable attention as molecular targets for anti-asthmatic agents. 3 ', 5'-cyclic adenosine monophosphate (cAMP) and 3', 5'-cyclic guanosine monophosphate (cGMP) are known secondary messengers that mediate cell functional responses to a multitude of hormones, neurotransmitters and autocoids. At least two therapeutically important effects of the phosphodiesterase inhibition, and the consequent increase in the 3 ', 5' monophosphate cyclic adenosine (cAMP) and the 3 ', 5' monoclonal cyclic guanosine (cGMP) in the main cells in the pathophysiology of asthma. These are relaxation activities of smooth muscles (which produce bronchodilation) and anti-inflammatory.

It is already known that there are multiple different PDE isoenzymes that differ in their cellular distribution. A variety of inhibitors have been synthesized that have a marked degree of selectivity for one isoenzyme or another. Structure-activity relationships (SAR) of selective isozyme inhibitors have been discussed in detail, for example in the article by Theodore J. Torphy et al., "Novel Phosphodiesterase Inhibitors for The Therapy of Asthma", Drug News & Prospectives, 6 (4) May 1993, pages 203-214. PDE enzymes can be grouped into five families according to their specificity to the hydrolysis of cAMP or cGMP, their sensitivity to regulation by calcium, calmodulin or cGMP, and their selective inhibition by various compounds. PDE I is stimulated by Ca2 calmodulin. PDE II is stimulated by cGMP, and occurs in the heart and adrenal glands. PDE III is cGMP-inhibited, and inhibition of this enzyme creates positive inotropic activity. PDE IV is specific cAMP, and its inhibition causes relaxation of the airways, anti-inflammatory and antidepressant activity. PDE V appears to be important in the regulation of cGMP content in vascular smooth muscles, and therefore PDE V inhibitors could have cardiovascular activity. Although there are compounds derived from numerous structure-activity studies that provide PDE III inhibition, the number of structural classes of PDE IV inhibitors is relatively limited. Rolipram analogs have been studied, which has the following structural formula (A): and from RO-20-1724, which has the following structural formula (B): U.S. Pat. No. 4,308,278 discloses compounds of the formula (C) i where Ri is (C3-C6) cycloalkyl or benzyl. R2 and R3 are hydrogen or (C1-C4) alkyl; R4 is R2 or alkoxycarbonyl; and R5 is hydrogen or alkoxycarbonyl. The compounds of the formula (D) are disclosed in U.S. Pat. No. 3,636,039. These compounds are benzylimidazolidinones which act as hypertensive agents.

The substituents R3.-R4 in Formula D represent a variety of groups, including hydrogen and lower alkyl. PCT publication WO 87/06576 discloses antidepressants of Formula E: where Ri is a polycycloalkyl group possessing from 7 to 11 carbon atoms; R2 is methyl or ethyl, X is 0 or NH; and Y comprises a mono or bicyclic heterocyclic group with optional substituents. Rolipra, which was initially studied for its activity as an antidepressant, was shown to be a selective inhibitor of the PDE IV enzyme, and since then this compound has become a conventional agent in the classification of PDE enzyme subtypes. There seems to be considerable therapeutic potential for PDE IV inhibitors. Early research focused on depression as a primary CNS therapeutic point and on inflammation, and subsequently extended to include related diseases such as dementia and asthma. It has been shown in vitro that roplipram, RO20-1724 and other PDE IV inhibitors inhibit (1) synthesis / release of mediators in mastoid, basophil, monocyte and eosinophil cells; (2) respiratory emergence, chemotaxis and degranulation in neutrophils and eosinophils; and (3) mitogen-dependent growth and differentiation in lymphocytes (The PDE IV Family of Calcium-Phosphodiesterases Enzymes, John A. Lowe, III, et al., Drugs of the Future 1992, 17 (9): 799-807). PDE IV is present in all major inflammatory cells in asthma, including eosinophils, neutrophils, T lymphocytes, macrophages and endothelial cells.

Its inhibition causes the hyporegulation of the act va n of inflammatory cells and relaxes the smooth muscle cells in the trachea and bronchi. On the other hand, the inhibition of PDE III, which is present in the myocardium, causes an increase in the strength and rhythm of cardiac contractility. These are undesirable side effects for an anti-inflammatory agent. Theophylline, a non-selective PDE inhibitor, inhibits PDE III and PDE IV, resulting in desirable anti-asthmatic effects and undesirable cardiovascular stimulation. With this well known distinction between PDE isozymes, the opportunity for concomitant anti-inflammation and bronchodilation is apparent without many of the side effects associated with theophylline therapy. The increased incidence of morbidity and mortality due to asthma in many Western countries during the last decade made the clinical emphasis focus on the inflammatory nature of this disease, and the benefit of inhaled steroids. The development of an agent that possesses both bronchodilatory and anti-inflammatory properties could be extremely advantageous. Apparently, selective PDE IV inhibitors may be more effective and have fewer side effects than theophylline. Clinical support has been demonstrated for this hypothesis. In addition, it would be desirable to provide PDE IV inhibitors that are more potent and selective than rolipram, and therefore with a lower IC 50 to reduce the amount of agent necessary to effect a PDE IV inhibition. In recent years, several different compounds have been suggested as possible therapeutic compositions that achieve the desired PDE IV inhibition without the side effects alluded to above. However, these investigations have been directed mainly to develop non-specific derivatives of particular classes of compounds, for example rolipram analogs, benzoxazoles, adenines, thioxanthines, etc. However, these investigations resulted in a multitude of compounds possessing a wide range of IC50 of PDE IV. Frequently, the general formulas that are disclosed produce several compounds that have poor levels of PDE IV inhibition, or lack sufficient specificity. Accordingly, these investigations often do not provide assurance that a particular derivative within the formula will have the desired combination of high PDE IV inhibition and selectivity. OBJECTS AND SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide new compounds that are selective PDE IV inhibitors more effective than the prior art compounds. It is another object of the present invention to provide new compounds that act as effective PDE IV inhibitors with lower PDE III inhibition. It is another object of the present invention to provide methods for treating a patient that requires PDE IV inhibition. It is another object of the present invention to provide new compounds for treating disease states associated with abnormally high physiological levels of inflammatory cytokines, including tumor necrosis factor. It is another object of the present invention to provide a method for synthesizing the novel compounds of the present invention. It is another object of the present invention to provide a method for treating a patient suffering from disease states such as asthma.; allergies; inflammation; depression; dementia, including Alzheimer's disease, vascular dementia and multi-infarct dementia; a disease caused by the Human Immunodeficiency Virus; and disease states associated with abnormally high physiological levels of inflammatory cytokines. Other objects and advantages of the present invention will become apparent from the following detailed description. Considering the above objects and others, the present invention comprises compounds having the general formula (I) (i) wherein: R3 is selected from the group consisting of: hydrogen; Cl-10 alkyl branched or unbranched and which is optionally substituted with substituents 1-3 selected from the group consisting of OH ,. Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H, = 0 or benzyloxy, wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3 -12-cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy; C2-10 branched alkenyl or. unbranched, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 with chloroquine, C-a cox, -cc or cox, with gen, halo (Cl-10) ) alkyl, = NOH, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkylolamine, Cl-10 dialkylamino, carbamyl , amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) alkoxy, nitro, trihalocarbon, benzyloxy , heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) lcoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroa (Cl-) 10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and where the methacrylate is its choice with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted in a position in the alkyl half with hydroxy, heterocyclyl which is optionally substituted in the carbons or nitrogens of the ring with sust 3 and 3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2 , phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with its own groups consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl- 10 alkoxy or C3-12 cycloalkoxy. R8 is selected from the group consisting of: hydrogen; Cl-10 branched or unbranched alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H, = 0 or benzyloxy , wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy; C2-10 branched or unbranched alkenyl, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = NOH, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = NOH, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents chosen from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) alkoxy, nitro, trihalocarbon, benzyloxy , heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroary (Cl-) 10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl half of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted in one position in half alkyl with hydroxy, heterocyclyl which is optionally substituted on the carbons or nitrogens of the ani with substitutes 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloaoxy, NH2, Cl-10 alkyloamino, Cl-10 d alkyl oam, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2 , phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy. R6a and R6b are independently selected from the group consisting of: hydrogen; Cl-10 branched or unbranched alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H, = 0 or benzyloxy , wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy; C2-10 branched or unbranched alkenyl, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkylolamine, Cl-10 dialkylamino, carbamyl , amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, where the aryl moiety is optionally substituted with substituents - eg the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) alkoxy, nitro, trihalocarbon , benzyloxy, heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroaryl ( Cl- 10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is substituted optionally with Cl-10 alkyl, and wherein the alkyl half of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted in a 'position in the alkyl half with hydroxy; heterocyclyl which is optionally substituted in the carbons or nitrogens of the anil with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3 -12 cc or OH, a , - a cox, - cc or cox, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy. Provided that when R3 is an unsubstituted benzyl group, R6a is a methyl or isopropyl group and R6b is a hydrogen atom; when R3, R6a and R6b are methyl groups, then R8 is different from a hydrogen atom; when R8 is methyl or a hydrogen atom, R3 is not methyl or hydrogen; when R8 is phenyl, R3 is not methyl; when R8 is pyridyl, R3 is not a hydrogen atom; and when R6a and R6b are both hydrogen, then R8 is not hydrogen or C (O) OH alkyl; and pharmaceutically acceptable salts thereof. In certain preferred embodiments, R3 is an ar (Cl- 4) alkyl, where the metal is optional or optional in positions 1-3 with halogen, nitro, alkoxy, cycloalkoxy or CF3, and where half alkyl is optionally substituted with OH, halogen, alkoxy and cycloalkoxy. Aralkyl can be a benzyl, which can be optionally substituted as described above. In other preferred embodiments, aralkyl is a benzyl substituted with alkoxy and cycloalkoxy. In other preferred embodiments, R6a is a hydrogen. In other preferred embodiments, R6a is hydrogen and R6b is selected from the group consisting of Cl-10 alkyl, preferably Cl-8 alkyl, which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; C2-10 alkenyl which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; C3-10 cycloalkyl, preferably C3-8 cycloalkyl, which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkenyl, which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0; aryl, which is optionally substituted with Cl-8 alkyl, OH, alkoxy, cycloalkoxy, halogen, NH2, alkyloamino, dialkylamino, carbamyl, amido, Cl-8 alkyl acido, Cl-3 dialkylolamido, Cl-8 acylamino, Cl-8 alkylsulfonylamino, C = N0H, C = NOCONH2, phenyl or benzyl; aralkyl Cl-4, wherein the m ary is optionally substituted with halogen, nitro, alkoxy, cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with OH, halogen, alkoxy and cycloalkoxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with Cl-8 alkyl, OH, halogen, alkoxy, cycloalkoxy, NH2, alkyloamino, dialkylamino, carbamyl, amido, Cl-8 alkyl acido, Cl-3 dialkylolamido, Cl-8 acyloamino , Cl-8-alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; and (C 1 -C 4) heterocyclylalkyl where the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with Cl-8 alkyl, OH, halogen, alkoxy, cycloalkoxy, NH 2, alkyloamino, dialkylamino, carbamyl, amido, Cl-8 alkylloido, Cl-3 dialkylolamido, Cl-8 acylamino, Cl-8 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, alkoxy, cycloalkoxy, halogen or haloalkyl; heteroaryl, which is optionally substituted with Cl-4 alkyl, halogen, nitro, CF 3, alkoxy or cycloalkoxy; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with Cl-4 alkyl, halogen, nitro, CF 3, alkoxy or cycloalkoxy. In other preferred embodiments, R6a is hydrogen and R6b is selected from the group consisting of Cl-10 alkyl, preferably Cl-8 alkyl, which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C2-10 alkenyl which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl, preferably C3-8 cycloalkyl, which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkenyl, which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0. In particular, R6a can be a hydrogen and R6b can be a Cl-8 branched or unbranched alkyl or is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = N0H, = N0C0NH2, C02H or = 0. In other preferred embodiments of the present invention, R6b, N and R6a form a ring of between 3 to 8 members containing at least one carbon atom, one to three nitrogen atoms, zero to two oxygen atoms, and zero to two sulfur atoms, optionally substituted with hydroxy, alkoxy, cycloalkoxy, Cl-4 alkyl, C02H, C0NH2, = N0H, = N0C0NH2, = 0. In other preferred embodiments, R8 is selected from the group consisting of Cl-10 alkyl, preferably Cl-8 alkyl, which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H o = 0; C2-10 alkenyl which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl, preferably C3-8 cycloalkyl, which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkenyl, which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0; C4-8 cycloalkylalkyl, wherein the cycloalkyl portion which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0; aryl, which is optionally substituted with Cl-8 alkyl, OH, alkoxy, cycloalkoxy, halogen, NH2, alkyloamino, dialkylamino, carbamyl, amido, Cl-8 alkyl acido, Cl-3 dialkylolamido, Cl-8 acylamino, Cl-8 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; aralkyl Cl-4, wherein the aryl moiety is optionally substituted with halogen, nitro, alkoxy, cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with OH, halogen, alkoxy and cycloalkoxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with Cl-8 alkyl, OH, halogen, alkoxy, cycloalkoxy, NH2, alkyloamino, dialkylamino, carbamyl, amido, Cl-8 alkyl acido, Cl-3 dialkylolamido, Cl-8 acyloamino , Cl-8 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; heterocyclylalkyl (C1-C4) where the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with Cl-8 alkyl, OH, halogen, alkoxy, cycloalkoxy, NH2, alkyl loam, d, alkyl, car am, am or, -acyloamido, Cl-3 dialkylolamido, Cl-8 acylamino, Cl-8 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, alkoxy, cycloalkoxy, halogen or haloalkyl; heteroaryl, which is optionally substituted with Cl-4 alkyl, halogen, nitro, CF 3, alkoxy or cycloalkoxy; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with Cl-4 alkyl, halogen, nitro, CF 3, alkoxy or cycloalkoxy. In other preferred embodiments, R8 is selected from the group consisting of Cl-8 alkyl, which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; and C3-8 cycloalkyl which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0. In other embodiments of the present invention, R3, R6a, R6b and R8 are selected from the group consisting of A and B, wherein A is selected from the group consisting of: hydrogen; Cl-10 branched or unbranched alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = N0H, = N0C0NH2, C02H, = 0 and benzyloxy , wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 with chloroquine, C-a cox, C-cc or with cox; branched or unbranched alkenyl, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkylolamine, Cl-10 dialkylamino, carbamyl , amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) alkoxy, nitro, trihalocarbon, benzyloxy , heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroary (Cl-) 10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl half of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted in one position in half alkyl with hydroxy, heterocyclyl which is optionally substituted on the carbons or nitrogens of the anil with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkaloamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cc or cox, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy. B is selected from the group consisting of: branched or unbranched Cl-10 alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and alkylamino; wherein the substituents are optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo; wherein Cl-10 alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl and C3-12 cycloalkyl; wherein the C3-10 cycloalkyl further substituted may be optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2 , C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, halo (Cl-10) alkyl y = 0; C3-12 cycloalkyl (Cl-10) alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, = N0H, = N0C0NH2 and C02H; aryl which is optionally substituted with substituents 1-3 selected from the group consisting of carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylated, Cl-10 acyloamino and Cl-10 alkylsulfunylamino; wherein the substituted aryl may further be substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 c-cloalkoxy, NH2, Cl-10 alkyl oam, C - dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, hydroxy (Cl-10) alkoxy, nitro, benzyloxy, heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroar (Cl-10) lkyloxy, heterocyclyloxy, CI-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl moiety of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy; and the ar (Cl-4) alkyl is further optionally substituted with substituents selected from the group consisting of halogen, hydroxy, trihalocarbon, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy and C3-12 cycloalkoxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of carbamyl, Cl-10 ac oam not and C- a qu osu on am no, =, =, phenyl or benzyl; wherein the substituted heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, C = NOH, C = NOCONH2, phenyl and benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 acylamino, Cl-10 alkylsulfonylamino and Cl-10 alkyl, wherein the Cl-10 alkyl is substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; wherein the (C 1 -C 4) -heterocyclic alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkoxy, C 3-12 cycloalkoxy, NH 2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido , Cl-10 Alkylolamido, Cl-10 Dialkylolamido; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy and C3-12 cycloalkoxy; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy o-cc or cox; already with cne that how much or less between R3, R6a, R6b and R8 is B. In certain preferred embodiments, R3 is A and is ar (Cl-4) alkyl, preferably benzyl, where the aryl moiety is optionally substituted with substituents 1 -3 selected from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with substituents 1-3 selected from the group consisting of OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy. When ar (Cl-4) alkyl is benzyl, the aryl moiety is preferably substituted with cyclopentyloxy and methoxy. In certain preferred embodiments, R6a is A and is hydrogen. In certain preferred embodiments R6b is A and is selected from the group consisting of: hydrogen; Cl-8 alkyl which is branched or unbranched and is optionally substituted by OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; and C3-8 cycloalkyl which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = NOH, = NOCONH2, C02H or = 0. In certain preferred embodiments, R8 is B and is selected from the group consisting of: Cl-10 branched or unbranched and substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and alk oam not , wherein optional substituents substituted with substituents 1-3 are selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo. In certain preferred embodiments R3 is A and is ar (Cl-4) alkyl, preferably benzyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with substituents 1-3 selected from the group consisting of OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy and when the ar (Cl-4) alkyl is benzyl, the aryl moiety is preferably substituted with cyclopentyloxy and methoxy; R6a is A and is hydrogen; R6a is A and is selected from the group consisting of hydrogen, Cl-8 alkyl which is branched or unbranched and is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; and C3-8 cycloalkyl which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = NOH, = N0C0NH2, C02H or = 0; and R8 is B and is selected from the group consisting of Cl-10 alkyl which is branched or unbranched and is substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and alkylamino, where the Substituents are optionally substituted with substituents - eg the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo. Certain preferred adenine compounds according to the present invention include: 6-ethylamino-3-hexyl-3H-purine; 3-hexyl-6-methylamino-3H-purine; 8-cyclopropyl-6-ethylamino-3- (3-methylbutyl) -3H-purine; 8-cyclopropyl-3-ethyl-6-propylamino-3H-purine; 8-cyclopropyl-3-ethyl-6-methylamino-3H-purine; 3-butyl-6-ethylamino-3H-purine; 3-butyl-8-cyclopropyl-6-ethylamino-3H-purine; 6-ethylamino-3-propyl-3H-purine; 8-cyclopropyl-6-ethylamino-3-propyl-3H-purine; 8-cyclopropyl-3-cylpropylmethyl-6-ethylamino-3H-purine; 3-benzyl-6-ethylamino-3H-purine; 8-cyclopropyl-6-cyclopropylamino-3-propyl-3H-purine; 3- (2-methylbutyl) -6- (2- (piperazin-1-yl) ethylamino) -3H-purine; 3-cyclohexylmethyl-6-ethyl-amino-3H-purine; 3-benzyl-6-ethylamino-8- (1-methylethyl) -3H-purine; 3-cyclohexymethyl-8-cyclopropyl-6-ethylamino-3H-purine; 3-cyclopropylmethyl-8-isopropyl-6-ethylamino-3H-purine; 3-ethyl-8-cyclopentyl-6-benzylamino-3H-purine; 3-ethyl-8-isopropyl-6-ethylamino-3H-purine; 3-ethyl-8-cyclopentyl-6-benzylamino-3H-purine; 3-ethyl-8-cyclopentyl-6-ethylamino-3H-purine; 3- (2-chlorobenzyl) -6-ethylamino-8-isopropyl-3H-purine; 6-benzylamino-8-cyclopropyl-3-propyl-3H-purine; 8-cyclopropyl-6-hexylamino-3-propyl-3H-purine; 8-cyclopropyl-3-propyl-6- (4-pyridylmethylamino) -3H-purine; 6-cyclopentylamino-8-cydopropyl-3-propyl-3H-pur na; 6-but lam no- -c c oprop -3-propyl-3H-purine; 8-cyclopropyl-6- (2-hydroxyethylamino) -3-propyl-3H-purine; 6- (3-cyclopentyloxy-4-methoxybenzylamino) -8-cyclopropyl-3-propyl-3H-purine; 6-amino-8-cyclopropyl-3-propyl-3H-purine; 3-ethyl-6-cyclopentylamino-8-isopropyl-3H-purine; 6-cyclohexylamino-8-isopropyl-3-propyl-3H-purine; 6-Cyclopentylamino-8-isopropyl-3-propyl-3H-purine; 3-ethyl-6-cyclopentylamino-8-cyclopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopentylamino-8-cyclopropyl-3H-purine; 6-cyclopentylamino-3- (3-cyclopentyloxy-4-methoxybenzyl) -8-isopropyl-3H-purine; 3- (2-chlorobenzyl) -6-cyclopentylamino-8-isopropyl-3H-purine; 8-cyclopropyl-6-diethylamino-3-propyl-3H-purine hydrochloride; 8-cyclopropyl-6- (3-pentylamino) -3-propyl-3H-purine hydrochloride; 6-ethylamino-8-isopropyl-3- (4-pridylmethyl) -3H-purine; 3-ethyl-8-isopropyl-6-ethylamino-3H-purine; 3-ethyl-8-cyclopentyl-6-benzylamino-3H-purine; 3-ethyl-8-cyclopentyl-6-ethylamino-3H-purine; 3-cyclohexylmethyl-6-ethylamino-3H-purine; 3-cyclohexyl-methyl-8-cyclopropyl-6-ethylamino-3H-purine; 8-cyclopropyl-6-ethylamino-3- (3-methylbutyl) -3H-purine; 8-cyclopropyl-3-ethyl-6-propylamino-3H-purine; 8-cyclopropyl-3-cyclopropylmethyl-6-ethylamino-3H-purine; 3-hexyl-6-methylamino-3H-purine; 3-cyclopropylmethyl-8-isopropyl-6-ethylamino-3H-purine; 3-ethyl-8-isopropyl-6-benzylamino-3H-purine; 3-butyl-6-ethylamino-3H-purine; 3-butyl-8-cyclopropyl-6-ethylamino-3H-purine; 8-cyclopropyl-β-ethylam non-3-prop l-3H-pur na; 8-c c oprop- -cyclopropylamino-3-propyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; and 3-ethyl-6-ethylamino-8- (3-cyclopentyloxy-4-methoxy-benzyl) -3H-purine. Other adenine compounds according to the present invention include: 3, 8-diethyl-6-morpholino-3H-purine; 3-ethyl-6-ethylamino-8- ((3-cyclopentyloxy-4-hydroxy) benzyl) -3H-purine; 3- [3- (3-trimethylsilylethoxymethoxy) cyclopentyloxy-4-methoxy) -cyanyl) -6-ethylamino-8-isopropyl-3H-purine; 6-Ethylamino-3- [3- (furan-2-yl-methoxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (3-hydroxycyclopentyloxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-3- [3- (3-hydroxycyclopentyloxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-Ethylamino-3- (3-butoxy-4-methoxy-benzyl) -8-isopropyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-ethylamino-2- (3, -dimethoxybenzyl) -8-isopropyl-3H-purine; 6-amino-3- (3-cyclopentyloxy-4-methoxybenzyl) -3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-dimethylamino-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (3-hydroxycyclopentyloxy) -4-methoxybenzyl)] -8- (l-hydroxy l-methylethyl-SH-purine; 6-ethylamino-9- [(3-cyclopentyloxy-4-metopxi ) benzyl] -8-isopropyl-3H-purine; 3- (3-methoxybenzyl-4-ciclopehtiloxi) -6-amino-8- isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (3-cyclopentyloxy-4-metoxibenzilamino) -8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- (4-methoxybenzyl) -3H-purine; 3- (3- ((3-hydroxy) cyclopentyloxy ) -4-methoxybenzyl) -6-ethylamino-8- isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (N-benzoyl-N-ethylamino) -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopropylamino-8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- [(4-methoxy-3- (4-hydroxybutoxy)) benzyl] -3H- purine; 6-ethylamino-3- (4-fluorobenzyl) -8-isopropyl-3H-purine; 3- (3-chlorobenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- [3- (3- hydroxy-cyclopentyloxy) -4-methoxy-benzyl] -8- (1-hydroxy-1-methyl-ethyl) 3H-purine; 3- [3- (3-hydroxy) -cyclopentyloxy)] -4-methoxy) -benzyl) - 6- ethylamino-8-isopropyl-3H-purine; 6-amino-3- (3,4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [3-cyclopentylmethoxy-4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-ethylamino-3- (3-hydroxy-4-methoxybenzyl-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2, 2-dimethylaminoethoxy-4-methoxy)] -8-isopropyl-3H -purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1-methyl-l-hydroxy) ethyl] -6-ethylamino-3H-purine; 3- (3-cyclopentyloxy-4-) methoxybenzyl) -6- ((2,2, 2-trifluoroethyl) amino) -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2,2,2) -azabicyclooctane-3-yloxy) - 4-methoxy] -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (l-methylpiperidin-4-yl-methoxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-8-isopropyl-3- [(4-methoxy-3 - ([(4-hydroxy-3-methoxy-8-isopropyl) -6-ethylamino-8-isopropyl- 3H-purine; 3- (4-chlorobenzyl) -6- ((1-hydroxy) cyclopentylamino) -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopentylamino-8-isopropyl-3H-purine; 6-amino-3 (3,4-methylenedioxybenzyl-8-isopropyl-3H-purine; 6-ethylamino-3- [(exo-8-methyl-8-azabicyclo (3,2,1) -octan-3) il-oxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 3- (4-chlorophenyl) -6-ethylamino-8-isopropyl-3H-purine; 6-ethylamino-3- [(3- hydroxy-4-methoxy) benzyl] -8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-ethylamino-3- [(3-pyridin-4-yl-methoxy) N-oxide- 4-methoxy] -8-isopropyl-3H-purine; 3- [3-ciclohexanil-4-oxy-4-methoxy-benzyl] -6-ethylamino-8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -2,6-di (ethylamino) -8-isopropyl-3H-purine; 6-amino-3- (3-hydroxy-4-methoxy) -benzyl) -8-isopropyl-3H-purine; 6-amino-3 - [3- (4-hydroxybutoxy-4-methoxy) benzyl] -8- (1-hydroxy-1-methylethyl) -3H-purine; 6-amino-3- (4-chlorobenzyl) -8-isop ropil-3H-purine; 6-amino-3-cyclopentylethyl-8-isopropyl-3H-purine; 8-cyclopropyl-3-methyl-6-ethylamino-3H-purine; 6-ethylamino-8-isopropyl-3- [3- (pyridin-4-yl-methoxy) -4-methoxy-benzyl] -3H-purine; 6-ethylamino-3- (l-oxopyridin-4-yl-methyl)8-isopropyl-3H-purine; and 6-amino-3- [(3-hydroxy-4-methoxy) benzyl)]] -8- [(1-hydroxy-1-methyl) ethyl] -3H-purine; 3- (3-COOmethyl-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-piperadine-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-COOH-4-methoxybenzyl) -6-ethylamino-8-isoprop l-3H-purine; 3- (3-p rro e-enz - -et am no- -isopropyl-3H-purine; 3-butyl-6-pentylamino-8-isopropyl-3H-purine; 3-butyl-6-cyclopentylamino-8-cyclopropyl -3H-purine: 3-butyl-6-dimethylamino-8-cyclopropyl-3H-purine and its pharmaceutically acceptable salts In other preferred embodiments, the adenine compound is selected from the group consisting of 6-amino-3- [( 3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (2-methoxy) benzyloxy-1-methyl) ethyl] -3H-purine; 6-amino-3- [3- (3-hydroxycyclopentyloxy) - 4-methoxy-benzyl] -8-isopropyl-3H-purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-8 - [(1-hydroxy-1-methyl) ethyl] -3H -purine; 6-ethylamino-3- (3-butoxy-4-methoxy-benzyl) -8-isopropyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8- [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-ethylamino-2- (3, 4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-amino-3- (3-cyclopentyloxy) 4-methoxybenzyl) -3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-dimethylamino-8-isopropyl-3H-purine; 6-ethylamino-3- [3- ( 3-hydroxycyclopentyloxy) -4-methoxybenzyl)] -8- (1-hydroxy-1-methylethyl-3H-purine; 6-ethylamino-9 - [(3-cyclopentyloxy-4-metophoxy) benzyl] -8-isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-amino-8-isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (3-cyclopentyloxy-4-methoxybenzylamino) -8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- (4-methoxybenzyl) -3H-purine; 3- (3- ((3-hydrox) c clopent lox-4-methox-enz--et am no- -isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (N-benzoyl -N-ethylamino) -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopropylamino-8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- [(4-methoxy) 3- (4-hydroxybutoxy)) benzyl] -3H-purine; 6-ethylamino-3- (4-fluorobenzyl) -8-isopropyl-3H-purine; 3- (3-chlorobenzyl) -6-ethylamino-8-isopropyl -3H-purine; 3- [3- (3-hydroxy-cyclopentyloxy) -4-methoxy-benzyl] -8- (1-hydroxy-1-methyl-ethyl) -3H-purine; 3- [3- (3 -hydroxy) cyclopentyloxy)] -4-methoxy) benzyl) -6-ethylamino-8-isopropyl-3H-purine; 6-amino-3- (3,4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [3-cyclopentylmethoxy-4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-ethylamino-3- (3-hydroxy-4-methoxybenzyl-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2, 2-dimethylaminoethoxy-4-methoxy)] -8-isopropyl-3H -purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1-methyl-l-hydroxy) ethyl] -6-ethylamino-3H-purine; 3- (3-cyclopentyloxy-4-) methoxybenzyl) -6- ((2,2, 2-trifluoroethyl) amino) -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2,2,2) -azabicyclooctane-3-yloxy) - 4-methoxy] -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (l-methylpiperidin-4-yl-methoxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-8-isopropyl-3- [(4-methoxy-3- ([(4-hydroxybutoxy)) benzyl] -3H-purine; 3- [2- (4-chlorophenyl) -ethyl] -6-ethylamino -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6- ((1-hydroxy) -cyclopentylamino) -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopentylamino-8- isopropyl-3H-purine; 6-amino-3 (3,4-methylenedioxybenzyl-8-isopropyl-3H-purine; 6-ethylamino-3- [(exo-8-methyl-8-azabicyclo) (3.2.1) -octan-3-yl-oxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 3- (4-chlorophenyl) -6-ethylamino-8-isopropyl-3H-purine; 6-ethylamino-3 - [(3-hydroxy-4-methoxy) benzyl] -8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-ethylamino-3- [(3-pyridin-4-yl-methoxy ) -oxide-4-methoxy] -8-isopropyl-3H-purine; 3- [3-cyclohexanyl-4-oxy-4-methoxy-benzyl] -6-ethylamino-8-isopropyl-3H-purine; 4-chlorobenzyl) -2,6-di (ethylamino) -8-isopropyl-3H-purine; 6-amino-3- (3-hydroxy-4-methoxy) -benzyl) -8-isopropyl-3H-purine; -amino-3- [3- (4-hydroxybutoxy-4-methoxy) benzyl] -8- (1-hydroxy-1-methylethyl) -3H-purine; 6-amino-3- (4-chlorobe) nzil) -8-isopropyl-3H-purine; 6-amino-3-cyclopentylethyl-8-isopropyl-3H-purine; 8-cyclopropyl-3-methyl-6-ethylamino-3H-purine; 6-ethylamino-8-isopropyl-3- [3- (pyridin-4-yl-methoxy) -4-methoxy-benzyl] -3H-purine; 6-ethylamino-3- (l-oxopyridin-4-yl-methyl) 8-isopropyl-3H-purine; and 6-amino-3- [(3-hydroxy-4-methoxy) benzyl)]] -8- [(1-hydroxy-1-methyl) ethyl] -3H-purine; 3- (3-COOmethyl-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-piperadine-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-COOH-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-pyrrole-benzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- [(3-Cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-8- (1-methyl-ethenyl) -3H-purine and its pharmaceutically acceptable salts. In certain preferred embodiments, the adenine compound is selected from 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-ethylamino-3H-purine (PDE IV I50 = 2.15 μM); 3- (4-chlorobenzyl) -6-ethylamino-8-isopropyl-3H-purine (PDE IV I50 = 1.13 μM); 3- (3-cyclopentyloxy-4-methoxobenzyl) -6-ethylamino-8-isopropyl-3H-purine (PDE IV I50 = 0.32 μM); Y (particularly preferred) 6-cyclopentyl-8-cyclopropyl-3-propyl-3H-purine (PDE IV I50 = 0.03 μM); and their pharmaceutically acceptable salts. The present invention is also related to isoguanine compounds which are precursors of the adenine compounds described above. In addition to their function as precursor compounds, it was discovered that surprisingly these compounds also possess a significant PDE IV inhibitory activity. Accordingly, the present invention is directed in part to a compound of the formula (II) (H) where: R2 is 0 or S; and R3, R6a, R6b and R8 are the same or different and represent the same groups as specified for the above compound (I). Preferred isoguanine compounds according to the present invention include 6-cyclopentylamino-8-cyclopropyl-3,7-dihydro-3-propyl-2-thio- "H-purin-2-one (PDE IV I50 = 7.41 μM); 8-cyclopropyl-3,7-dihydro-6- (2-hydroxytylamino) -2-thio-2H-purin-2-one (PDE IV I50 = 4.48 μM); (particularly preferred) 8-cyclopropyl-3,7 -dihydro-6- (4-pyridylmethyl-amino) -2-thio-2H-purin-2-one (PDE IV I50 = 0.41 μM) and its pharmaceutically acceptable salts The present invention is also related to compounds of 2, 6-dithioxanthine which are precursors of the adenine compounds described above In addition to their function as precursor compounds, it was found that surprisingly these compounds also possess a significant inhibitory activity of PDE IV.Therefore, the present invention is directed in part to a composed of the formula (III) (ip) where R3 and R8 are the same or different and represent the same groups as those specified with respect to the above compound (I). Preferred dithioxanthine compounds according to the present invention include 3- (benzyl-3,7-dihydro-8- (1-methylethyl) -2,6-dithio-1H-purin-2,6-dione (PDE IV I5o = 3.40 μM), 3-cyclohexylmethyl-8-cyclopropyl-3,7-dihydro-2,6-dithio-lH-purin-2,6-dione (PDE IV I50 = 3.03 μM), 3- (4-chlorobenzyl) -8-isopropyl-3,7-dihydro-2,6-dithio-3,7-purin-2,6-dione (PDE IV I50 = 2.40 μM); 8-cyclopropyl-3-cyclopropylmethyl-3,7-dihydro -2,6-dithio-lH-purin-2,6-dione (PDE IV I50 = 2.27 μM) 3- (3-cyclopentyloxy-4-methoxybenzyl) -3,7-dihydro-8-isopropyl-2,6 -dithio-lH-purin-2,6-dione (PDE IV I50 = 0.80 μM); (particularly preferred) 8-cyclopropyl-3, 7- ro-, - e -, - o- -pur n-, - one 50 = 0.42 μM); and their pharmaceutically acceptable salts. As used herein, the following terms will have the following meanings as understood by persons skilled in the art, and are specifically intended to include the meanings specified below: As used herein, the The term "alkyl" means a linear or branched saturated aliphatic hydrocarbon group possessing a single radical and 1-10 carbon atoms. Examples of alkyl groups include methyl, propyl, isopropyl, butyl, n-butyl, isobutyl, sec-butyl, tert-butyl and pentyl. A branched alkyl means that one or more alkyl groups such as methyl, ethyl or propyl, substitute one or both hydrogens in a -CH2- group of a linear alkyl chain. The term "cycloalkyl" means a ring system of mono or multicyclic non-aromatic hydrocarbons with a single radical and from 3 to 12 carbon atoms. Monocyclic cycloalkyl rings include cyclopropyl, cyclopentyl and cyclohexyl. Exemplary rings of the muticyclic cycloalkyl include adamantyl and norbornyl. The term "alkenyl" means a group of linear or branched aliphatic hydrocarbons containing a carbon-carbon double bond with a single radical and from 2 to 10 carbon atoms. A "branched" alkenyl means that one or more alkyl groups such as methyl, ethyl or propyl substitute one or both hydrogens in a linear chain of alkenyl -CH2- or -CH =. Exemplary alkenyl groups include ethenyl, 1- and 2-propenyl, 1-, 2- and 3-butenyl, 3-methylbut-2-enyl, 2-propenyl, heptenyl, octenyl and decenyl. The term "cycloalkenyl" means a non-aromatic monocyclic or multicyclic ring system of hydrocarbons containing a carbon-carbon double bond and a single radical and from 3 to 12 carbon atoms. Exemplary monocyclic rings of cycloalkynyl include cyclopropenyl, cyclopentenyl, cyclohexenyl or cycloheptenyl. A cycloalkenyl muticyclic ring is norbornenyl. The term "cycloalkylalkyl" or "cycloalkyl-alkyl" means a non-aromatic mono- or multicyclic ring system, wherein the ring is substituted by an alkyl group, as defined above to include a straight or branched group of aliphatic hydrocarbons possessing a single radical. The term "aryl" means a carbocyclic aromatic ring system containing one, two or three rings which may be attached to each other in a pendent or fused manner, and which contain a single radical. Exemplary aryl groups include phenyl and naphthyl. The term "aralkyl" or "arylalkyl" or "aryl-alkyl" means an alkyl group as defined above that includes a group of linear or branched aliphatic hydrocarbons with a single radical, wherein the alkyl is substituted with an aryl group, as defined above to include an aromatic carbocyclic ring system containing one, two or three rings which may be linked together in a pendent or fused manner, and which contain a single radical. The term "heterocyclic" or "heterocyclyl" means cyclic compounds possessing one or more heteroatoms (other atoms besides carbon) in the ring, and possessing a single radical. The ring may be saturated, partially saturated or unsaturated, and the heteroatoms may be selected from the group consisting of nitrogen, sulfur and oxygen. Examples of saturated heterocyclic radicals include 3 to 6 membered heteromonocyclic groups containing 1 to 4 nitrogen atoms, such as pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl; saturated heteromonocyclic groups of between 3 to 6 members containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as morpholinyl; 3 to 6 membered saturated heteromonocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolidinyl. Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran and dihydrofuran. The term "heteroaryl" means unsaturated heterocyclic radicals, wherein heterocyclic means what was described above. Exemplary heteroaryl groups include unsaturated heteromonocyclic groups of from 3 to 6 members containing from 1 to 4 nitrogen atoms, such as pyrrolyl, pyridyl, pyrimidyl and pyrazinyl; unsaturated condensed heterocyclic groups containing from 1 to 5 nitrogen atoms, such as indolyl, quinolyl, isquinolyl; unsaturated heteromonocyclic groups with 3 to 6 members containing an oxygen atom, such as furyl; unsaturated heteromonocyclic groups with 3 to 6 members containing a sulfur atom, such as thienyl; unsaturated heteromonocyclic groups with 3 to 6 members containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as oxazolyl; unsaturated condensed heterocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, such as benzoxazolyl; unsaturated heteromonocyclic groups with 3 to 6 members containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as thiazolyl; unsaturated heteromonocyclic groups with 3 to 6 members containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, such as benzothiazolyl. The term "heteroaryl" also includes unsaturated heterocyclic radicals, wherein heterocyclic is what is described above, wherein the heterocyclic group is fused to an aryl group, wherein aryl is what was described above. Exemplary fused radicals include benzofuran, benzdioxole and benzothiophene. The term "heterocyclylalkyl" means heterocyclic groups, as defined above to include compounds that possess one or more heteroatoms (other atoms besides carbon) in the ring, and which possess a single radical, where the ring may be saturated, partially saturated or unsaturated, and the heteroatoms may be selected from the group consisting of nitrogen, sulfur and oxygen, in which the heterocyclic group is substituted by an alkyl group, as defined above to include a straight or branched group of saturated hydrated hydrocarbons possessing a only radical. Exemplary heterocyclylalkyl groups include pyrrolidinyl-methyl, imidazolidinyl-methyl, piperidino-methyl, piperazinyl-methyl, mofolinyl-methyl and thiazolidinyl-methyl. The term "heteroaralkyl" or "heteroarylalkyl" means heteroaryl radicals, wherein heteroaryl is as described above, wherein the heteroaryl group is substituted with an alkyl group as defined above to include a straight or branched group of saturated aliphatic hydrocarbons that possess a single radical. Exemplary heteroaralkyl groups include pyrrolyl-methyl, pyridyl-methyl, pyrimidyl-methyl, pyrazinyl-methyl, indolyl-methyl, quinolyl-methyl, isoquinolyl-methyl, furyl-methyl, thienyl-methyl, oxazolyl-methyl, benzoxazolyl-methyl, thiazolyl-methyl, benzothiazolyl-methyl, benzofuran-methyl and benzothiophene-methyl. The term "acyl" means a group H-C (O) - or alkyl-C (O) -group wherein the alkyl group is as described above. Exemplary acyl groups include formyl, acetyl, propanoyl and 2-methylpropanoyl. The term "alkoxy" means an alkyl-0 group in which the alkyl group is as described above, to include a straight or branched group of saturated aliphatic hydrocarbons possessing a single radical. Exemplary alkoxy groups include methoxy, ethoxy, n-propoxy, 1-propoxy and n-butoxy. The term "cycloalkoxy" means a cycloalkyl-0 group in which the cycloalkyl group is as defined above, to include mono or multicyclic nonaromatic hydrocarbon ring systems that possess a single radical. Exemplary cycloalkoxy groups include cyclopentyloxy. The term "amido" or "aminocarbonyl" means -C (0) NH2. The term "amino" means the group -NH2-. The term "Alkylamino" means an amino group that was substituted with an alkyl group as described above, and the term dialkylamino means an amino group that was substituted with two alkyl groups, as defined above. The term "acylamino" means an "amino" group that was substituted with an acyl group, as defined above. The term "carbamyl" is the group CH2NO. The term "sulfonyl" means the divalent radical S02. The term "alkylsulfonylamino" means a sulfonyl group which is substituted with an amino group as defined above, and an alkyl group as defined above. As used herein, the term "patient" includes humans and other mammals. The intention of the invention disclosed herein is to encompass all pharmaceutically acceptable salts of the disclosed compounds. Pharmaceutically acceptable salts include, without limitation, metal salts such as sodium salts, potassium salts, cesium salts and the like; alkaline earth metals such as calcium salts, magnesium salts and the like; organic amino salts such as triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt and the like; salts of inorganic acids such as hydrochloride, hydrobromide, sulfate, phosphate and the like; salts of organic acids such as formate, acetate, tr-fluoroacetate, maleate, tartrate and the like; sulfonates such as methanesulfonate, benzenesulfonate, p-toluenesulfonate and the like; salts of amino acids such as arginate, asparginate, glutamate and the like. The invention disclosed herein is also intended to encompass all prodrugs of the disclosed compounds. Any vehicle with covalence bonds that release the active mother drug in vivo is considered a prodrug. The invention disclosed herein is also intended to encompass the in vivo metabolic products of the disclosed compounds. These products can result, for example, from the oxidation, reduction, hydrolysis, amidation, esterification and the like of the compounds administered, primarily due to enzymatic processes. Accordingly, the present invention includes compounds produced by a process comprising contacting a compound of the present invention with a mammal for a time sufficient to produce a metabolic product thereof. These products are typically identified by preparing a compound of the present invention with a radioactive label, to be administered parenterally in a detectable dose to an animal such as rat, mouse, guinea pig, monkey or man, giving sufficient time for the metabolism to occur and to isolate its products. for the conversion of urine, blood and other biological mixtures. The invention disclosed herein is also intended to reveal the revealed compounds labeled with isotopes by having one or more atoms substituted with an atom having an atomic mass or different mass number. Examples of isotopes that can be incorporated into the disclosed compounds include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine and chlorine, such as 2H, 3H, 13C, 14C, 15N, 180, 170, 31P, 32P, 35S, 18F and 36C1, respectively. Some of the compounds disclosed herein may contain one or more asymmetric centers and consequently may raise enaniometers, diastereomers and other stereoisomeric forms. The present invention is also intended to encompass all possible forms as well as their racemic and resolved forms and mixtures thereof. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless otherwise specified, they are intended to encompass geometric isomers E and Z. It is intended that all tautomers are also encompassed by the present invention. As used herein, the term "stereoisomers" is a general term for all isomers of individual molecules that differ only in the orientation of their atoms in space. It includes enanomers and isomers of compounds with more than one chiral center that are not mirror images of one another (diastereomers). The term "chiral center" refers to a carbon atom a. that four different groups come together. The term "enancimer" or "enanciomer" refers to a molecule that can not be superimposed on its mirror image and therefore is optically active, where the enanomer rotates the plane of polarized light in one direction and its specular image rotates in the plane of polarized light in the opposite direction. The term "racemic" refers to a mixture of equal parts of enanomers and which is optically inactive. The term "resolution" refers to the separation or concentration or depletion of one of the two enanciomeric forms of a molecule. DETAILED DESCRIPTION OF THE INVENTION The compounds of the present invention can be administered to anyone requiring PDE IV inhibition. The administration can be oral, topical, in suppository, inhalation or insufflation, or parentérica. The present invention also encompasses all pharmaceutically acceptable salts of the above compounds. The person skilled in the art will recognize that addition of acid salts of the renounced compounds can be prepared by reaction of the compounds with the appropriate acid by a variety of known methods. Various oral dosage forms can be used, including solid forms such as tablets, capsules, granules, dragees and powders, and liquid forms such as emulsions, solutions and suspensions. The compounds of the present invention can be administered alone or can be combined with various pharmaceutically acceptable carriers or excipients known to those skilled in the art, including but not limited to diluents, suspending agents, solubilizers, binders, disintegrants, preservatives, coloring agents, lubricants and similar. When the compounds of the present invention are incorporated into oral tablets, these tablets can be tabletted, tablet milled, enteric coated, sugar coated, film coated, multiple compressed or multilayer. Liquid oral dosage forms include aqueous and non-aqueous solutions, emulsions, suspensions and solutions or suspensions reconstituted from non-effervering granules, containing suitable solvents, preservatives, emulsifying agents, suspending agents, diluents, endoliants, coloring agents and agents. flavors. When the compounds of the present invention are injected parentically, they can be, for example, in the form of sterile isotonic solution. Alternatively, when the compounds of the present invention are inhaled, they can be formulated in a dry aerosol, or they can be formulated in an aqueous or partially aqueous solution. In addition, when the compounds of the present invention are incorporated in oral dosage forms, it is contemplated that these dosage forms may provide an immediate release of the compound in the gastrointestinal tract, or alternatively may provide a controlled or sustained release through the gastrointestinal. A wide variety of controlled or sustained release formulations are known to those skilled in the art and are contemplated for use in connection with the formulas of the present invention. Controlled or sustained release can be provided, for example, by a coating in the oral dosage form or by incorporating the compounds of the present invention into a sustained or controlled release matrix. Specific examples of pharmaceutically acceptable carriers and excipients that can be used to formulate oral dosage forms are described by Handboo of Pharmaceutical Excipients, American Pharmaceutical Association (1986), incorporated herein by reference. Techniques and compositions for producing oral solid dosage forms are described in Pharmaceut ca Dosage Forms: a ets e erman, Lachman and Schwartz, eds.) 2nd edition, published by Marcel Dekker, inc., Incorporated herein by reference. Also described are techniques and compositions for forming tablets (compressed and molded), capsules (hard and soft gelatin) and pills are described in Remington's Pharmaceutical Sciences (Arthur Osol, editor), 1553-1593 (1980), incorporated into the present by reference. Techniques and compositions for making liquid oral dosage forms are described in Pharmaceutical Dosage Forms: Disperse Systems, (Lieberman, Rieger and Banker, editors) published by Marcel Dekker, Inc, incorporated herein by reference. When the compounds of the present invention are incorporated for parenteral administration by injection, (i.e., continuous infusion or bolus injection), the formulation for parenteral administration may be in the form of suspensions, solutions, emulsions in oily or aqueous vehicles., and for formulations which may also comprise pharmaceutically necessary additives such as stabilizing agents, suspending agents, dispersing agents and the like. The compounds of the present invention may also be in the form of a powder to be reconstituted as an injectable formulation. The dose of the compounds of the present invention is dependent on the disease to be treated, the severity of the symptoms, the route of administration, the frequency of the dose range, the presence of any harmful side effects, and the particular compound used, between other things. The following examples illustrate various aspects of the present invention, and should not be construed as limiting the claims in any way. EXAMPLE 1 3, 8 Diethyl-6 morpholino-3H-purine (i) 3, 8-Diethyl-hypoxanthine 3,8-Diethyl-2-thioxanthine (18.9g) was dissolved in 370 ml of 2N NaOH nickel aluminum alloy (75.6 g) (1.4 M Al and 0.6 M Ni) that were added in portions for 1.5 hrs at 65 ° C. After 0.5 hours more at 65-70 ° C, the product was filtered in the reaction, washed with 200 ml of IN of NaOH, and the filtrate was neutralized with 183 ml of 5N HCl for a pH of 7. The hydroxide was filtered off. aluminum formed, the filtrate was concentrated to dryness, the residue was suspended in 500 ml of absolute ethanol at 90 ° C, and the insoluble NaCl was filtered and washed. The filtrate was concentrated to dryness, dissolved in 200 ml of chloroform, filtered and concentrated to dryness again. The residue was crystallized from 150 ml of ethanol to produce 3,8-di-ethyl-hypoxanthine (12.68 g) with mp (sublimation at 220 ° C) 305-307 ° C under decomposition. (ii) 3,8-Diethyl-6-thiohipoxanthine The product from step (i) (8.65g) and phosphorus penta sulfide (12.0g) were refluxed in 150ml pyridine for one hour. 59.4 ml of 2N NaOH was added dropwise under cooling, the solid was filtered and washed with water. The filtrate was concentrated in vacuo to dryness and the residue suspended in 200ml of water and collected. The filtrate was extracted three times with 600 ml of chloroform. The residue of the organic phase was combined with the collected solid (a total of 6.08 g), dissolved in 500 ml of chloroform and filtered through 24 g of silica gel. Fractions 2 and 3 eluted 4. 63g of crude product that was crystallized from 120ml of methanol to produce 3,8-diethyl-6-thiohipoxanthin (3.58g) with mp (sublimation at 210 ° C) 250-270 ° C under decomposition. A second yield produced 0.58g. Elemental analysis:% cale C 51.90 H 5.81 N 26.90 S 15.40% found C 51.76 H 6.01 N26.82 S 15.64 (iii) 3, 8-Diethyl-6 morpholino-3H-purine The product of step (ii) (52mg) in 5ml of morpholine it was refluxed for 21 hours. Evaporation in vacuo afforded 65 mg of crude 3,8-diethyl-6-morpholino-3H-purine. EXAMPLE 2 3, 8-Diethyl-6-morpholino-3H-purine (i) 3, 8-Diethyl-2,6-dithioxanthine 19.14g of 3,3-diethyl-2-thioxanthine and 22.75g of phosphoric pentasulfide in 280ml were refluxed of pyridine for 4.5 hours. After cooling to room temperature 113 ml of 2N NaOH were added for 15 minutes under vigorous stirring and cooling. The suspension was filtered, washed with pyridine and concentrated in vacuo. The residue was suspended in 150 ml of water and concentrated to remove the pyridine. The suspension in water and the collection of the solid gave the crude product, which was dissolved in 150 ml of IN NaOH, treated with two 0.5 g portions of carbon, and filtered. The filtrate was acidified slowly with 38ml of 5N HCL to obtain a pH of 3 and a solid was collected. The dried crude product (19.85g) was suspended in 400ml of 2-propanol at 95 ° C. After cooling to room temperature, the solid was collected and washed (17.62g). (ii) 3, 8-diethyl-3,7-dihydro-6-morpholino-2H-purine-2-thione The product of step (i) (14.42g) was refluxed in 78.4ml (900mmol) of morpholine for 30 minutes. hours. After cooling to room temperature, the reaction product was suspended in 100 ml of acetone, and the title product was collected and washed (16.49 g). Melting point of 3, 8-diethyl-3,7-dihydro-6-morpholino-2H-purine-2-thione: 295-298 ° C (with decomposition). Elementary analysis: Cale C53.22 H 6.53 N 23.87 S 10.93 discovered C53.01 H 6.77 N 23.82 S 10.97 (iii) 3, 8-diethyl-6-morpholino.3H-purine The product of step (ii) (7.34g) was dissolved in 150ml of 2NaOH. 50% Ni-Al alloy (22.95g) (425mmol Al and 196mmol Ni) was added for 1.25 hours at 65 ° C. After a further 1.5 hours at 65-70 ° C, an additional 15 ml of ION NaOH and in portions 11.48 of 50% Ni Al alloy were added. After another 0.5 hour at 65-70 ° C, the product of the reaction was allowed to stand overnight. Dichloromethane (100 ml) was added, the suspension was filtered and the nickel was washed with dichloromethane (200 ml) and water (100 ml). The organic phase was separated, washed twice with water and concentrated. The residue was triturated in 50ml of petroleum ether to yield the title product as a solid (5.40g) mp 103-107 ° C. Elemental analysis% calc C 59.75 H 7.33 N 26.80% discovered C 59.64 H.7.55 N 26.35 The crystallized HCL salt of acetone has a mp (sublimation 145 ° C) 220-222 ° C. EXAMPLE 3 8-Cyclopropyl-3-ethyl-6-ethylamino-3H-purine (i) 8-cyclopropyl-3-ethyl-6-ethylamino-3,7-dihydro-2H-purine-2-thione. 8-Cyclopropyl-3-ethyl-2,6-dithioxanthine was prepared (20.19g) according to the method of Example 2 (i), and 70% ethylamine in water (320ml 4.0OM) was placed in a 450ml pressure reactor and heated at 150 ° C for 6 hours. The reaction solution was cooled to room temperature, treated with 2 portions of carbon (0.2 g), filtered, and evaporated to dryness. The residue was triturated in methanol (300ml), concentrated to approximately 200ml, and the solid was collected (16.48g), mp 265 ° with decomposition. (ii) 8-Cyclopropyl-3-ethyl-6-ethylamino-3H-purine The product of step (i) (11.85g) was dissolved in 2N NaOH (270ml) and ION NaOH (27ml) was heated at 65 ° C. 1.25 hours later, 50% Ni-Al alloy (518 mmol of Ni and 1125 mmol of Al) (60.8 g) was added under vigorous stirring at 65-70 ° C.

After 0.75 more hours, at the same temperature, the reaction mixture was cooled to room temperature and treated with chloroform (400ml). The nickel was filtered and washed with 350 ml of chloroform and 150 ml of water. The filtrate was separated and evaporated to leave the chloroform layer dry. The residue (19.64g) was dissolved in acetone (100ml), treated with 2 portions of carbon (0.15g), filtered and evaporated. The residue was treated with diethyl ether (100 ml) and crystals were collected 86.10 g), mp 80-96 ° C. A second production produced 1.25g. A sample recrystallized from diisopropyl ether had an mp 103-105 ° C. Elemental analysis with 3.3% water% Calc C60.25 H 7.54 N29.28 0 2.93% discovered C60.52 H 7.46 N 29.10 O 2.92 »m (by difference) HCl salt was crystallized from methanol-acetone with mp 183- 191 ° C. EXAMPLE 4 A. 8- (3-Cyclopentyloxy-4-methoxybenzyl) -3-ethyl-6-ethylamino-3H-purine B. 8- (3-cyclopentyloxy-4-hydroxybenzyl) -3-ethyl-6-ethylamino hydrochloride -3H purine (i) 3-cyclopentyloxy-4-methoxy-benzyl alcohol To a solution of 48.70g (220mmol) of 3-cyclopentyloxy-4-methoxybenzaldehyde in 250ml of methanol was added portionwise 8.57g (220mmol) of 97% strength. sodium borohydride in a lapse of 10 minutes at 15-22 ° C under cooling. After 20 more minutes the methanol was removed in vacuo and the residue was taken in 10 ml of water and 300 ml of ether. The ether phase was evaporated to dry: 48.5g (99.2%) of liquid benzyl alcohol, (ii) 3-cyclopentyloxy-4-methoxybenzyl cyanide in a solution of 40.00g (180mmol) of benzyl alcohol in 530ml of dichloromethane 32.7ml (450mmol) of thionyl chloride was added in a lapse of 5 minutes. The solution was evaporated in vacuo until dry, which was repeated after adding toluene: 46.30g (106.9%) of crude benzyl chloride, which was dissolved in 230ml of dimethylformamide and treated with 23.50g (360mmol) of potassium cyanide. . The mixture was heated for 40 hours at 50-55 ° C. The salts were filtered and the filtrate was evaporated in vacuo until dry, which was repeated after adding water, and the residue was taken up in ether and extracted with an IN NaOH. The ether phase was evaporated to dryness to yield 41.20g (99.0%) of crude benzyl cyanide, (iii) (3-cyclopentyloxy-4-methoxy-phenyl) acetyl chloride. 42.02g (180mmol) of benzyl cyanide was refluxed in 410ml of 94% ethanol, 106ml of water and 180ml of ION NaOH for 20 hours. The ethanol was removed in vacuo, the solution was diluted to 800 ml with water, treated 2 times with 2 g of carbon, filtered and acidified with 185 ml of 10 N HCl. The acid slowly crystallized, was collected and dried at 30 ° C: 42.2 g (92.9%) of acid. It was possible to extract 1.51g (2.3%) by ether from the filtrate. Both parts (173 moles) were combined and refluxed in 500ml of bichloromethane and 31.4ml (433mmol) of thionyl chloride for 1.5 hours. The solution was treated twice with 2 g of carbon, filtered and evaporated to dryness. This was repeated 2 times with little toluene: 48.70g (> 100%) of crude acetyl chloride in the form of a reddish liquid. (iv) 8- (3-cyclopentyloxy-4-methoxy-benzyl) -3-ethyl-2-thioxanthine 10.02g (45mmol) of 5,6-diamino-1-ethyl-2-thiouracil hydrochloride in 200ml of pyridine were dissolved. , treated with 6.05g (57mmol) of sodium carbonate and 15.5g (56mmol) of Example 4 (iii) were dissolved in 25ml of ether which were added in a lapse of 10 minutes at 5-10 ° C. After 1.5 hours at room temperature, the solid was filtered and the filtrate was evaporated in vacuo until dry. The residue was dissolved in 100 ml of 2N NaOH and 200 ml of water and refluxed., and 70ml were distilled in the lapse of 1 hour. The solution was filtered and neutralized to a pH of 7.5 with 52ml of 5NHCL. The solid was collected and dried: 14.37g (79.7%) of crude 2-thioxanthine (4.2g of acetic acid phenyl was recovered from the water), which was suspended in 250ml of hot methanol and re-collected: 10.68g (59.3% ) of purified 2-dioxanthine, which was dissolved in 100 ml of IN NaOH and filtered. The filtrate was acidified to pH 6 and the solid was collected: 8.82g (48.9%) of 2 thioxanthine with mp (260 ° C) 280-310 ° C under decomposition. (v) 8- (3-cyclopentyloxy-4-methoxy-benzyl) -3-ethyl-2,6-dithioxanthine 8.41g (21 mmol) of 2-dioxanthine were refluxed with 5.60 g (25.2 mmol) of phosphoric pentasulfide in 80 ml of pyridine . After 5.5 hours, 27.7ml (55.4mmol) of 2N NaOH was added at 5-10 ° C. The solid was filtered and washed with pyridine. The filtrate was evaporated in vacuo to dryness, the residue was suspended in 200 ml of water with little tetrahydrofuran (THF) for crystallization, the suspension was concentrated and the solid was collected and washed at pH 8. It was redissolved in lOO of 0.5 N NaOH, treated with charcoal (20%), filtered and acidified to a pH of 6, which produced 7.84 g of solid crude dithioxanthine (89.6%). Crystallization of chloroform and suspension in hot methanol yielded 5.31 g (60.7%) with dithioxanthine with mp 241-3 ° C. The mother liquors were combined (2.36 g) and filtered with chloroform through 60 g of silica gel in a column: 1.73 g (19.8%) were isolated as the second yield. (vi) 8- (3-cyclopentyloxy-4-methoxy-benzyl) -3-ethyl-6-ethylamino-3,7-dihydro-2H-purine-2-thione. 6.67g (16 mmol) of dithioxanthine and 52 ml of ethylamine were heated. 70% in water at 150 ° C in a pressure reactor (250 psi) for .12 hours under nitrogen. The solution was treated with charcoal (5%), filtered and evaporated in vacuo to dryness. The residue was suspended in water, acidified with IN HCl to obtain a pH of 4 and neutralized to a pH of 8 with sodium bicarbonate. The solid was collected, washed and dried to yield 6.66g (97.4%) of crude thioisoguanine. (vii) A. 8- (3-Cyclopentyloxy-4-methoxy-benzyl) -3-ethyl-6-ethylamino-3H-purine hydrochloride and. B 8- (3-Cyclopentyloxy-4-hydroxy-benzyl) -3-ethyl-6-ethylamino-3H-purine hydrochloride 6.41g (15mmol) of crude thioisoguanine and 9.70g (165mmol) of neutral Raney-nickel were refluxed. 70ml of 1-propanol for 3 hours. The nickel was filtered and the filtrate was evaporated in vacuo to dryness. The residue (5.86g / 98.8%) was dissolved in chloroform and extracted extensively with IN NaOH. The NaOH solution was acidified with 5N HCl to obtain a pH of 4 and neutralized with sodium bicarbonate at a pH of 7.5. It was precipitated in oil, which crystallized slowly and the solid was collected: 049 g of 8- (3-cyclopentyloxy-4-hydroxy-benzyl) -3-ethyl-6-ethylamino-3H-purine with mp 172-4 ° C. The chloroform solution was evaporated to dry: 3.76 g (63.4%) of crude 3 H purine, which was dissolved in 30 ml of methanol and treated with 1 ml of IN of methanolic HCl. The solution was evaporated in vacuo to dryness and the residue of acetone-ethyl acetate: 3.66g (56.5%) of 8 (cyclopentyl-phenyl-4-methoxybenzyl) -3-ethyl-6-ethylamino-3H purine hydrochloride was crystallized with mp 169 -71 ° C.

Elemental analysis of C22 H30 CIN502 Cale C 61.17 H7.00 N16.21 Discovered C 61.09 H 6.77 N 16.18 EXAMPLE 5 3- (3-Cyclopentyloxy-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine hydrochloride ( i) 3-Cyclopentyloxy-4-methoxy-benzaldehyde 77.70g (500mmol) of isovaniline and 69.40g (600mmol) of 97% potassium butoxide (t-BuOK) were dissolved in 800ml of 1-propanol, 69.Ol ( 630 mmol), and the solution was refluxed. After 3 hours, another 9.25g (dOmmoles) of t-BuOK was added at 80 ° C and the suspension was refluxed for another 3 hours. The solid was filtered and the filtrate was evaporated in vacuo to dryness. The residue was dissolved in ether and extracted with IN NaOH. The ether phase was evaporated to dry: 85.40g (77.5%) of cyclopentyloxybenzaldehyde were isolated. (ii) 3-Cyclopentyloxy-4-methoxy-benzaldehyde-oxime 85.4g (388 mmol) of 3-cyclopentyloxy-4-methoxy-benzaldehyde were dissolved in 350 ml of 94% ethanol and added in a lapse of 10 minutes to 15-20 ° C to a solution of 29.7g (427mmol) of hydroxylammonium chloride and 52.8g (388mmol) of sodium acetate trihydrate (3H20) in 230ml of water. After 2 hours the ethanol was removed in vacuo, the residue was treated with 16.3 g (194 mmol) of sodium bicarbonate until the formation of Co2 ceased and it was extracted with ether. Evaporation of the ether phase yielded 91.Og (99.7%) of oxime as a mixture of the 2 isomers. (iii) 3-cyclopentyloxy-4-methoxy-benzylamine. 73.5 g (32 Omityles) of oxime, 80 ml of methanol, 55 g of liquid ammonia and 18.5 g of neutral Raney-nickel were placed in a 450 ml pressure reactor. Hydrogen gas was added to a pressure of I 200 psi and the whole was heated to 75-80 ° C, when the low pressure to 600 psi hydrogen gas was added to obtain again 1 200 psi. After 4 hours the pressure reached 1080 psi and remained constant. The nickel was filtered and washed with methanol. The filtrate was evaporated to dryness, dissolved in ether and extracted with IN NaOH. The ether phase was evaporated to dry: 68.9 g (97.3%) benzyl amine. (iv) 3-Cyclopentyloxy-4-methoxy-benzyl-isothiosiana. 82.3 g (372 mmol) of benzylamine were dissolved in 10 ml of toluene and added at 15-20 ° C (with cooling) in the course of 20 minutes to an emulsion of 22.5ml (372mmol) of carbon disulfide and 14.88g (372mmol) of NaOH in 52ml of water. The reaction mixture was heated at 75-80 ° C for one hour and cooled to 40 ° C. Over the course of 15 minutes, 35.4ml (372mmol) of ethyl chloroformate was added at 40-45 ° C. The emulsion was made to stand at a pH of 8 with 2N NaOH and heated to 55-60 ° C, gas formation ceased after 10 hours keeping the Ph at 8 with 2N NaOH (a total of about 8ml). The organic layer was collected and the solvent was evaporated: 96.3 g (98.3%) of benzyl isothiocyanate. (v) 1- (3-cyclopentyloxy-4-methoxy-benzyl) -2-thiourea 96.3g (366mmol) of benzylisothiocyanate were dissolved in 100ml or THF and treated with 44.2ml (732 mmol) of 32% ammonia solution. After 0.5 hours a 40-45 ° C, 300ml of water was added and the THF was removed in vacuo. The slurry was treated with 200ml of ether, the crystals were collected and washed with water and ether.

It was suspended in 300 ml of methylene chloride and the collection produced 65.77g (64.2%) of benzyl-2-thiourea with mp 144-5 ° C. (vi) 6-Amino-1- (3-cyclopentyloxy-4-methoxy-benzyl) -2-thiouracil. 29.65 g (256 mmol) of 97% t-BuOK were dissolved in 240 ml of 2-propanol. 65.33g (233mmol) of 2-thiourea and 25.3ml (238mmol) of ethyl cyanoacetate were added at 80 ° C. After 30 minutes at reflux, a solution formed and after 4.5 hours an additional 2.96 g (25.6 mmol) of t-BuOK and 4.97 ml (46.6 mmol) of ethyl cyanoacetate were added. After 22 hours of reflux, the solid was collected, combined with the filtrate residue, dissolved in 1 liter of water and precipitated with approximately 50 ml of 5N HCl (pH 3-4). The solid was collected, washed, dried, recrystallized by suspension in 1 l of refluxing acetone, concentrated approximately 300 ml and collected at 23 ° C: 80.65 g (85.7%) of uracil containing one equivalent of acetone, mp-225-7 ° C. (vii) 6-Amino-l- (3-cyclopentyloxy-4-methoxy-benzyl) -5-nitroso-2-thiouracil. 68.9g (170mmol) of uracil were dissolved in 650ml of acetic acid, to be removed with acetone, 100ml was distilled in vacuo, and 43.4 ml (174 mmol) of 4N sodium nitrite solution were added over the course of 10 minutes at 65-70 ° C. After another five minutes the suspension was cooled to 30 ° C and diluted with 1.7 1 of water. The solid was collected, washed and dried: 64.08 g (100%) of nitrosouracil, which was dissolved in 330 ml of IN NaOH and 300 ml of water, filtered, and acidified with 5N HCl to a pH of 2, 2 1 were added. of water to keep it in suspension. The solid was collected and washed, suspended in 60 ml of methanol and re-harvested: 54.2 g (84.7%) of nitrosouracil. (viii) 1- (3-cyclopentyloxy-4-methoxy-benzyl) -5,6-diamino-2-thiouracil. 15.06g (40mmol) of nitrosouracil were suspended in 300ml of THF and hydrogenated with hydrogen gas and 600g of Raney- Neutral nickel for 2.5 hours, when the absorption of hydrogen ceased. After one hour, everything dissolved and a new precipitate was formed, which was dissolved in a mixture of methylene chloride and methanol. The nickel was filtered and the filtrate was evaporated in vacuo to dry: 13.96g (96.3%) of crude diaminouracil. (ix) 6-Amino-1- (3-cyclopentyloxy-4-methoxy-benzyl) -5-isobutyrylamino-2-thiouracil. A two-phase solution of 15.01 g (41.4 mmol) was heated at 55 ° C under nitrogen for one hour. ) of diaminouracil, 180ml of THF, 150ml of water, 6.96g (82.8mmol) of sodium bicarbonate and 10.52ml (62.5mmol) of isobutyl anhydride. The THF was evaporated in vacuo and the residue was diluted with 200 ml of water (Ph 8). The solid was collected, washed and dried: 16.25g (90.7%) of isobutyrylaminouracil. (x) 3- (3-cyclopentyloxy-4-methoxy-benzyl) -8-isopropyl-2-thioxanthine 17.81g (41.2 mmol) of isobutyrylaminouracil were refluxed for 0.75 hours in 120 ml of IN NaOH and 80 ml of water. The solution was treated twice with 0.5 g of carbon, filtered, acidified with 5N HCl and set at a pH of 7-8 with a solution of sodium bicarbonate. The solid was collected, washed and dried: 15.31 g (89.6%) of 2-thioxanthine with mp 270-6 ° C (with decomposition). (xi) 3- (3-cyclopentyloxy-4-methoxy-benzyl) -8-isopropyl-2,6-dithioxanthine) 15.17g (36.6mmol) of 2-th oxanathane and 9.76g (43.9mmol) of pentasulfurophosphoric were refluxed under nitrogen in 140ml of pyridine for 5.5 hours. 48.3 ml (96.6 mmol) of 2N NaOH was added dropwise at 5-10 ° C. The solid was filtered and washed with pyridine. The filtrate was evaporated in vacuo to dryness and treated with 300 ml of water. The suspension was adjusted to a Ph of 7 with sodium bicarbonate solution and the solid was collected, washed and dissolved in 200ml of 0.5N NaOH solution, treated twice with 1.6g of carbon, filtered, acidified with 5N of HCl and neutralized with sodium bicarbonate solution to a pH of 7. The solid was collected, washed and dried: 14.64g (92.9%) of crude dithioxanthine, which was dissolved in 4000ml of methylene chloride and filtered through 60g of silica gel in a column. The solvent was evaporated and the residue was suspended in 20ml of 100% ethanol and collected: 14.34g (82.2%) of dithioxanthine with mp 204-6 ° C (containing one mole EtOH). (xii) 3- (3-cyclopentyloxy-4-methoxy-benzyl) -3,7-dihydro-6-ethylamino-8-isopropyl-2H-purine-2-thione 6.20g (13 mmol) of dithioxanthine were added and 42ml of 70% ethylamine in water in a 450ml pressure reactor and heated to 150 ° C (240 psi) for 12 hours. The solution was filtered and evaporated to dryness. The residue was suspended in water, acidified with IN HCl at a pH of 3, and neutralized with a sodium bicarbonate solution at a pH of 7-8. The seed was collected, stocked and dried or:. g (95.5%) of thioisoguanine with mp 72-7 ° C. (xiii) 3- (3-Cyclopentyloxy-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine hydrochloride. 5.43g (12.3mmol) of thioisoguanin and 7.9g of neutral Raney-nickel in 60ml were refluxed. 1-propanol of 4.5 hours. The nickel was filtered and the filtrate was evaporated in vacuo to dryness: 4.9 g (97.2%) of crude purine, which was dissolved in 20 ml of chloroform, extracted with IN NaOH and filtered through 30 g of silica gel in a column. The solvent was evaporated, the residue was dissolved in 25 ml of methanol, treated with 11 ml of IN methanolic HCl solution and evaporated to dryness. The residue was suspended in 80ml of ethyl acetate and collected: 3.49g (63.6%) of 3H-purine hydrochloride with mp 202-12 ° C Elemental analysis of C23, H32 C1N502 Cale C61.94 H7.23 N15.70 07.17 Discovered C62.17 H7.02 N 15.66 07.30 EXAMPLE 6 3- (3-Cyclopentyloxy-4-methoxybenzyl) -6-ethylamino-3H-purine hydrochloride (i) 3- (3-cyclopentyloxy-4-methoxy-benzyl) - 2- thioxanthin 14.62g (40 mmol) of l- (3-cyclopentyloxy-4-methoxy-benzyl) -5,6-diamino-2-thiouracil in 200ml of formic acid was dissolved. The solution was concentrated in vacuo at room temperature to remove the water. 50ml of formic acid was added and the procedure was repeated. After a total of 1 hour, the formic acid solution was concentrated to 300 ml at 25 ° and diluted with 300 ml of water. The crystals were collected, washed and dried: 13.48g (86.3%) of crude 5-formamide (mp 210-30 ° C), which were refluxed in 86ml of IN NaOH for 15 minutes. The cloudy solution was treated twice with 0.6 g of carbon, filtered, acidified with 5N HCl to a Ph of 2, and neutralized to a pH of 6.5. The amorphous solid was collected, washed and dried at 60 ° C: 11.93g (80.1%) of crude 2-thioxanthine, which was dissolved in 150 ml of THF, treated with charcoal (5%), filtered, concentrated to 40ml and it was diluted with 250 ml of ethanol. After a concentration of 120 ml, the solid formed was collected, washed and dried: 9.21 g (61.9%) of 2-thioxanthine with mp 254-65 ° C Elemental analysis for Ci8H20N4O3S Cale C58 H 5.41 N15.04 O 12.89 Discovery C 58.13 H 5.41 N 14.93 or 13.11 (ii) 3- (3-Cyclopentyloxy-4-methoxy-benzyl) -2,6-dithioxanthine. 8.94g (24mmol) of thioxanthines and 6.40g (28.8mmol) of phosphorus pentasulfide in 96ml of pyridine were refluxed under nitrogen for 1.5 hours. At 5-10 ° C, 31.7 ml (63.4 mmol) of 2N NaOH was added under cooling and the mixture was diluted with 30 ml of pyridine. The solid was filtered and the filtrate was evaporated in vacuo to dryness. The residue was suspended in 30ml of water and the solid was collected, dissolved in 160ml of 0.5N NaOH, filtered, treated with charcoal (20%), refiltered, acidified with 5N HCl to a pH of 5. , the solid was collected, washed and dried: 9.03g (96.9%) of crude dithioxanthine. The product was dissolved in 400 ml of chloroform and filtered through 30 g of silica gel in a column. The solvent was removed in vacuo, the residue was dissolved in 50 ml of THF, filtered, concentrated to 30 ml, diluted with 200 ml of ethanol, concentrated again to 150 ml and the solid collected, washed and dried: 8.65 g (92.8%) of dithioxanthin with mp 215-8 ° C Elemental analysis of C? 8H20N4O2S2 with 0.25M ethanol and 0.5M water. Cale C54.32 H 5.54 N13.70 O 10.76 Discovered C 54.67 H 5.32 N 13.80 O 10.20 (iii) 3- (3-Cyclopentyloxy-4-methoxy-benzyl) -3,7-dihydro-6-ethylamino-2H-purine -2-thione 4.66 g (12 mmol) of dithioxanthine and 48.3 ml (60 mmol) of 70% ethylamine in water at 150 ° C were heated in a 450 ml pressure reactor under N2 for 12 hours (240 psi). The solution was treated with carbon (5%), filtered and evaporated to dryness. The residue was taken in 100 ml of water, acidified with IN HCl at a pH of 3 and neutralized with sodium bicarbonate at a pH of 7, and the solid collected: 4.43 g (92.5%) of crude thioisoguanin with mp 99 -103 ° C. (iv) 3- (Cyclopentyloxy-4-methoxy-benzyl) -6-ethylamino-3H-purine hydrochloride. 4.39g (llmmoles) of thioisoguanin and 7.10g (121mmoles) of neutral Raney-nickel in 150ml of 1-propanol were refluxed. for 4.5 hours. The nickel was filtered and the filtrate was evaporated to dryness. The residue (3.39 g / 93.8%) was dissolved in 20 ml of chloroform and 0.4 ml of methanol and filtered through 24 g of silica gel on a column, also with 2% methanol. The combined fractions were washed with IN NaOH and the organic phase was evaporated to dryness. The residue (2.69g / 66.6%) was dissolved in 30ml of dichloromethane and 0.6ml methanol and refiltered through 30g of silica gel. A total of 1.86 g (46.0%) of 3 H-purine was isolated, which was dissolved in 20 ml of methanol, treated with 5.4 ml of IN of methanolic HCl, and evaporated in vacuo to dryness. Crystallization and recrystallization from dichloromethane and ethyl acetate yielded 1.75g (39.4%) of 3H-purine hydrochloride with mp 170-85 ° C. Elemental Analysis of C2oH26C? N5o2 Cale C59.47 H6.49 N17.34 07.92 Discovered C59.72 H6.44 N 17.25 08.24 EXAMPLE 7 8-Cyclopropyl-6- (4-pyridylmethyl-amine) -3-propyl 1,3-hydrochloride -3H-pur na (i) 8-Cyclopropyl-3-propyl-2,6-dithioxanthin 2.2 liters of pyridine and 8-cyclopropyl-3-propyl-2-thioxanthine (220g, 0.88mol) were placed in a 3-flask. necks of 5 liters equipped with a mechanical agitator and a condenser with a drying tube. Phosphorus pentasulfide (236g, 1.96 mol) was added and the mixture was heated under reflux for 5 hours and stored overnight at room temperature. The reaction mixture was cooled to 5-10 ° C and 3N aqueous sodium hydroxide (770ml) was added over 1.5 hours with stirring. Stirring was continued for 30 minutes after removing the cooling bath, and the precipitated product was collected by suction filtration. The filtrate residues were washed successively with pyridine (300ml) and four 300ml portions of tretrahydrofuran. The solvents were evaporated in vacuo and the solid residue was stirred with water (750ml), filtered and washed with water. The crude product was dissolved in 1.7 L of IN sodium hydroxide and stirred with 15 g of Darco G-60. The carbon was filtered and the treatment was repeated with a new portion of carbon. The solution was acidified to a pH of 1.5 with 6N hydrochloric acid and a pale yellow precipitate was collected. The solid was dissolved again in 1.7 liters of ln of sodium hydroxide and treated successively with two portions of carbon, as described above. The solution was added and the precipitate was added with water. After drying at a constant weight at 54 ° C under vacuum, 128g (56%) of the title compound was obtained, mp of more than 245 ° C (ii) 8-Cyclopropyl-3,7-dihydro-3-propyl-6 - (4-pyridylmethylamino) -2H-purine-2-thione. 5.33g (20mmol) of 8-cyclopropyl-3-n-propyl-2,6-dithioxanthine and 21.3ml (200mmol) were heated under argon at 150-5 ° C. ) of 95% 4-picolylamine. After 14 hours, the cooled solution was poured into 100 ml of water, acidified with 19 ml of ION HCl and IN of HCl to a pH of 6, where an orange-colored gum was formed. The mixture was neutralized at pH 7 with sodium bicarbonate. Over time, the gum crystallized and the solid was collected and washed. The residue was suspended in acetone and the crystals were collected: 3.92 (57.6%) of the crude product. The filtrate was evaporated to dryness, dissolved in 40ml of 0.5n NaOH, extracted 4 times with methylene chloride, and re-acidified with 5N of HCl to a Ph of 6. Again the gum crystallized for 48 hours in the mixture was neutralized a Ph of 7 with bicarbonate and the solid was collected: 1.75g (25.7%) of crude product. Both parts were dissolved in 30 ml of methylene chloride and filtered through 30 g of silica gel in a column. 150mg (28%) of initial material was recovered first, then 5.04g (74.0%) of the product was recovered with 5% methanol, which was dissolved in 32ml. of an N HCl, they were treated with 250mg of carbon, filtered and neutralized with 7.5ml of 2N NaOH and with sodium bicarbonate solution at a pH of 7-8. The water phase of the gum was decanted, and the latter was washed with water and crystallized with acetone: 4.08 g (59.9%) of thioisoguanine with mp 204-210 ° C with decomposition, (iii) 8-cyclopropyl dihydrochloride 6- (4-pyridylmethylamino) -3-propyl-3H-purine 3.06g (9mmol) of thioisoguanin and 5.8g of neutral Raney-nickel were refluxed under argon in 1-propanol for 4 hours. The nickel was filtered and washed with methanol. The filtrate was evaporated to dryness, the residue was dissolved in 20 ml of methylene chloride, the solution was extracted with IN of NaOH, and evaporated to dry: 2.43 g (87.4%) of crude purine, which was dissolved in 20 ml of methanol, it was treated with 17 ml of IN of methanolic HCl and evaporated again to dryness. The crystallization from isopropanol produces 1.09 g (36.3%) of purine dihydrochloride with mp of 157-65 ° C. EXAMPLE 8 6-Cyclopentylamino-8-cyclopropyl-3-propyl-3H purine hydrochloride. (i) 6-Cylcopentylamino-8-cyclopropyl-3,7-dihydro-3,7-propyl-2H-2-purine-2-thione 5.33g (20 mmol) of 8-cyclopropyl-3n-propyl-2, -dt-oxant were heated na ymecc opent am na in a 450 ml pressure reactor at 150 ° C. (50psi) with the exclusion of air. After 20 hours the solution was transferred with methanol to a round flask and evaporated in vacuo to dryness. The residue was treated with 60ml of water and 5N of HCl to obtain a pH of 2. The suspension was neutralized with bicarbonate to a pH of 7, the solid was collected, washed, dried, suspended in refluxing acetone and turned to collect: 5.98g of thioisoguanine with mp 274-6 ° C. (decomp) (ii) 6-Cyclopentylamino-8-cyclopropyl-3-n-propyl-3H-purine hydrochloride 4.49g (14.1mmol) of thioisoguanin and 9.2 neutral Raney-nickel in 45ml of 1-propanol were refluxed. hours. The nickel was filtered and the filtrate was evaporated to dryness. The residue (more than 100%) was dissolved in 30 ml of methanol, treated with 16.9 ml of IN solution of methanolic HCl, and evaporated to dryness. The residue was dissolved in methylene chloride, treated with 0.12 g of carbon, filtered, concentrated, diluted with acetone and the remaining methylene chloride was distilled off. The crystals were collected: 4.18g (92.3%) of purine hydrochloride with mp 218-221 ° C. Elemental analysis for C? SH24CIN5 M.W.321.86. Cale C59.71 H 7.52 N21.76 Cl 11.01 Discovered C 59.82 H 7.40 N 21.76 Cl 11.02 (dif) EXAMPLE 9 Clorh drato of -am no- - - ens ox - - me etil) -3- (3-cyclopentyloxy-4 -methoxy-benzyl) -3H-purine. To 6-Amino -5- (2-benzyloxy-2-methyl-propionylamino) -l-3-cyclopentyloxy-4-methoxy-benzyl) -2-thiouracil A solution was added with 26.39g (124mM) of 2-chloride. benzyloxy-2-methyl-propionyl in 86 ml of THF at 5-10 ° C within 20 minutes at a stirred suspension with 31.9 g (84.4 mM) of l- (3-cyclopentyloxy-4-methoxy-benzyl) -4 , 5-diamino-2-thiouracil in 315 ml of THF and 26.5 ml of triethyl amine. After 2 hours at room temperature the solid was filtered and the solution was evaporated to dryness. The residues were treated with 400ml of ether, 50ml of saturated sodium bicarbonate solution and 100ml of water. The crystals were collected after 2 hours and washed with ether and water: 30.14g (66.3%) of amide. The ether phase was evaporated to dryness and the methanol residue was crystallized: 5.30g (11.7%) of amide with mp 198-202 ° C. B 8- (1-Benzyloxy-1-methyl-ethyl) -3- (3-cyclopentyloxy-4-methoxy-benzyl) -2-thioxanthine 35.44g (65.8mM) of the aforementioned amide (A) was added to 70 ° C to a solution with 29.53 g of t-BuOK in 350 ml of isopropanol and refluxed for 0.5 hours. The solvent was evaporated in vacuo, the residue was dissolved in 350 ml of water, the solution was treated twice with 3.0 g of carbon and filtered. The solution was neutralized at 5 ° C with 5 ml of 5n HCl at a pH of 7. After 2.5 hours the solid was collected and suspended for 1.5 hours in 300 ml of methanol, it was cooled to 5 ° C and the solid was collected again: 21.15g (61.7%) of exantine. The filtrate was evaporated in vacuo, the residue was dissolved in dichloromethane and filtered through 60g of silica gel on a column: the crystallization of methanol produced another 5.7g (16.8%) of exantine with mp 158-160 / 235-237 / 288-290 ° C. C 8- (1-Benzyloxy-1-methyl-ethyl) -3- (3-cyclopentyloxy-4-methoxy-benzyl) -hypoxanthine A solution was treated with 22.39 g (43 mM) of the aforementioned xanthine (B) in 580 ml of 1-propanol with 25 g of Raney-nickel (washed with 0.1% aqueous acetic acid) and refluxed for 2 hours. It was filtered through nickel and the solvent was evaporated in vacuo. The 120ml residue of methanol was crystallized: 12.73g (60.6%) of hypoxanthine with mp 161-162 ° C, and a second yield produced 1.97g (9.4%) of hypoxanthine. D 6-amino-8- (1-benzyloxy-l-methyl-ethyl) -3- (3-cyclopentyloxy-4-methoxy-benzyl) -3-H-purine hydrochloride 2.44g (5mM) of hypoxanthine were heated above mentioned (C) and 25 ml of phosphorus oxychloride at 65-70 ° C for 35 minutes. The solution was evaporated in vacuo and repeated twice with toluene. The residue was dissolved in 55 ml of THF and added to 3.3 ml of 32% aqueous ammonia solution. After transferring a 450ml pressure reactor and a 50g supplement of liquid ammonia, the mixture was heated to 60 ° C (340psi) for 3.5 hours. The solid was filtered and the solvent was evaporated in vacuo. The residue was dissolved in chloroform and extracted with lN NaOH solution. The chloroform residue was dissolved in 25 ml of methanol, and treated with 5 ml with 1 ml methanolic HCl solution. The solvents were evaporated in vacuo and the residue was suspended in hot methanol and the solid was collected at 5 ° C: 2.07g (79.0%) of adenine at 201-213 ° C mp, a second acetone yield of 0.28 was collected. g (10.7%). Elemental analysis of C28H34CIN503 / 524.06% calc C64.17 H 6.54 N 13.36 OR 9.16% discovered C64.13 H 6.58 N13.31 OR 9.15 EXAMPLE 10 De-8- (1-benzyloxy-1-methyl-ethyl) -3- (3-cyclopentyloxy-4-methoxy-benzyl) -6-ethylamino-3H-purine hydrochloride 1.5g (4mM) of 8- (1-benzyloxy-1-methyl-ethyl) -3- (3-cyclopentyloxy-4-methoxy-benzyl) -hypoxanthine and 20 ml of phosphorus oxychloride at 70 ° C for 0.5 hours. The solution was evaporated in vacuo and repeated twice with toluene. The residue was dissolved in 30 ml of THF and added to 16 ml of 70% ethylamine aqueous solution at 5 ° C. After one hour at room temperature, the solvents were evaporated in vacuo. The residue was dissolved in 50 ml of dichloromethane and extracted with ln NaOH solution. The organic phase was evaporated in vacuo, the residue was dissolved in 20 ml of methanol, treated with 4.4 ml with 1 ml of methanolic HCl solution and re-evaporated. The ethyl acetate residue was crystallized: 1.85g (83.7%) of adenine with mp 148-150 ° C. A second yield of 0.17 g (7.7%) was obtained from ethyl ether acetate. Elemental analysis of C3oH28CIN5? 3 / 552.12% cale C 65.26 H 6.94 N 12.68 0 8.69% discovered C 65.07 H 6.95 N12.53 08.96 EXAMPLE 11 Chlorohydrate-6-amino-3- (3,4-methylenedioxybenzyl) -8- (1 -4) - (3-cyclopentyloxy-l-methyl-ethyl) -3H-purine A 6-amino-1- (3,4-dimethoxy-benzyl) 5- (2- (4-fluorobenzyloxy) -2-methyl -propionylamino) -2-thiouracil A solution with 3.70g (15mM) of 2- (4-fluoro-benzyloxy) -2-methyl-propionylchloride in lOml of THF at 0-5 ° C was added in a lapse of 5 minutes to obtain a suspension with 3.19g (10.3mM) of 5,6-diamino-l- (3, 4-dimethoxybenzyl) -2-thiuracil and 3.5ml of (25mm) of triethylamine in 30ml of THF. The solid was filtered after 4 hours and the solvent was evaporated in vacuo. The residue was dissolved in 40 ml of ethyl acetate and extracted with 20 ml of ln HCl solution. A precipitate was formed and collected: 2.11g (40.6%) of amide. The ethyl acetate phase was washed with sodium bicarbonate solution and evaporated to dry: 3. g e a mixture with two mainly compounds. The separation of a solution of dichloromethane, comprising 2% methanol, in 60 g of silica gel in a column produced first after crystallization of acetone l.llg (15.4%) of the diamide with mp 194-197 ° C and subsequent fractions yielded 1.06 g (20.4%) of amide with mp 110-180 ° C as the second yield. B 3- (3, 4-dimethoxybenzyl) -8- (1- (4-fluorobenzyloxy-1-methyl-ethyl) -2-thioxanthine A solution was refluxed with 3.07 g (6.1 mM) of the above amide (A) in 30 ml of NaOH for 15 minutes, treated twice with 0.2 carbon, filtered and neutralized with 6.2 ml of 5n HCl, the solid was collected, suspended in 30 ml of hot methanol and collected again at 5 ° C: 2.34g (79.1%) of xanthine with mp 300-302 ° CC 3- (3,4-dimethoxybenzyl) -8- (1- (4-fluorobenzyloxy) -1-methyl-ethyl) -hypoxanthine 2.18g (4.5 mM) of xanthine (B) and 2.6 g of Raney-nickel (treated with 0.1% aqueous acetic acid) in 30 ml of 1-propanol for 2.5 hours.The nickel was filtered and the solution was evaporated in vacuo until it was dried. The residue was taken up in 40 ml of ethyl acetate and extracted with sodium bicarbonate solution The solid formed was filtered and the organic phase was evaporated in vacuo to dryness (1.95 g) A dichloromethane solution, comprising 2% of methanol, in 19 g of silica gel in a column. Crystallization of ethyl acetate yielded 1.37 g (67.2%) of hypoxanthine with mp 159-161 ° C, and a second yield yielded 0.5 g (2.0%) of hypoxanthine. D 6-amino-3 (3,4-dimethoxybenzyl) -8- (1- (4-fluorobenzyloxy-1-methyl-ethyl) -3H-purine hydrochloride 1.27g (2.8mM) of the above hypoxanthine were heated in 13ml of phosphorus oxychloride at 70 ° C for 30 minutes.The evaporation in vacuo and the double repetition with toluene produced the crude intermediate 6-chlorine, which was dissolved in 40ml of THF and added at 0-5 ° C to 12ml of aqueous ammonia at 32% After adding 50 g of liquid ammonia the solution was heated at 60 ° C in a 450 ml pressure reactor (340 psi) After 3.5 hours the solid was filtered and the solution was evaporated in vacuo to dryness. dissolved the residue in dichloromethane, it was extracted with an lN NaOH and evaporated again until dry. The residue was dissolved in 20 ml of methanol, treated with 2.9 ml of methanolic HCl, and evaporated to dryness. Crystallization from ethyl acetate yielded 1.24g (90.5%) of the title adenine with mp 172-175 ° C. Elemental analysis of C24H27CIFNS 03 / 487.96% calc C 59.07 H 5.58 N 14.35 OR 9.84 discovered C 58.95 H5.75 N14.24 OR 10.10 EXAMPLE 12 6- amino-3- (3-cyclopentyloxy-4-methoxy-benzyl) hydrochloride - (1- (4-methoxybenzyloxy) -1-methyl-ethyl) -3H-purine A 6-amino-1- (3-cyclopentyloxy-4-methoxy-benzyl) -5- (2- (4-methoxybenzyloxy) - 2-methyl-propionylamino) -2-thiuracil. A solution with 2.91g (12mM) of crude 2- (4-methoxybenzyloxy) -2-methylpropionyl chloride in 9ml of THF was added over a period of 90 minutes to a stirred suspension with 3.62g (10mM) of 5, 6-diamino-l- (3-cyclopentyloxy-4-methoxy-benzyl) -2-thiouracil. After 20 hours, another 485 mg of chloride was added in 5 ml of THF in a lapse of 30 minutes. After 3 hours the solid was filtered and the solution was vaporized in vacuo to dry. The residue was dissolved in ethyl acetate, extracted with sodium bicarbonate solution and the organic phase was evaporated in vacuo to dryness. The methanol residue crystallized: 1.71g (30.1%) of amide with mp 172-184 ° C. B 3 (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-methoxybenzyloxy) -1-methyl-ethyl) -2-dioxanthine 3.30g (5.8mM) of the above amide were refluxed (A) and 2.60g of t-BuOK (23mM) in 33ml of isopropanol for 45 minutes. The solvent was removed in vacuo, the residue was dissolved in 50 ml of water, treated twice with 0.3 g of carbon, filtered, acidified with 4.5 ml of 5n HCl at pH 4.5 and neutralized with bicarbonate solution. sodium.

The solid was collected and crystallized from methanol: 2.48g (77.7%) of xanthine with mp 169 / 276-279 ° C. C 3- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-methoxybenzyloxy) -1-methyl-ethyl) -hypoxanthine A solution with 2.34 g (4.25 mM) of the aforementioned xanthine was refluxed. (B) and 2.5g of Raney-nickel (treated with 1% aqueous acetic acid) in 35ml of 1-propanol. After 2.5 hours the nickel was filtered and the solvent was evaporated in vacuo. The residue was dissolved in ethyl acetate, extracted with sodium bicarbonate solution and concentrated in vacuo to about 10 ml. Crystallization from one day to the next produced 1.29g (58.6%) of hypoxanthine with mp 156-157 ° C. D- 6-Amino-3- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-methoxybenzyloxy) -1-methyl-ethyl) -3H-purine hydrochloride. 1.14g (2.2mM) of the previous hypoxanthine © and 12ml of phosphorus oxychloride were heated to 70 ° C. for 40 minutes. Evaporation in vacuo and double repetition with toluene produced the crude 6-chloro derivative which was dissolved in 40 ml of THF and added to 12 ml of 32% aqueous ammonia solution. After supplying 5 g of liquid ammonia, the solution was heated at 60 ° C in a 450 ml pressure reactor (340 psi) for 3.5 hours. The solvent was evaporated in vacuo, the residue was dissolved in chloroform, the solution was extracted with lN NaOH and evaporated in vacuo to dryness. The residue was dissolved in methanol treated with 2.3 ml of methanolic HCl and evaporated in vacuo to dryness. The acetone residue was crystallized and suspended in water-ether. EXAMPLE 13 6-Amino-3- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-pyridylmethoxy) -1-methyl-ethyl) -3H-purine dihydrochloride. l- (3-Cyclopentyloxy-4-methoxy-benzyl) -5- (2- (4-pyridylmethoxy) -2-methyl-ethyl) propionylamino-2-thiouracil. 3.58 g (14.3 mM) of 2- (4-pyridylmethoxy-2-methyl-propionyl-chloro) hydrochloride was added to a solution of 3.61 g (10 mM) of 1- (3-cyclopentyloxy-4-methoxy-benzyl) - 5,6-diamino-2-thiuracil in 82ml of pyridine. After 48 hours the solution was heated at 50 ° C for 3 hours. 4.15g (30mM) of potassium carbonate was added and after an additional 24 hours of stirring the solid was filtered and the solution was evaporated in vacuo to dryness. The residue was suspended in 50ml of water and lOml of THF. The crystals were collected suspended in 50 ml of hot and concentrated acetone. The solid was collected at 0-5 ° C. : 3.34g (61.9%) of amide with mp 245-247 ° C. B-3- (3-cyclop-butyloxy-4-methoxy-benzyl) -8- (1- (4-pyridylmethoxy) -1-methyl-ethyl) -2-thioxanthine 3.24g (6p? M) of the above amide were refluxed (A) for 40 minutes to a solution of 2.78 g (24 mM) of t-BuOK in 32 ml of isopropanol. The solution was evaporated in vacuo to dryness, the residue was dissolved in 50 ml of water, the solution was treated twice with 0.3 g of carbon, filtered and neutralized with 4.5 ml of 5n HCl. The solid was collected, suspended in 40ml of hot methanol, concentrated to 20ml and re-collected at 0-5 ° C: 2.40g (76.7%) of xanthine with mp 210-213 / 286-288 ° C. C 3- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-pyridylmethoxy) -1-methyl-ethyl) -hypoxanthine 2.19g (4.2mM) of the above xanthine were refluxed (B) with 2.5 g of Raney-nickel (treated with aqueous acetic acid at 01%) in 30 ml of 1-propanol for 2.5 hours. The nickel was filtered and the solution was evaporated in vacuo to dryness. The residue was dissolved in 40 ml of dichloromethane, the solution was extracted with the sodium bicarbonate solution and the organic phase was evaporated in vacuo to dryness. The residue was dissolved in a 19: 1 mixture of dichloromethane and methanol, filtered through 30g of silica gel in a column, and evaporated again to dry: 1.48g (71.8%) of crude hypoxanthine. D 6-Amino- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-pyridylmethoxy) -1-methyl-ethyl) -3H-purine dihydrochloride. 1.48g (3.0mM) of crude anterior hypoxanthine © and 15ml of phosphorus oxychloride at 65-70 ° C were heated.For 40 minutes. The solution immediately acquired a violet color and was evaporated in vacuo to dryness and repeated twice with toluene. The crude chloride was dissolved in 40ml of THF and 12ml of 32% aqueous ammonia. After transfer to a 450ml pressure reactor supplemented with 50g of liquid ammonia and heated at 60 ° C for 40 hours (340psi). The mixture was evaporated in vacuo to dryness. The residue was dissolved in chloroform, the solution was extracted with ln-NaOH solution and the organic phase was evaporated in vacuo to dryness. The residue was dissolved in a 19: 1 mixture of dichloromethane and methanol and chromatographed on 30 g of silica gel in a column. EXAMPLE 14 6-Amino-8- (1-benzyloxy-1-methyl-ethyl) -3- (3, 4-dimethoxybenzyl) -3H-purine hydrochloride In analogy to Example 9, we prepare the following compounds from 5, 6-diamino-1- (3,4-dimethoxybenzyl) -2-thiuracil and 2-benzyloxy-2-methyl-propionyl chloride: A. 6-Amino-5- (2-benzyloxy-2-methyl-propionyl) - 1 (3, 4-dimethoxybenzyl) -2-thiuracil B. 8- (1-benzyloxy-1-methyl-ethyl) -3- (3,4-dimethoxybenzyl) -2-thioxanthine C. 8 (1-benzyloxy-1-methyl- ethyl) -3 (3,4-dimethoxybenzyl) -hypoxanthine with mp 164- 166 ° C D. 6-Amino-8- (bensyloxy-1-methyl-ethyl) -3 (3,4-dimethoxybenzyl) -3H purine hydrochloride With mp 184 / 190-191 ° C Elemental analysis for C24H28CIN5 03% calc C61.34 H 6.01 N 14.90 010.21% discovered C61.31 H 6.15 N 14.89 OR 10.28 EXAMPLE 15 6-Amino-3- (3-cyclopentyloxy) hydrochloride 4-methoxyl benzyl-) -8- (1- (4-fluorobenzyloxy) -1-methyl-ethyl) -3H-purine In analogy to example 9, we prepare the following compounds from l- (3-cyclopentyloxy-4-m) ethoxy-benzyl) -4,5-diamino-2-thiouracil and 2- (4-fluorobenzyloxy) -2-methyl-propionyl chloride: A 6-Amino-l (3-cyclopentioxy-4-methoxy-benzyl) -5 (2 - (4-fluorobenzyloxy) -2-methylpropionylamino) -thiouracil with mp 185-193 ° C B. 3 (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-fluorobenzyloxy) -1-methyl- ethyl) thioxanthine with mp 188-192 / 288-296 ° CC 3- (3-Cyclopentyloxy-4-methoxy-benzyl) 8- (1- (4-fluorobenzyloxy) -1-methyl-ethyl) -hypoxanthine with mp 131-134 ° CD 6 Hydrochloride of Amino-3- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1- (4-fluorobenzyloxy) -1-methylethyl) -3H purine with mp of 165-174 ° C EXAMPLE 16 Hydrochloride of 8-benzyloxymethyl-3 - (3-Cuclopentyloxy-4-methoxy-benzyl) -6-ethylamino-3H-purine. In analogy to example 9, we prepared the following compounds from benzyloxyacetyl chloride and l- (3-cyclopentyloxy-4-methoxy-benzyl) -4,5-diamino-2-thiuracil: -3- (2-cyclopentyloxy-4-methoxy) benzyl) -2-thioxanthine c A 6 Amino-5-benzyloxyacetylamino-2-thiouracil with an mp of 195-196 ° CB 8-benzyloxymethyl-3- (3-cyclopentyloxy-4-methoxy-benzyl) -2 thioxanthine with mp of 101 -103 ° CC 8-benzyloxymethyl-3- (3-cyclopentyloxy-4-methoxy-benzyl) -hypoxanthine with mp 190-194 ° CD 8-Benzyloxymethyl-3 hydrochloride (3-cyclopentyloxy-4-methoxy-benzyl) -6 -ethylamino-3H purine with mp 179 / 196-198 ° C Elemental analysis for C28 H34 CIN4 03 / 524.06% calc C 64.17 H 6.54 N 13.36 09.16% discovered C 63.91 H 6.52 N13.39 0 9.14 EXAMPLE 17 TIOSIGUANINE DERIVATIVES Following the methods described above, the following thioisoguanine derivatives of the present invention were synthesized. The chemical name and melting point are given in Table 1 below. purin-2-one 3-butyl-3,7-dihydro-6 (220) ethylamino-2-thio-2H-purin-2-246-248-one-2-butyl-8-cyclopropyl-3, 7- 226-228 dihydro-6 -ethylamino-2-thio-2H-purin-2-one 6-ethylamino-3,7-dihydro-3,747-251 propyl-2-thio-2H-purn-2-one 8-cyclopropyl-6-ethylamino-3, 7- 238-239 dihydro-3-propyl-2-thio-2H-purin-2-one 8-cyclopropyl-3-cyclopropyl-247-249 methyl-6-ethylamino-3,7-dihydro-2-thio-2H-purin-2- ona 3-benzyl-6-ethylamino-3, 7-254-257 dihydro-2-thio-2H-purin-2-one 8-cyclopropy-6- 208-226 cyclopropylamino-3-propyl-dec 3, 7. dihydro-2-thio -2H-purin-2-one 3- ((2-methyl) (butyl) -6- (2- (piperazin-1-yl) ethylamino-3-cyclohexymethyl-3,7-dihydro-295-300 EXAMPLE 18 ELEMENTAL ANALYSIS OF THIOISOGUANINE DERIVATIVES A Elemental analysis of 6-butylamino-8-cyclo-propyl-3,7-dihydro-propyl-2H-purine-2-thione. Cale C58.98 H 7.59 N 22.93 Discovered C58.99 H 7.52 N 22.92 B 3-cyclopropylmethyl) -3,7-dihydro-8-isopropyl-6-propylamino-2H-purine-2-thione Melting point: 208-210 ° C Elemental analysis Cale C 62.26 H 8.01 N 24.20 Discovered C 62.34 H8- 06 N23.89 EXAMPLE 19 INHIBITION OF PDE IV BY COMPOUNDS OF TIOSIGUANINE The PDE IV inhibitory activity of some of the above thioisoguanine compounds were determined according to the procedures that are specified below. The results are shown in Table 2. Protocol for isolating the Fosfodiesterase type IV enzyme PDE type IV is isolated from smooth muscle tracheal bobino using a procedure similar to that previously described by Silver.P.J; Hamel, LT; Perrone, M.H Bentley, RG Bushover, CR; Evans, DB: Eur J Paharmacol 150: 180 (1). Briefly, smooth muscle of trachea coil is milled and homogenized using a 10-volume polytron of an extraction buffer containing 10mM tris-acetate (Ph 7.5), 2mM magnesium chloride, 1mM dithiothreitol, and 2000 units / ml aprotinin. . These and the subsequent procedures are carried out at 0 to 4 ° C. The homogenate is subjected to sounds and then centrifuged at 48,000xg for 30 minutes. The resulting supernatant is applied to a DEAE Trisacryl M column previously equilibrated with sodium acetate and dithiothreitol. After applying the sample, the column is washed with sodium acetate / dithiothreitol, after which different forms of PDE are diluted from the column using a linear gradient Tris-HCl / NaCl. Fractions containing type IV PDE are collected, dialysed and concentrated to 14% of the original volume. The concentrated fractions are diluted to 50% with ethylene glycol and stored at minus -20 ° C.

Measurement of PDE Activity IV Pole Enzyme activity is evaluated by measuring hydrolysis of (H3) cyclic AMP, as described by Thomson, WJ, Teraski, W.L, Epstein, P.N, Strada, SJ; Adv Ciclic Nucleotide Res. 10: 69.1979. The cyclic AMP concentration used in this assay is 0.2uM, which approximates the Km value. The protein concentration is adjusted to ensure that no more than 15% of the available substrate is hydrolyzed during the incubation period. All test compounds are dissolved in dimethyl sulfoxide (final concentration 2.5%). This concentration of dimethyl sulfoxide inhibits the activity of enzymes by approximately 10%.

EXAMPLE 21 ELEMENTAL ANALYSIS OF ADENINS It was performed on elemental analysis of some of the compounds described in the previous table. The results appear below.

Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20, HCl) Cale. C 53.29 H6.80 N 25.90 O 0.53 Give. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20, HCl) Cale. C 53.29 H6.80 N 25.90 O 0.53 Give. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20, HCl) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride '99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H.7.01 N 26.01 O 0.34 Elemental analysis for Hydrochloride of 8 cc oprop o- -e- -e am no-pur Na 99% + l% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H 0; HC) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 O 0.34 Elemental analysis for 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine hydrochloride 99% + 1% (H20; HC1) Cale. C 53.29 H6.80 N 25.90 O 0.53 Desc. C 52.97 H 7.01 N 26.01 OR 0.34 EXAMPLE 22-INHIBITION OF IV PDE BY ADENIN COMPOUNDS The inhibitory effect of PDE IV of some of the aforementioned compounds was examined according to the previous methods described. The results appear in the following table 4.

EXAMPLE 23 Dithioxanthine derivatives of the present invention were manufactured and analyzed. The results appear in the following Table 5.

EXAMPLE 24 - PHARMACOLOGICAL TESTS Isolated Guinea Pig Trap The test compound was dissolved in dimethyl sulfoxide. Tracheal muscle isolated from guinea pig was mounted in a bath containing Krebs solution maintained at 37.5 ° C and with carbógeno bubbles (95% 02, 5% C02). Voltage changes were recorded isometrically using force displacement transducers in conjunction with potentiometric registers. The ability of test compounds to relax airway muscles by constructing cumulative concentration effect curves was investigated. Each concentration of the test compound was allowed to equilibrate with the tissue for 5 minutes before an increase in concentration was made (tenfold). In each tissue, the test compound was compared with theophylline as a rule. Compound In vitro activity Theophylline 1 8-cyclopropyl-3-ethyl-6-ethylamino-3H-purine 43.7 6-ethylamino-3-hexyl-3H-purine 25.6 3-benzyl-6-ethylamino-3H-purine 18.5 EXAMPLE 25 IN VIVO STUDIES (i) The effect of test compounds on a model of hyperresponsiveness (BHR) and cellular infiltration in the guinea pig induced by ovalbumin was studied (see, for example, Morley et al., Agents and Actions, Supplement , 1988, 23, 187).

The test compound was administered at doses of 0.5 and 1.0 ml mg / kg / day subcutaneously for 7 days with an osmotic mini-pump. Theophylline and salbutamol were used as standard at concentrations of 1 mg / kg / day. Response curves to histamine (1-50ug / kg) were constructed for each animal. Figures 1-2 show the results obtained, (ii) Sensitization and challenge procedure: i.p. to Dunkin Hartley male guinea pigs (Charles River) (200-250g) with ovalbumin (OVA) (0.5 ml / animal; 20 ug OVA in Al (OH) 3 (wet gel), this preparation produced a stable injectable suspension containing excess of Al (OH) 3. Substitute animals were injected with 0.5 ml Al (OH) 3 alone After a period of 18 to 21 days, the animals were exposed to an OVA aerosol (100 ug / ml) during a time in an exposure chamber (iii) Bronchoalveolar lavage: the animals were anesthetized 24 hours after exposure to the aerosol, with urethane (25% / v, 7 ml / kg, ip) and the trachea cannulated. performed bronchoalveolar lavage (BAL) by instilling 5 ml of sterile saline into the lungs through the tracheal cannula and removing the fluid immediately, the fluid was reinjected and the procedure was repeated 5 times in total. recovery of between 40 and 60% of BAL fluid from the lungs of the guinea pig. The use of an improved Neubauer haemocytometer is used. Cytospin preparations were prepared using a Shandon Cytospin 2 centrifuge. Two drops of BAL fluid were added to each cup of cytospin and the samples were centrifuged for 1 minute at 1,300 rpm. Slides were fixed in acetone and stained with hemotoxylin and carotrophic chromotrope according to the method described by Lendrum (Lendrum 1944). Differential cell biometries were performed on each slide counting 200 cells randomly, cell types were classified as neutrophils, eosinophils and mononuclear cells according to a conventional morphological criterion. Cells were counted blindly. The results are expressed as number of neutrophils, eosinophils and mononuclear cells per ml of BAL fluid. The remaining BAL fluid was centrifuged (10 min, lOOOg) and the resulting cells and supernatants were divided without cells, and frozen for later assays. The compounds were solubilized in DMSO or saline administered intraperitoneally at a dose of 5 mg / kg one hour before challenge with ovalbumin. The results are given in Table 6.

EXAMPLE 26 - SYNTHESIS AND ASSAY OF ADENNO COMPOUND Following the above-specified methods, the following adenine derivatives of the present invention were synthesized and assays of PDE IV inhibitory activity were made, as specified in the following Table 7.

While the present invention was illustrated with respect to the production and use of particular compounds, it is apparent that various variations and modifications may be made to the present invention without departing from the spirit and scope of the present invention.

Claims

CLAIMS A compound of the formula (I) (i) and pharmaceutically acceptable salts thereof, wherein: R3, R6a, R6b and R8 are selected from the group consisting of A and B, wherein A is selected from the group consisting of: hydrogen; Cl-10 alkyl branched or unbranched and which is optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H, = 0 and benzyloxy , wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy; C2-10 branched or unbranched alkenyl, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkylolamine, Cl-10 dialkylamino, carbamyl , amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) lcoxy, nitro, trihalocarbon, benzyloxy , heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) lkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) to cox, heteroar lox, heteroar ( Cl-10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is substituted optionally with Cl-10 alkyl, and wherein the alkyl half of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted at a the alkyl half with hydroxy, heterocyclyl which is optionally substituted in the carbons or nitrogens of the ring or with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2 , phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy. B is selected from the group consisting of: branched or unbranched Cl-10 alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and alkylamino; wherein the substituents are optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo; wherein Cl-10 alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl and C3-12 cycloalkyl; wherein the C3-10 cycloalkyl further substituted may be optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2 , C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, halo (Cl-10) alkyl y = 0; C3-12 cycloalkyl (Cl-10) alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, = N0H, = N0C0NH2 and C02H; aryl which is optionally substituted with substituents 1-3 selected from the group consisting of carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylamido, Cl-10 acylamino and Cl-10 alkylsulfunylamino; wherein the substituted aryl may further be substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino , carbamyl, amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, hydroxy (Cl-10) alkoxy, nitro, benzyloxy, heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroar (Cl-10) alkyloxy, heterocyclyloxy, CI-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl moiety of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy, and the ar (Cl-4) alkyl is furthermore optionally substituted with substituents selected from the group consisting of halogen, hydroxy, trihalocarbon, Cl- Alkyl, C3-12 cycloalkyl, Cl-10 alkoxy and C3-12 cycloalkoxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of carbamyl, Cl-10 acylamino and Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; wherein the substituted heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, amido, • Cl-10 alkylolamido,. Cl-10 dialkylamido, C = NOH, C = N0C0NH2, phenyl and benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 acylamino, Cl-10 alkylsulfonylamino and Cl-10 alkyl, wherein the Cl-10 alkyl is substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; wherein the (C 1 -C 4) heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkoxy, C 3-12 cycloalkoxy, NH 2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkylolamido, Cl-10 Dialkylolamido; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy and C3-12 cycloalkoxy; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy; and provided that at least one of R3, R6a, R6b and R8 is B.
2. The compound of claim 1, wherein R3 is A and is ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 chosen from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with substituents 1-3 selected from the group consisting of OH, halogen, Cl -10 alkoxy and C3-12 cycloalkoxy.
3. The compound of claim 2, wherein the aralkyl is benzyl.
4. The compound of claim 3, wherein the aryl moiety of the benzyl is substituted with substituents 1-3 selected from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy and CF3.
5. The compound of claim 4, wherein the benzyl is substituted with cyclopentyloxy and methoxy.
6. The compound of claim 2, wherein R6a is A and is hydrogen.
7. The compound of claims 1-6, wherein R6b is A and is selected from the group consisting of: hydrogen; Cl-8 alkyl which is branched or unbranched and is optionally substituted by OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; and C3-8 cycloalkyl which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = NOH, = N0C0NH2, C02H or = 0.
8. The compound of claims 1-7, wherein R8 is B and is selected from the group consisting of: Cl-10 branched or unbranched alkyl and substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl , pyridylmethoxy, thienylmethoxy and alkylamino, wherein substituents optionally substituted with substituents 1-3 are selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo. A compound of the formula (II) (H) and pharmaceutically acceptable salts thereof, wherein: R3, R6a, R6b and R8 are selected from the group consisting of A and B, wherein A is selected from the group consisting of: hydrogen; Cl-10 alkyl branched or unbranched and which is optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = NOCONH2, C02H, = 0 and benzyloxy , wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy; C2-10 branched or unbranched alkenyl, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = NOH, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkylolamine, Cl-10 dialkylamino, carbamyl , amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = N0H, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) alkoxy, nitro, trihalocarbon, benzyloxy , heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroary (Cl-) 10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and where the alkyl half of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted in one position in half alkyl with hydroxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens, of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3-12 cycloalkyl, OH, halogen, Cl- 10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy. B is selected from the group consisting of: branched or unbranched Cl-10 alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and alkylamino; wherein the substituents are optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo; wherein Cl-10 alkyl is further optionally substituted with i-3 substituents selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl and C3-12 cycloalkyl; wherein the C3-10 cycloalkyl further substituted may be optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2 , C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, halo (Cl-10) alkyl y = 0; C3-12 cycloalkyl (Cl-10) alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, = N0H, = N0C0NH2 and C02H; aryl which is optionally substituted with substituents 1-3 selected from the group consisting of carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylamido, Cl-10 acylamino and Cl-10 alkylsulfunylamino; wherein the substituted aryl may further be substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino , carbamyl, amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, hydroxy (Cl-10) alkoxy, nitro, benzyloxy, heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroar (Cl-10) alkyloxy, heterocyclyloxy, CI-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl moiety of ar (Cl-4) ) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy, and the ar (Cl-4) alkyl is further substituted optionally with substituents selected from the group consisting of halogen, hydroxy, trihalocarbon, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy and C3-12 cycloalkoxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of carbamyl, Cl-10 acylamino and Cl-10 alkylsulfonylamino, C = NOH, C = NOCONH2, phenyl or benzyl; wherein the substituted heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, C = NOH, C = N0C0NH2, phenyl and benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 acylamino, Cl-10 alkylsulfonylamino and Cl-10 alkyl, wherein the Cl-10 alkyl is substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; wherein the (C 1 -C 4) heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkoxy, C 3-12 cycloalkoxy, NH 2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkylolamido, Cl-10 Dialkylolamido; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy and C3-12 cycloalkoxy; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy; and provided that at least one of R3, R6a, R6b and R8 is B. 10. The compound of claim 9, wherein R3 is A and is y is ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with substituents 1-3 selected from the group consisting of OH, halogen , Cl-10 alkoxy and C3-12 cycloalkoxy. 11. The compound of claim 10, wherein the aralkyl is benzyl. The compound of claim 11, wherein the aryl moiety of the benzyl is substituted with substituents 1-3 selected from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy or CF3. The compound of claim 12, wherein the benzyl is substituted with cyclopentyloxy and methoxy. The compound of claim 9, wherein R6a is A and is hydrogen. 15. The compound of claim 9, wherein R6b is A and is selected from the group consisting of: hydrogen; Cl-8 alkyl which is branched or unbranched and is optionally substituted by OH, alkoxy, cycloalkoxy, halogen, = NOH, = NOCONH2, C02H or = 0; and C3-8 cycloalkyl which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = NOH, = NOCONH2, C02H or = 0. 16. The compound of claims 9-15, wherein R8 is B and is selected from the group consisting of: Cl-10 branched or unbranched alkyl and substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy , thienylmethoxy and alkylamino, wherein substituents optionally substituted with substituents 1-3 are selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo. 17. A compound of the formula (III) (III) and pharmaceutically acceptable salts thereof, wherein R3, R6a, R6b and R8 are selected from the group consisting of A and B, wherein A is selected from the group consisting of: hydrogen; Cl-10 branched or unbranched alkyl and optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H, = 0 and benzyloxy, wherein the benzyloxy is optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy; C2-10 branched or unbranched alkenyl, optionally substituted with substituents 1-3 selected from the group consisting of OH, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = N0H, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = NOH, = NOCONH2, C02H or = 0; C3-10 'cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl , = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen , halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; aryl which is optionally substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, NH2, Cl-10 alkylolamine, Cl-10 dialkylamino, carbamyl , amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, halogen, hydroxy, hydroxy (Cl-10) alkoxy, nitro, trihalocarbon, benzyloxy , heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) alkoxy, heteroaryloxy, heteroary (Cl-) 10) alkyloxy, heterocyclyloxy, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl half of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted in one position in half alkyl with hydroxy, heterocyclyl which is optionally substituted on the carbons or nitrogens of the an with substituted substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkaloamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C 3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkyloamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2 , phenyl or benzyl, and wherein the alkyl moiety is optionally substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy, C3-12 cycloalkoxy or oxo; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy. B is selected from the group consisting of: branched or unbranched Cl-10 alkyl and which is optionally substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, ethylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and at least one; They are optionally substituted with substituents 1-3 selected from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo; wherein Cl-10 alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; C3-10 cycloalkyl optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl and C3-12 cycloalkyl; wherein the C3-10 cycloalkyl further substituted may be optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2 , C02H or = 0; C3-10 cycloalkenyl which is optionally substituted with substituents 1-3 of the group consisting of OH, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy, halogen, halo (Cl-10) alkyl, = N0H, = N0C0NH2, C02H or = 0; C3-12 cycloalkyl (Cl-10) alkyl wherein the cycloalkyl portion is optionally substituted with substituents 1-3 of the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, halo (Cl-10) alkyl y = 0; C3-12 cycloalkyl (Cl-10) alkyl is further optionally substituted with substituents 1-3 selected from the group consisting of OH, Cl-10 alkoxy, C3-12 cycloalkoxy, = N0H, = N0C0NH2 and C02H; aryl which is optionally substituted with substituents 1-3 selected from the group consisting of carbamyl, amido, Cl-10 alkylolamido, Cl-10 dialkylamido, Cl-10 acylamino and Cl-10 alkylsulfunylamino; wherein the substituted aryl may further be substituted with substituents selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino , carbamyl, amido, Cl-10 alkylolamido, Cl-10 alkylolamido, Cl-10 dialkylolamido, Cl-10 acylamino, Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of carboxy, Cl-10 alkylcarboxy, hydroxy (Cl-10) alkoxy, nitro, benzyloxy, heterocyclyl, Cl-10 cycloalkyl (C3-12) alkyloxy, ar (Cl-10) alkyloxy, aryloxy, amino (Cl-10) alkoxy, Cl-10 (alkylamino (Cl-10) lcoxy, heteroaryloxy, heteroar (Cl-10) alkyloxy, heterocyclyloxy, CI-10 alkoxy or C3-12 cycloalkoxy, wherein the alkoxy and cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy and the heterocyclyl is optionally substituted with Cl-10 alkyl, and wherein the alkyl moiety of ar (Cl-4) alkyl is optionally substituted with OH, halogen, Cl-10 alkoxy and C3-12 cycloalkoxy wherein the alkoxy and the cycloalkoxy are optionally substituted at one position on the alkyl moiety with hydroxy; and the ar (Cl-4) alkyl is further optionally substituted with substituents selected from the group consisting of halogen, hydroxy, trihalocarbon, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy and C3-12 cycloalkoxy; heterocyclyl which is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of carbamyl, Cl-10 acylamino and Cl-10 alkylsulfonylamino, C = NOH, C = N0C0NH2, phenyl or benzyl; wherein the substituted heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, OH, halogen, Cl-10 alkoxy, C3-12 cycloalkoxy, NH2, Cl-10 alkylamino, Cl-10 dialkylamino, amido, Cl-10 alkylolamido, Cl-10 dialkylolamido, C = NOH, C = NOCONH2, phenyl and benzyl; (C 1 -C 4) heterocyclyl alkyl, wherein the heterocyclyl moiety is optionally substituted on the carbons or nitrogens of the ring with substituents 1-3 selected from the group consisting of Cl-10 acylamino, Cl-10 alkylsulfonylamino and Cl-10 alkyl, wherein the Cl-10 alkyl is substituted with OH, Cl-10 alkoxy, C3-12 cycloalkoxy, C3-12 cycloalkyl, halogen or halo (Cl-10) alkyl; wherein the (C 1 -C 4) heterocyclyl is further optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkoxy, C 3-12 cycloalkoxy, NH 2, Cl-10 alkylamino, Cl-10 dialkylamino, carbamyl, amido, Cl-10 Alkylolamido, Cl-10 Dialkylolamido; heteroaryl, optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro, CF3, Cl-10 alkoxy and C3-12 cycloalkoxy; and heteroaryl (Cl-4) alkyl, wherein the heteroaryl moiety is optionally substituted with substituents 1-3 selected from the group consisting of Cl-10 alkyl, C3-12 cycloalkyl, halogen, nitro trihalocarbon, Cl-10 alkoxy or C3-12 cycloalkoxy; and provided that at least one of R3, R6a, R6b and R8 is B. 18. The compound of claim 17, wherein R3 is A and is ar (Cl-4) alkyl, wherein the aryl moiety is optionally substituted with substituents 1-3 chosen from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy or CF3, and wherein the alkyl moiety is optionally substituted with substituents 1-3 selected from the group consisting of OH, halogen, Cl -10 alkoxy and C3-12 cycloalkoxy. 19. The compound of claim 18, wherein the aralkyl is benzyl. The compound of claim 19, wherein the aryl moiety of the benzyl is substituted with substituents 1-3 selected from the group consisting of halogen, nitro, Cl-10 alkoxy, C3-12 cycloalkoxy and CF3. 21. The compound of claim 20, wherein the benzyl is substituted with cyclopetoxy and methoxy. 22. The compound of claim 17, wherein R6a is A and is hydrogen. 23. The compound of claims 17-22, wherein R6b is A and is selected from the group consisting of: hydrogen; Cl-8 alkyl which is branched or unbranched and is optionally substituted by OH, alkoxy, cycloalkoxy, halogen, = NOH, = N0C0NH2, C02H or = 0; and C3-8 cycloalkyl which is optionally substituted with OH, alkoxy, cycloalkoxy, halogen, haloalkyl, = N0H, = N0C0NH2, C02H or = 0. The compound of claims 17-23, wherein R 8 is B and is Cl-10 branched or unbranched alkyl and substituted with substituents 1-3 selected from the group consisting of benzyloxy, methylenedioxybenzyloxy, methylenedioxyphenyl, pyridylmethoxy, thienylmethoxy and alkylamino, wherein substituents optionally substituted with substituents 1-3 are chosen from the group consisting of halogen, Cl-10 alkyl, C3-12 cycloalkyl, Cl-10 alkoxy, C3-12 cycloalkoxy and oxo. 25. A compound of claim 1, selected from the group consisting of 6-amino-3- (3-cyclopentyloxy-4-methoxy-benzyl) -8- (1-methyletenyl) -3H-purine; 6-amino-8-benzylozimethyl-3- (3-cyclopentyloxy-4-methoxy-benzyl) -3H-purine; 6-amino-8 - [(1-benzyloxy-1-methyl) ethyl] -3-t (3-cyclopentyloxy-4-methoxy) benzyl] -3H-purine; 6-amino-3- (3-cyclopentyloxy-4-methoxybenzyl) -8- [1- (4-flurobenzyloxy) -1-methyl-ethyl] -3H-purine; [8- (1-benzyloxy-1-methyl) ethyl] 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-3H-purine; 6-amino-8-benzyloxymethyl-3- (3-cyclopentyloxy-4-methoxy-benzyl) -3H-purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-ethylamino-3- (3-butoxy-4-methoxy-benzyl) -8-isopropyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1-hydroxy-1-methyl-ethyl] -3H-purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-d- (1-methyl-ethenyl) -3H-purine; 6-ethylamino-2- (3, 4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-amino-3- ( 3-cyclopentyloxy-4-methoxybenzyl) -3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-dimethylamino-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (3-hydroxycyclopentyloxy ) -4-methoxybenzyl)] -8- (1-hydroxy-l-methylethyl) -3H-purine; 6-ethylamino-3- (3,4-methylenedioxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8-isopropyl-3H-purine; 3- (3-Benzyloxy-4-methoxy-benzyl) -6-ethylamino-8-isopropyl-3H-purine; 6-amino-3- (3,4-dimethoxybenzyl) -8- [1- (4-fluorobenzyloxy) -1-methylethyl] -3H-purine;; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-amino-8-isopropyl-3H-purine; 6- (amino-8- (1-benzyloxy-1-methylethyl) -3- (3, 4-dimethoxybenzyl) -3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (3-cyclopentyloxy) 4-methoxybenzylamino) -8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- (4-methoxybenzyl) -3H-purine; 3- (3- ((3-hydroxy) cyclopentyloxy) -4-methoxybenzyl ) -6-ethylamino-8-isopropyl-3H-purine: 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (N-benzoyl-N-ethylamino) -8-isopropyl-3H-purine; -chlorobenzyl-6-cyclopropylamino-8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- [(4-methoxy-3- (4-hydroxybutoxy)) benzyl] -3H-purine; 6-ethylamino- 3- (4-flurobenzyl) -8-isopropyl-3H-purine; 3- (3-chlorobenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- [3- (3-hydroxy-cyclopentyloxy) -4 -methoxy-benzyl] -8- (1-hydroxy-l-methyl-ethyl) -3H-purine; 3- [3- (3-hydroxy) -cyclopentyloxy))] -4-methoxy) -benzyl) -6-ethylamino- 8-isopropyl-3H-purine; 6-amino-3- (3,4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [3-cyclopentylmethoxy-4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-ethylamino-3- (3-hydroxy-4-methoxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2, 2-dimethylamino-ethoxy-4-methoxy)] -8-isopropyl-3H-purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1-methyl-1-hydroxy) ethyl] -3H-purine; 6-amino-3- [(3-benzyloxy-4-methoxy) benzyl] -8 - [(1-benzyloxy-1-methyl) ethyl] -3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- ((2,2,2-trifluoroethyl) amino-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2,2,2) azabicyclooctan-3-yloxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-3- (3,4-dimethioxybenzyl) -8- (1-methylethyl) -3H-purine; 6-amino-8-isopropyl-3- [(4-methoxy-3 - ([(4-hydroxybutoxy)) benzyl] -3H-purine; 3- [2- (4-chlorophenyl) -ethyl] -6-ethylamino -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6- ((1-hydroxy) -cyclopentylamino) -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopentylamino-8- isopropyl-3H-purine; 6-amino-3 (3,4-methylenedioxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [(exo-8-methyl-8-azabicyclo) (3.2.1 ) -octan-3-yl-oxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-3- ((3-benzyloxy-4-methoxy) -bezyl) -8-isopropyl- 3H-purine; 3- (4-chlorophenyl) -6-ethylamino-8-isopropyl-3H-purine; 6-ethylamino-3- [(3-hydroxy-4-methoxy) benzyl] -8- [(1-hydroxy -l-methyl) ethyl-3H-purine; 6-ethylamino-3- [(3-pyridin-4-yl-methoxy) N-oxide-4-ethoxy] -8-isopropyl-3H-purine; 3- [3-cyclohexanil 4-oxy-4-methoxy-benzyl] -6-ethylamino-8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -2,6-di (ethylamino) -8-isopropyl-3H-purine; amino-3- (3-hydroxy-4-methoxy) -benzyl) -8-isopropyl-3H-purine; 6-amino-3- [3- (4-hydroxyproxy-4-methoxy) benzyl] -8- (1-hydroxy-1-methylethyl) -3H-purine hydrochloride; 6-amino-3- (4-chlorobenzyl) -8-isopropyl-3H-purine; 6-amino-3-cyclopentylmethyl-8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- [3- (pyridin-4-yl-methoxy) -4-methoxy-benzyl] -3H-purine; 6-ethylamino-3- (l-oxopyridin-4-yl-methyl) -8-isopropyl-3H-purine; 6-amino-3- [(3-hydroxy-4-methoxy) benzyl)]] -8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (2-methoxy) benzyloxy-1-methyl) ethyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (3-methoxy) benzyloxy-1-methyl) ethyl-3H-purine; 6-amino-3- [(3,4-dimethoxy) benzyl] -8 - [(1- (4-methyl) benzyloxy-1-methyl) ethyl] -3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (4-chloro) benzyloxy-1-methyl) ethyl] -3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (2-fluoro) -enzyloxy-1-methyl) ethyl] -3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (3-fluoro) benzyloxy-1-methyl) ethyl] -3H-purine; 6- (3-fluoro) benzyloxyamino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (3-fluoro) benzyloxy-1-methyl) ethyl] -3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (3,5-dimethoxy) benzyloxy-1-methyl) ethyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (3,4-fluoro) benzyloxy-1-methyl) ethyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(3,4-methylenedioxy) benzyloxy-1-methyl) ethyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(2-thienylmethoxy-1-methyl) ethyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(3-thienylmethoxy-1-ethyl) ethyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1- (1-oxo-octyl) amino-1-methyl) ethyl-3H-purine; 6-amino-3- (3,4-methylenedioxybenzyl) -8 - [(1- (4-fluorobenzyloxy) -l-methyl-ethyl-3H-purine; 6-amino-8-benzyloxymethyl-3- (3-cyclopentyloxy -4-methoxy-benzyl) -3H-purine and pharmaceutically acceptable salts thereof 26. A compound selected from the group consisting of 3-ethyl-6-ethylamino-8- ((3-cyclopentyloxy-4-hydroxy) benzyl) -3H-purine; 3- [3- (3-trimethylsilylethoxymethoxy) cyclopentyloxy-4-methoxy) benzyl) -6-ethylamino-8-isopropyl-3H-purine; 6-Ethylamino-3- [3- (furan-2-yl-methoxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (3-hydroxycyclopentyloxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-3- [3- (3-hydroxycyclopentyloxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -6-ethylamino-8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-Ethylamino-3- (3-butoxy-4-methoxy-benzyl) -8-isopropyl-3H-purine; 6-amino-3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8 - [(1-hydroxy-1-methyl) ethyl] -3H-purine; 6-ethylamino-2- (3,4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-amino-3- (3-cyclopentyloxy-4-methoxybenzyl) -3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-dimethylamino-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (3-hydroxycyclopentyloxy) -4-methoxybenzyl)] -8- (l-hydroxy-l-methylethyl-3H-purine; 6-ethylamino-9 - [(3-cyclopentyloxy-4-) metopxy) benzyl] -8-isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6-amino-8-isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6 - '(3-cyclopentyloxy-4-methoxybenzylamino) -8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- (4-methoxybenzyl) -3H-purine; 3- (3- ((3-hydroxy ) cyclopentyloxy) -4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- (N-benzoyl-N-ethylamino) -8-isopropyl-3H -purine; 3- (4-chlorobenzyl) -6-cyclopropylamino-8-isopropyl-3H-purine; 6-ethylamino-8-isopropyl-3- [(4-methoxy-3- (4-hydroxybutoxy)) benzyl] - 3H-purine; 6-ethylamino-3- (4-fluorobenzyl) -8-isopropyl-3H-purine; 3- (3-chlorobenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- [3- ( 3-hydroxy-cyclopentyloxy) -4-methoxy-benzyl] -8- (1-hydroxy-1-methyl-ethyl) -3H-purine; 3- [3- (3-hydroxy) -cyclopentyloxy)] - -methoxy) -benzyl ) - 6-ethyl amino-8-isopropyl-3H-purine; 6-amino-3- (3,4-dimethoxybenzyl) -8-isopropyl-3H-purine; 6-ethylamino-3- [3-cyclopentylmethoxy-4-methoxy-benzyl] -8-isopropyl-3H-purine; 6- ethylamino-3- (3-hydroxy-4-methoxybenzyl-8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2, 2-dimethylamino-ethoxy-4-methoxy)] -8- isopropyl-3H -purine; 3- [(3-cyclopentyloxy-4-methoxy) benzyl] -8- [(1-methyl-1-hydroxy) ethyl] -6-ethylamino-3H-purine; 3- (3-cyclopentyloxy-4-methoxybenzyl) -6- ((2,2, 2-trifluoroethyl) amino) -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (2, 2, 2) -azabicyclooctane-3-yloxy) -4-methoxy] -8-isopropyl-3H-purine; 6-ethylamino-3- [3- (l-methylpiperidin-4-yl-methoxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 6-amino-8-isopropyl-3- [(4-methoxy-3- ([(4-hydroxybutoxy)) benzyl] -3H-purine; 3- [2- (4-chlorophenyl) -ethyl] -6-ethylamino -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6- ((1-hydroxy) -cyclopentylamino) -8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -6-cyclopentylamino-8- isopropyl-3H-purine; 6-amino-3 (3,4-methylenedioxybenzyl-8-isopro-yl-3H-purine; 6-ethylamino-3- [(exo-8-methyl-8-azabicyclo (3.2, 1) -octan-3-yl-oxy) -4-methoxy-benzyl] -8-isopropyl-3H-purine; 3- (4-chlorophenyl) -6-ethylamino-8-isopropyl-3H-purine; 6-ethylamino -3- [(3-hydroxy-4-methoxy) benzyl] -8 - [(1-hydroxy-l-methyl) ethyl] -3H-purine; 6-ethylamino-3- [(3-pyridin-4-yl -methoxy) N-oxide-4-methoxy] -8-isopropyl-3H-purine; 3- [3-cyclohexanyl-4-oxy-4-methoxy-benzyl] -6-ethylamino-8-isopropyl-3H-purine; 3- (4-chlorobenzyl) -2,6-di (ethylamino) -8-isopropyl-3H-purine; 6-amino-3- (3-hydroxy-4-methoxy) -benzyl) -8-isopropyl-3H- purine; 6-amino-3- [3- (4-hydroxybutoxy-4-methoxy) benzyl] -8- (1-hydroxy-1-methylethyl) -3H-purine; 6-amino-3- (4-chloroben zil) -8-isopropyl-3H-purine; 6-amino-3-cyclopentylethyl-8-isopropyl-3H-purine; 8-cyclopropyl-3-methyl-6-ethylamino-3H-purine; 6-ethylamino-8-isopropyl-3- [3- (pyridin-4-yl-methoxy) -4-methoxy-benzyl] -3H-purine; 6-ethylamino-3- (l-oxopyridin-4-yl-methyl) 8-isopropyl-3H-purine; and 6-amino-3- [(3-hydroxy-4-methoxy) benzyl)]] -8- [(1-hydroxy-1-methyl) ethyl] -3H-purine; 3- (3-COOmethyl-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-piperadine-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-COOH-4-methoxybenzyl) -6-ethylamino-8-isopropyl-3H-purine; 3- (3-pyrrole-benzyl) -6-ethylamino-8-isopropyl-3H-purine; 3-Butyl-6-pentylamino-8-isopropyl-3H-purine; 3-butyl-6-cyclopentylamino-8-cyclopropyl-3H-purine; 3-Butyl-6-dimethylamino-8-cyclopropyl-3H-purine and its pharmaceutically acceptable salts. 27. A method for selectively performing PDE IV inhibition, compared to PDE III inhibition, in a patient suffering from a disease selected from the group consisting of asthma, allergies, inflammation, depression, Alzheimer's disease, vascular dementia, multiple dementia. infarction, a disease caused by the Human Immunodeficiency Virus and disease states associated with physiological levels abnormally to ecstasy ns ama or as, in the method comprises the administration of a compound of claims 1 to 26. 28. A A pharmaceutical composition comprising a compound of claims 1 to 26 and a pharmaceutically acceptable excipient.