MX2007001557A

MX2007001557A - Tricyclic delta- opioid modulators

Info

Publication number: MX2007001557A
Application number: MXMX/A/2007/001557A
Authority: MX
Inventors: James J Mcnally; Li Liu; Scott L Dax; Bart Decorte; Mark Mcdonnell
Original assignee: Janssen Pharmaceutica Nv
Priority date: 2004-08-05
Filing date: 2007-02-06
Publication date: 2008-10-03

Abstract

The invention is directed to delta opioid receptor modulators. More specifically, the invention relates to tricyclicÎ´-opioid modulators, of formula (I). Pharmaceutical and veterinary compositions and methods of treating mild to severe pain and various diseases using compounds of the invention are also described.

Description

TRICICLIC DELTA-OPIOID MODULATORS INTERREFERENCE WITH RELATED REQUESTS This application claims the priority of U.S. Provisional Patent Application No. 60 / 599,131, filed August 5, 2004, which is incorporated herein by reference in its entirety.

DECLARATION ON RESEARCH OR DEVELOPMENT WITH FEDERAL SPONSORSHIP The research and development of the invention described below were not federally sponsored.

BACKGROUND OF THE INVENTION The term "opiate" has been used to designate pharmacologically active alkaloids derived from opium, for example, morphine, codeine and many semisynthetic congeners of morphine. After the isolation of peptide compounds with actions similar to morphine, the term opioid was introduced to refer generically to all drugs with actions similar to morphine. Among the opioids included are several peptides that exhibit activity similar to morphine, such as endorphins, enkephalins and dynorphins. However, some sources use the term "opiate" in a generic sense and, in such a context, opiate and opioid are interchangeable. Additionally, the term opioid has been used to refer to antagonists of drugs similar to morphine, and also to characterize receptors or binding sites that combine with such agents. Opioids are generally used as analgesics, but they can also have many other pharmacological effects. Morphine and related opioids produce some of their main effects on the central nervous system and the digestive system. The effects are diverse, including analgesia, drowsiness, mood swings, respiratory depression, dizziness, obtundation, dysphoria, pruritus, increased pressure in the biliary tract, decreased gastrointestinal motility, nausea, vomiting and alterations of the endocrine systems and nervous self When therapeutic doses of morphine are administered to patients with pain, they report that the pain is less intense, less bothersome or disappears completely. In addition to experiencing pain relief, some patients experience euphoria. However, when morphine is administered at a selected pain-relieving dose to an individual without pain, the experience is not always pleasurable; Nausea is common and vomiting may also occur. Drowsiness, inability to concentrate, difficulty remembering, apathy, decreased physical activity, decreased visual acuity and lethargy may ensue. Opioid receptors can be linked with two different classes of opioid molecules: opioid peptides (for example enkephalins, dynorphins and endorphins) and alkaloid opiates (for example morphine, etorphine, diprenorphine and naloxone). After the initial exposure of opiate binding sites (Pert, CB and Snyder, SH, Science (1973) 179: 101 1-1014), the differential pharmacological and physiological effects of both opioid and opiate peptides analogues alkaloids, served to delineate the multiple opioid receptors. Therefore, three types of opioid, anatomically and pharmacologically distinct receptors have been described: delta, kappa and mu. In addition, each type is believed to have subtypes (Wollemann, M., J Neurochem (1990) 54: 1095-1 101; Lord, J. A., et al., Nature (1977) 267: 495-499). It seems that these three types of opioid receptors share the same functional mechanisms in the cell. For example, opioid receptors inhibit adenylate cyclase and inhibit neurotransmitter release by activation of the potassium channel and inhibition of Ca2 + channels (Evans, CJ, in: "Biological Basis of Substance Abuse", SG Korenman and JD Barchas, eds., Oxford University Press (1993), North, AR, et al., Proc Nati Acad Sci USA (1990) 87: 7025-29; Gross, RA, et al., Proc Nati Acad Sci USA (1990) 87: 7025- 29; Sharma, SK, et al., Proc Nati Acad Sci USA (1975) 72: 3092-96). Although the functional mechanisms are the same, the manifestations of receptor-selective drugs on behavior differ greatly (Gilbert, P. E. and Martin, W.R., J Pharmacol Exp Ther (1976) 198: 66-82). Such differences can be attributed in part to the location anatomical of the different receptors. The delta receptors have a more discrete distribution within the mammalian CNS than the mu or kappa receptors, with high concentrations in the amygdaloid complex, striatum, substantia nigra, olfactory bulb, olfactory tubercles, hippocampal formation and the cerebral cortex (Mansour, A. and others, Trends in Neurosci (1988) 1 1: 308-14). Notably, the rat cerebellum is devoid of opioid receptors, including delta opioid receptors. D. Delorme, E. Roberts and Z. Wei, WO / 28275 (1998), describe diaryl-methylidene piperidines which are opioid analgesics, but do not describe or suggest the compounds of the present invention. C. Kaiser et al. (J. Me. Chem. 1974, volume 17, pp. 57-61) describe some piperidylidene derivatives of thioxanthenes, xanthenes, dibenoxepines and acridans, which are neuroleptic agents. However, these authors neither describe nor suggest the structure or activity of the compounds of the present invention. The British patent GB 1 128734 (1966) describes derivatives of 6, -dihydrodibenzo [b, e] oxepine which are anticholinergic, anticonvulsant, muscle relaxant, sedative, diuretic, and / or vasoactive agents. However, these agents differ significantly from the compounds of the present invention, both structurally and pharmacologically.

There is a continuing need for new delta-opioid receptor modulators as analgesics. In addition, there is a need for selective delta-opioid receptor agonists as analgesics, which have reduced side effects. There is also a need for delta-opioid receptor antagonists such as immunosuppressants, anti-inflammatories, agents for the treatment of neurological and psychiatric conditions, agents for the treatment of urological and reproductive conditions, drugs for the abuse of drugs and alcohol, agents for the treatment of gastritis and diarrhea, cardiovascular agents, and agents for the treatment of respiratory diseases, which have reduced side effects.

BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to compositions comprising a compound of formula (I): Formula (I) wherein: G is -C (Z) NRiR2, aryl of Ce-io. C6-io arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, and pyridinyl; wherein the C6-io aryl group of the G6 substituents containing C6-io aryl, and the heterocycles of G, are optionally substituted with one to three substituents independently selected from the group consisting of C2 alkylene, C2 alkenyl -8, C2-8 alkynyl, Ci-8 alkanoyloxy, C-1-8 hydroxyalkanyl, Ci-8 carboxyalkyl, (Ci-8) alkylaminocarbonyl, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino , C 1-6 alkylamino of C 1-6 dialkanylamino, C 1-8 alkyllthio, C 1-8 alkylsulphonyl, C 8 alkylsulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, alkanyl. 8) aminocarbonyl, dialkanyl (C-8) aminocarbonyl, and C 1 6 alkanoxycarbonylamino; R1 is a substituent selected from the group consisting of hydrogen, C1-8 alkanyl, C2-8 alkenyl and C2-8 alkynyl; R2 is a substituent selected from the group consisting of hydrogen; Ci-8 alkanyl; C2-8 alkenyl; C2-e alkynyl; C6-10 aryl; and C3.8 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted Ci_8 alkanyl; and wherein the C-i-8 alkanyl of R 2 is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci_6 alkanoylamino, C-i-6 dialkylamino, Ci-6 alkanoyloxy, Ci-alkanoylthio. 6, hydroxy, fluorine, chlorine, cyano, aminocarbonyl, alkanyl (Ci.sub.8) aminocarbonyl, dialkanyl (C ^) aminocarbonyl, alkanyl (Ci.6) oxycarbonyl and aryloxy; wherein the phenyl and aryloxy substituents of Ci-8 alkanyl, and the substituents C6-10 aryl and C3-8 cycloalkanyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of C6 alkanyl. 8, C ^ .e alkenyl, C2-8 alkynyl. Ci-e alkanoyloxy, trifluoromethyl, trifluoromethoxy, phenyl, halogen, cyano, hydroxy, Ci-alkanoylthio. 8, Ci-8 alkylsulfonyl, and alkanyl (Ci-8) sulfonylamino or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three Ci-4 alkanyl substituents or C1.4 alkanoyloxy) and from one to two additional substituents independently selected from the group consisting of Ci-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, alkylamino of Ci-6, C1.6 dialkanylamino and halogen; or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, Ci-6 alkylamino, dialkanyl (Ci-6) amino and halogen; R3 is a substituent selected from the group consisting of hydrogen, Ci.8 alkanyl, halo (i-3) C1-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkanyl, cycloalkanyl- Ci-8 alkanyl, alkanoyloxy (Ci. 8) C1-8 alkanyl, Ci-8 alkanyl (C1-8) thioalkanyl > C1-8 hydroxyalkanyl, (C1-8) alkynyloxycarbonyl, halo (i-3) alkanyl (Ci-8) carbonyl, formyl, thioformyl, carbamimidoyl, phenyliminoalkanyl of Ci-8, phenylalkyl of C8, phenyl-alkenyl of C1-8, C 1-8 phenyl-alkynyl, Ci-8 naphthyl-alkanyl and Ci-heteroaryl-alkanyl. 8, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl , pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, thiazolyl; wherein the phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, C 2-6 alkenyl of C-6 alkynyl, amino, Ci-6 alkylamino, dialkanylamino of Ci.6, (C 1-6) alkoxycarbonyl, alkanyl (Ci.6) carbonyloxy, alkanyl (Ci-6) carbonylamino, alkanylthio of Ci-6, (C 1-6) alkylsulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6, thioureido and fluoroalkanyl (Ci-6) oxy; alternatively, when phenyl and heteroaryl are optionally substituted with alkanyl or alkanoyloxy substituents attached to adjacent carbon atoms, the two substituents may together form a fused cyclic alkanyl or cycloheteroalkanyl, selected from the group consisting of - (CH2) 3-5- , -0 (CH2) 2-4-, - (CH2) 2-4O- and -0 (CH2) 1-30-R4 is one to three substituents independently selected from the group consisting of hydrogen, cyano 6, C2.6 alkenyl, C2-6 alkynyl, C2-6 arylalkynyl, d-6 alkynyloxy, amino, Ci-6 alkylamino, d-e dialkanylamino, Ci-6alkylcarbonyl, Ci-6alkyloxycarbonyloxy, Ci-6alkyloxycarbonyl, aminocarbonyl, alkaliC. 6) aminocarbonyl, dialkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino, alkanylthio of Ci-6, alkanyl (C 1-6) sulfonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, -C (= NOH) phenyl, aminomethyl, hydroxymethyl, methanesulfonylamino, arylamino of? E- ?? (wherein the C6-io aryl is optionally substituted with one to three substituents independently selected from the group consisting of C6 alkanyl, Ci-6 alkoxy, halogen and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C6-io aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkannyloxy; or optionally, when R4 comprises two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the fused portion is selected from the group consisting of - (CH2) 3-5-, -0 (CH2) 2-4-, - (CH2) 2-40-, -0 (CH2) 1-30- and -SC (NH2) = N-; R5 is one to two substituents independently selected from the group consisting of hydrogen, C1-6 alkanoyl, C2-6 alkenyl, C4 alkanoyloxy, amino, Ci-6 alkanoylamino, C1-6 dialkylamino, alkynyl 6) carbonyl, alkanyl (Ci.6) carbonyloxy, alkanyl (Ci-6) oxycarbonyl, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci. 6) carbonylamino, Ci-6 alkanthio, Ci (6) alkylsulfonyl, halogen, hydroxy, cyano, C6 fluoroalkanyl and C1-6 fluoroalkanyloxy; A is absent or is - (CH2) m-, where m is 2 or 3; Y is - (CH2) nX- or -X (CH2) n-; X is O, or S n is 0 or 1; Z is O, S, NH, N- (alkanyl of d.6), N (OH), N- (O-alkanyl of Ci. 6), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates or pharmaceutically acceptable salts thereof. The present invention is also directed to compositions comprising a compound of formula (Ib): Formula (Ib) wherein: G is bromine, chlorine, cyano, trifluoromethanesulfonyloxy, alkany! 8) oxycarbonyl, carboxy, -C (Z) NR R2, C6-io aryl, C6-io arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl and pyridinyl; where the aryl group of? ß- ?? of substituents of G containing C6-io aryl, and heterocycles of G, are optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanyl, C2-8 alkenyl, C2 alkynyl. 8, Ci.8-alkanoyloxy, C8-hydroxyalkanyl, Ci-8-carboxyalkanyl, C8-alkynyl-carbonyl amino, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino, Ci_6 alkanoylamino, cycloalkylamino 6, C 1-8 alkanthio, Ci-8 alkylsulphonyl, Ci-8 alkylsulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, (C- | 8) aminocarbonyl, dialkanyl (Ci-8) aminocarbonyl and alkanyl ( Ci-6) oxycarbonylamino; Ri is a substituent selected from the group consisting of hydrogen, Ci-8 alkanyl, C2.8 alkenyl and C2.8 alkynyl; R2 is a substituent selected from the group consisting of hydrogen; C1-8 alkanyl; C2-8 alkenyl; C2.8 alkynyl; C6-io aryl; and C3-8 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted C1-8 alkanyl; and wherein the C1-8 alkanyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, C1-6 alkylamino, Ci-6 dialkylamino, Ci-6 alkanoyloxy, Ci. 6, hydroxy, fluorine, chlorine, cyano, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialkanyl (Ci-8) aminocarbonyl, (C 1-6) alkyloxycarbonyl and aryloxy; where the phenyl and aryloxy substituents of Ci.sub.8 alkanyl) and aryl substituents of C & 10 and C3-8 cycloalkanyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of C-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, C -8 alkanoyloxy, trifluoromethyl , trifluoromethoxy, phenyl, halogen, cyano, hydroxy, alkanylthio of Ci. 8, alkanyl (Ci-8) sulfonyl and alkanyl (Ci-8) sulfonylamino or Ri and R2, taken together with the nitrogen to which they are attached, form a cycloheteroalkyl of 5-7 members, optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three Ci-4 alkanyl substituents or Ci-4 alkanoyloxy) and from one to two additional substituents independently selected from the group consisting of C- | 8 alkanyl, C 1-8 hydroxyalkanyl > hydroxy, ammonium, C-i.6 alkanamino, dialkanyl (Ci-6) amino and halogen; or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, C 1 alkanoylamino, dialkyl (C 1-6) amino and halogen; R3 is a substituent selected from the group consisting of hydrogen, C1-8 alkanyl, halo (i-3) Ci-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, C3.8 cycloalkanyl, cycloalkanyl- C 1-8 alkanyl, C 8 alkynyloxy (Ci. 8) C 1-8 alkanyl, C 1-8 alkynyl (Ci-8) thioalkanyl, Ci-8 hydroxyalkanyl, C8 alkynyloxycarbonyl, halo (i-3) -alkanyl (Ci-8) carbonyl, formyl, thioformil, carbamimidoyl, Ci-β phenyliminoalkanyl, Ci-s phenylallanyl, Ci-8 phenyl-alkenyl, Ci-8 phenyl-alkynyl, Ci-8 naphthyl-alkanyl and heteroaryl-alkanyl of 8, wherein the heteroaryl is selected of the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl , tetrazolyl, thiazolyl; wherein phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6 alkanyl, C2-6 alkenyl, Ci.6 alkanoyloxy, amino, Ci-6 alkylamino, dialkanylamino of Ci-6, C6 carbonyl, C6-C6-alkoxycarbonyloxy, Ci-6-alkylaminocarbonylamino, C -6 alkanthio, C6-6 alkylsulfonyl, halogen, hydroxy, cyano, fluoroalkanyl, Ci-6, thioureido and fluoroalkannoxy of C1-6; alternatively, when phenyl and heteroaryl are optionally substituted with alkanyl or alkanoyloxy substituents attached to adjacent carbon atoms, the two substituents may together form a fused cyclic alkanyl or cycloheteroalkanyl, selected from the group consisting of - (CH2) 3-5- , -0 (CH2) 2-4-, - (CH2) 2-4O- and - R4 is one to three substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 arylalkynyl, C1-6 alkanoyloxy, amino, alkylamino of Ci-6, dialkyl-amino of Ci.6l alkanyl (Ci-6) carbonyloxy, alkanyl (Ci-6) oxycarbonyl, aminocarbonyl, alkanyl (Ci. 6) aminocarbonyl, dialkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino, alkanylthio of Ci-6, alkanyl (Ci-6) sulfonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, -C (= NOH) -phenyl, aminomethyl, hydroxymethyl, methanesulfonyl-amino, aryl (C6-io) amino (wherein the C6-io aryl is optionally substituted with one to three substituents, independently selected from the group consisting of Ci alkanyl -6, Ci-6 alkoxy, halogen and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C6-io aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indplinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkanyl; or optionally, when R4 comprises two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the fused portion is selected from the group consisting of - (CH2) 3-5-, -0 (CH2) 2-4-, - (CH2) 2-40-, -0 (CH2) -30- and - SC (NH2) = N-; R5 is one to two substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, C2-6 alkenyl, d.6 alkynyloxy, amino, Ci_6 alkanoylamino, dialkyl amino, de (C1-6) alkynyl carbonyl , alkanyl (Ci.6) carbonyloxy, alkanyl (C- | 6) oxycarbonyl, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci. 6) carbonylamino, C 1-6 alkthylthio, (C 1-6) alkylsulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci_6 and fluoroalkannyloxy of Ci-6; A is absent or is - (CH2) m-, where m is 2 or 3; - (CH2) nX- or -X (CH2) n X is O, or S; n is 0 or 1; Z is O, S, NH, N- (Ci-6 alkanyl), N (OH), N- (O-alkanyl of d.6), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates or pharmaceutically acceptable salts thereof. Finally, the present invention is directed to pharmaceutical and veterinary compositions containing the compounds of formula (I) and formula (Ib), wherein the compositions are used to treat mild to severe pain in warm-blooded animals.

DETAILED DESCRIPTION OF THE INVENTION As used herein, the following underlined terms have the following meanings: "Ca '(where a and b are integers) refers to a radical containing aab carbon atoms, inclusive, eg, C1-3 denotes a radical containing 1, 2 or 3 carbon atoms. "Alkyl" refers to a branched, straight or cyclic monovalent hydrocarbon radical, saturated or unsaturated, derived from the removal of a hydrogen atom of a single carbon atom of an original alkane, alkene or alkyne. Typical alkyl groups include, without limitation, methyl; ethyl esters such as ethanyl, ethenyl, ethynyl; propyl such as propan-1-yl, propan-2-yl, cyclopropan-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl , cycloprop-1-en-1-yl-cycloprop-2-en-1-yl, prop-1-yn-1-yl, prop-2-yn-1-yl, etc .; butyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl, but-1-en-1-yl , but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1, 3 -dien-1-yl, buta-1, 3-dien-2-yl, cyclobut-1-en-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl, but-1-in-butyl, but-1-in-3-yl, but-3-yn-1-yl, etc .; and similar. When considering specific degrees of saturation the nomenclature "alkanyl", "alkenyl" and / or "alkynyl" is used, as defined below. In preferred embodiments, the alkyl groups are CrC6 alkyl, with C1-C3 being particularly preferred. "Alkanyl" refers to a saturated, branched, straight or cyclic monovalent hydrocarbon radical derived by the removal of a hydrogen atom from a single carbon atom of an original alkane. Typical alkanyl groups include, without limitation, methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl, cyclopropan-1-yl, etc .; butanyls such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl, etc., and the like. In preferred embodiments, the alkanyl groups are Ci_8 alkanyl, with Ci-3 being particularly preferred. "Alkenyl" refers to an unsaturated, branched, straight or cyclic monovalent hydrocarbon radical having at least one double bond carbon-carbon, derived by the removal of a hydrogen atom from a single carbon atom of an original alkene. The radical can be in the cis or trans conformation on the double bond. Typical alkenyl groups include, without limitation, ethenyl; propenyls such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl, prop-2-en-2-yl, cycloprop-1-en-1 -ilo; cycloprop-2-en-1-yl; butenyls such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2 -in-2-yl, buta-1, 3-dien-1-yl, buta-1,3-dien-2-yl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl , cyclobuta-1, 3-dien-1-yl, etc .; and similar. "Alkynyl" refers to an unsaturated, branched, straight or cyclic monovalent hydrocarbon radical having at least one carbon-carbon triple bond, derived by the removal of one hydrogen atom from a single carbon atom of an original alkyne. Typical alkynyl groups include, without limitation, ethynyl; propynyls such as prop-1-yn-1-yl, prop-2-yn-1-yl, etc .; butynyls such as but-1-in-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc .; and similar. "Heteroalkyl" and "heteroalkanyl" refer to alkyl or alkanyl radicals, respectively, in which one or more carbon atoms (and any associated hydrogen atom that is necessary) are independently replaced with one or more identical or different heteroatoms (including any hydrogen atom or other necessary atom). Typical heteroatoms for replacing carbon atoms include, without limitation, N, P, O, S, Si, etc. The preferred heteroatoms are O, N and S. In this manner, the heteroalkanyl radicals may contain one or more groups heteroatomics the same or different including, by way of example and not limitation, the epoxy groups (-0-), epidioxy (-O-0-), thioether (-S-), epidithium (-SS-), epoxythium (-0-S-), epoxyimino (-O-NR'-), mino (-NR'- ), biimino (-NR'-NR'-), azino (= NN =), azo (-N = N-), azoxy (-N-0-N-), azimino (-NR'-N = N- ), phosphine (-PH-), A4-sulfan (-SH2-), sulfonyl (-S (0) 2-), and the like, wherein each R 'is independently hydrogen or CrC6 alkyl. "Original aromatic ring system" refers to an unsaturated, cyclic or polycyclic ring system, which has a conjugated rr electron system. The definition of "original aromatic ring system" specifically includes fused ring systems in which one or more rings are aromatic and one or more rings are saturated or unsaturated, such as for example indane, indene, phenalene, etc. Typical original aromatic ring systems include, without limitation, aceanthylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronenne, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indane, indene, naphthalene, octazene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, piceno, pleiadene, pyrene, pyrantrene, rubiceno, triphenylene, trinaphthalene, and the like. "Arito" refers to a monovalent aromatic hydrocarbon radical, derived by the removal of a hydrogen atom from a single carbon atom of an original aromatic ring system. Typical aryl groups include, without limitation, the radicals derived from aceanthylene, acenaphthylene, acephenanthylene, anthracene, azulene, benzene, chrysene, coroneno, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, piceno, pleiadene, pyrene, pyrantrene, rubiceno, triphenylene, trinaphthalene, and the like. In preferred embodiments, the aryl group is C5-20 aryl, with C5-10 being particularly preferred. Particularly preferred aryl groups are phenyl and naphthyl. "Arylalkyl" refers to an acyclic alkyl group in which one of the hydrogen atoms attached to a carbon atom, usually a terminal carbon atom, is replaced with an aryl radical. Typical arylalkyl groups include, without limitation, benzyl, 2-phenylethan-1-yl, 2-phenyleth-1-yl, naphthylmethyl, 2-naphthyl-1-yl, 2-naphthyleten-1-yl, naphthobenzyl, -naptophenyletan-1-yl and the like. When the specific alkyl portions are considered, the arylalkanyl, arylalkenyl and / or arylalkynyl nomenclature is used. In preferred embodiments, the arylalkyl group is C6-26 aralkyl, for example, the alkanyl, alkenyl or alkynyl portion of the arylalkyl group is d. 6 and the aryl portion is C5.2o- In particularly preferred embodiments, the arylalkyl group is C6.13; for example, the alkanyl, alkenyl or alkynyl portion of the arylalkyl group is d-3 and the aryl portion is C5-10. The most preferred arylalkyl groups are phenylalkanyl. "Alkanyloxy" refers to a saturated, branched, straight or cyclic monovalent hydrocarbon alcohol radical, derived by the removal of the hydrogen atom from the oxygen hydroxide of the alcohol. The alkanoyloxy groups typical include, without limitation, methanoyloxy; ethanyloxy; propanyloxy groups such as propan-1-yloxy (CH3CH2CH2O-), propan-2-yloxy ((CH3) 2CHO-), cyclopropan-1-yloxy, etc .; butanyloxy groups such as butan-1-yloxy, butan-2-yloxy, 2-methyl-propan-1-yloxy, 2-methyl-propan-2-yloxy, cyclobutan-1-yloxy, etc .; and similar. In preferred embodiments, the alkyloxy groups are C1-8 alkanoyloxy groups, with C1-3 being particularly preferred. "Original heteroaromatic ring system" refers to an original aromatic ring system in which a carbon atom is replaced with a heteroatom. Heteroatoms to replace carbon atoms include N, O, and S. The definition of "original heteroaromatic ring system" specifically includes fused ring systems in which one or more rings are aromatic and one or more rings are saturated or unsaturated, such as, for example, arsindol, chroman, chromene, indole, indoline, xanthene, etc. The original heteroaromatic ring systems include, without limitation, carbazole, imidazole, indazole, indole, indoline, indolizine, isoindol, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine. , pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like. "Heteroaryl" refers to a monovalent heteroaromatic radical derived by the removal of a hydrogen atom from a single atom of an original heteroaromatic ring system. Typical heteroaryl groups include, without limitation, the radicals derived from carbazole, imidazole, indazole, indole, indoline, indolizine, isoindoine, isoindoine, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, purine, pyrano, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and the like. In preferred embodiments, the heteroaryl group is a heteroaryl of 5-20 members, with 5-membered heteroaryl being particularly preferred. "Cycloheteroalkyl" refers to a saturated or unsaturated, monocyclic or bicyclic alkyl radical, wherein a carbon atom is replaced with N, O, or S. In some specific embodiments, the cycloheteroalkyl may contain up to four heteroatoms independently selected from N, O, or S. Typical cycloheteroalkyl moieties include, without limitation, radicals derived from imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, and the like. In preferred embodiments, the cycloheteroalkyl is a 3-6 membered cycloheteroalkyl. "Cycloheteroalkanyl" refers to a saturated, monocyclic or bicyclic alkanyl radical, in which a carbon atom is replaced with N, O, or S. In some specific embodiments, the cycloheteroalkanyl may contain up to four heteroatoms independently selected from N, O , or S. Typical cycloheteroalkanyl moieties include, without limitation, the radicals derived from imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine and the like. In preferred embodiments, the cycloheteroalkanyl is a 3-6 membered cycloheteroalkanyl.

"Cycloheteroalkenyl" refers to a saturated, monocyclic or bicyclic alkenyl radical, in which a carbon atom is replaced with N, O, or S. In some specific embodiments, the cycloheteroalkenyl may contain up to four heteroatoms independently selected from N, O , or S. Typical cycloheteroalkenyl moieties include, without limitation, the radicals derived from imidazoline, pyrazoline, pyrroline, indoline, pyran, and the like. In preferred embodiments, the cycloheteroalkanyl is a 3-6 membered cycloheteroalkanyl. "Substituted" refers to a radical in which one or more hydrogen atoms are independently replaced with one or more identical or different substituents. Typical substituents include, without limitation, -X, -R, -O ', = 0, -OR, -O-OR, -SR, -S ", = S, -NRR, = NR, -CX3, -CN , -OCN, -SCN, -NCO, -NCS, -NO, -NO2, = N2, -N3, -NHOH, -S (O) 2O-, -S (O) 2OH, -S (O) 2R, -P (O) (O) 2, -P (O) (OH) 2, -C (O) R, -C (O) X, -C (S) R, -C (S) X, -C (O) OR, -C (O) O-, -C (S) OR, -C (O) SR, -C (S) SR, -C (O) NRR, -C (S) NRR and -C (NR) NRR, wherein each X is independently a halogen (preferably -F, -Cl or -Br) and each R is independently -H, alkyl, alkanyl, alkenyl, alkynyl, alkylidene, alkylidino, aryl, arylalkyl, arylheteroalkyl, heteroaryl, heteroarylalkyl or heteroaryl heteroalkyl, as defined herein Preferred substituents include hydroxy, halogen, Ci-e alkyl, C 1-8 alkynyloxy, fluorinated alkanoyloxy, fluorinated alkyl, Ci-8 alkylthio, C3 cycloalkyl. , C3-8 cycloalkanyloxy, nitro, amino, Cie alkylamino, Ci-8 dialkylamino, C3.8 cycloalkylamino, cyano, carboxy, alkynyloxy (Ci-7) -carbonyl, alkyl (Ci. 7) Carbonyloxy, formyl, carbamoyl, phenyl, aroyl, carbamoyl, amidino, alkylamino (Ci.sub.8) carbonyl, (arylamino) carbonyl and aryl-alkyl (C 1-8) carbonyl. With respect to substituents, the term "independently" means that when more than one of these substituents is possible, the substituents may be the same or different from each other. Throughout this description, the terminal portion of the designated side chain is first described, followed by functionality adjacent to the point of attachment. Thus, for example, a substituent "phenyl-alkanyl (Ci-6) aminocarbonyl-Ci-6 alkyl" refers to a group of formula: One embodiment of the present invention is directed to a compound of formula (I) and formula (Ib) wherein the structure is numbered as defined herein: Formula (I) and Formula (Ib) The present invention is directed to analgesic uses and antipyretics of the compositions comprising a compound of formula Formula (I) wherein: G is -C (Z) NRi R2, C6-io aryl, Ce-ar arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl , imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl and pyridinyl; wherein the C6-io aryl group of the Ce-ar aryl-containing G substituents, and the heterocycles of G, are optionally substituted with one to three substituents independently selected from the group consisting of d-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, Ci_8 alkanoyloxy, Ci-8 hydroxyalkanyl, C13.8 carboxyalkanyl, C8-8 alkynyl, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino, C 1-6 alkylamino, C 1-6 dialkylamino, Cv 8 alkanylthio, Ci.sub.8 alkylsulfonyl C 1 sulphonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, alkanyl (Ci. 8) aminocarbonyl, dialkanyl (Ci-8) aminocarbonyl and alkanyl ( Ci-6) oxycarbonylamino; Ri is a substituent selected from the group consisting of hydrogen, C-i-e alkanyl, C 2-8 alkenyl and C 2-8 alkynyl, R 2 is a substituent selected from the group consisting of hydrogen; C1-8 alkanyl; C2-8 alkenyl C2-8 alkynyl; C6-10 aryl; and C3-8i cycloalkanyl with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted C8 alkanyl; and wherein the C1-8 alkanyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci-6 alkylamino, Ci-6 dialkylamino, 0-6 alkynyloxy, C1. 6, hydroxy, fluorine, chlorine, cyano, aminocarbonyl, (1-8) alkylaminocarbonyl, dialkanyl (Ci-8) aminocarbonyl, alkanyl (Ci-6) oxycarbonyl and aryloxy; wherein the substituents phenyl and aryloxy of alkanyl of C-i-e, and the substituents aryl of C6. 10 and C3-8 cycloalkanyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of ds alkanoyl, C2.8 alkenyl, C2-8 alkynyl, C1-8 alkanoyloxy, trifluoromethyl, trifluoromethoxy , phenyl, halogen, cyano, hydroxy, C-alkanoylthio. 8, C -8 alkylsulfonite, and alkanyl (Ci.8) sulfonylamino; or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three Ci-4 alkanyl substituents or Ci. 4) and one to two additional substituents independently selected from the group consisting of C1-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, C ^ alkanoylamino, dialkyl (C 1-6) amino and halogen; or Ri and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, Ci-6 alkylamino, dialkanyl (C-6) amino and halogen; R3 is a substituent selected from the group consisting of hydrogen, C -8 alkanyl, halo (i-3) alkanyl Ci.e, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkanyl, cycloalkanyl- Ci-8 alkanyl, Ci-8 alkanoyloxy (Ci. 8) alkanyl, Ci-8 alkanyl (Ci-8) thioalkanyl, Ci-8 hydroxyalkanyl, alkynyloxy (Ci.8) carbonyl, halo (i-3) C3-8 alkynyl, carbonyl, formyl, thioformyl, carbamimidoyl, phenyliminoalkanyl of Ci_8, phenylalcanyl of C 1-8, phenyl-alkenyl of Ci-8, phenyl-alkynyl of Ci-8, naphthyl-alkanyl of da and heteroaryl-alkanyl of C- | 8, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl , pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, thiazolyl; wherein the phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of d6 alkanyl, C2-6 alkenyl, C6 alkanoyloxy, amino, Ci.6 alkylamino, dialkyl amino Ci-6, (C 1-6) alkoxycarbonyl, (C 1-6) alkoxycarbonyloxy, (C 1-6) alkylaminocarbonylamino, C 1-6 alktoxythia, (C 1-6) alkylsulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6, thioureido and fluoroalkanyl (Ci.6) oxy; alternatively, when phenyl and heteroaryl are optionally substituted with alkanyl or alkanoyloxy substituents attached to adjacent carbon atoms, the two substituents may together form a fused cyclic alkanyl or cycloheteroalkanyl, selected from the group consisting of - (CH2) 3-5- , -0 (CH2) 2-4-, - (CH2) 2.40- and -O (CH2) 1-30-; R4 is one to three substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, C2.6 alkenyl > C 2-6 alkynyl, C 2-6 alkynyl, d-6-alkanoyloxy, amino, Ci.6-alkylamino, Ci-6 dialkylamino, Ci-6-alkynyl, C-6-alkanoycarbonyloxy , alkanyl (Ci-6) oxycarbonyl, aminocarbonyl, alkanoyl. 6) aminocarbonyl, dialcanyl (Cv6) aminocarbonyl, alkanoyl (C- | 6) carbonylamino, alkanylthio of Ci-6, alkanyl (Ci-6) sulfonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, -C (= NOH) phenyl, aminomethyl, hydroxymethyl, methanesulfonylamino, C6-io arylamino (wherein the aryl of Ce-? Is optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, C1-6l halogen and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C6-io aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkannyloxy; or optionally, when R4 comprises two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the fused portion is selected from the group consisting of - (CH2) 3-5-, -0 (CH2) 2-4-, - (CH2) 2-40-, -0 (CH2) 1-3O- and -SC (NH2) = N-; R5 is one to two substituents independently selected from the group consisting of hydrogen, C1-6 alkanyl, C2-6 alkenyl, Ci-6 alkanoyloxy, amino, Ci-6 alkylamino, d-6 dialkanylamino, alkanyl (C1) -6) carbonyl, alkanyl (Ci-6) carbonyloxy, (C 1-6) alkanoxycarbonyl, (C 1-6) alkylaminocarbonyl, alkanyl (d. 6) carbonylamino, Ci-6 alkanthio, Ci (6) alkylsulfonyl, halogen, hydroxy, cyano, Ci-6 fluoroalkanyl and Ci-6 fluoroalkanyloxy; A is absent or is - (CH2) m-, where m is 2 or 3; Y is - (CH2) nX- or -X (CH2) n-; X is O, or S n is 0 or 1; Z is O, S, NH, N- (C 1-6 alkanyl), N (OH), N- (0-alkanyl of d-6), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof. The present invention is also directed to the analgesic and antipyretic uses of the compositions comprising a compound of formula (Ib): Formula (Ib) wherein: G is bromine, chlorine, cyano, trifluoromethanesulfonyloxy, C 8 alkanoxycarbonyl, carboxy, -C (Z) NR- | R2, C6-io aryl, C6-io arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinium, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl and pyridinyl; wherein the aryl group of C6-io of the substituents of G containing C6-io aryl, and the heterocycles of G, are optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanyl, alkenyl of C2-8, C2-8 alkynyl, C1-8 alkanoyloxy, Ci-8 hydroxyalkanyl, C -8 carboxyalkanyl, Ci (8) alkanyl, halogen, hydroxy, cyano, nitro, oxo, thioxo amino, alkylamino of d-6, dialkanyl amino of C1.6, alkanylthio of C1-8, alkylsulphonyl of Ci.s, alkanyl (C1-8) sulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, alkanyl (Ci. 8) aminocarbonyl , dialkanyl (Ci.sub.8) aminocarbonyl and alkanyl (Ci-6) oxycarbonylammon; Ri is a substituent selected from the group consisting of hydrogen, Ci-8 alkanyl, C2-8 alkenyl and C2-8 alkynyl; R2 is a substituent selected from the group consisting of hydrogen; Ci-8 alkanyl; C2-8 alkenyl; C2-8 alkynyl, Ce-ar aryl; and C3-8 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted Ci-8 alkanyl; and wherein the Ci-8 alkanyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci.6 alkylamino, Ci-6 dialkylamino, Ci-6 alkanoyloxy, Ci_6, hydroxy, fluoro, chloro, cyano, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialcanyl (Ci.8) aminocarbonyl, alkanyl (Ci-6) oxycarbonyl and aryloxy; wherein the phenyl and aryloxy substituents of the Ci-8 alkanyl, and the substituents of C6-io aryl and C3-8 cycloalkanyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-alkanyl. 8, C2-8 alkenyl of C2-s, C 1-8 alkynyloxy, trifluoromethyl, trifluoromethoxy, phenyl, halogen, cyano, hydroxy, C ^ 8 alkanthio, C 1-8 alkylsulphonyl, and C 1-8 alkylsulfonylamino; or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three substituents of Ci.4 alkanoy or C1- alkanoyloxy) ) and one to two additional substituents independently selected from the group consisting of C1-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, Ci-6 alkanoylamino, dialkanyl (Ci-6) amino and halogen; or Ri and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl, d-8 hydroxyalkanyl, hydroxy, amino, d-6 alkylamino, dialkanyl (Ci-6) amino and halogen; R3 is a substituent selected from the group consisting of hydrogen, Ci-8 alkanyl, halo (1-3) alkanyl of Ci-s, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkanyl, Ci-8 cycloalkanyl-alkanyl, alkanoyloxy (Ci. ) Ci.sub.8 l alkanyl (C 1-8) thioalkanyl thioalkanyl, C 1-8 hydroxyalkanyl, alkynyloxy (Ci-8) carbonyl, halo (i-3) -alkanyl (Ci-8) carbonyl, formyl, thioformyl , carbamimidoyl, phenyliminoalkanyl of Ci-8, phenylallanyl of Ci.8, phenyl-alkenyl of C 1-8, phenyl-alkynyl of Ci-8, naphthyl-alkanyl of Ci-8 and heteroaryl-alkanyl of Ci_ 8, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl , isoquinolinyl, tetrazolyl, thiazolyl; wherein the phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C 1-6 alkanyl, C 2-6 alkenyl, C 1-6 alkynyloxy, amino, Ci-6 alkylamino, dialkanylamino of C1-6, alkanyl (Ci-6) carbonyl, alkanoyl (C -6) carbonyloxy, alkanyl (Ci-6) carbonylamino, alkanylthio of Ci-6, alkanyl (Ci.6) sulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6, thioureido and fluoroalkannoxy of Ci.6; alternatively, when the phenyl and the heteroaryl are optionally substituted with alkanyl or alkanoyloxy substituents attached to adjacent carbon atoms, the two substituents can together form a cyclic fused alkanyl or cycloheteroalkanyl, selected from the group consisting of - (CH2) 3-5-, -O (CH2) 2-4-, - (CH2) 2- O- and -O (CH2) 1-3O-R4 is one to three substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, C2-6 alkenyl , C2-6 alkynyl, C2-6 arylalkynyl, d-6alkynyloxy, amino, Ci-6alkylamine, Ci-6 dialkylamino, alkynyl (Ci-6) carbonyl, C6-6alkynylcarbonyloxy , alkanyl (Ci-6) oxycarbonyl, aminocarbonyl, alkanoylcarbonyl, dialkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino, alkanylthio of Ci-6, alkanyl (C 1-6) sulfonyl, halogen , hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, -C (= NOH) -phenyl, aminomethyl, hydroxymethyl, methanesulfonyl-amino, aryl (C6-io) amino (where the aryl of C6.1 0 is optionally substituted with one to three substituents, independently selected from the group consisting of Ci-6 alkanyl, Ci-6 alkoxy, halogen and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C6 aryl io, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkanyloxy; or optionally, when R4 comprises two substituents bonded to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the fused portion is selected from the group consisting of - (CH2) 3-5-, -0 (CH2) 2-4-, - (CH2) 2-4O-, -0 (CH2) 1-30- and -SC (NH2) = N-; R5 is one to two substituents independently selected from the group consisting of hydrogen, d-6 alkanyl, C2-6 alkenyl, Ci.6 alkanoyloxy, amino, Ci-6 alkanoylamino, Ci-6 dialkylamino, alkane (Ci-6) carbonyl, alkanyl (Ci-6) carbonyloxy, alkanyl (Ci.6) oxycarbonyl, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci. 6) carbonylamino, C1-6 alkanoylthio, (C-i-6) alkylsulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6 and fluoroalkannoxy of? H.H; A is absent or is - (CH2) m-, where m is 2 or 3; Y is - (CH2) nX- or -X (CH2) n-; X is O, or S; n is 0 or 1; Z is O, S, NH, N- (C 1-6 alkanyl), N (OH), N- (0-alkanyl of d.sub.6), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof. The embodiments of the present invention include the compounds of formula (I) wherein, preferably: (a) G is -C ^ NR ^, phenyl, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents, independently selected from the group consisting of Ci-8 alkanyl, Ci.sub.8 alkanoyloxy) Ci.sub.8 l carboxyalkanyl hydroxyalkanyl, alkanyl ( Ci-8) carbonylamino, halogen, hydroxy, cyano, oxo, thioxo, amino, Ci-6 alkanoylamino, C1.6 dialkanylamino, Ci-8 alkanylthio, aminocarbonyl, aminothiocarbonyl, alkanoyl (Ci.8) aminocarbonyl, dialcanil ( Ci-8) aminocarbonyl and alkanyl (Ci. 6) oxycarbonylamino; (b) G is -C (Z) NR1R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl , isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and heterocycles of G are optionally substituted with one to three substituents, independently selected from the group consisting of Ci-4 alkanyl, Ci-4 alkanoyloxy, Ci-4 hydroxyalkanyl, Ci-4 carboxyalkanyl, alkanyl (C 1-4) carbonylamino, hydroxy, cyano, oxo, thioxo, amino, Ci-6 alkylamino, Ci-6 dialkanylamino, Ci.8 alkanoyl, aminocarbonyl, aminothiocarbonyl, alkanoyl (Ci-8) aminocarbonyl and dialkanyl (Ci -8) aminocarbonyl; (c) G is -C (Z) NRiR2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, thienyl, isothiazolyl, isoxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents, independently selected from the group consisting of Ci-4 alkanyl, Ci-4 alkanoyloxy, Ci-4 hydroxyalkanyl, alkanoy (Ci-4) carbonylamino , hydroxy, cyano, oxo, thioxo and aminocarbonyl; (d) Ri is a substituent selected from the group consisting of hydrogen and alkanyl of Ci-4i (e) Ri is selected from the group consisting of hydrogen, methyl, ethyl and propyl; (f) Ri is selected from the group consisting of hydrogen, methyl, or ethyl; (g) R2 is selected from the group consisting of hydrogen; Ci-4 alkanyl; phenyl; and C3.6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted C1-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci-6 alkylamino, C 1-6 dialkylamino, C 1-4 alkynyloxy, hydroxy, fluoro, chloro, cyano, aminocarbonyl, alkaniC ^ aminocarbonyl, dialkanyl (Ci.8) aminocarbonyl and phenoxy; wherein the substituents phenyl and phenoxy of the C 1-4 alkanyl, and the substituents phenyl and C 3-6 cycloalkanyl of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci_8 alkanyl, alkanoyloxy of, trifluoromethyl, phenyl, fluorine, hydroxy, alkanylthio of C ^ e, alkanyl (Ci-8) sulfonyl and (C 1-8) alkylsulfonylamino; or and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein the phenyl is optionally substituted with C 4 alkanoyloxy or hydroxy), C 1-4 alkanoyl, or hydroxy; (h) R 2 is selected from the group consisting of C 4 alkanyl, phenyl and cycloalkanyl of β-β; with the proviso that when Z is O, or S, R2 is different from C- unsubstituted alkanyl; and wherein the C 1 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy, fluoro, aminocarbonyl, C 1 aminocarbonyl, dialkanyl (Ci 8) aminocarbonyl and phenoxy; wherein the phenyl and phenoxy substituents of the C 1-4 alkanyl, and the phenyl of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, Ci_6 alkanoyloxy, fluoro, hydroxy and alkanthio from C1-6; or Ri and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of Ci-4 alkanyl and hydroxy; (i) R2 is selected from the group consisting of Ci_ alkanyl 4 and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the C1-4 alkanyl is optionally substituted with one to three selected substituents independently of the group consisting of phenyl, C1-4 alkanoyloxy, hydroxy, fluorine and phenoxy; wherein the phenyl and phenoxy substituents of the C 1-4 alkanyl, and the phenyl of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of C- | 6 alkanyl, C-6 alkanoyloxy , fluorine and hydroxy; or R < And R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C1.3 alkanyl and hydroxy; (j) R3 is selected from the group consisting of hydrogen, Ci-8 alkanyl, C2.8 alkenyl, C2-8 alkynyl, alkynyloxy (Ci-8) -alkanyl of C1-8, alkanyl (C1-8) -cycloalkanyl of Ci-8, hydroxyalkanyl of Ci-8, thiomorhyl, phenyliminoalkanyl of Ci-8, phenylallanyl of Ci-8 and heteroaryl-alkanyl of Ci-8 wherein heteroaryl is selected from the group consisting of benzo [1, 3 ] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl and heteroaryl are optionally substituted with one to three substituents, independently selected from the group consisting of Ci-6 alkanoyloxy and hydroxy; or optionally, when the phenyl and heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the portion is selected from -O (CH2) i-30-; (k) R3 is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl and heteroaryl-alkanyl of Ci-8 wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl in any phenyl-containing substituent is optionally substituted with a hydroxyl group; (I) R3 is hydrogen, methyl, allyl, or heteroarylmethyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl and thienyl; (m) R4 is one to three substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, Ci-6 alkanoyloxy, aminocarbonyl, aminothiocarbonyl, hydroxyamidino, formylamino, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) 6) carbonylamino, halogen, hydroxy, C6-io aryl, chromanyl, chromanyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl and thienyl; (n) R4 is one to two substituents independently selected from the group consisting of hydrogen, Ci-4 alkanyl, Ci.sub.4 haloalkyloxy, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl. , oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; (o) R4 is one to two substituents independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl and hydroxy; (p) R5 is one to two substituents independently selected from the group consisting of hydrogen and halogen; (q) R5 is hydrogen; (r) A is absent or is - (CH2) 2-; (s) A is - (CH2) 2-; (t) X is O, or S; (u) n is 0; (v) Z is O, NH, N- (C 1-6 alkanyl), N (OH), N- (O-C 1-6 alkanyl), or N- (phenyl); (w) Z is O, NH, or N (OH); (x) Z is O, or NH; and combinations of (a) to (x). One embodiment of the present invention is a compound of formula (I) wherein: G is -C (Z) NR1R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl , tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; where the phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl, Ci-8 alkanoyloxy, Ci-8alkyl carboxyalkanyl hydroxyalkanyl, C 1-8 alkoxycarbonylamino, halogen, hydroxy, cyano , oxo, thioxo, amino, Ci-6-alkylamino, Ci-6-dialkanylamino, C -8-alktoxyl, aminocarbonyl, aminothiocarbonyl, alkanoyl (Ci-8) aminocarbonyl, dialkanyl (Ci-8) aminocarbonyl and alkanol C !. 6) oxycarbonylamino; Ri is hydrogen or C 4 alkanyl; R2 is selected from the group consisting of hydrogen; Ci-4-phenyl alkanyl; and C3_6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted C1-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, C ^ ealkylamino, Ci.6 dialkylamino, Ci-4 alkanoyloxy, hydroxy, fluoro, chlorine, cyano, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialcani C !. 8) aminocarbonyl and phenoxy; wherein the phenyl and phenoxy substituents of Ci-4 alkanyl) and the substituents phenyl and cycloalkanyl of C3-6 of R2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci.sub.8 alkanyl, alkanoyloxy Cve. trifluoromethyl, phenyl, fluorine, hydroxy, alkanylthio of Ci-8l alkaniCSi sulphonyl and alkanyl (Ci-8) sulfonylamino; or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein the phenyl is optionally substituted with Ci-4 alkanoyloxy or hydroxy), C 1-4 alkanyl or hydroxy; R3 is selected from the group consisting of hydrogen, C1-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl alkanoyloxy (Ci-8) alkanyl Ci-8, alkanyl (C1-8) thioalkanyl C1-8 , Ci-8 hydroxyalkanyl, thioformyl, Ci.8 phenyliminoalkanyl, Ci-8 phenylalkyl and Ci-8 heteroaryl-alkanyl wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl , pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl and the heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of (Ci_6) alkyloxy and hydroxy; or optionally, when the phenyl and the heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the portion is selected from -0 (CH2) i-3O-; R4 is one to three substituents independently selected from the group consisting of hydrogen, d-6 alkanyl, Ci-6 alkanoyloxy, aminocarbonyl, aminothiocarbonyl, hydroxyamidino, formylamino, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino , halogen, hydroxy, C6-10 aryl, chromanyl, chromanyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl and thienyl; R5 is one to two substituents independently selected from the group consisting of hydrogen and halogen; A is absent or is CH2CH2; Y is O, S, CH20, or OCH2iZ is O, NH, N- (Ci-6 alkanyl), N (OH), N- (0-6C1-6 alkanyl), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof. Another embodiment of the present invention is a compound of formula (I) wherein: G is -C ^ NR ^, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and heterocycles of G are optionally substituted with one to three substituents, independently selected from the group consisting of Ci-4 alkanyl, Ci-4 alkanoyloxy, Ci-4 hydroxyalkanyl, Ci-4-carboxy-alkanyl , alkanyl (Ci-) carbonylamino, hydroxy, cyano, oxo, thioxo, amino, Ci.6 alkanylamino, C1-6 dialkylamino, C -8 alkanoyld, aminocarbonyl, aminothiocarbonyl, methanediamine, and dialkyl (Ci-8) aminocarbonyl; R1 is selected from the group consisting of hydrogen, methyl, ethyl and propyl; R2 is selected from the group consisting of Ci-4 alkanyl, phenyl and C3.6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the C 1-4 alkanyl is optionally substituted with one to three substituents, independently selected from the group consisting of phenyl, C 1-4 alkyloxy, fluoro, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialkanyl (Ci. 8) aminocarbonyl and phenoxy; wherein the phenyl and phenoxy substituents of the Ci-4 alkanyl, and the phenyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of C6 alkanyl, Ci-6 alkanoyloxy, fluorine, hydroxy and Ci-6 alkanthio; or Ri and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C1-3 alkanyl and hydroxy; R3 is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl and heteroaryl-C1-8 alkynyl wherein the heteroaryl is selected from the group it consists of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, wherein the phenyl in any phenyl-containing substituent is optionally substituted with a hydroxyl group; R4 is one to two selected substituents independently of the group consisting of hydrogen, Ci-4 alkanyl, C-, -haloxy, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl , pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; R5 is hydrogen; A is CH2CH2; And it is O, or S; Z is O, NH, or N (OH); and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof. Another embodiment of the present invention is directed to compositions comprising a compound of formula (I) wherein: G is -C (Z) NR R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl , oxathiadiazolyl, thienyl, isothiazolyl, isoxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents, independently selected from the group consisting of C 1-4 alkanyl, C 1-4 alkanoyloxy, C 1-6 alkynyl (C 1-4) -carbonylamino , hydroxy, cyano, oxo, thioxo and aminocarbonyl; Ri is hydrogen, methyl, or ethyl; R2 is selected from the group consisting of C1- alkanyl, phenyl and C3_6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkyloxy hydroxy, fluorine, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialkanyl (Ci. aminocarbonyl and phenoxy; wherein the substituents phenyl and phenoxy of the C- alkanyl, and the phenyl of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, Ci-6 alkanoyloxy, fluoro, hydroxy and Ci-6i alkanthio or Ri and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C1-alkanyl -3 and hydroxy; R3 is hydrogen, methyl, allyl, or heteroarylmethyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, midazolyl, furanyl, pyridinyl, and thienyl; R is one to two substituents independently selected from the group consisting of hydrogen, Ci-4 alkanyl, alkanoyloxy halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; A is CH2CH2; And it is O, or S; Z is O, or NH; and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof. Another embodiment of the present invention is a compound of formula (I) wherein: G is selected from -C (Z) NRi R2, 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1 / - / - tetrazol-5-yl, 2-methyl-tetrazol-5-yl, 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl, 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl, 4 / - / - [1, 2,4] thiadiazol-5-??? -3-yl, [1, 2,3,5] oxathiadiazol-2-oxo-4-yl, or pyridin-3-yl; Ri is hydrogen, methyl, or ethyl; R2 is selected from the group consisting of CM alkanyl and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci.4 alkanyl; and wherein the C 1-4 alkanyl is optionally substituted with one to three substituents, independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy, fluoro and phenoxy; wherein the phenyl and phenoxy substituents of the Ci-4 alkanyl, and the phenyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of C6 alkanyl, C1-6 alkanoyloxy, fluorine and hydroxy; or R- \ and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring; R3 is selected from the group consisting of hydrogen, C1.8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, (C1-8) alkynyl of d-e, alkanyl (Ci.8) tioalcanilo Ci-8 hidroxialcanilo of Ci.8, tioformilo, feniliminoalcanilo Ci-8 fenilalcanilo Ci-8 alkanyl and heteroaryl-Ci-8 wherein the heteroaryl is selected from the group consisting of hydrogen, methyl, allyl, or heteroarylmethyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, and thienyl; wherein the phenyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanoyloxy and hydroxy; or optionally, when phenyl and heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion, wherein the portion is selected from -0 (CH2) i-30-; R4 is one to three substituents independently selected from the group consisting of hydrogen, d-4 alkanyl, C 1-4 alkanyloxy of halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl , pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; R5 is hydrogen; A is CH2CH2; And it is O, or S; Z is O, or NH; and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.

Another embodiment of the present invention is directed to compositions comprising a compound of formula (I) wherein G is independently selected from: -C (Z) NR R2, 2-metilcarbonilaminofenilo, 2-aminocarbonyl-phenyl, 1 H-tetrazol 5-yl, 2-methyl-tetrazol-5-yl, 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl, 4H- [1,4] -oxadiazole-5-thioxo- 3-yl, 4H- [1, 2,4] thiadiazol-5-yl-3-yl, [1, 2,3,5] oxathiadiazol-2-oxo-4-yl and pyridin-3-yl; Ri is hydrogen, methyl, or ethyl; R2 is a substituent selected from the group consisting of Ci-4 alkanyl and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the C 4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, d-4-alkanoyloxy, hydroxy and 2,6-dimethyl-phenoxy; wherein the phenyl of R2 is optionally substituted with one to three substituents, independently selected from the group consisting of C1-3 alkanyl, Ci-3 alkanoyloxy, or hydroxy; or and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C1-3 alkanyl and hydroxy; R3 is a substituent selected from the group consisting of benzo [1, 3] dioxol-5-ylmethyl, carbamimidoyl, 1 - / - / - imidazol-4-ylmethyl, feniliminometilo, 1 -prop-2-ynyl, tioformilo, 2- hydroxyphenyl-methyl, hydroxy-ethyl, methoxy-ethyl, 2-methyl-allyl, 2-methyl-but-2-enyl, allyl, furan-3-ylmethyl, H, me, methylthioethyl, phenethyl, pyridin-2-yl- methyl and thiophen-2-ylmethyl; R4 is one to two selected substituents independently from the group consisting of hydrogen, Ci-4 alkanyl, C 1-4 alkanyloxy of halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; A is CH2CH2; And it is O, or S; and Z is O, or NH. Another embodiment of the present invention is directed to compositions comprising a compound of formula (I) wherein G is selected from: -C (Z) NR R2, 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1 / - / - tetrazole -5-yl, 2-methyl-tetrazol-5-yl, 4 / - / - [1,4] -oxadiazol-5-oxo-3-yl, 4H- [1,4] -oxadiazole- 5-thioxo-3-yl, 4H- [1, 2,4] thiadiazol-5-oxo-3-yl, [1, 2,3,5] -oxathiadiazol-2-oxo-4-yl, or pyridine- 3-ilo; R- is hydrogen, methyl, or ethyl; R2 is a substituent selected from the group consisting of Ci-4 alkanyl and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the C1-4 alkanyl is optionally substituted with one to three substituents, independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy and 2,6-dimethyl-phenoxy; and wherein the phenyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of C3 alkanyl, C3-3 alkanoyloxy, fluoro, or hydroxy; or and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C1.3 alkanyl and hydroxy; R3 is a substituent selected from the group consisting of benzo [1,3] dioxol-5-ylmethyl, carbamimidoyl, 1-H-imidazol-4-yl-methyl, phenyliminomethyl, 1-prop-2-ynyl, thioformyl, 2- hydroxyphenyl-methyl, hydroxyethyl, methoxyethyl, allyl, furan-3-yl-methyl, H, Me, methylthioethyl and phenethyl; R4 is one to two substituents independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl, and hydroxy; A is CH2CH2; And it is O, or S; and Z is O, or NH. Another embodiment of the present invention is directed to compositions comprising a compound of formula (I) wherein G is selected from: -C (Z) NR R2, 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1H-tetrazole-5 ilo, 2-methyl-tetrazol-5-yl, 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl, 4H- [1, 2,4] -oxadiazol-5-thioxo-3 ilo, 4H- [1, 2,4] thiadiazol-5-oxo-3-yl, [1, 2,3,5] -oxathiadiazol-2-oxo-4-yl, or pyridin-3-yl; is hydrogen, methyl, or ethyl; R2 is a substituent selected from the group consisting of alkanoyl of d-4 and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, C 1-4 alkyloxy, and 2,6-dimethyl-phenoxy; wherein the phenyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-3 alkanyl, C1-3 alkanoyloxy, fluorine, or hydroxy; or R1 and R2, taken together with the nitrogen to which they are bound, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of Ci-3 alkanyl and hydroxy; R3 is a substituent selected from the group consisting of H, benzo [1,3] dioxol-5-ylmethyl, 1-H-imidazol-4-yl-methyl, furan-3-ylmethyl, pyridin-2-ylmethyl and phenyliminomethyl; R4 is a substituent independently selected from the group consisting of hydrogen, methyl, methoxy, bromine, fluorine, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl, and hydroxy; A is CH2CH2; And it is O, or S; and Z is O, or NH. Another embodiment of the present invention is directed to a compound of formula (I) wherein the R4 substituent is preferably in the 5 or 6 position of the formula (I). Another embodiment of the present invention is directed to compositions comprising a compound selected from the group consisting of: a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl, R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl, R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-methoxy-etl) - / \ / - methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 - / - [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H, R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / JV-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1,2,3,5] oxathiazole-2-oxo-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N- (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - [2- (2,6-dimethylphenoxy) -1-methyl-ethyl] aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -phenyl-A / -methyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-l) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is A / - (2-phenylethyl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 1-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-cyclohexyl-A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxymethyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-hydroxyamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-ethyl-1 / - / - imidazol-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (f?) - hydroxymethyl-2-phenyl-et-1-yl) -aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N, N-diisobutylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 S-methoxymethyl-2-phenyl-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 2-methoxy-pyridin-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4,5-dihydro-1 H-imidazol-2-ylo; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (4-pheny!) -cyclohexyl-aminocarbonyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 3-methyl-4 H- [, 2,4] triazol-5-yl; R3 is H; R4.es H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-methyl- [1, 2,4] oxadiazol-4-yl, R 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-1-methoxycarbonyl) aminocarbonyl R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxy-phenol; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is isopropylamine; R3 it's H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenyl-methylaminocarbonyl; R3 is H, R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1,4,6,6-tetrahydropyrimidin-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-aminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is C-piperidin-1-yl-methyleneamine; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methoxyphenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is cyclopentylaminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylphenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, / V-bis (2,2,2-trifluoro-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is isobutylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is C-morpholin-4-yl-methyleneamine; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-fluorophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -benzyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-methanesulfonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-fluorophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is thiophen-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-dimethylamino-et-1-yl) -W-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methoxyphenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenyl-methylaminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylaminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is cyclopentylaminocarbonyl; R3 is ethoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-dimethylamino-et-1-l) - / V-methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V - [(4-trifluoromethyl) - cyclohexyl] -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methanesulfonyl-aminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-2,2,2-trifluoroethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3 - [(3-methoxy) phenyl] piperidin-1-yl-carbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / 4-fluorophenyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (f?) - hydroxymethyl-3-methyl-but-1-yl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N- (dimethylaminocarbonylmethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (R) -hydroxy) pyrrolidin-1 -carbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (S) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is - (2-hydroxy-ethyl) - / /-methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 s H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 s H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazole-5-ylR3 s H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylthio; R3 is H; R4 s H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is 5-hydroxy! R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-1,1-dimethylethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is fur-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is thien-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H, and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-pyrazol-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H, and Y is S; a compound of formula (I) wherein G is pihdin-3-yl; R3 is methyl; R4 is H; R5 is H; and Y is S, a compound of formula (I) wherein G is pyridin-3-yl; R3 is 1 H-imidazol-2-methylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is pyridin-2-ylmethyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is methyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is pyridin-2-ylmethyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -aminocarbonyl; R3 is f-butoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-hydroxyethyl) - aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-hydroxyethyl) - / \ / - methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /./ V-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /./ V-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (ft) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is trifluoromethylcarbonyl; R is H; R5 is H; and Y is OR; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; Y a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H1 and Y is O. Another embodiment of the present invention is directed to compositions comprising a compound selected from the group consisting of: a compound of formula (I) wherein G is 1H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / \ / - (2-methoxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O, a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, / V-diethylamidinoR3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R is H, R5 is H; and Y is O; a compound of formula (I) wherein G is A - (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - [2- (2,6-d.methylphenoxy) -1-methyl-etl] aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-phenyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-phenylethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-tetrazol-5-yl, R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-cyclohexyl-N-methyl- aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxymethyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-hydroxyamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminophenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-ethyl-1H-imidazol-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (R) -hydroxymethyl-2-phenyl-et-1-yl) -aminocarbonyl; R3 is H; R is H; R5 is H, and Y is O; a compound of formula (I) wherein G is N, N-diisobutylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-methylcarbonylamino-phenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 S-methoxymethyl-2-phenyl-et-1-yl) aminocarbonyl! R 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methoxypyridin-5-yl! R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4,5-dihydro-1 H -amidazol-2-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (4-phenyl) -cyclohexyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methyl-4H- [1, 2,4] triazol-5-yl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is A / - (2-dimethylamino-et-1-l) -N-methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methanesulfonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -2,2,2, -trifluoroethyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3 - [(3-methoxy) phenyl] piperidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-4-fluorophenyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - (dimethylaminocarbonylmethyl) - / \ / - methyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (f?) -hydroxy) pyrroline-1-carbonylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (S) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 s H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 s H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is AH - [,, 2,4] -oxadiazol-5-oxo-3-yl, R 3 is H, R 4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-t-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H, R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-1,1-dimethyl-ethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is fur-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H, and Y is O; a compound of formula (I) wherein G is thien-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-pyrazol-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is methyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is fur-3-ylmethyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -am'inocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / JV-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (R) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl, R3 is H, R4 is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is 5-hydroxy; R5 is H; and Y is O. Another embodiment of the present invention is directed to compositions comprising a compound selected from the group consisting of: a compound of formula (I) wherein G is 1 H-tetrazol-5-ylloR3 it's H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1 -carbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-methoxy-ethyl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-??? - 3-???; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, / / / diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H, R is H; R5 is H, and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - [2- (2,6-dimethylphenoxy) -1-methyl-ethyl] aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / phenyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-l) aminocarbonyl, R 3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-phenylethyl) -N-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -cyclohexyl-A / -methyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxymethyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-hydroxyamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-ethyl-1H-imidazol-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (f?) - hydroxymethyl-5-2-phenyl-et-1-yl) -aminocarbonyl! R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-dimethylamino-et-1-yl) -A / -methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-2,2,2-trifluoroethyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; A compound of formula (I) wherein G is 3 - [(3-methoxy) phenyl] piperidin-1-ylcarbonyl; R3 is H; R is H; R5 is H, and Y is O; a compound of formula (I) wherein G is / V-4-fluorophenyl-A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is AZI S (dimethylaminocarbonylmethyl) - / \ / - methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (S) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - - tetrazol - 5 - yl, R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 it's H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl, R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 - / - [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is H-tetrazol-5-yl, R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is fur-3-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is 1 / - / - imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl, R3 is H; R 4 is 5-hydroxy; R5 is H1 and Y is O. Another embodiment of the present invention is directed to compositions comprising a compound selected from the group consisting of: a compound of formula (I) wherein G is 1 H-tetrazol-5-yl! R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazole-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl, R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-methoxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is A / JV-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - [2- (2,6-dimethylphenoxy) -1-methyl-ethyl] aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -phenyl-W-methyl- aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-yl) aminocarbonyl R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-phenylethyl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H, R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-dimethylamino-et-1-yl) - / V-methyl-aminocarbonyl; R3 is ethoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - (dimethylaminocarbonylmethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 it's H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H, R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-γ-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is A /./ V-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl, R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R is 5-hydroxy; R5 is H, and Y is O. Another embodiment of the present invention is directed to compositions comprising a compound selected from the group consisting of: a compound of formula (Ib) wherein G is carboxy; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is ethoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (Ib) wherein G is cyano; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R 4 is 6-methoxycarbonyl; R5 is H; and Y is O; a compound of formula (Ib) wherein G is bromine; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (Ib) wherein G is bromine; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (Ib) wherein G is cyano; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (Ib) wherein G is cyano; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is cyano; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is cyano; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is cyano; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is carboxy; R3 is t-butoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is carboxy; R3 is H; R is H; R5 is H; and Y is O; and a compound of formula (Ib) wherein G is carboxy; R3 is H; R4 is H; R5 is H; and Y is O. Another embodiment of the present invention is a composition comprising the dextrorotatory enantiomer of a compound of formula (I), wherein said composition is substantially free of the levorotatory isomer of said compound. In the present context, substantially free means less than 25%, preferably less than 10%, preferably less than 5%, preferably less than 2%, and most preferably less than 1%, of the isomer levorotatory, calculated as: (levorotatory mass)% levorotatory = x 100 (dextrorotatory mass) + (levorotatory mass) Another embodiment of the present invention is a composition that comprises the levorotatory enantiomer of a compound of formula (I), in wherein said composition is substantially free of the isomer dextrorotatory of said compound. In the present context, substantially free means less than 25%, preferably less than 10%, preferably less than 5%, preferably less than 2%, and very less than 1% preference, of the dextrorotatory isomer, calculated as: (dextrorotatory mass)% dextrorotatory = x 100 (dextrorotatory mass) + (levorotatory mass) The compounds of the present invention may also be present in the form of pharmaceutically acceptable salts. To be used in medicine, the salts of the compounds of this invention refer to the "pharmaceutically acceptable salts" harmless. { Ref. International J. Pharm., 1986, 33, 201-217; J. Pharm Sci., 1997 (January), 66, 1, 1). However, other salts well known to those skilled in the art may be useful in the Preparation of the compounds according to this invention or their salts pharmaceutically acceptable Representative organic or inorganic acids include, without limitation, hydrochloric, hydrobromic, hydroiodic, perchloric, sulfuric, nitric, phosphoric, acetic, propionic, glycolic, lactic, succinic, maleic, fumaric, malic, tartaric, citric, benzoic, mandelic, methanesulfonic , hydroxylethanesulfonic, benzenesulfonic, oxalic, pamoic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, salicylic, saccharinic or trifluoroacetic. Representative organic or inorganic bases include, without limitation, basic or cationic salts such as benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, aluminum, calcium, lithium, magnesium, potassium, sodium and zinc. The present invention includes within its scope prodrugs of the compounds of this invention. In general, said prodrugs will be functional derivatives of the compounds, which are readily convertible in vivo to the required compound. Thus, in the methods of treatment of the present invention, the term "administer" encompasses the treatment of the various disorders indicated with the specifically described compound, or with a compound that may not be specifically described but that is converted in vivo in the specified compound after its administration to the patient. Conventional procedures for selecting and preparing suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985. The compounds according to this invention which have at least less a chiral center can consequently exist as enantiomers. Additionally, compounds that possess two or more chiral centers can exist as diastereomers. It is understood that such isomers and their mixtures are included within the scope of the present invention. In addition, some of the crystalline forms of the compounds can exist as polymorphs and as such are considered included in the present invention. In addition, some of the compounds may form solvates in water (ie, hydrates) or common organic solvents, and such solvates are also considered to be included within the scope of this invention. When the methods of preparing the compounds according to the invention produce a mixture of stereoisomers, these isomers can be separated by conventional techniques, such as preparative chromatography. The compounds can be prepared in racemic form, or individual enantiomers can be prepared by enantiospecific synthesis or by resolution. For example, the compounds can be resolved into their component enantiomers by standard techniques, such as the formation of diastereomeric pairs by salt formation with an optically active acid, such as (-) - di-p-toluoyl-d-tartaric acid. or (+) - di-p-toluoyl-l-tartaric acid, followed by fractional crystallization and regeneration of the free base. The compounds can also be resolved by the formation of diastereomeric esters or amides, followed by chromatographic separation and removal of the chiral auxiliary. Alternatively, the compounds can be resolved using a chiral HPLC column.

During any of the methods of preparing the compounds of the present invention it may be necessary or desirable to protect the sensitive or reactive groups in any of the molecules involved. This can be done by means of conventional protecting groups, such as those described in: "Protective Groups in Organic Chemistry", ed. J. F. W. McOmie, Plenum Press, 1973; and T. W. Greene & P. G. M. Wuts, "Protective Groups in Organic Synthesis", John Wiley & Sons, 1991. Protective groups can be removed in a convenient subsequent step using known methods. Although the compounds of the present invention (including their pharmaceutically acceptable salts and solvates) can be administered alone, they will generally be administered in admixture with a pharmaceutical carrier, excipient or diluent, selected appropriately for the intended administration route and according to pharmaceutical practice. or normal veterinary. Thus, the present invention is directed to pharmaceutical and veterinary compositions comprising the compounds of formula (I) and one or more pharmaceutically acceptable carriers, excipients or diluents. By way of example, in the pharmaceutical and veterinary compositions of the present invention, the compounds of the present invention can be mixed with any suitable binder, lubricant, suspending agent, coating agent or solubilizing agent. Tablets or capsules of the compounds can be administered one to one or two or more at a time, as appropriate. It is also possible to administer the compounds in sustained release formulations. Alternatively, the compounds of general formula (I) can be administered by inhalation or in the form of a suppository or pessary, or they can be applied topically in the form of a lotion, solution, cream, ointment or powder. An alternative means of transdermal administration is the use of a skin patch. For example, they can be incorporated into a cream consisting of an aqueous emulsion of polyethylene glycols or liquid paraffin. They can also be incorporated, at a concentration between 1% and 10% by weight, into an ointment consisting of a white wax base or white soft paraffin, together with stabilizers and preservatives as required. For some applications it is preferable to administer the compositions orally in the form of tablets containing excipients such as starch or lactose; or in capsules or ovules, alone or in admixture with excipients; or in the form of elixirs, solutions or suspensions containing flavoring or coloring agents. The compositions (and also the compounds alone) can be injected parenterally, for example intracavernously, intravenously, intramuscularly or subcutaneously. In this case, the compositions will comprise a suitable vehicle or diluent. For parenteral administration, the compositions are best used in the form of a sterile aqueous solution which may contain other substances, for example salts or monosaccharides, to make the solution isotonic with the blood.

For buccal or sublingual administration, the compositions can be administered in the form of tablets or lozenges that can be formulated in the conventional manner. By way of further example, pharmaceutical and veterinary compositions containing one or more of the compounds of the invention described herein as active ingredient, can be prepared by intimately mixing the compound or compounds with a pharmaceutical carrier according to the conventional techniques of pharmaceutical composition. The vehicle can take a wide variety of forms depending on the desired route of administration (eg, oral, parenteral). Thus, for liquid oral preparations such as suspensions, elixirs and solutions, suitable carriers and additives include water, glycols, alcohols, flavoring agents, preservatives, stabilizers, coloring agents and the like.; for solid oral preparations such as powders, capsules and tablets, suitable carriers and additives include starches, sugars, diluents, granulating agents, lubricants, binders, disintegrating agents and the like. Solid oral preparations can also be coated with substances such as sugars, or with enteric coatings, in order to modulate the greater site of absorption. For parenteral administration, the vehicle will usually consist of sterile water, and other ingredients may be added to increase solubility or preservation. Suspensions or injectable solutions can also be prepared using aqueous vehicles together with the appropriate additives.

Conveniently, the compounds of the present invention can be administered in a single daily dose, or the total daily dose can be administered in divided doses of two, three or four times a day. In addition, the compounds of the present invention can be administered in intranasal form by the topical use of suitable intranasal vehicles, or by means of transdermal patches well known to those skilled in the art. Of course, for administration in the form of a transdermal delivery system, the dosage will be continuous instead of intermittent throughout the dosing regimen. It is also evident to the person skilled in the art that the therapeutically effective dose of the active compounds of the invention, or a pharmaceutical composition thereof, will vary according to the desired effect. Therefore, the doses to be administered can be easily determined, and will vary with the particular compound used, the mode of administration, the concentration of the preparation and the progress of the pathological condition. In addition, it will be necessary to adjust the dose to an appropriate therapeutic concentration taking into account the factors associated with the particular subject treated, including the subject's age, weight and diet, and the administration schedule. Thus, the above dosages are exemplary of the average case. Of course, there may be individual cases that merit higher or lower dosing scales and are within the scope of this invention. Whenever it is required to use the compounds of the invention As analgesics for a subject in need thereof, the compounds of this invention can be administered in any of the aforementioned compositions and dosage regimens, or by means of the compositions and dosage regimens established in the art. The invention also provides a pharmaceutical or veterinary package or equipment comprising one or more containers containing one or more of the ingredients of the pharmaceutical and veterinary compositions of the invention. Optionally, there may be an instruction associated with said containers, in the form prescribed by the governmental agency that regulates the manufacture, use or sale of pharmaceutical or biological products; said instruction indicates the approval, by the agency, of the manufacture, use or sale for human administration. The compounds of the present invention can be used to treat pain, from mild to severe, in warm-blooded animals such as humans, by administering an analgesically effective dose. The dosage scale would be from about 0.1 mg to about 15,000 mg, in particular from about 50 mg to about 3,500 mg or, more in particular, from about 100 mg to about 1000 mg of the active ingredient, at a rate of about 1 to 4 times a day for an average person (70 kg); however, it is obvious to the person skilled in the art that the therapeutically effective amount of the active compounds of the invention will vary according to the types of pain treated. For oral administration, preferably a pharmaceutical composition is provided in the form of tablets containing 0.01, 10.0, 50.0, 100, 50, 200, 250 and 500 milligrams of the active ingredient for symptomatic adjustment of the dose to the subject treated. Examples of pain types considered within the scope of the present invention include, without limitation, inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, pain related to structural or soft tissue injury, pain related to progressive disease, neuropathic pain and acute pain, such as that caused by acute injury, trauma or surgery, and chronic pain such as headache and that caused by neuropathic conditions, post-stroke conditions, cancer and migraine. The compounds of the present invention are also useful as immunosuppressants, anti-inflammatories, agents for the treatment and prevention of neurological and psychiatric conditions, for example depression and Parkinson's disease, agents for the treatment of urological and reproductive conditions, for example urinary incontinence and premature ejaculation, agents for the abuse of drugs and alcohol, agents for the treatment of gastritis and diarrhea, cardiovascular agents and cardioprotective agents, and agents for the treatment of respiratory diseases. The compounds of the present invention are also useful in the treatment of pain caused by osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, snake bite (particularly venomous snake bite), spider bite, insect bite, neurogenic bladder, hypertrophy benign prosthetics, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, mandibular joint neuralgia, peripheral neuritis, polyneuritis, stump pain, phantom limb pain , postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, meralgia paresthetica, burning mouth syndrome, postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache , peripheral neuropathy, bilateral peripheral neuropathy, neuropathy diabetic, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, postfebrile neuritis, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, neuralgia mammary, Morton neuralgia, nasociliary neuralgia, occipital neuralgia, red neuralgia, Sluder neuralgia, splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, sinusitis headache, tension headache, labor, childbirth, menstrual cramps and cancer. With respect to the use of the present compounds in the Treatment of diseases or conditions such as those mentioned above, those skilled in the art can determine a therapeutically effective dose using the established animal models. Such a dose would probably be on the scale of about 0.01 mg to about 15,000 mg of active ingredient, administered 1 to 4 times a day, for an average person (70 kg).

General Methods of Synthesis Representative compounds of the present invention can be synthesized according to the general methods of synthesis described below and illustrated in the following schemes. Since the schemes are an illustration, the invention should not be considered as limited by the chemical reactions and conditions expressed. The preparation of the various starting materials used in the schemes is within the domain of those skilled in the art. The preparation of the compounds of this invention is illustrated in schemes 1 and 2. Both schemes proceed with the same general strategy. In step 1, an intermediate 1 is prepared with two benzene rings linked by a linker -Y-. The linker -Y- would be of the form - (CH2) n -X-, where X can be oxygen or sulfur and n can be zero or one. A benzene ring carries a group, Q, which is a group easily transformable into a substituent G as defined herein. Examples of said Q groups are fluorine, bromine, cyano, iodine, carboxy, or trifluoromethanesulfonyloxy. In some cases the substituents Q may be the same substituents G of the formula (Ib). A benzene ring must carry a carboxylic acid, or a carboxylic acid precursor, in ortho position with respect to the -Y- linker. The X atom can be attached to the benzene ring bearing the Q group or to the benzene ring lacking the Q group. Schemes 1 and 2 differ in that in scheme 1 the carboxylic acid is in the benzene ring that carries the group Q (1A and 1 B), while in scheme 2 the carboxylic acid function is in the benzene ring that does not carry the group Q (1 C, 1 D and 1 E).

SCHEME 1 Step G SCHEME 2 Step l Steps 3-6 Intermedians Mono Adieos 6 step 1 the linker -Y- is constructed between two monocyclic intermediates. For scheme 1, step 1, the bridge can be constructed by nucleophilic aromatic displacement of intermediate fluoride int 2 (where Q 'is an electron-withdrawing group, easily convertible to a carboxylic acid, for example cyano or carbalkoxy), with a phenoxide, thiophene oxide , benzyl oxide or thiobenzyl oxide, int 1. The compounds 1A are then obtained by hydrolysis with an alkali metal hydroxide. For the construction of the bridge of the compounds of type 1 B, an intermediate compound of benzyl halide (int 5) is prepared by means of NBS bromination of the corresponding toluene (int 4). Reaction of int 5 with a phenoxide or phenylthioxide produces int 6. Compound 1 B can be obtained by hydrolysis of int 6 with alkali metal hydroxide.

SCHEME 1. STEP 1 For scheme 2, step 1, to prepare compounds 1 C, a phthalide (int 7) can be reacted with a phenoxide or phenylthioxide (int 8). To prepare the compounds of formula 1 D, the bridge can be constructed by aromatic nucleophilic displacement of the intermediate fluoride int 9 with phenoxides or phenylthioxides (int 8). The compounds of formula 1 D are then obtained by hydrolysis of the int 10 with an alkali metal hydroxide. For the construction of the linker Y of the compounds of intermediate 13, benzyl bromide compounds of int 12 can be reacted with a phenoxide or phenylthioxide (int 1 1). The compounds of formula 1 E can then be obtained by hydrolysis of int 13 with an alkali metal hydroxide.

SCHEME 2, STEP 1 Nt 11 ¡nt 12 inrt 1 3 After step 1, the schemes come together. In step 2, the compounds of formula 1 are converted by cycloacylation to the ketones of formula 2, using for example BF3 Et20-trifluoroacetic acid or polyphosphoric acid. Alternatively, cyclization can be effected by converting an acid of formula 1 to an acid chloride, using a chlorinating agent such as thionyl chloride or the like, followed by Friedel-Crafts ring closure in the presence of a Lewis acid, such as aluminum chloride. In addition, steps 1 and 2 can be done in an inverted order to give the compounds of formula 2, which are ready to go to step 3. For example, the Friedel-Crafts acylation between a methyl ether (nt 14) and an appropriately substituted acid chloride provides the ketone (int 16), which simultaneously demethylates under the reaction conditions. The subsequent formation of the bridge -Y- by means of a nucleophilic aromatic displacement, gives the compounds of formula 2, ready to enter step 3.

SCHEME 3, STEPS 1 AND 2 tnt 14 int 15 int 1 6 In step 3, the Q function of the compounds of formula 2 is converted to group G, which may be -C (Z) NR1R2, an aryl substituent, an aryl thioether, or a heterocycle suitable, as defined herein, to give the compounds of formula 3. When the Q-function of the compounds of formula 2 is a halogen or trifluoromethanesulfonyloxy, it can be converted to an ester by alkoxycarbonylation, using carbon monoxide, an aliphatic alcohol , a trialkanlamine, and a palladium catalyst such as bis (triphenylphosphine) palladium (II) dichloride. Subsequently, when Q is an ester, the ester can be hydrolyzed to form a carboxylic acid. The carboxylic acid can then be coupled with an appropriately functionalized amine to form a primary, secondary or tertiary amide. Alternatively, the conversion of a carboxylic acid to an amide can be carried out by an acid chloride, using thionyl chloride, oxalyl chloride or the like, followed by a Schotten-Baumann reaction using an appropriately functionalized amine, in the presence of an alkali metal hydroxide. Alternatively, the ester can be converted directly to the amide by the action of a dimethylaluminum amide. Instead of proceeding to the compounds of formula 3 by of an ester, the group Q can be transformed into a substituent G (where G is an amidino or heterocycle) by means of a nitrile. The synthesis of the nitrile can be done by treatment of the compounds of formula 2 (wherein Q is bromine or trifluoromethanesulfonyloxy) with Zn (CN) 2 and a palladium catalyst such as (Ph3P) 4Pd, or by treatment of the compounds of formula 2 with CuCN at elevated temperature. For the synthesis of amidino functional groups, the nitrile is treated with hydroxylamine under basic conditions to produce an oxime. The treatment of the oxime with a primary or secondary amine, CuCl and an alkali metal carbonate, in an alcoholic solvent and under microwave irradiation, provides the amidino compounds of the present invention. Reactions can be accelerated by microwave using a CEM Discover microwave instrument or a Personal Chemistry Smith Synthesizer. The oxime described above is instrumental in the preparation of the compounds wherein G is a heterocycle. The oxime can be cyclized with a variety of known electrophiles to give the heterocycles of the present invention. For example, the reaction of the oxime with CDI provides oxadiazolones, and the treatment of the oxime with TCDI provides the corresponding oxadiazoliones. Similarly, treatment of the oxime with thionyl chloride in the presence of a tertiary amine gives the oxathiadiazoles of the present invention. An aryl substituent can be placed in place of the functional group Q by coupling the compounds of formula 2 (when Q is bromine or trifluoromethanesulfonyloxy) with a substituted arylboronic acid suitably, in the presence of a palladium catalyst and an alkali metal carbonate. To perform step 4, a ring substituted on A is attached to the tricyclic system by replacing the ketone, to give compounds of formula 4 wherein m is 0, 2, or 3, as defined herein. This operation can be carried out by means of the condensation of McMurray of ketones of formula 3 with 4-piperidinones (m is 0) or 8-nortropinones (m is 2) or an azabicyclo (3.3.1) nonanone (m is 3), in the presence of a titanium reagent of lower valence. Said reagent can be formed from the addition of titanium tetrachloride to zinc powder. Alternatively, an appropriately substituted magnesium halide can be added to the ketones of formula 3 to produce carbinoles. Dehydration of said carbinoles with acid reagents such as formic acid, sulfuric acid or trifluoroacetic acid, also produces the compounds of formula 4. If desired, the operation of steps 3 and 4 can be carried out in an inverted order. As illustrated in schemes 1 and 2, the nitrogen atoms of the compounds of formula 4 carry a P group. This group may be an alkanyl, alkenyl or aralkanyl, in which case they are the therapeutically useful products of this invention. The group P can also be trifluoromethylcarbonyl, alkoxycarbonyl or aralkoxycarbonyl. These latter groups can be converted to secondary amines of formula 5 as illustrated in step 5. These transformations can be performed using some acid reagents such as hydrogen bromide or trimethylsilyl iodide.

Or when P is a trifluoromethylcarbonyl, basic reagents such as potassium carbonate in an alcoholic solvent can be used to remove P. Compounds of formula 4 carrying easily separable groups such as methyl, allyl or benzyl, can be transformed into the derivatives alkoxycarbonyl mentioned above by treatment with alkanyl chloroformates, such as ethyl chloroformate or 1-chloroethyl chloroformate. Finally, the secondary amines of formula 5 can be substituted with R3 to provide the compounds of formula 6 shown in step 6. These transformations can be effected by reductive alkylation using a carbonyl-containing compound and a reducing agent such as sodium borohydride, sodium cyanoborohydride, tetramethylammonium triacetoxyborohydride, or sodium triacetoxyborohydride. The R3 substituent can also be introduced by a conventional alkylation, using an alkanyl, alkenyl or aralkyl halide, and an organic or inorganic base. The person skilled in the art will recognize that alkylating agents with different halide leaving groups are equally useful for this transformation. The desired end products of the present invention may include chemical modifications in R4. Such transformations may include dealkylation of lower alkyl ethers to give the corresponding alcohols, using reagents such as boron trihalides. Compounds wherein R 4 is a halogen atom may participate in transition metal-mediated coupling reactions, such as Chemistry of Suzuki, Stille or Negishi. Scheme 4 shows the preparation of the compounds of the present invention wherein R 4 is different from hydroxy or mercapto. A compound of the formula of int 17 can be converted to its triflate by treatment with N, N-bis (trifluoromethylsulfonyl) phenylamine or similar reagents, to produce a compound of the formula of int 18. Triflate treatment with a source of cyanide such as zinc cyanide, in the presence of a palladium catalyst, provides the compounds of the formula of int 19, which can subsequently be hydrolyzed with hydroxide anion in the presence of hydrogen peroxide to produce the compounds of the formula of int 20 wherein R is an aminocarbonyl.

SCHEME 4 NH2OH.HCI base The cyano group of a compound of the formula of int 19 is also a precursor for other R4 substituents of the present invention. For example, a compound of the formula of int 19 can be treated with ammonium hydroxide in the presence of a base such as a tertiary amine, to produce a hydroxyamidino compound of the formula of int 21. The deprotection of the compounds of the formula int 21 produces the compounds of the formula 5-1.

As illustrated in scheme 5, a compound of the formula of int 18 can be treated with an amino synthon, wherein a synthon is a synthetic equivalent or a functional group that is related to some other structural unit, by a reaction or sequence of reliable reactions. An example of an amino-synthon group includes without limitation benzophenone-imine. The benzophenone imine can be used in the presence of an appropriate palladium catalyst under basic conditions, which by treatment with ammonium hydroxide produces compounds of the formula of int 22. The aniline can be formylated with formic acetic anhydride, followed by removal of P. using the methods that are exposed here. Lawesson's reagent can be used to convert carbonyl-containing R4 substituents into their corresponding thiocarbonyl analogs.

SCHEME 5 The preparation of the compounds wherein R4 is Ce-io arylamino can be done using a palladium-catalyzed amination of a compound of the formula of int 18 with the C6-io arylamine and an inorganic base such as cesium carbonate.

Anilines of the formula of int 22 can be converted to corresponding aminothiazoles of formula 6-2 by reaction appropriate reagents, such as potassium thiocyanate.

The compounds where the bridge -A- is - (CH2) 2-3- are chiral. They can be separated into their enantiomers by chromatography in a chiral stationary phase after steps 4, 5, or 6. Alternatively, the basic compounds of formulas 4, 5 and 6 can be converted to diastereomeric salts by mixing with a chiral acid, and they can be resolved in their enantiomers by fractional crystallization. It is generally preferable that the respective product of each process step be separated from other components of the reaction mixture, and be subjected to purification before use as a starting material in a subsequent step. Separation techniques typically include evaporation, extraction, precipitation and filtration. Purification techniques typically include column chromatography (Still, W. C. et al., J. Org. Chem. 1978, 43, 2921), thin layer chromatography, crystallization and distillation. The structures of the final products, intermediates and starting materials are confirmed by means of spectroscopic, spectrometric and analytical methods, including nuclear magnetic resonance (NMR), mass spectrometry (MS) and liquid chromatography (HPLC). In the descriptions for the preparation of the compounds of this invention, ethyl ether, tetrahydrofuran and dioxane are common examples of an ethereal solvent; benzene, toluene, hexane and heptane are typical hydrocarbon solvents; and dichloromethane and dichloroethane are representative halogenated hydrocarbon solvents. In cases where the product is isolated as the acid addition salt, the free base can be obtained by techniques known to those skilled in the art. In cases where the product is isolated as an acid addition salt, the salt may contain one or more equivalents of the acid. The enantiomers of the compounds of the present invention can be separated using chiral HPLC. Representative compounds of the present invention can be synthesized according to the general synthesis methods described above, and are illustrated more particularly in the schemes that follow. Since the schemes are illustrations, the invention should not be considered limited by the chemical reactions and conditions expressed. The preparation of the various starting materials used in the schemes is within the domain of those skilled in the art.

Abbreviations 1, 1 '-carbonyldiimidazole 1,8-diazabicyclo [5.4.0] -7-undequene A / / V-dimethylformamide 1,1' -bis (diphenylphosphino) ferrocene ethyl hour (s) methyl minute (s) 1, 1'-thiocarbonyldiimidazole polyphosphoric acid tert-butoxycarbonyl, 1'-thiocarbonyldiimidazole trifluoroacetic acid tetrahydrofuran microwave irradiation watt (s) EXAMPLES EXAMPLE 1 H Procedure A 4-Bromo-2-phenoxybenzoic acid (1b). 4-Bromo-2-chloro-benzoic acid (10 g, 42 mmol), phenol (4.19 g, 44 mmol), hexafluorophosphate was added. of tetrakisacetonitrile-copper (3.95 g, 0.6 mmol), and cesium carbonate (27.6 g, 85 mmol), to a 1 L 3-necked round bottom flask, equipped with magnetic stirrer, reflux condenser, and containing toluene (350 mL).

The reaction was refluxed overnight under nitrogen with stirring.

After cooling, ethyl acetate (200 mL) was added and the reaction was acidified with aqueous 2N HCl. The organic phase was separated, dried (MgSO4) and it leaked The filtrate was concentrated to yield 4-bromo-2-phenoxybenzoic acid (12.4 g), which was used in subsequent reactions without further purification.

Procedure B 3-Bromo-xanten-9-one (1 c). Polyphosphoric acid (260 g, 20: 1; p: p) was added to 4-bromo-2-phenoxybenzoic acid (13.5 g). The reaction was heated (120 ° C) by stirring rapidly with a mechanical stirrer to homogenize. After 2h, the heating apparatus was removed. Once the reaction temperature reached less than 70 ° C, the mixture was emptied on crushed ice. The resulting aqueous solution was extracted with chloroform (3 x 100 mL). The combined organic extract was washed with sodium bicarbonate solution (100 mL, 1 M), dried (MgSO4), and concentrated, to yield 3-bromo-xanthen-9-one (1.4 g), which was used in subsequent reactions without further purification.

Procedure C / V-f2- (9-Qxo-9H-xanten-3-yl) -phenn-acetamide (1d). Into a 5 mL reaction vessel, 3-bromo-xanthen-9-one (0.25 g, 0.9 mmol), 2-acetamidophenylboronic acid (0.99 mmol), 1,1 '-bis- dichloride were microwaved. diphenyl-phosphino) ferrocene-palladium (II) (33 mg, 0.045 mmol), cesium carbonate (0.59 g, 1.8 mmol), dioxane (4 mL) and ethanol (2 mL), at 100 ° C for 5 min. The reaction was filtered and concentrated. The residue was purified by reverse phase chromatography to yield? / - [2- (9-??? - 9 / - / - xanthen-3-yl) -phenyl] -acetamide.

Procedure D A / - (2-r 9 - (8-Aza-bicyclo [3.2.1 loct-3-ylidene) -9 H-xanten-3-n-phenyl) -acetamide (Compound 2). A suspension of zinc powder (0.317 g, 4.8 mmol) in THF (100 ml_) at room temperature was treated with titanium (IV) chloride (0.266 ml_, 2.4 mmol) by dropwise addition. The resulting mixture was heated to reflux for 2 h under a nitrogen atmosphere. The resulting solution was cooled to room temperature. A portion of 3-oxo-8-aza-bicyclo [3.2.1] octane-8-carboxylic acid tert-butyl ester (0.136 g, 0.6 mmol) and A / - [2- (9-oxo- 9H-xanten-3-yl) -phenyl] -acetamide (0.20 g, 0.6 mmol), and the solution was refluxed for 2 h. The reaction was diluted with ethyl acetate (15 mL) and 1 N aqueous hydrochloric acid (20 mL). The organic layer was separated, dried (MgSO4), and filtered. The filtrate was evaporated in vacuo. The crude product was purified by reverse phase preparative HPLC, using a gradient of acetonitrile (10% to 90%) in water with trifluoroacetic acid (0.1%), to give the trifluoroacetic acid salt of compound 2 (0.124 g). MS m / z (MH +) 423.2; 1 H NMR (DMSO-d 6) d 1.32 (m, 2 H), 1.79 (m, 2 H), 1.88 (s, 3 H), 2.92-3.0 (m, 4 H), 4.04 (m, 2 H), 7.21-7.47 (m , 1 1 H), 8.67 (bs, 1 H), 9.05 (d, 1 H), 9.35 (s, 1 H).

EXAMPLE 2 H 3- (3-Pyridin-3-yl-xanten-9-ylidene) -8-aza-bicyclof3.2.1 loctane (Compound 12). The title compound was prepared using the method described in example 1, substituting in procedure C the 2-acetamidophenylboronic acid with 3-pyridylboronic acid, and using an adaptation of procedure D. MS m / z (MH +) 367.1; 1 H NMR (DMSO-d 6) d 1.29 (d, 2 H, J = 9.2 Hz), 1.78 (m, 2 H), 2.91-3.09 (m, 4 H), 4.01 (s, 2 H), 7.24 (t, 1 H, J = 7.4 Hz), 7.31 (d, 1 H, J = 6.8 Hz), 7.38 (d, 1 H, J = 7.0 Hz), 7.43 (d, 1 H, J = 7.7 Hz), 7.54 (d, 1 H, J = 8.0 Hz), 7.62-7.73 (m, 2H), 7.73 (s, 1 H), 8.32 (d, 1H, J = 8.0 Hz), 8.68 (m, 1 H), 8.81 (m, 1 H), 9.05 (s, 1 H), 9.1 1 (m, 1 H).

EXAMPLE 3 Dimethyl ester of 2-phenoxy-terephthalic acid (3b). The title compound was prepared according to the method described in process A, and 4-bromo-2-chloro-benzoic acid was substituted with 2-iodo-terephthalic acid dimethyl ester. Methyl ester of 9-oxo-9H-xanthene-3-carboxylic acid (3c). The title compound was prepared according to the method described in process B, substituting 4-bromo-2-phenoxybenzoic acid with 2-phenoxyterephthalic acid dimethyl ester.

Procedure E 9-Oxo-9H-xanthene-3-carboxylic acid (3d). A solution of 9-oxo-9H-xanthene-3-carboxylic acid methyl ester (3.75 mmol) and 3 N sodium hydroxide (4.12 mmol) in MeOH (30 mL), refluxed for 2 h. The solution was cooled to room temperature and acidified with 2N hydrochloric acid. The mixture was concentrated in vacuo and then diluted with water. The resulting solid was collected by filtration, washed with water and dried in air to yield the title compound.

Procedure F 3- (Pyrrolidin-1 -carbonyl) -xanten-9-one (3e). 9-Oxo-9H-xanthene-3-carboxylic acid (9 g, 37.4 mmol) was added to thionyl chloride (28 mL, 334 mmol). The mixture was refluxed for 5 h. At that time, the thionyl chloride was removed in vacuo and the remaining residue was diluted with toluene and concentrated to dryness, to give 9-oxo-9H-xanthene-3-carbonyl chloride. A portion of the 9-oxo-9H-xanthene-3-carbonyl chloride (0.25 g, 0.96 mmol) was dissolved in acetonitrile (7 mL). To the mixture was added diisopropylethylamine (335 pL, 1.9 mmol) with the subsequent addition of pyrrolidine (1 13 pL, 1.3 mmol). After stirring 2 h, the solvent was concentrated and the residue was purified by reverse phase preparative HPLC, using a gradient of acetonitrile (10% -90%) in water with trifluoroacetic acid (0.1%), to produce 3- ( pyrrolidin-1 -carbonyl) -xanten-9-one. MS m / z (MH +) 294.1. r9- (8-Aza-bicylchlor3.2.1loct-3-ylidene) -9H-xanten-3-yl-pyrrolidin-1-yl-methanone (Compound 6). The title compound was prepared according to procedure D, substituting 3- (pyrrolidin-1-carbonyl) -xanten-9-one for the / V- [2- (9-oxo-9H-xanten-3-yl) phenyl] -acetamide, and was obtained as a TFA salt after preparative reverse phase HPLC. MS m / z (MH +) 387.2; 1 H NMR (DMSO-d 6) 51 .28 (d, 2 H, J = 1 1.2 Hz), 1.80-1.89 (m, 6H), 2.95 (q, 4H, J = 16.1 Hz), 3.41 (t, 2H, J = 6.2 Hz), 3.47 (t, 2H, J = 6.8 Hz), 4.0 (s, 2H), 7.23 (t, 1 H, J = 7.3 Hz), 7.28-7.46 (m, 6H), 8.80 (bs, 1 H), 9.1 (m, 1 H).

EXAMPLE 4 9-Oxo-9 / - / - xanthene-3-carboxylic acid (2-hydroxy-ethyl) -methyl-amide (4a). The title compound 4a was prepared using the method described in procedure F, substituting pyrrolidine with 2-methylamino-ethanol. Ethyl ester of 3- acid. { 3-f (2-hydroxyethyl) -methyl-carbamoyl-xanten-9-ylidene) -8-aza-bicyclo [3.2.11octane-8-carboxylic acid (4b). The desired product 4b was prepared using the method described in procedure D, substituting 9-oxo-9H-xanthene-3-carboxylic acid (2-hydroxy-ethyl) -methyl-amide for A / - [2 - (9-oxo-9H-xanten-3-yl) -phenyl] acetamide, and substituting with 3-Oxo-8-aza-bicyclo [3.2.1] octane-8-carboxylic acid ethyl ester 3-oxo-8-aza-bicyclo [3.2.1] octane-8-carboxylic acid tert-butyl ester.

Process G- (8-aza-bicyclo [3.2.1loct-3-ylidene] -9 / - / - xanthene-3-carboxylic acid (2-hydroxy-ethyl) -methyl-amide (Compound 61) . A sample of compound 4b (0.20 g, 0.43 mmol) was dissolved in 1 ml of acetic acid, and to the reaction was added 2 ml_ of 30% HBr HBr in acetic acid under argon, before heating to 80 ° C for 1 hour. h. The reaction was cooled, added to ice-cold NaOH, and extracted with CHCl3. The combined organic phase was concentrated. The resulting residue was purified by reverse phase HPLC, using a gradient of acetonitrile (10% to 90%) in water with trifluoroacetic acid (0.1%) to give the trifluoroacetic acid salt of compound 61 (0.146 g). MS m / z (MH +) 391.0; 1 H NMR (DMSO-d 6) d 1.26 (m, 2 H), 2.93-3.04 (m, 6 H), 3.28 (m, 1 H), 3.49 (m, 2 H), 3.61 (m, 1 H), 4.00 (m , 3H), 7.21 -7.42 (m, 1 H, J = 7.0 Hz), 8.65 (m, 1 H), 9.05 (m, 1 H).

EXAMPLE 5 Method H 8- (2,2,2-Trifluoroacetyl) -8-aza-bicyclo3.2.noctan-3-one (5b). To a solution of nortropinone hydrochloride (10 g, 61.87 mmol) and pyridine (20 mmol, 247 mmol) in CH 2 Cl 2 (120 mL), trifluoroacetic anhydride (12.4 mL, 87.79 mmol) was added dropwise at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 h and at room temperature for 1 h more. Added the mix a portion of 2N HCl (65 mL). The organic phase was washed with brine, dried (MgSO 4) and concentrated. The crude compound 5b was used in the next reaction without further purification. MS m / z (MH +) 221.9; 1 H NMR (CDCl 3) d 1.78 (m, 1 H), 1.90 (m, 1 H), 2.19 (m, 2 H), 2.49 (d, 2 H), 2.72 (m, 2 H), 4.71 (m, 1 H). 4.99 (m, 1 H).

Procedure I 4-Bromo-2-phenoxy-benzonitrile (5c). Sodium hydride (12 g, 300 mmol) (60% by weight) was weighed into a flask and washed of oil with several hexane rinses. The hexane was decanted and discarded and DMF was added to the flask. A solution of phenol (23.5 g, 250 mmol) in DMF (100 mL) was added dropwise, and the mixture was stirred at room temperature. To the mixture was added a solution of 4-bromo-2-fluoro-benzonitrile (50 g, 250 mmol, 100 mL DMF), dropwise. Upon completion of the addition, the reaction was refluxed for 20 h. The reaction was cooled to room temperature and emptied into cold 1 N NaOH. A fine tan precipitate formed, which was collected by vacuum filtration to give compound 5c. MS m / z (MH +) 277.

Procedure J 4-Bromo-2-phenoxy-benzoic acid (1 b). Compound 5c (35.3 g, 129 mmol) was added to 130 mL of EtOH, followed by the addition of 340 mL of 20% aqueous NaOH. The reaction was heated to reflux for 20 h. Then, the mixture was cooled to room temperature and emptied into 6N HCl.

The solid was collected by vacuum filtration, dissolved in THF-ethyl ether 3: 1, and washed with brine. The organic phase was dried (MgSO4) and concentrated. The solid was dried under vacuum in an oven at 60 ° C overnight, to give the desired compound 1 b. MS m / z (MH +) 292.

Procedure K 3-Bromo-xanten-9-one (1 c). To a suspension of 4-bromo-2-phenoxy-benzoic acid (5 g, 17 mmol) in CH 2 Cl 2 (50 mL) was added trifluoroacetic anhydride (2.9 mL, 20.53 mmol), at room temperature. The mixture was stirred at room temperature for 5 min. To this solution was added dropwise boron trifluoride diethyl ether (0.215 mL, 1.7 mmol) at 0 ° C. After 30 min, the reaction was allowed to warm to room temperature. The mixture was stirred at room temperature for 2 h, after which the mixture was poured into 1 N NaOH (35 mL) which was cooled to about 3 ° C. The aqueous layer was extracted with CH2Cl2 (2 x 10 mL). The combined organic layer was washed with brine, dried (MgSO 4) and concentrated. To the residue was added heptane and the resulting solid was collected by filtration to give compound 1c. MS m / z (MH +) 276.7; 1 H NMR (CDCl 3) d 7.43 (t, 1 H), 7.52 (m, 2 H), 7.76 (m, 2 H), 8.23 (d, 1 H), 8.35 (dd, 1 H). 1-f3- (3-Bromo-xanten-9-liden) -8-aza-biciclof3.2.1 loct-8-n-2,2,2-trifluoro-ethanone (5d). The title compound 5d was prepared using the method described in procedure D, substituting for the compound 1c the A / - [2- (9-oxo-9H-xanten-3-yl) -phenyl] -acetamide, and substituting with compound 5b the tert-butyl ester of 3-oxo-8-aza-bicyclo [3.2.1] octane-8-carboxylic acid. MS m / z (MH +) 463.6, 465.8; H NMR (CDCl 3) d 1.43 (m, 2H), 1.82 (m, 2H), 2.94 (m, 4H), 4.42 (m, 6 H), 4.72 (m, H), 7.20 (m, 6H), 7.4 (m, 1 H).

Procedure L 9-r8- (2,212-Trifluoro-acetyl) -8-aza-bicyclof3.2.noct-3-ylidene-9H-xanthene-3-carbonitrile (5e). To a solution of compound 5d (3 g, 6.46 mmol) in DMF (100 mL), CuCN (0.69 g, 7.70 mmol) was added. The reaction mixture was refluxed for 2 d and then cooled to room temperature. The mixture was poured into water (100 mL), and extracted with EtOAc (3 x 100 mL). The combined organic layer was washed sequentially with H20 (100 mL), brine (100 mL); then it was dried (MgSO4) and concentrated. The crude product was purified by normal phase chromatography, using a gradient of ethyl acetate (0% to 10%) in heptane to give compound 5e. MS m / z (M + H +) 410.9; 1 H NMR (CDCl 3) d 1.41 (m, 2 H), 1.85 (m, 2 H), 2.96 (m, 4 H), 4.44 (m, 1 H), 4.73 (m, 1 H), 7.23 (m, 3 H), 7.33 (m, 2H), 7.43 (dt, 1 H), 7.51 (m, 1 H).

Method M 2,2,2-Trifluoro-1- (3-f3- (1 H -tetrazol-5-yl) -xanten-9-ylidene-8-aza-biciclof3.2.11oct-8-yl) -ethanone ( 5f). To a solution of compound 5e (0.232 g, 0.56 mmol) in DMF (5 mL) was added NaN3 (0.1 1 g, 1.69 mmol) and NH4Cl (0.09 g, 1.68 mmol). The reaction mixture was heated at 120 ° C for 14 h, and then cooled to room temperature. An insoluble material was collected by filtration and washed with DMF (5 mL). The filtrate was acidified with 2N HCl (10 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layer was washed with H20 (10 mL), dried (MgSO4), and concentrated, to give the title compound 5f which was used for subsequent reactions without further purification. MS m / z (MH +) 453.9.

Procedure N 3- [3- (1 H-Tetrazol-5-yl) -xanten-9-ylidene-8-aza-bicichlor3.2.1 loctane (Compound 1). To a solution of compound 5f (0.2 g, 0.44 mmol) in CH3OH (4 mL) and H20 (1 mL) was added K2C03 (0.152 g, 1.1 mmol). The mixture was stirred at room temperature for 14 h and purified by reverse phase HPLC to give the title compound 1, as the TFA salt. MS m / z (MH +) 357.9; H NMR (DMSO-d6) d 1.27 (m, 2H), 1.77 (m, 2H), 2.97 (m, 4H), 4.00 (m, 2H), 7.36 (m, 4H), 7.63 (d, 1 H) , 7.91 (m, 3H), 8.82 (m, 1 H), 9.17 (m, 1 H).

EXAMPLE 6 Procedure O / V- Hydroxy-9-[8-(2,2,2- trifluoroacetyl) -8-aza-biciclof3.2.11oct-3-ylidenl-9H-xanthene-3-carboxamidine (6a). To a suspension of compound 5e (0.44 g, 1.07 mmol) in EtOH (5 mL) was added NH2OH HCI (0.223 g, 3.19 mmol) and K2CO3 (0.3 g, 2.17 mmol). The reaction mixture was refluxed for 4 h. After cooling the mixture to room temperature, H2O (1 mL) was added. The mixture was extracted with CH2Cl2 (2 x 5mL), dried (MgSO4), and concentrated, to yield compound 6a. The product 6a was used in the next reaction without further purification. MS m / z (MH +) 443.9.

Procedure P 3- (9-r8- (2,2,2-Trifluoro-acetyl) -8-aza-bicyclo3.2, noct-3-yldenden-9H-xanten-3-yl) -4H- [1 , 2,4] oxadiazol-5-one (6b). To a solution of compound 6a (0.1 g, 0.23 mmol) in 1,4-dioxane (4 mL) was added 1, 1 '-carbonyldiimidazole (CDI, 0.055 g, 0.34 mmol). The mixture was stirred at 10 ° C for 40 min under a nitrogen atmosphere. After cooling, the reaction concentrated. The crude compound 6b was used in the next reaction without further purification. MS m / z (MH +) 469.8.

Procedure Q 3-r 9- (8-Aza-biciclof 3.2.11oct-3-ylidene) -9H-xanten-3-yl-1-4H- [1,4-oxadiazol-5-one (Compound 4). The title compound 4 was prepared as a TFA salt using an adaptation of the method described in procedure N and substituting compound 6b for compound 5f. MS m / z (MH +) 374.0; 1 H NMR (CH 3 OH-d 4) d 1.48 (m, 2 H), 1.94 (m, 2 H), 3.1 1 (m, 4 H), 4.06 (m, 2 H), 7.26 (m, 2 H), 7.38 (m, 2 H) , 7.51 (d, 1 H), 7.62 (m, 3H). 2,2,2-Trifluoro-1- (3-r3- (5-thioxo-4,5-dihydro-r, 2,4-loxanediazol-3-yl) -xanten-9-ylidene-8-aza-bicyclo [3.2 11oct-8-yl) -ethanone (7a). The title compound 7a was prepared using an adaptation of procedure P, replacing the CDI with 1, 1'-thiocarbonyldiimidazole (TCDI), and adding 1,8-diazabicyclo [5.4.0] -7-undequene (DBN, 1 equivalent) . The crude compound 7a was used in the next reaction without further purification. MS m / z (MH +) 485.8. 3-f9- (8-Aza-bicichlor3.2.1 loct-3-ylidene) -9 / - / - xanten-3-ill-4H-n, 2,41-oxadiazole-5-thone (Compound 5). The title compound 5 was prepared as a TFA salt using an adaptation of the method of procedure N, and substituting compound 7a with compound 5f. MS m / z (MH +) 389.9; H NMR (CH 3 OH-d 4) d 1.47 (m, 2 H), 1.93 (m, 2 H), 3.10 (m, 4 H), 4.06 (m, 2 H), 7.27 (m, 2 H), 7.37 (m, 2 H), 7.53 (d, 1 H), 7.67 (m, 3H).

EXAMPLE 8 Method R 2.2.2-Trifluoro-1 - (3-f3- (2-oxo-2,3-dihydro-2l4-f1.2.3.5loxathiadiazol-4-yl) -xanten-9-yliden-8-aza -bicyclo [3.2.11oct-8-yl] -ethanone (8a). To a solution of compound 6a (0.071 g, 0.16 mmol) and pyridine (0.026 mL, 0.32 mmol) in CH2Cl2 (1 mL), a solution of thionyl chloride (0.013) was added dropwise. mL, 0.18 mmol) in CH2Cl2 (1 mL), at -70 ° C. After stirring 1 h at -70 ° C, the mixture was allowed to warm to room temperature and then washed sequentially with water and brine, dried (MgSO 4) and concentrated. The resulting compound 8a was used in the next reaction without further purification. MS m / z (MH +) 489.7. 3-f3- (2-Oxo-2,3-dihydro-2l4-f 1, 2,3, 51-oxathiadiazol-4-yl) -xanten-9-ylidene-8-aza-bicyclo [3.2.11octane (Compound 10) . The title compound 10 was prepared as a TFA salt using an adaptation of procedure N and substituting compound 5a with compound 8a. MS m / z (MH +) 393.9; 1 H NMR (CH 3 OH-d 4 d 1.49 (m, 2 H), 1.94 (m, 2 H), 3.1 1 (m, 4 H), 4.06 (m, 2 H), 7.28 (m, 2 H), 7.39 (m , 2H), 7.54 (d, 1 H), 7.70 (m, 3H).

Procedure S 3- (9-f8- (2,2,2-Trifluoro-acetyl) -8-aza-biciclof3.2.1 loct-3-yliden1-9 / - / - xanten-3-yl) -4H-f 1 , 2,4] thiadiazol-5-one (9a). A mixture of compound 6a (0.0417 g, 0.094 mmol) and TCDI (0.025 g, 0.14 mmol) in THF (2 mL) was stirred at room temperature for 45 min. The mixture was diluted with H20 (2 mL) and it was extracted with EtOAc (3 x 5ml_). The combined organic extract was washed with H20 (15 mL), dried (MgSO4), and concentrated. The residue was dissolved in THF (2 mL). To the solution was added boron trifluoride diethyl ether, and the resulting mixture was stirred at room temperature for 1 h. The mixture was diluted with H20 (2 mL) and extracted with EtOAc (3 x 5 mL). The organic layer was dried (MgSO4) and concentrated. The resulting compound 9a was used in the next reaction without further purification. MS m / z (MH +) 485.8. 3-r9- (8-Aza-bicyclo [3.2.1 loct-3-ylidene) -9H-xanten-3-iH-4H-ri, 2,41-thiadiazol-5-one (Compound 8). The title compound 8 was prepared as a TFA salt using an adaptation of procedure N and substituting compound 9a with compound 5f. MS m / z (MH +) 389.9; 1 H NMR (CH 3 OH-d 4) d 1.48 (m, 2 H), 1.93 (m, 2 H), 3.1 1 (m, 4 H), 4.05 (m, 2 H), 7.27 (m, 2 H), 7.38 (m, 2 H) , 7.50 (d, 1 H), 7.76 (m, 3H).

EXAMPLE 10 Comp. 5e 9- (8-Aza-bicyclo3.2.1loct-3-ylidene) -A /, A / -diethyl-9H-xanthene-3-carboxamidine (Compound 9). A mixture of compound 5e (0.06 g, 0.146 mmol), diethylamine (0.766 mL, 7.31 mmol) and Cu (1) CI (0.0724 g, 0.731 mmol) in eOH (1 mL) was exposed to microwave irradiation (300 W 140 ° C for 20 min. A portion of K2C03 (0.2 g, 1.45 mmol) was added to the reaction mixture and stirred at room temperature for 3 h. The solid was collected by vacuum filtration and the crude product was purified by reverse phase HPLC, to give compound 9 as the TFA salt. MS m / z (MH +) 387.9; 1 H NMR (CH 3 OH-d 4) d 1.22 (t, 3 H), 1.39 (t, 3 H), 1.48 (d, 2 H), 1.96 (m, 2 H), 3.12 (m, 4 H), 3.42 (q, 2 H), 3.7 (q, 2H), 4.07 (m, 2H), 7.28 (m, 2H), 7.40 (m, 3H), 7.53 (d, 1 H), 7.61 (d, 1 H).

EXAMPLE 11 Procedure T Acetic hydrazide of benzenesulfonic acid (1 1 a). To a solution of acetic hydrazide (2 g, 27.0 mmol) in EtOH (5 mL) was added benzenesulfonic acid (4.7 g, 29.7 mmol) in small portions. A white solid formed. A volume of Et2O (5 mL) was added to the mixture. The resulting solid was collected by filtration, washed with Et2O, and dried to give compound 1 a. 1 H NMR (D 2 O) d 1.95 (s, 3 H), 7.45 (m, 3 H), 7.75 (d, 2 H).

Procedure U 3-r 3 - (5-Methyl-4 H-H, 2,41-triazol-3-yl) -xanten-9-ylidene-8-aza-bicyclo [3.2. Noctane (35). A mixture of the compounds 1 1 a (0.029 g, 0.125 mmol) and 5e (0.051 g, 0.124 mmol) was exposed to microwave irradiation (300 W) at 200 ° C for 10 min. After cooling the reaction mixture, MeOH (1 mL) and 1 N NaOH (1 mL) were added, and the mixture was stirred at room temperature for 30 min. The crude product was purified by reverse phase HPLC to give compound 35 as a TFA salt. MS m / z (MH +) 371 .0; 1 H NMR (CH 3 OH-d 4) d 1 .40 (d, 2 H), 1.85 (m, 2 H), 1.441 (s, 3 H), 3.02 (m, 4 H), 3.91 (m, 2 H), 7.19 (m, 4H), 7.33 (d, 2H), 7.84 (d, 1 H), 7.85 (s, 1 H).

EXAMPLE 12 Comp. 5e 12th Comp. 2G Method V 9-r8- (2,2,2-Trifluoro-acetyl) -8-aza-bicyclo [3.2.noct-3-ylidene-9H-xanthene-3-carboxamidine (12a). To a solution of n-BuLi (2.5M in hexane, 0.487 mL, 1.22 mmol) in Et 2 O (1 mL) was added dropwise a solution of 1,1,1,3,3-hexamethyldisilazane (0.257). mL, 1.22 mmol) in Et 2 O (1 mL) at 0 ° C. The mixture was stirred at 0 ° C for 30 min. To this mixture was added the Compound 5e (0.2g, 0.49 mmol) and stirred at room temperature for 2 h. The mixture was drained in 2N HCl (2 mL) cooled with ice and extracted with Et20 (2 x 3 mL). The aqueous phase was adjusted to pH ~ 8 with 1N NaOH and extracted with CH2Cl2 (2 x 3 mL). The combined organic layer was dried over MgSO4, filtered and concentrated. The resulting compound 12a was used in the next reaction without further purification. MS m / z (MH +) 427.8.

Procedure W 3-r 3 - (5-Ethyl-1 H-imidazol-2-yl) -xanten-9-ylidene-8-aza-bicyclo3.2.1-octane (Compound 26). A mixture of compound 12a (0.050 g, 0.1 12 mmol), 1-bromo-2-butanone (0.012 g, 0.1 18 mmol) and NaHCO 3 (0.02 g, 0.238 mmol) in EtOH (1 mL) was exposed to microwave (300 W) at 150 ° C for 20 min. After cooling the reaction mixture, 1 N NaOH (0.5 mL) was added and stirred at room temperature for 30 min. The crude product was purified by reverse phase HPLC to give compound 26, as a TFA salt. MS m / z (MH +) 384.0; 1 H NMR (CH 3 OH-d 4) d 1.39 (m, 3 H), 1.52 (m, 2 H), 1.96 (m, 2 H), 2.83 (q, 2 H), 3.15 (m, 4 H), 4.09 (m, 2 H) ), 7.30 (m, 2H), 7.43 (m, 3H), 7.63 (m, 1 H), 7.72 (m, 1 H), 7.85 (m, 1 H).

EXAMPLE 13 Procedure X 2,2l2-Trifluoro-1 - (3-r3- (1-methyl-1 H-tetrazol-5-yl) -xanten-9-ylidene-8-aza-bicyclo3.2.1loct-8-i) | -ethanone (13a) and 2,2,2-Trifluoro-1 - (3-y3- (2-methyl-2H-tetrazol-5-yl) -xanten-9-ylidene-8-aza-biciclof3.2.1 loct- 8-yl) -ethanone (13b). A mixture of compound 5f (0.16g, 0.35 mmol), methyl iodide (0.044 mL, 0.71 mmol) and potassium carbonate (0.24 g, 1.74 mmol) in acetone (8 mL), was heated to reflux (water bath). oil, 60 ° C) for 2 h. The mixture was allowed to cool to room temperature and the solid was removed by filtration. The solvent was removed in vacuo. The mixture of crude products 13a and 13b was used in the next reaction without further purification. MS m / z (MH +) 467.9. 3-r3- (1-Methyl-1 H-tetrazol-5-yl) -xanten-9-ylidene-8-aza-bicyclo [3.2.1 l-octane (Compound 21) and 3-r3- (2-Methyl) -2 / - / - tetrazol-5-yl) -xanten-9-ylidene-8-aza-bicyclo [3.2. Noctane (Compound 16). Using an adaptation of procedure N and substituting with compound mixture 13a and 13b compound 5f, a mixture of compounds 21 and 16 was prepared. Compounds 21 and 16 were separated and purified by reverse phase HPLC as their TFA salts . Comp. 21: MS m / z (MH +) 371.9; 1 H NMR (CH 3 OH-d 4) d 1.52 (d, 2 H), 1.97 (m, 2 H), 3.15 (m, 4 H), 4.08 (m, 2 H), 4.27 (s, 3 H), 7.29 (m, 2 H), 7.41 (m, 2H), 7.67 (m, 2H), 7.76 (d, 1 H). Comp. 16: MS m / z (MH +) 371.9; 1 H NMR (CH 3 OH-d 4) d 1.52 (d, 2 H), 1.95 (m, 2 H), 3.12 (m, 4 H), 4.06 (m, 2 H), 4.45 (s, 3 H), 7.24 (m, 2 H), 7.37 (m, 2H), 7.53 (d, 1 H), 7.96 (m, 2H).

EXAMPLE 14 Comp. 6a Procedure Y 3-f3- (5-Methyl-1, 2,4-oxadiazol-3-yl) -xanten-9-ylidene-8-aza-bicyclo [3.2.1 loctane (Compound 36). A mixture of compound 6a (0.046g, 0.104 mmol) and NaH (60% in oil, 0.0042 mg, 0.105 mmol) in THF (4 mL) it was refluxed for 1 h. After cooling the mixture, acetic acid methyl ester (0.0082 mL, 0. 03 mmol) was added. The mixture was stirred at reflux temperature overnight. The mixture was poured into ice water and extracted with CH2Cl2 (2 x 5 mL). The organic phase was washed with H2O, dried over MgSO4 and concentrated. The crude product was purified by reverse phase HPLC, to give compound 36 as a TFA salt. MS m / z (MH +) 371.9; 1 H NMR (CH 3 OH-d 4) d 1.52 (d, 2 H), 1.95 (m, 2 H), 2.66 (s, 3 H), 3.12 (m, 4 H), 4.05 (m, 2 H), 7.23 (m, 1 H) , 7.31 (m, 1 H), 7.39 (m, 2H), 7.52 (d, 1 H), 7.83 (d, 1 H), 7.84 (s, 1 H). EXAMPLE 15 4-Bromo-2-phenylsulfanyl-benzonitrile (15a) and 2,4-Bis-phenylsulfanyl-benzonitrile (15b). Using the method described in procedure I, substituting phenol for benzenethiol, a mixture of the title compounds 15a and 15b was prepared. The mixture was separated by normal phase chromatography (eluent gradient: 0 to 20% EtOAc in heptane), to yield compounds 15a and 15b. Compound 15a: MS m / z (MH +) 291.8; Compound 1 5b: MS m / z (MH +) 319.8. 4-Bromo-2-phenylsulfanyl-benzoic acid (15c). Compound 15c was prepared using the method described in procedure J, substituting compound 5c with compound 15a. MS m / z (MH +) 308.7. 3-Bromo-thioxanten-9-one (15d). Compound 15d was prepared using the method described in procedure K, substituting compound 15b for compound 1b. MS m / z (MH +) 290.7. 1-f3- (3-Bromo-thioxanten-9-ylidene) -8-aza-bicyclo3.2.1 loct-8-in-2,2,2-trifluoro-ethanone (15e). Compound 15e was prepared using the method described in procedure D, substituting with the compound 15d the / V- [2- (9-oxo-9H-xanten-3-yl) -phenyl] -acetamide, and substituting with compound 5b the 3-oxo-8-aza-bicyclo- [3.2.1] carboxylic acid tert-butyl ester. MS m / z (MH +) 481 .6. 3- (3-Bromo-thioxanten-9-ylidene) -8-aza-bicyclo [3.2.1 loctane (84). The title compound 84 was prepared as a TFA salt using the method described in procedure N, substituting compound 15e with compound 5f. MS m / z (MH +) 385.6; 1 H NMR (DMSO-d6) d 1.27 (m, 2H), 1.77 (m, 2H), 2.97 (m, 4H), 4.00 (m, 2H), 7.36 (m, 4H), 7.63 (d, 1 H), 7.91 (m, 3H) ), 8.82 (m, 1 H), 9.17 (m, 1 H).

EXAMPLE 16 16c Comp. 83 3- (3-Phenylsulfanyl-thioxanten-9-ylidene) -8-aza-bicyclo [3.2.1-octane (16a). The title compound 16a was prepared using the method described in procedure J, substituting compound 5c with compound 15b. MS m / z (MH +) 338.7. 3-Phenylsulfanyl-thioxanthen-9-one (6b). Compound 16b was prepared using the method described in procedure K, substituting compound 16b for compound 16b. MS m / z (MH +) 320.9. 2,2,2-Trifluoro-1 - [3- (3-phenylsulfanyl-thioxanthen-9-ylidene) -8-aza-bicyclo [3.2.1 loct-8-ill-ethanone (16c). Compound 16c was prepared using the method described in procedure D, substituting for the compound 16b the A / - [2- (9-oxo-9 / - / - xanten-3-yl) -phenyl] -acetamide, and substituting with the compound 5b the tert-butyl ester of 3-oxo-8-aza-bicyclo- [3.2.1] carboxylic acid. MS m / z (MH +) 509.7. 3- (3-Phenylsulfanyl-thioxanten-9-ylidene) -8-aza-bicyclof3.2.11octane (83). The title compound 83 was prepared as a TFA salt using the method described in procedure N, substituting compound 16c for compound 5f. MS m / z (MH +) 413.7; 1 H NMR (CH 3 OH-d 4) d 1 .32 (m, 2 H), 1.76 (m, 2 H), 2.74 (m, 4 H), 3.84 (m, 2 H), 7.25 (m, 1 1 H), 7.41 (d , H).

EXAMPLE 17 9-f8- (2,2,2-Trifluoro-acetyl) -8-aza-bicyclo [3.2.1loct-3-ylidene-9H-thioxanthene-3-carbonitrile (17a). The title compound 17a was prepared using the method described in procedure L, substituting compound 15e with compound 5d. MS m / z (MH +) 426.7; 1 H NMR (CDCl 3) d 1.41 (m, 2 H), 1.83 (m, 2 H), 2.76 (m, 4 H), 4.40 (m, 1 H), 4.70 (m, 1 H), 7.33 (m, 4 H), 7.56 (m, 2H), 7.51 (s, 1 H). 9- (8-Aza-bichlor3.2.1 loct-3-ylidene) -9H-thioxanthene-3-carbonitrile (85). The title compound 85 was prepared using the method described in procedure N, replacing compound 17a with compound 5f. MS m / z (MH +) 330.9; H NMR (CH 3 OH-d 4) d 1.33 (m, 2 H), 1.81 (m, 2 H), 2.78 (m, 4H), 3.91 (m, 2H), 7.21 (m, 3H), 7.38 (d, 1 H), 7.49 (d, 1 H), 7.57 (dd, 1 H), 7.85 (d, 1 H) ).

Comp. 102 (from 18c) Comp. 103 (from 18d) 9-f (1 RS, 5SR) -8- (2,2,2-Trifluoro-acetyl) -8-aza-biciclof3.2.1 loct-3-ylidene-1H-thioxanthene-3-carbonitrile (18a) and 9-f (1SR, 5RS) -8- (2,2,2-trifluoroacetyl) -8-aza-bicyclo [3.2.1 loct-3-ylidene-9H-thioxanthene-3-carbonitrile (18b). The racemic compound 17a was separated by chiral chromatography on its enantiomers using a Chiralpack AD column (500g) and an eluent mixture of heptane: ethanol 1: 1 (UV monitoring at 220 nm, and flow rate of 80 mL / min), producing the compounds 18a (first isomer that is eluye) and 18b (second isomer eluting). 2,2,2-Trifluoro-1 - (3- [3- (1 H-tetrazol-5-yl-Myoxanten-9-ylidene-r (1 RS.5SR) -8-aza-bicichlor3.2. im-ethanone (18c) and 2.2, 2-trif luoro-1 -. {3-G3- (1 H-tetrazol-5-yl) -thioxanten-9-ylidene-f (1 SR, 5RS) -8- aza-bicyclo3.2.11oct-8-ylV ethanone (18d) The title compound 18c was prepared using the method described in procedure M, substituting compound 18e with compound 5e MS m / z (MH +) 469.8 Similarly, the title compound 18d was prepared using the method described in procedure M, substituting compound 5e with compound 18b (1 RS, 5SR) -3- [3- (1 / - / - Tetrazol-5- il) -thioxanten-9-ylidene-8-aza-bicyclo [3.2.noctane (Compound 102) and (1 SR, 5RS) -3-f3- (H-Tetrazol-5-yl) -thioxanten-9-ylidene- 8-aza-bicyclo [3.2.1 loctane (Compound 103) The title compound 102 was prepared as a TFA salt using the method described in procedure N, substituting compound 18c for compound 5f. z (MH +) 373.8; 1 H NMR (CH 3 OH-d 4) d 1 .37 (m, 2H) , 1.79 (m, 2H), 2.84 (m, 4H), 3.89 (m, 2H), 7.25 (m, 3H), 7.43 (d, 1 H), 7.50 (d, 1 H), 7.91 (dd) , 1 H), 8.13 (d, 1 H). Similarly, using the method of procedure N, the title compound 103 was prepared as a TFA salt by substituting compound 5f for compound 18d.

EXAMPLE 19 19th Comp. 112 Procedure Z 2,2,2-Trifluoro-1-y3- (3-pyridin-3-yl-thioxanten-9-ylidene) -8-azabicyclof 3.2.1 loct-8-ill-ethanone (19a) A suspension of compound 15e (0.3g, 0.625 mmol), cesium carbonate (0.51g, 1565 mmol) and 3-pyridinboronic acid (0.0844g, 0.687 mmol) in dioxane (4 ml_) and EtOH (1 ml_), was added 1, 1'-bis (diphenylphosphino) -ferrocene-palladium (II) dichloride (46 mg, 0.063 mmol). The mixture was heated at 90 ° C for 3 h, and cooled to room temperature. The solid was filtered and washed with CH3OH (10mL) and H20 (10mL). The filtrate was concentrated under reduced pressure to produce a crude product. The crude product 19a was used in the next reaction without further purification. MS m / z (MH +) 479.0. 3- (3-Pyridin-3-yl-thioxanten-9-ylidene) -8-aza-bicyclo [3.2.1 loctane (Compound 1 12). The title compound 12 was prepared as a TFA salt using the method described in procedure N, substituting compound 19f for compound 5f. MS m / z (MH +) 383.3; 1 H NMR (CDCl 3) d 1.50 (m, 2H), 2.02 (m, 2H), 2.80 (t, 2H), 3.12 (m, 2H), 4.00 (m, 2H), 7.31 (m, 3H), 7.42 (d, 2H), 7.55 (dd, 1 H), 7.78 (s, 1 H), 7.92 (dd, 1 H), 8.40 (d, 1 H), 8.76 (d, 1 H), 9.08 (s, 1 H).

EXAMPLE 20 Method AA 8-Furan-3-ylmethyl-3- (3-pyridin-3-yl-thioxanten-9-ylidene) -8-aza-bicyclo [3.2.noctane (16). A mixture of compound 1 12 (20 mg, 0.04 mmol), 3-furaldehyde (13.5 mg, 0.156 mmol) and tetramethylammonium triacetoxyborohydride (16 mg, 0.061 mmol) in dichloroethane (2 mL) was stirred at 80 ° C during the night in a sealed tube. The solvent was removed under reduced pressure. The crude product was purified by reverse phase HPLC to give compound 16 as a TFA salt. MS m / z (MH +) 463.2; 1 H NMR (CD 3 CN) d 1.45 (d, 2 H), 2.06 (m, 2 H), 2.90 (m, 2 H), 3.80 (m, 2 H), 3.98 (m, 2 H), 6.69 (s, 1 H), 7.35 (m, 3H), 7.48 (d, 1 H), 7.61 (m, 4H), 7.78 (m, 1 H), 7.96 (s, 1 H), 8.41 (d, 1 H), 8.75 (d, 1) H), 9.01 (s, 1 H).

EXAMPLE 21 H Comp. 132 4-Bromo-2- (2-methoxy-phenoxy) -benzonitrile (21 b). The title compound 21 b was prepared using the method described in procedure I, substituting phenol for 2-methoxyphenol. MS m / z (MH +) 303.8, 305.8. 4-Bromo-2- (2-methoxy-phenoxy) -benzoic acid (21 c). The title compound 21 c was prepared using the method described in procedure J, substituting compound 21b with compound 5c. MS m / z (MH +) 322.8, 324.7. 3-Bromo-5-methoxy-xanten-9-one (21 d). The title compound 21 d was prepared using the method described in procedure K, substituting compound 21b with compound 21b. MS m / z (MH +) 304.8, 306.7. 1-f3- (3-Bromo-5-methoxy-xanten-9-ylidene) -8-aza-bicyclo [3.2.1loct-8-ill-2,2,2-trifluoro-ethanone (21e). The title compound 21 e was prepared using the method described in procedure D, substituting the compound 21c with the compound 21d, and substituting the 3-oxo-8-aza-3-oxo-3-azobutyl ester with the compound 5b. bicyclo [3.2.1] -octane-8-carboxylic acid. MS m / z (MH +) 467.7, 469.7. 5-Methoxy-9-f8- (2,2,2-trifluoro-acetyl) -8-aza-bicyclo3.2.1 loct-3-ylidene-9H-xanthene-3-carbonitrile (21 f). The title compound 21 e was prepared using the method described in procedure L, substituting compound 21 e for compound 5d. MS m / z (M + 23) 462.7. 3-r9- (8-Aza-biciclof3.2, noct-3-ylidene) -5-methoxy-9H-xanten-3-ill-4H-n, 2,41-oxadiazol-5-one (21 q). The title compound 21 g was prepared using the method described in procedure O, substituting compound 21e with compound 21e. MS m / z (MH +) 473.9. 3- (5-Methoxy-9- [8- (2,2,2-trifluoro-acetyl) -8-aza-bicichlor3.2.1 loct-3-ylidenl-9H-xanten-3-yl) -4H-f 1 , 2.41-oxadiazol-5-one (21 h). The title compound 21 h was prepared using the method described in procedure P, substituting compound 21a with compound 21a. MS m / z (MH +) 499.8. 3- [9- (8-Aza-bicyclo [3.2.noct-3-ylidene-5-methoxy-9H-xanten-3-ill-4H- [1, 2,41-oxadiazol-5-one (132).) The title compound 132 was prepared as a TFA salt using the method described in procedure N, substituting with compound 21h compound 5f MS m / z (MH +) 403.9; 1H NMR (DMSO-d6) d 1.28 (m, 2H ), 1.79 (m, 2H), 2.98 (m, 4H), 3.90 (s, 3H), 4.03 (m, 2H), 6.98 (d, 1 H), 7.10 (d, 1 H), 7.19 (t, 1 H), 7.65 (m, 2H), 7.74 (s, 1 H). 22 »Comp. 134 Procedure BB 3- (5-Hydroxy-9-f8- (2,2,2-trifluoro-acetyl) -8-aza-bicyclo3.2.noct-3-ylidene-9H-xanten-3-yl) -4 / - / - f 1, 2,41-oxadiazol-5-one (22a). To a solution of compound 21 h (0.355 g, 1.19 mmol) in CH 2 Cl 2 (30 mL) was added BBr 3 (1.0 M in CH 2 Cl 2, 5.97 mL, 5.97 mmol) at 0 ° C. The mixture was stirred at room temperature for 24 h, and quenched with a saturated solution of NaHCO 3 (20 mL). The organic layer was dried over MgSO4 and concentrated. The crude product was used in the next reaction without further purification. MS m / z (MH +) 485.8. 3-f9- (8-Aza-biciclof3.2.1loct-3-ylidene) -5-hydroxy-9 / - / - xanten-3-ill-4 / - / - [1, 2,41-oxadiazol-5-one ( 134). The title compound 134 was prepared as a TFA salt using the method described in procedure N, substituting compound 5a with compound 22a. MS m / z (MH +) 389.9; 1 H NMR (CH 3 OH-d 4) d 1.43 (m, 2 H), 1.82 (m, 2 H), 2.95 (m, 2 H), 3.22 (t, 2 H), 3.94 (m, 2 H), 6.75 (m, 2 H) ), 7.00 (t, 1 H), 7.42 (d, 1 H), 7.51 (dd, 1 H), 7.65 (s, 1 H).

EXAMPLE 23 Comp. 2,2,2-Trifluoro-1- (3-f5-methoxy-3- (5-thioxo-4,5-dihydro- [1,2,4-oxadiazol-3-yl) -xanten-9-yl) den-8-aza-bicyclo [3.2.1 loct-8-yl] -ethanone (23a). The title compound 23a was prepared using the method described in procedure P, substituting compound 6a for compound 21g, substituting CDI for 1, 1'-thiocarbonyldiimidazole (TCDI), and adding 1,8-diazabicyclo [5.4 .0] -7-undequene (DBN, 1 equivalent). MS m / z (MH +) 515.8. 3- [9- (8-Aza-biciclof3.2, noct-3-ylidene) -5-methoxy-9H-xanten-3-ill-4H-H, 2,41-oxadiazole-5-thione (133). The title compound 133 was prepared as a TFA salt using the method described in procedure N, substituting compound 23f with compound 23f. MS m / z (MH +) 419.9; H NMR (DMSO-de) d 1.26 (m, 2H), 1.78 (m, 2H), 2.93 (m, 2H), 3.32 (t, 2H), .90 (s, 3H), 4.00 (m, 2H) , 6.98 (t, 1 H), 7.10 (t, 1 H), 7.28 (t, 1 H), 7.58 (d, 1 H), .81 (d, 1 H), 7.90 (s, 1 H).

Procedure CC 3,6-Dihydroxy-xanten-9-one (24a). Compound 24a was prepared following a literature procedure (Janjic, N. et al., J. Am. Chem. Soc. 1989, 1 1 1, 6374-6375). MS m / z (MH +) 228.9. Process DD Ester of 9-oxo-6-trifluoromethane-sulfonyloxy-9 / - / - xanthen-3-yl of trifluoromethanesulfonic acid (24b). Compound 24a (1.18 g, 5.18 mmol) was suspended in 30 mL of dichloromethane, treated with pyridine (836 mL), and stirred at room temperature for 10 min. After cooling to 0 ° C, triflic anhydride (1.73 mL, 10.3 mmol) was added dropwise. The mixture was stirred at 0 ° C for 1 h and then allowed to warm to room temperature, stirring continued overnight. After the reaction is finished, The mixture was concentrated under reduced pressure. The resulting residue was purified by normal phase chromatography using dichloromethane as eluent, to give compound 24b. MS m / z (MH +) 492.6.

Process EE Dimethyl ester of Q-oxo-QH-xanthene-S.B-dicarboxylic acid (24c). Compound 24b (0.52 g, 1.06 mmol) and DIEA (553 pL) were added to a mixture of DMF: MeOH (1: 1, 20 ml_ of total volume), and the flask was purged with argon gas. The mixture was then treated with Pd (dppf) CI2 (43 mg, 0.053 mmol) and purged; then it was charged with carbon monoxide and heated at 75 ° C for 8 h. The mixture was cooled to room temperature and concentrated under reduced pressure at 50 ° C. The resulting residue was taken up in CH 2 Cl 2 and washed sequentially with 1 N HCl, saturated aqueous solution of NaHCO 3, and brine. The organic phase was partitioned, dried over magnesium sulfate and filtered; the filtrate was concentrated until a residue remained. The residue was purified by normal phase chromatography using as eluent a gradient of 0.1% MeOH to 0.4% in dichloromethane, to give compound 24c. Dimethyl ester of 9- (8-aza-bicyclo [3.2. Loct-3-ylidene] -9 / - / - xanthene-3,6-dicarboxylic acid (78). The title compound was prepared according to procedure D, substituting the / V- [2- (9-oxo-9H-xanten-3-yl) -phenyl] -acetamide for 9-oxo-9H- dimethyl ester Xanthene-3,6-dicarboxylic acid. Compounds 1 to 134 of formula (la) in the following table (in where R5 is H and A is CH2CH2), they were synthesized using the methods described above.

Formula (the) BIOLOGICAL EXAMPLES EXAMPLE 1 Delta opioid receptor binding test in the rat brain Procedure: Male Sprague Dawley rats (150-250 g, VAF, Charles River, Kingston, New York) were sacrificed by CO2 and their Brains were excised and immediately placed in ice-cold Tris HCI buffer (50 mM, pH 7.4). The forebrains were separated from the rest of the brain by a coronal transection, starting dorsally in the colliculus and passing ventrally through the mesencephalon-bridge junction. After dissection, the forebrains were homogenized in Tris buffer in a Teflon®-glass homogenizer. The homogenate was diluted to a concentration of 1 g of forebrain tissue for 80 mL of Tris, and centrifuged at 39,000 x g for 10 min. The pellet was resuspended in the same volume of Tris buffer, which contains 5 mM MgCl2, with several short pulses from a Polytron homogenizer. This particulate preparation was used for the delta-opioid binding tests. After incubation with the selective peptide ligand of delta [3 H] DPDPE ~ 4 nM, at 25 ° C for 2.5 h, in a 96-well plate with a total volume of 1 ml, the contents of the plate were filtered through Wallac filtermat B leaves in a 96-well Tomtec harvester. The filters were rinsed three times with 2 mL of 10 mM HEPES (pH7.4), and dried twice in a 650 W microwave oven for 1.75 min. To each sample area were added 2 x 40 μ? of scintillation fluid Betaplate Scint (LKB) and the radioactivity was quantified in a liquid scintillation counter BetaPlate LKB 1205 (Wallac). Analysis: The scintillation counter data were used to calculate the% inhibition compared to the control link (when only one concentration of test compound was evaluated), or a value of K; (when a scale of concentrations was analyzed). % Inhibition was calculated as: [(total dpm - test compound dpm) / (total dpm - nonspecific dpm)] * 100. The values of Kd and Ki were calculated using a GraphPad PRISM data analysis program.

EXAMPLE 2 Mu-opioid receptor binding test in the rat brain Procedure: Male Sprague Dawley rats (50-250 g, VAF, Charles River, Kingston, New York) were sacrificed by CO2 and their brains were removed and immediately placed in ice-cold Tris HCI buffer (50 mM, pH 7.4). The forebrains were separated from the rest of the brain by a coronal transection, starting dorsally in the colliculus and passing ventrally through the mesencephalon-bridge junction. After dissection, the forebrains were homogenized in Tris buffer in a Teflon®-glass homogenizer. The homogenate was diluted to a concentration of 1 g of forebrain tissue for 80 mL of Tris, and centrifuged at 39,000 x g for 10 min. The pellet was resuspended in the same volume of Tris buffer, which contains 5 mM MgCl2, with several short pulses from a Polytron homogenizer. This particulate preparation was used for delta opioid binding tests. After incubation with selective mu [3H] DAMGO -0.8 nM peptide, at 25 ° C for 2.5 h, in a 96-well plate with a total test volume of 1 ml, the content of the plate was filtered through Wallac filtermat B sheets in a 96-well Tomtec harvester. The filters were rinsed three times with 2 ml_ of 10 mM HEPES (pH 7.4), and dried twice in a 650 W microwave for 1.75 min. To each sample area were added 2 x 40 pL of scintillation fluid Betaplate Scint (LKB) and the radioactivity was quantified in a liquid scintillation counter BetaPlate LKB 1205 (Wallac). Analysis: The scintillation counter data were used to calculate the% inhibition compared to the control binding (when only one concentration of test compound was evaluated), or a value of K, (when a concentration scale was analyzed. ). % Inhibition was calculated as: [(total dpm - test compound dpm) / (total dpm - nonspecific dpm)] * 100. The values of Kd and Ki were calculated using a GraphPad PRISM data analysis program.

EXAMPLE 3 Binding test of r35S1GTPyS on membranes of NG108-15 cells (opioid delta) Methods: Membranes of NG108-15 cells were purchased at Applied Cell Sciences (Rockville, Maryland). An 8 mg / mL portion of membrane protein was suspended in 10 mM TRIS-HC, pH 7.2, 2 mM EDTA, 10% sucrose. The membranes were maintained at 4-8 ° C. Added a volume of 1 ml of the membranes in 10 ml of cold binding test buffer. The test buffer contained 50 mM Tris, pH 7.6, 5 mM MgCl2, 100 mM NaCl, 1 mM DTT and 1 mM EGTA. The membrane suspension was homogenized 2 times with a Polytron and centrifuged at 3000 rpm for 10 min. Then, the supernatant was centrifuged at 18,000 rpm for 20 min. To the tube containing the pellet was added 10 ml of test buffer. The pellet and the buffer were mixed with a Polytron. Incubation procedure: The pelleted membranes (75 g / ml) were preincubated with SPA (10 mg / ml) at 25 ° C for 45 min in the test buffer. The SPA (5 mg / ml) coupled with the membranes (37.5 pg / ml) was then incubated with 0.1 nM [35S] GTPyS in the same Tris buffer containing 100 μg GDP. in a total volume of 200 μ ?. Increasing concentrations of receptor agonists were used to stimulate the binding of [35 S] -GTPyS. The basal union was tested in the absence of agonists and the non-specific binding was tested in the presence of 10 μ? of GTPyS without marking. The data was analyzed in a Packard Top counter. Data:% of basal union = (stimulated union - non-specific binding) * 100 / (basal union - nonspecific binding). The EC50 values were calculated using GraphPad Prism.

EXAMPLE 4 F35S1GTPyS Binding Assays in CHO-hMOR Cell Membranes Methods: Membranes of CHO-hMOR cells were purchased from Receptor Biology, Inc. (Baltimore, Maryland). Approximately 10 mg / mL of membrane protein was suspended in 10 mM TRIS-HCl pH 7.2, 2 mM EDTA, 10% sucrose, and the suspension was kept on ice. A volume of 1 ml_ of membranes was added to 15 mL of binding assay buffer containing 50 mM HEPES pH 7.6, 5 mM MgCl 2, 100 mM NaCl, 1 mM DTT and 1 mM EDTA. The membrane suspension was homogenized with a Polytron and centrifuged at 3,000 rpm for 10 min. Then the supernatant was centrifuged at 18,000 rpm for 20 min. The pellet was resuspended in 10 mL of test buffer with a Polytron. The membranes were preincubated with SPA pellets coated with wheat germ agglutinin (Amersham), at 25 ° C for 45 min, in the test buffer. Then, the membranes (10 pg / mL) coupled with the SPA pellets (5 mg / mL) were incubated with 0.5 nM of [35S] GTPyS in the test buffer. The basal union was the one that occurred in the absence of test compound; this unmodulated junction was considered as 100%, and the agonist-stimulated junction was raised to significantly higher values. A scale of receptor agonist concentrations was used to stimulate the binding of [35S] GTPyS. Basal and non-specific binding was analyzed in the absence of agonist; the determination of non-specific binding included 10 μ? of GTPyS unmarked.

The activity of the compounds as antagonists was analyzed evaluating its potential to inhibit the binding of GTPYS stimulated by agonist The radioactivity was quantified in a Packard TopCount. HE calculated the following parameters: (cpm test compound - nonspecific binding cpm) % of stimulation = X 100 (cpm of basal union - cpm of nonspecific binding) (% stimulation with DA GO 1 μ? -% stimulation with test compound) % inhibition = - X 100 (% stimulation with DAMGO 1 μ? - 100) The CE5o values were calculated using GraphPad Prism.

BIOLOGICAL AND MASS SPECTRUM DATA Comp. Ki DOR Ki MOR CE50 CE50 Peak MS cale. No. (nM) (nM) GTPYS GTPyS original DOR (nM) hMOR obs. (nM) 1 1 .99 637 189 / 70.3 357.9 357.42 2 4.36 1 136 394.0 423.2 422.53 3 10000 10000 490.4 489.62 4 6.78 768 128.0 374.0 373.41 6.89 1017 104.0 389.9 389.48 6 7.40 1396 59.0 387.2 386.49 7 7.63 1815 173.0 405.2 404.51 8 10.79 1083 359.0 389.9 389.48 9 14 3537 387.9 387.53 15.15 819 393.9 393.46 BIOLOGICAL AND MASS SPECTRUM DATA (Continued) Comp. K¡ DOR K¡ MOR CE50 CE50 Peak MS cale.

No. (nM) (nM) GTPYS GTPyS original DOR (nM) hMOR obs. (nM) 1 1 18.52 739 209.0 441 .3 440.52 12 24 2132 587.0 0.47 367.1 366.46 13 23.57 2922 641.0 495.6 494.63 14 27.10 1 157 423.2 422.53 27.48 414 79.0 467.3 466.58 16 30 1458 573.0 0.48 371 .9 371 .44 17 37.01 37 451 .2 450.58 18 38 1537 409.2 408.50 19 44.99 438 437.4 436.55 46.58 2802 423.5 422.53 21 54 1743 371 .9 371 .44 22 54.90 1 124 429.5 428.58 23 75 3507 396.4 395.50 24 76.83 621 347.9 347.42 77.42 1665 381.22 380.49 26 81 249 384.0 383.49 27 100.33 100 467.1 466.58 28 107.45 3103 444.0 443.63 29 133 1817 367.0 366.46 139 2738 423.3 422.53 31 142.33 660 481 .5 480.61 32 160 10000 397.2 396.49 33 223.50 315 357.9 357.46 34 246.87 6237 491.5 or 490.65 266 673 371 .0 370.46 36 373 3550 371 .9 371 .44 37 412.14 950 435.3 434.49 38 418 706 382.2 381 .47 39 441 .1 5 5169 374.0 373.50 40 456.10 3087 423.4 422.53 41 464.1 5 875 372.0 371 .48 42 490 1314 381 .2 380.49 43 496.07 5341 399.9 399.54 44 659 7583 396.1 395.50 BIOLOGICAL AND MASS SPECTRUM DATA (Continued) Comp. Ki DOR Ki MOR CE50 CE50 Peak MS cale.

No. (nM) (nM) GTPYS GTPYS original DOR (nM) hMOR obs. (nM) 45 673.20 3099 401 .4 400.52 46 723 10000 380.1 379.50 47 812.60 1 197 409.4 408.50 48 938.60 2061 496.45 49 1325.85 4019 388.0 387.53 50 1757.50 14910 402.0 401.51 51 2445 16470 384.4 383.47 52 2732.95 1831 437.2 436.55 53 3144 3290 444.1 443.56 54 4470 10000 384.3 383.47 55 4724 9282 372.2 371.50 56 4929.75 28456 417.9 417.55 57 6958 19660 396.1 395.50 58 10000 10000 495.3 494.59 59 10000 10000 481 .1 480.56 60 473.6 472.58 61 6.25 876 391 .0 390.48 62 309 7400 483.5 482.55 63 161 5120 459.4 458.58 64 52 41 1 415.4 414.43 65 88 317 507.5 506.65 66 93 935 441 .5 440.52 67 360 1568 433.4 432.56 68 8.5 2389 5960 / 98.8 0.0 431 .54 69 105 2060 403.4 402.49 70 63 1660 403.3 402.49 71 5.7 1 145 1940.0 396.49 72 216 1960 333.39 73 1008 6345 347.41 74 - - 419.48 75 4468 10000 462.55 76 370 4743 363.48 77 2707 2476 314.39 78 1 152 7002 405.45 BIOLOGICAL AND MASS SPECTRUM DATA (Continued) Comp. K¡ DOR Ki MOR CE50 CE50 Peak MS cale.

No. (nM) (nM) GTPyS GTPyS original DOR (nM) hMOR obs. (nM) 79 191.7 4776 398.30 80 87.1 / 1.38 7523/2571 226.0 357.9 357.42 81 0.5 261 183 / 17.1 357.9 357.42 82 5.6 307 88.4 387.44 83 8506 > 10000 413.7 413.60 84 2899.0 > 10000 258.6 384.34 85 628.6 231 1 330.9 330.45 86 - - 314.9 314.39 87 - - 314.9 314.39 88 - - 410.7 410.39 89 - - 410.7 410.39 90 13 / 0.4 0.7 / 6.0 0.7 90 373.42 91 0.76 > 10000 72.2 373.8 373.41 92 0.07 502 102.0 374 373.41 93 0.37 3744 631.0 389.9 389.48 94 0.04 219 126.0 389.9 389.48 95 159 4928 389.9 389.48 96 - - 347.41 97 266 1895 404.51 98 - - 433.50 99 - - 333.39 100 - - 333.39 101 7.0 465 281.0 389.9 389.48 102 54 2771 373.8 373.48 103 10.1 329 49.6 373.8 373.48 104 246 1713 446.55 105 88 497 385.46 106 281 2744 401.53 107 106 597 396.49 108 33.9 426 1 17.0 452.55 109 2.22 31 94.2 1226 432.52 1 10 - - 377.2 376.46 1 1 1 220 2645 370.2 369.47 1 12 481 101 1 383.3 382.53 BIOLOGICAL AND MASS SPECTRUM DATA (Continued) Comp. K¡ DOR K¡ MOR CE50 CE50 Original peak MS cale.

No. (nM) (nM) GTPyS GTPyS obs. DOR (nM) hMOR (nM) 113 90 1518 439.2 438.59 114 108 109 397.2 396.56 1 15 91 60 463.2 462.62 1 16 93 1 13 463.2 462.61 117 95 97 474.1 473.64 118 612 2071 453.1 452.62 119 142 349 519.3 518.68 120 54 183 519.2 518.68 121 3.7 137 530.2 529.71 122 > 10000 > 10000 476.57 123 106 1016 376.46 124 > 10000 > 10000 491.2 490.60 125 6.3 2049 78.3 > 10,000 388.2 387.53 126 1414 > 10000 > 10,000 > 10,000 388.2 387.53 127 191 907 403.2 402.49 128 > 10000 > 10000 463.2 462.47 129 > 10000 > 10000 463.2 462.47 130 > 10000 > 10000 519.2 518.53 131 > 10000 > 10000 519.2 518.53 132 0.32 254 403.9 403.44 133 2.37 371 419.9 419.50 134 0.12 2 389.9 389.41 Ki DOR: Rat delta-opioid receptor binding constant Ki MOR: Rat mu-opioid receptor binding constant EXAMPLE 5 Inflammatory radiant heat pain model of CFA in rat The intraplantar injection of Freund's complete adjuvant (CFA) in rodents produces a severe and prolonged inflammatory reaction, characterized by a chronic and pronounced hyperalgesia to both thermal and mechanical stimuli. These effects reach a maximum between 24 and 72 hours after the injection and can last from several days to a few weeks. To determine the ability of the compounds to reverse thermal hyperalgesia, CFA (CFA: 1: 1, 100 μ? _) Was administered to the left hind paw of male Sprague-Dawley rats (200-350 g). After an incubation period of 24 hours, response latencies were obtained in the radiant heat leg (RH) stimulator apparatus, and compared with the baseline latencies (pre-CFA). The RH device automatically records the lifting of the leg of the glass surface. Only rats that exhibited a reduction of at least 25% baseline response latency (ie, hyperalgesia) were included in the subsequent analyzes. After the post-CFA latency determination, the rats were orally administered the test compound (2.5 mL / kg) or vehicle (hydroxypropylmethylcellulose, HPMC). The percent reversion of hyperalgesia was calculated for each animal as (Response to treatment-Post-CFA response) / (Pre-CFA response - Post-CFA response) x 100. Therefore, the return to normal pre-CFA thresholds it was defined as 100% efficacy, while no change in the post-CFA thresholds was 0% efficacy. Then the% average reversion of hyperalgesia was calculated for each treatment group (n = 6-8 rats / group).

EXAMPLE 6 The therapeutic effect of delta-opioid agonists has been demonstrated in: Pain (Fang (1995) Shengli Kexue Jinzhan 26: 137-40; Garzon, (1995) Analgesia (Elmsford, New York) 1: 131-44; Matthes, Maldonado, Simontn, Valverde, Slowe, Kitchen, Befort, Dierich, Le Meur et al. (1996) Nature (London) 383,819-823; Stevens (1996) Journal of Pharmacology and Experimental Therapeutics 276: 440-8; Dondio, Ronzoni and Petrillo (1997) Expert Opinion on Therapeutic Patents 7: 1075-1098; Hutcheson , Sanchez-Blazquez, Rodriguez-Diaz, Garzon, Schmidhammer, Borsodi, Roques and Maldonado (1999) European Journal of Pharmacology 383: 29-37; Fraser, Pradhan, Clarke and Wahlestedt (2000) Journal of Pharmacology and Experimental Therapeutics 295: 1 135-1 141; Scheideler (2000) Current Opinion in Central &Periferal Nervous System Investigational Drugs 2: 171-177; Wei, Brown, Takasaki, Plobeck, Delorme, Zhou, Yang, Jones, Gawell, Gagnon, Schmidt, Yue, Walpole, Payza, St-Onge, Labarre, Godbout, Jakob, Butterworth, Kamassah, Morin, Projean, Ducharme and Roberts (2000) Journal of Medicin to Chemistry 43: 3895-3905; Nagase, Yajima, Fujii, Kawamura, Narita, Kamei and Suzuki (2001) Life Sciences 68: 2227-2231; Abeyta, Dettmer, Barnes, Vega, Letter, Gallegos, Raymond-Stintz, Savage, Valenzuela and Saland (2002) Brain Research 931: 100-5. Reference number FIELD: FIELD Journal Code: 0045503 FIELD Cali Number:; Cahill, Morinville, Hoffert, O'Donnell and Beaudet (2003) Pain 101: 199-208; Collina, Azzolina, Vercesi, Brusotti, Rossi, Barbieri, Lanza, Mennuni, Alcaro, Battaglia, Linati and Ghislandi (2003) Drug 58: 939-946; Hurley, Banfor and Hammond (2003) Neuroscience (Oxford, United Kingdom) 1 18: 789-796).

States of inflammatory pain (Stein, Millan, Shippenberg, Peter and Herz (1989) Journal of Pharmacology and Experimental Therapeutics 248: 1269-75; Antonijevic, Mousa, Schaefer and Stein (1995) Journal of Neuroscience 15: 165-72; Ballet, Mauborgne, Benoliel, Bourgoin, Hamon, Cesselin and Collin (1998) Brain Research 796: 198-208, Hurley and Hammond (2001) Journal of Neuroscience 21: 2536-2545, Przewlocki and Przewlocka (2001) European Journal of Pharmacology 429: 79 -91; Spetea, Rydelius, Nilander, Ahmed, Bileviciute-Ljungar, Lundeberg, Svensson and Kreicbergs (2002) European Journal of Pharmacology 435: 245-252; Bao, Jin, Zhang, Wang, Xu, Zhang, Wang, Ning, Cai , Guan, Xiao, Xu, He, Hokfelt, Zhou and Zhang (2003) Neuron 37: 121-133, Cahill, Morinville, Hoffert, O'Donnell and Beaudet (2003) Pain 101: 199-208, Martin, Matifas, Maldonado and Kieffer Brigitte (2003) European Journal of Neuroscience 17: 701-8, FIELD Reference Number: FIELD Journal Code: 89181 10 FIELD Cali Number: Petrillo, Angelici, Bin gham, Ficalora, Garnier, Zaratin, Petrone, Pozzi, Sbacchi, Stean, Upton, Dondio and Scheideler (2003) Journal of Pharmacology and Experimental Therapeutics 307: 1079-1089).

Visceral pain (Schmauss and Yaksh (1984) Journal of Pharmacology and Experimental Therapeutics 228: 1-12; Craft, Henley, Haaset, Hruby and Porreca (1995) Journal of Pharmacology and Experimental Therapeutics 275: 1535-42; Su, Wachtel and Gebhart (1998) Journal of Neurophysiology 80:31 12-31 19; Gebhart, Su, Joshi, Ozaki and Sengupta (1999) Progress in Pain Research and Management 14: 225-235; Sora, Li, Fuñada, Kinsey and Uhl (1999) European Journal of Pharmacology 366.R3-R5; Gebhart (2000) Regional Anesthesia and Pain Medicine 25: 632-638; Martin, Matifas, Maldonado and Kieffer Brigitte (2003) European Journal of Neuroscience 17: 701-8).

Lung (Kuo, Rohde, Barnes and Rogers (1992) British Journal of Pharmacology 105: 361 -6; Campa, Schreiber, Bepler, Bishop, McNutt, Chang and Patz (1996) Cancer Research 56: 1695-701; Bolli, Shinmura, Tang, Kodani, Xuan, Guo and Dawn (2002) Cardiovascular Research 55: 506-519; Janssens, Leenaerts, Fernandez-Gadea, Gomez-Sanchez, Flameng, Herijgers, Meert and Borgers (2003) PCT International Application P. 75; McLeod , Tuishian and Hey (2003) Expert Opinion on Therapeutic Patents 13: 1501 -1512).

Cardioprotection (Schultz, Hsu, Nagase and Gross (1998) American Journal of Physiology 274: H909-H914¡ Fryer, Hsu, Eells, Nagase and Gross (1999) Circulation Research 84: 846-851; Fryer, Hsu, Nagase and Gross ( 2000) Journal of Pharmacology and Experimental Therapeutics 294: 451-457; Fryer, Hsu and Gross (2001) Basic Research in Cardiology 96: 136-142; Fryer, Patel, Hsu and Gross (2001) American Journal of Physiology 281: H 184 -H 92; Fryer, Pratt, Hsu and Gross (2001) Journal of Pharmacology and Experimental Therapeutics 296: 642-649; Fryer, Wang, Hsu and Gross (2001) American Journal of Physiology 280: H1346-H1353; Fryer, Wang, Hsu, Nagase and Gross (2001) Journal of Pharmacology and Experimental Therapeutics 299: 477-482; Huh, Gross, Nagase and Liang (2001) American Journal of Physiology 280: H377-H383; Karck, Tanaka, Bolling, Simon, Su, Oeltgen and Haverich (2001) Journal of Thoracic and Cardiovascular Surgery 122: 986-992, McPherson and Yao (2001) Anesthesiology 94: 1082-1088; Patel, Hsu, Moore and Gross ( 2001) Journal of Molecular and Cellular Cardiology 33: 1455-1465; Rebrova, Maslov and Tam (2001) Voprosy Meditsinskoi Khimii 47: 338-345; Patel, Ludwig, Fryer, Hsu, Warltier and Gross (2002) FASEB Journal 16: 1468-1470, 0.1096 / fj.02-0170fje; Sigg, Coles, Oeltgen and Laizzo (2002) American Journal of Physiology 282: H1953-H1960; Zhang, McPherson, Liu, Baman, McPherson, Rock and Yao (2002) Journal of Pharmacology and Experimental Therapeutics 301: 1012-1019; Patel, Hsu and Gross (2004) Basic Research in Cardiology 99: 38-45; Patel, Hsu and Gross (2004) Life Sciences 75: 129-140; Pear and Gross (2004) Basic research in cardiology 99: 29-37. Reference number FIELD: FIELD Journal Code: 0360342 FIELD Cali Number; Shinmura, Nagai, Tamaki and Bolli (2004) Basic Research In Cardiology 99: 46-55.

Urinary dysfunction (Dray and Metsch (1984) Neuroscience Letters 47:81 -4; Dray (1985) Journal of Pharmacological Methods 13: 157-65; Craft, Henley, Haaset, Hruby and Porreca (1995) Journal of Pharmacology and Experimental Therapeutics 275 : 1535-42; Murase, Hamada and Asaki (1996) PCT international application p, 93; Su, Sengupta and Gebhart (1997) Journal of Neurophysiology 77: 1566-1580; Sezen, Kenigs and Kapusta (1998) Journal of Pharmacology and Experimental Therapeutics 287: 238-245; Chang, Gengo, Biciunas, Ma, Pendergast and Jan (2003) PCT International Application P. 73; Igari, Yanai and Goya (2004) PCT International Application p.30).

Cough (Kamei, Iwamoto, Suzuki, Nagase, Misawa and Kasuya (1993) European Journal of Pharmacology 234: 1 17-20; Kotzer, Hay, Dondio, Giardina, Petrillo and Underwood (2000) Journal of Pharmacology and Experimental Therapeutics 292: 803 -9; McLeod, Tuishian and Hey (2003) Expert Opinion on Therapeutic Patents 13: 1501-1512).

Anxiety (Roberts, Gold, Polis, McDonald, Filliol, Kieffer and Koob (2001) Alcoholism: Clinical and Experimental Research 25: 1249-1256; Gaveriaux-Ruff and Kieffer (2002) Neuropeptides (Edinburgh, United Kingdom) 36: 62-71 Masuda, Suzuki, Takemura, Sugawara, Guo, Liu, Kawarada, Shimizu and Sugiyama (2003) Tohoku Journal of Experimental Medicine 201: 23-27, Noble and Roques (2003) Drugs of Today 39: 897-908).

Depression (Broom, Jutkiewicz, Folk, Traynor, Rice and Woods (2002) Psychopharmacology (Berlin, Germany) 164: 42-48; Broom, Jutkiewicz, Folk, Traynor, Rice and Woods (2002) Neuropsychopharmacology 26: 744-755; Broom, Jutkiewicz, Rice, Traynor and Woods (2002) Japanese Journal of Pharmacology 90: 1-6; Varona, Gil, Saracibar, Maza, Echevarría and Irazusta (2003) Arzneimittel-Forschung 53:21 -25).

Parkinson's disease (Barneoud, Descombris, Aubin and Abrous (2000) European Journal of Neuroscience 12: 322-36, Hill, Hille and Brotchie (2000) Drug News &Perspectives 13: 261-268; Hudzik, Howell, Payza and Cross (2000) European Journal of Pharmacology 396: 101-107; Hille, Fox, Maneuf, Crossman and Brotchie (2001) Experimental Neurology 172: 189-198).

EXAMPLE 7 The therapeutic effect of mu-opioid agonists has been demonstrated in: Pain (Pasternak (1986) Advances in Pain Research and Therapy 8: 337-44; Garzon and Sanchez-Blazques (1995) Life Sciences 56: PL237-PL242; Matthes, Maldonado, Simonin, Valverde, Slowe, Kitchen, Befort, Dierich, Le Meur et al. (1996), Nature (London) 383: 819-823; Stevens (1996) Journal of Pharmacology and Experimental Therapeutics 276: 440-8; Dayer, Desmeules and Collart (1997) Drugs 53: 18-24; Valverde , Maldonado and Kieffer (1998) CNS Drugs 10: 1-10, Kharkevich and Churukanov (1999) European Journal of Pharmacology 375: 121-131, Pasternak (2000) Progress in Pain Research and Management 16: 147-162, Gutstein and Akil , JG Hardman and LE Limbird (2001) The pharmacological basis of therapeutics 569-619; Pasternak (2001) Neuroscientist 7.220-231; Smith, Ross, Nielsen and Saini (2001) European Journal of Pain (London, United Kingdom) 5: 135 -136; Wells, Bartlett, Ananthan and Bilsky (2001) Journal of Pharmacology and Experimental Therapeutics 297: 597-605; Abbadie and Pasternak (2003) Handbook of Chemi cal Neuroanatomy 20: 1-29; Collina, Azzolina, Vercesi, Brusotti, Rossi, Barbieri, Lanza, Mennuni, Alcaro, Battaglia, Linati and Ghislandi (2003) Drug 58: 939-946; Cowan (2003) International Journal of Clinical Practice, Supplement 133: 3-8; Hurley, Banfor and Hammond (2003) Neuroscience (Oxford, United Kingdom) 1 18: 789-796; Neilan, King, Rossi, Ansonoff, Pintar, Schiller and Pasternak (2003) Brain Research 974: 254-257; Porreca and Hruby (2003) Pain 407-419; Servin (2003) Advances in Experimental Medicine and Biology 523: 245-260; Gilbert, Hosztafi, Mahurter and Pasternak (2004) European Journal of Pharmacology 492: 123-130).

Inflammatory pain (Gutstein and Akil, J. G. Hardman and L. E. Limbird (2001) "The pharmacological basis of therapeutics" 569-619).

Immune function (Renaud and Tomer (1996) "Advances in Experimental Medicine and Biology" 402: 63-69; Priest, Bianchi, Manfredi and Panerai (1997) Pain 72: 325-330; Carrigan, Saurer, Ijames and Lysle (2004) International Immunopharmacology 4: 419-428).

Visceral pain (Kharkevich and Churukanov (1999) European Journal of Pharmacology 375: 121-131; Gebhart (2000) Regional Anesthesia and Pain Medicine 25: 632-638; Churukanov (2003) Eksperimental'naya i Klinicheskaya Farmakologiya 66: 24-31) .

Esophageal reflux (Tonini, de Giorgio and de Ponti (2004) Drugs 64: 347-361).

Muscle pain Nielsen, Matiesen and Blackburn-Munro (2004) European Journal of Pharmacology 487: 93-103).

Pain of cancer (Gutstein and Akil, JG Hardman and L E. Limbird (2001) "The pharmacological basis of therapeutics" 569-619; Wells, Bartlett, Ananthan and Bilsky (2001) Journal of Pharmacology and Experimental Therapeutics 297: 597-605 Valenzano, Miller, Chen, Shan, Crumley, Victory, Davies, Huang, Allie, Nolan, Rotshteyn, Kile and Brogle (2004) Journal of Pharmacology and Experimental Therapeutics 310: 783-792).

Cough (Gutstein and Akil, J. G. Hardman and L. E. Limbird (2001) "The pharmacological basis of therapeutics" 569-619).

EXAMPLE 8 Analgesic synergy delta and mu It has been repeatedly demonstrated that delta and mu opioid agonists produce antinociceptive synergy. Vaught and Takemori (1979) Journal of Pharmacology and Experimental Therapeutics 21 1: 280-3; Vaught and Takemori (1979) Journal of Pharmacology and Experimental Therapeutics 208: 86-90; Porreca, Jiang and Tallarida (1990) European Journal of Pharmacology 179: 463-8; Sutters, Miakowski, Taiwo and Levine (1990) Brain Research 530: 290-4; Horan, Tallarida, Haaset, Matsunaga, Hruby and Porreca (1992) Life Sciences 50: 1535-41; Malmberg and Yaksh (1992) Journal of Pharmacology and Experimental Therapeutics 263: 264-75; Adams, Tallarida, Geller and Adler (1993) Journal of Pharmacology and Experimental Therapeutics 266: 1261-7; Dykstra, Schoenbaum, Yarbrough, McNutt and Chang (1993) Journal of Pharmacology and Experimental Therapeutics 267: 875-82; Rossi, Pasternak and Bodnar (1994) Brain Research 665: 85-93; Negri, Improta, Lattanzi, Potenza, Luchetti and Melchiorri (1995) British Journal of Pharmacology 1 16: 2931-8; Dykstra, Granger, Alien, Zhang and Rice (2002) Psychopharmacology (Berlin, Germany) 163: 420-429.

EXAMPLE 9 Profile of reduced side effects delta and mu It has been demonstrated that combinations of delta and mu opioid agonists have reduced side effects, lower incidence of Straub's tail and lower respiratory depression (O'Neill, Collins, Pettit, McNutt and Chang (1997) Journal of Pharmacology and Experimental Therapeutics 282: 271-277; Su, McNutt and Chang (1998) Journal of Pharmacology and Experimental Therapeutics 287: 815-823). Therefore, compounds with dual opioid pharmacological function, delta and mu, will have a greater analgesic action and a profile of reduced side effects compared to those with a single pharmacological function.

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A compound of formula (I): Formula (I) wherein: G is -C (Z) NRiR2, C6-io aryl. C6-io arylthio, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl , oxazolyl, isoxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, and pyridinyl; wherein the C6-io aryl group of the substituents of G containing C-6-10 aryl, and the heterocycles of G, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl , C2-8 alkenyl, C2-8 alkynyl, C1-8 alkanoyloxy. hydroxyalkanyl of C 1-8, carboxyalkanyl of Ci-8, alkanyl (Ci-8) carbonylamino, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino, Ci-6-alkylamino, dialkyl-amino-C1-6, 8, Ci-8alkylsulfonyl, (1-8) alkylsulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, (C-i. 8) aminocarbonyl, dialkanyl (C-i-8) aminocarbonyl, and alkanyl (Ci-6) -oxycarbonylamino; Ri is a substituent selected from the group consisting of hydrogen, Ci-e alkanyl, C 2-8 alkenyl and C 2-8 alkynyl; R2 is a substituent selected from the group consisting of hydrogen; C-i alkanyl. 8 C2-8 alkenyl; C2-8 alkynyl; C6-io aryl; and C3-8i cycloalkanyl with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted Ci-8 alkanyl; and wherein the C1-8 alkanyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci-6 alkylamino, Ci-6 dialkylamino, Ci-6 alkanoyloxy, Ci-6, hydroxy, fluorine, chlorine, cyano, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialcanyl (C- | 8) aminocarbonyl, alkanyl (Ci-6) oxycarbonyl and aryloxy; wherein the phenyl and aryloxy substituents of Ci-8 alkanyl, and the substituents C6-io aryl and C3-8 cycloalkanyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of C6 alkanyl. 8, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkanoyloxy, trifluoromethyl, trifluoromethoxy, phenyl, halogen, cyano, hydroxy, alkanylthio of d. a, alkanyl (Ci-8) sulfonyl and alkanyl (Ci-8) sulfonylamino; or R- [and R 2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with phenyl (wherein phenyl is optionally substituted with one to three substituents of C 1-4 alkanoy or alkynyloxy of C1. 4) and from one to two additional substituents independently selected from the group consisting of C-i-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, C 1-6 alkylamino, C 1-6 dialkanylamino and halogen; or Ri and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl, optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl, C -8 hydroxyalkanyl, hydroxy, amino, Ci-6 alkylamino, Ci-6 dialkanylamino and halogen; R3 is a substituent selected from the group consisting of hydrogen, Ci-8 alkanyl, halo (I-3) C 1-8 alkanoyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkanyl, cycloalkanyl- Ci-8 alkanyl, Ci-8 alkanoyloxy Ci-8 alkanyl, Ci-8 alkanyl thioalkanyl, Ci-8 hydroxyalkanyl, alkynyloxy (Ci-8) carbonyl, halo (i-3) alkanyl (Ci-8) carbonyl, formyl, thioformyl, carbamimidoyl, phenyliminoalkanyl of Ci-8, phenylallanyl of C 1-8, phenyl-alkenyl of C- | 8, phenyl-alkynyl of Ci-8, naphthyl-alkanyl of Ci- 8 and Ci-8 heteroaryl-alkanyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl , oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, thiazolyl; wherein the phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, C2-6 alkenyl, Ci-6 alkanoyloxy, amino, Ci-6 alkanoylamino, dialkanylamino of Ci-6, alkanilC ^ carbonyl, alkanyl (Ci-6) carbonyloxy, alkanyl (Ci-6) carbonylamino, Ci-6 alkanylthio, Ci-6alkylsulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6, thioureido and fluoroalkanol (Ci-6) oxy; alternatively, when phenyl and heteroaryl are optionally substituted with alkanyl or alkanoyloxy substituents attached to adjacent carbon atoms, the two substituents may together form a fused cyclic alkanyl or cycloheteroalkanyl, selected from the group consisting of - (CH2) 3-5- , -O (CH2) 2-4-, - (CH2) 2-4O- and -0 (CH2) i-30-; R4 is one to three substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 arylalkynyl, C1-6 alkanoyloxy, amino, Ci-6alkylamino, d-6 dialkanylamino, C6-6alkylcarbonyl, C6-C6alkyloxycarbonyloxy, C6-6alkyloxycarbonyl, aminocarbonyl, C6-6alkylaminocarbonyl, alkanyl (Cv6) arninocarbonyl, alkanyl (Ci-6) carbonylamino, alkanylthio of Ci-6, alkanyl (Ci-6) sulfonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, -C (= NOH) phenyl, aminomethyl, hydroxymethyl, methanesulfonylamino, C6-io arylamino (wherein the C6-i0 aryl is optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, Ci-6 alkoxy, halogen and hydroxy ), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, C6-io aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkannyloxy; or optionally, when R4 comprises two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the fused portion is selected from the group consisting of - (CH2) 3-5-. -O (CH2) 2-4-, - (CH2) 2-4O-, -0 (CH2) 1-30- and -S-C (NH2) = N-; R5 is one to two substituents independently selected from the group consisting of hydrogen, Ci-6 alkanyl, C2-6 alkenyl, Ci-6 alkanoyloxy, amino, C6 alkylamino, Ci-6 dialkanylamino, CiCi -6) carbonyl, alkanyl- ^ -carbonyloxy, alkanoxycarbonyl, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino, alkanoyldio of C 1-6, alkanyl (Ci-6) sulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6 and fluoroalkanyloxy of C-6; A is absent or is - (CH2) m- > where m is 2 or 3; Y is - (CH2) nX- or -X (CH2) n-; X is O, or S; n is 0 or 1; Z is O, S, NH, N- (C6 alkanyl), N (OH), N- (O-C6 alkanyl), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates or pharmaceutically acceptable salts thereof.

2. The compound according to claim 1, further characterized in that G is -C (Z) NR- | R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanoyloxy alkanoyl. Ci-8, hydroxyalkanyl of Ci-8, carboxyalkanyl of C 1-8, alkanyl (Ci-8) carbonylamino, halogen, hydroxy, cyano, oxo, thioxo, amino, Ci-6-alkylamino, dialkyl-amino-Ci-6, alkanylthio Ci-8, aminocarbonyl, aminothiocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialkanyl (Ci-8) aminocarbonyl and alkanyl (Ci.6) oxycarbonylamino.

3. The compound according to claim 1, further characterized in that G is -CÍZJNR ^, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of Ci-4 alkanyl, Ci-4 alkanoyloxy, Ci-4 hydroxyalkanyl, Ci-4 carboxy-alkanyl, (C- | 4) alkanoyl, carbonylamino, hydroxy, cyano, oxo, thioxo, amino, C 1-6 alkylamino, dialkyl-amino-Ci-6, alkanylthio-Ci-8, aminocarbonyl, aminothiocarbonyl, alkanyl (Ci-8) aminocarbonyl and dialcanyl (C -8) aminocarbonyl.

4. The compound according to claim 1, further characterized in that G is -C (Z) NR- | R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, thienyl, isothiazolyl, isoxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three selected substituents independently of the group consisting of C 1 - alkanyl, C 1-4 alkynyloxy, C 1-4 hydroxyalkanyl, C 1-4 alkynyl carbonylamino, hydroxy, cyano, oxo, thioxo and aminocarbonyl.

5. The compound according to claim 1, further characterized in that Ri is a substituent selected from the group consisting of hydrogen and alkanyl of C- | .4.

6. The compound according to claim 1, further characterized in that R-i is selected from the group consisting of hydrogen, methyl, ethyl and propyl.

7. The compound according to claim 1, further characterized in that Ri is selected from the group consisting of hydrogen, methyl and ethyl.

8. The compound according to claim 1, further characterized in that R2 is selected from the group consisting of hydrogen; alkanoyl of d-4; phenyl; and C3-6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted C -4 alkanyl; and wherein the C 1-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci-6-alkanylamino, Ci-6-dialkylamino > C 1-4 alkanoyloxy, hydroxy, fluoro, chloro, cyano, aminocarbonyl, alkanyl (Ci. 8) aminocarbonyl, dialkyl (C 1-8) aminocarbonyl and phenoxy; wherein the substituents phenyl and phenoxy of the alkanyl of C-, and the substituents phenyl and cycloalkanyl of C3-6 of R2, are optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanyl, d-e alkanoyloxy, trifluoromethyl, phenyl, fluorine, hydroxy, C1-8 alkanthio, C 1 sulphonyl alkanoy (Ci-8) sulfonylamino; or Ri and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein the phenyl is optionally substituted with Ci-4 alkanoyloxy or hydroxy), Ci-4 alkanoyl , or hydroxy.

9. The compound according to claim 1, further characterized in that R2 is selected from the group consisting of Ci-4 alkanyl, phenyl and C3-6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy, fluoro, aminocarbonyl, (Ci_8) aminocarbonyl, dialkanyl (Ci. 8) aminocarbonyl and phenoxy; wherein the substituents phenyl and phenoxy of the alkanyl of Ci-, and the phenyl of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, Ci-6 alkanoyloxy, fluorine, hydroxy and Ci-6 alkanthio; or Ri and R2, taken together with the nitrogen to which they are attached, form a olidinyl or piperidinyl ring, wherein said olidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of Ci-4 alkanyl and hydroxy.

10. The compound according to claim 1, further characterized in that R2 is selected from the group consisting of C and phenyl alkanyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted C1-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy, fluoro and phenoxy; wherein the phenyl and phenoxy substituents of Ci-4 alkanyl, and the phenyl of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, d-6 alkanoyloxy, fluorine and hydroxy; or Ri and R2, taken together with the nitrogen to which they are attached, form a olidinyl or piperidinyl ring, wherein said olidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of Ci-3 alkanyl and hydroxy.

11. The compound according to claim 1, further characterized in that R3 is selected from the group consisting of hydrogen, C1-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, alkynyloxy (Ci-8) -alkanyl of Ci-8, alkanyl (Ci-8) ) -cycloalkanyl of Ci-8, hydroxyalkanyl of Ci-8, thiomorhyl, phenyliminoalkanyl of Ci-8, phenylallanyl of Ci-8 and heteroaryl-alkanyl of C 1-8 wherein heteroaryl is selected from the group consisting of benzo [1, 3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl and heteroaryl are optionally substituted with one to three substituents, independently selected from the group consisting of Ci-6 alkanoyloxy and hydroxy; or optionally, when the phenyl and heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the portion is selected from -O (CH2) i-30-.

12. The compound according to claim 1, further characterized in that R3 is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl and heteroaryl. -alkyl of Cis wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl in any phenyl-containing substituent is optionally substituted with a hydroxyl group.

13. The compound according to claim 1, further characterized in that R3 is hydrogen, methyl, allyl, or heteroarylmethyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl and thienyl.

14. The compound according to claim 1, further characterized in that R4 is one to three substituents independently selected from the group consisting of hydrogen, C6 alkanoyloxyC6 alkyloxy, aminocarbonyl, aminothiocarbonyl, hydroxyamidino, formylamino, alkanyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino, halogen, hydroxy, C6-io aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl and thienyl.

15. The compound according to claim 1, further characterized in that R4 is one to two substituents independently selected from the group consisting of hydrogen, alkanoyl of C- | 4, alkanoyloxy of Ci-4, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl.

16. The compound according to claim 1, further characterized in that R4 is one to two substituents independently selected from the group consisting of hydrogen, methyl, methoxy, bromine, fluorine, 5- or 6-phenyl, 5- or 6- pyridinyl, 5- or 6-furanyl and hydroxy.

17. The compound according to claim 1, further characterized in that R5 is one to two substituents independently selected from the group consisting of hydrogen and halogen.

18. The compound according to claim 1, further characterized in that R5 is hydrogen.

19. The compound according to claim 1, further characterized in that A is absent or is - (CH2) 2-.

20. The compound according to claim 1, further characterized because A is - (CH2) 2-.

21. The compound according to claim 1, further characterized in that X is O, or S.

22. The compound according to claim 1, further characterized in that n is 0.

23. The compound according to claim 1, further characterized in that Z is O, NH, N- (C 1-6 alkanyl) > N (OH), N- (0-alkanyl of C-6), or N- (phenyl).

24. The compound according to claim 1, further characterized in that Z is O, NH, or N (OH).

25. The compound according to claim 1, further characterized in that Z is O, or NH.

26. - A compound of formula (I): Formula (I) wherein: G is -C (Z) NR R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl, C 1-8 alkynyloxy, hydroxyalkanyl of 1-8, carboxyalkanyl of Ci-8, alkanil ( Ci.8) carbonylamino, halogen, hydroxy, cyano, oxo, thioxo, amino, Ci-6 alkanylamino, C 1-6 dialkanylamino, Ci-8 alkanthio, aminocarbonyl, aminothiocarbonyl, alkanoyl (Ci-8) aminocarbonyl, dialcanil ( C1-8) aminocarbonyl and (C1-6) alkanoxycarbonylamino; R-i is hydrogen or C 4 alkanyl; R2 is selected from the group consisting of hydrogen; C1-4 alkanyl; phenyl; and C3-6 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted Ci-4 alkanyl; and wherein the C1- alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, amino, Ci-6 alkylamino, C1-6 dialkylamino, Ci-4 alkanoyloxy, hydroxy, fluorine, chlorine , cyano, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialkanyl (Ci-8) aminocarbonyl and phenoxy; wherein the substituents phenyl and phenoxy of the C 1-4 alkanyl, and the substituents Phenyl and cycloalkanyl of C 3-6 of R 2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-8 alkanyl, alkanoyloxy C1-8, trifluoromethyl, phenyl, fluorine, hydroxy, Ci-8 alkanylthio, Ci-8alkylsulfonyl and (C -8) alkylsulfonylamino; or R1 and R2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein the phenyl is optionally substituted with Ci-4 alkanoyloxy or hydroxy), Ci-4 alkanyl, or hydroxy; R3 is selected from the group consisting of hydrogen, Ci-8 alkanyl, C2-8 alkenyl of C2-8 alkynyl, alkanoyloxy (Ci-8) alkanyl of C1-8, alkanyl (C1-8) thioalkanyl of C- 8, Ci-8 hydroxyalkanyl, thiomorhyl, phenyliminoalkanyl of Cia, phenylallanyl of Ci. 8 and Ci-8 heteroaryl-alkanyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indolyl, indolinyl, isoquinolinyl, pyrazinyl, pyrazolyl, pyridazinyl , pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of (C -6) oxy and hydroxy; or optionally, when the phenyl and the heteroaryl are optionally substituted with two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the portion is selected from -O (CH2) i-3O-; R 4 is one to three substituents independently selected from the group consisting of hydrogen, d-6 alkanyl, d-β-alkanoyloxy, aminocarbonyl, aminothiocarbonyl, hydroxyamidino, formylamino, (C 1-6) alkylaminocarbonyl, (C 1-6) alkylaminocarbonyl , halogen, hydroxy, C6-io aryl, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl , quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl and thienyl; R5 is one to two substituents independently selected from the group consisting of hydrogen and halogen; A is absent or is - (CH2) 2-; Y is O, S, CH2O, or OCH2; Z is O, NH, N- (alkanyl of d-6), N (OH), N- (0-alkanyl of C 1-6), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.

27. A compound of formula (I): Formula (I) wherein: G is -C (Z) NRiR2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, isothiazolyl, isoxazolyl, oxazolyl , isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and heterocycles of G are optionally substituted with one to three substituents, independently selected from the group consisting of C 1-4 alkanyl, C 1-4 alkynyloxy, C 1-4 hydroxyalkanyl, C 1-4 carboxy-alkanyl , (C 1-4) alkylaminocarbonylamino, hydroxy, cyano, oxo, thioxo, amino, Ci-6-alkylamino, d-6-dialkanylamino, C 1-8 alkyllthio, aminocarbonyl, aminothiocarbonyl, (C-8) aminocarbonyl and dialkanyl (Ci.8) aminocarbonyl; Ri is selected from the group consisting of hydrogen, methyl, ethyl and propyl; R2 is selected from the group consisting of Ci-4 alkanyl, phenyl and cycloalkanyl of C3-6I with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three substituents, independently selected from the group consisting of phenyl, Ci-4alkynyloxy, hydroxy, fluoro, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialcani C! . 8) aminocarbonyl and phenoxy; wherein the phenyl and phenoxy substituents of the Ci-4 alkanyl, and the phenyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, Ci-6 alkanoyloxy, fluorine, hydroxy and C1-6 alkanoylthio; or Ri and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from the group consisting of C 1 -3 alkanyl and hydroxy; R3 is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl, and heteroaryl-C3-alkanyl wherein the heteroaryl is selected from the group consisting of it consists of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, wherein the phenyl in any phenyl-containing substituent is optionally substituted with a hydroxyl group; R4 is one to two substituents independently selected from the group consisting of hydrogen, d-4 alkanyl, C-, -halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; R5 is hydrogen; A is - (CH2) 2-; And it is O, or S; Z is O, NH, or N (OH); and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.

28. The compound according to claim 27, further characterized in that G is -C (Z) NR R2, phenyl, or a heterocycle selected from the group consisting of imidazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, thienyl, isothiazolyl, isoxazolyl, isoxadiazolyl, quinolinyl and pyridinyl; wherein the phenyl and the heterocycles of G are optionally substituted with one to three substituents independently selected from the group consisting of C 1 alkanoyloxy alkanyl, C 1-4 hydroxyalkanyl, C 1-4 alkylaminocarbonyl, hydroxy , cyano, oxo, thioxo and aminocarbonyl.

29. - The compound according to claim 27, further characterized in that G is -C (Z) NR1R2, 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1 / - / - tetrazol-5-yl, 2-methyl-tetrazol-5-yl, 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl, 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl, 4H- [1, 2,4] thiadiazol-5-yl-3-yl, [1, 2,3,5] oxathiadiazol-2-oxo-4-yl, or pyridin-3-yl.

30. The compound according to claim 27, further characterized in that R2 is selected from the group consisting of Ci-4 alkanyl and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three selected substituents independently of the group consisting of phenyl, Ci_4 alkanoyloxy, hydroxy, fluoro and phenoxy; wherein the phenyl and phenoxy substituents of the Ci-4 alkanyl, and the phenyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, C6 .6 alkanoyloxy, fluorine and hydroxy; or Ri and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinium ring, wherein said pyrrolidinyl or piperidinium is optionally substituted with a substituent selected from the group consisting of Ci-3 alkanyl and hydroxy; and R3 is a substituent selected from the group consisting of benzo [1,3] dioxol-5-ylmethyl, carbamimidoyl, 1H-imidazol-4-ylmethyl, phenyliminomethyl, 1-prop-2-ynyl, thioformyl, -hydroxyphenyl-methyl, hydroxy-ethyl, methoxy-ethyl, 2-methyl-allyl, 2-methyl-but-2-enyl, allyl, furan-3-ylmethyl, H, Me, methylthioethyl, phenethyl, pyridin-2-yl -methyl and thiophen-2-ylmethyl.

31. A compound of formula (I): Formula (I) wherein: G is selected from -C (Z) NRiR2 > 2-methylcarbonylaminophenyl, 2-aminocarbonyl-phenyl, 1H-tetrazol-5-yl, 2-methyl-tetrazol-5-yl, 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl, 4H - [1, 2,4] -oxadiazol-5-thioxo-3-yl, 4H- [1, 2,4] thiadiazole-5- ??? - 3-yl, [1, 2,3,5] oxathiadiazol-2-oxo-4-yl, or pyridin-3-yl; Ri is hydrogen, methyl, or ethyl; R2 is selected from the group consisting of Ci-4 alkanyl and phenyl; with the proviso that when Z is O, or S, R 2 is different from unsubstituted C 4 alkanyl; and wherein the C 4 alkanyl is optionally substituted with one to three substituents, independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy, fluoro and phenoxy; wherein the phenyl and phenoxy substituents of the C1-4 alkanyl, and the phenyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, Ci-6 alkanoyloxy, fluorine and hydroxy; or Ri and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from Ci-3 alkanyl or hydroxy; R3 is selected from the group consisting of hydrogen, methyl, allyl, 2-methyl-allyl, propynyl, hydroxyethyl, methylthioethyl, methoxyethyl, thioformyl, phenyliminomethyl, phenethyl and heteroaryl-C8 alkanyl wherein the heteroaryl is selected from the group consists of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl; wherein the phenyl in any phenyl-containing substituent is optionally substituted with a hydroxyl group; R4 is one to three substituents independently selected from the group consisting of hydrogen, Ci-4 alkanoyl, Ci-4 alkanoyloxy, halogen, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl , pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl, tetrazolyl, thiazolyl, thienyl, hydroxy and aminocarbonyl; R5 is hydrogen; A is - (CH2) 2-; And it is O, or S; Z is O, or NH; and enantiomers, diastereomers, tautomers, solvates and pharmaceutically acceptable salts thereof.

32. The compound according to claim 31, further characterized in that R2 is a substituent selected from the group consisting of Ci-4 alkanyl and phenyl; with the proviso that when Z is O, or S, R2 is different from unsubstituted Ci-4 alkanyl; and wherein the Ci-4 alkanyl is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, Ci-4 alkanoyloxy, hydroxy and 2,6-dimethyl-phenoxy; from one to three substituents independently selected from the group consisting of alkanyl of d-6. C-i-6 alkanoyloxy, fluorine and hydroxy; or R1 and R2, taken together with the nitrogen to which they are attached, form a pyrrolidinyl or piperidinyl ring, wherein said pyrrolidinyl or piperidinyl is optionally substituted with a substituent selected from Ci-3 alkanyl or hydroxy.

33. The compound according to claim 31, further characterized in that R3 is a substituent selected from the group consisting of benzo [1,3] dioxol-5-ylmethyl, carbamimidoyl, 1-H-imidazol-4-ylmethyl, phenyliminomethyl , 1-prop-2-ynyl, thioformyl, 2-hydroxyphenyl-methyl, hydroxy-ethyl, methoxy-ethyl, 2-methyl-allyl, 2-methyl-but-2-enyl, allyl, furan-3-ylmethyl, H , Me, rethylthioethyl, phenethyl, pyridin-2-yl-methyl and thiophen-2-ylmethyl; and R4 is one to two substituents independently selected from the group consisting of hydrogen, Ci-4 alkanyl, Ci-4l alkanoyloxy, phenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinolinyl , tetrazolyl, thiazolyl, thienyl and hydroxy.

34. The compound according to claim 31, further characterized in that R3 is a substituent selected from the group consisting of benzo [1,3] dioxol-5-ylmethyl, carbamidoyl, 1H-imidazol-4-yl-methyl , phenyliminomethyl, 1-prop-2-ynyl, thiomorhyl, 2-hydroxyphenyl-methyl, hydroxyethyl, methoxyethyl, allyl, furan-3-yl-methyl, H, Me, methylthioethyl and phenethyl; R4 is one to two substituents independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl and hydroxy.

35. The compound according to claim 31, further characterized in that R3 is a substituent selected from the group consisting of H, benzo [1, 3] d -oxo-5-ylmethyl, 1-H-imidazole-4-yl; l-methyl, furan-3-ylmethyl, pyridin-2-ylmethyl and phenyliminomethyl; and R 4 is a substituent independently selected from the group consisting of hydrogen, methyl, methoxy, bromo, fluoro, 5- or 6-phenyl, 5- or 6-pyridinyl, 5- or 6-furanyl and hydroxy.

36.- A compound of formula (I): Formula (I) selected from the group consisting of: a compound of formula (I) wherein G is 1 - / - tetrazol-5-yl, R 3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - (2-hydroxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-methoxy-ethyl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, / V-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - [2- (2,6-dimethylphenoxy) -1-methyl-etl] aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -phenyl-A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-phenylethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methylene-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -cyclohexyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxymethyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N-hydroxyamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-ethyl-1 / - / - imidazol-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (R) -hydroxymethyl-2-phenyl-et-1-yl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, A / -diisobutylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 S-methoxymethyl-2-phenyl-et-1-yl) aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methoxy-pyridin-5-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4,5-dihydro-1 / - / - imidazole-2-ylo; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (4-phenyl) -cyclohexylaminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methyl-4H- [1, 2,4] triazol-5-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-methyl- [1, 2,4] oxadiazol-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (1 (S) -hydroxymethyl-1-methoxycarbonyl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxy-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is isopropylamine; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylmethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1, 4,5,6-tetrahydropyridin-2-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-aminophenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is C-piperidin-1-yl-methyleneamine; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methoxyphenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is cyclopentylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylphenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N, N-bis (2,2,2-trifluoro-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is isobutylamidino; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is C-morpholin-4-yl-methyleneamine; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-fluorophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-benzyl-N-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-methanesulfonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-fluorophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is thiophen-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-dimethylamino-et-1 -yl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methoxyphenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylmethylaminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylaminocarbonyl; R3 is ethoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is cyclopentylaminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-dimethylamino-et-1-yl) -A / -methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V - [(4-trifluoromethyl) -cyclohexyl] -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methanesulfonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - 2,2,2, -trifluoroethyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3 - [(3-methoxy) phenyl] piperidin-1-ylcarbonyl R 3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - 4-fluorophenyl-N-methyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (1 (f?) - hydroxymethyl-3-methyl-but-1-yl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (dimethylaminocarbonylmethyl) - / V-methylalcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (R) -hydroxy) pyrrolidin-1-carbonylcarbon; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (S) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-llo; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -A / -methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) in where G is 1 H-tetrazol-5-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is phenylthio; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-t -oxo-3-ylo; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazole-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 - [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-1,1-dimethyl-ethyl) -aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H, and Y is O; a compound of formula (I) wherein G is H-tetrazole-5-yl; R3 is H; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is fur-3-ylo; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is thien-3-ylo; R3 is H; R is 5-methoxy; R5 is H, and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-pyrazol-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is methyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is pyridin-2-ylmethyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is methyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -aminocarbonyl; R3 is t-butoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) in where G is A / - (2-hydroxyethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-hydroxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, A / -d-ethylamidino; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V, / V-d-ethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (R) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is trifluoromethylcarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is trifluoromethylcarbonyl; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O.

37.- A compound of formula (I): Formula (I) selected from the group consisting of: a compound of formula (I) wherein G is / - / - tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is ?? - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-methoxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? /, / V-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? / - [2- (2,6-dimethylphenoxy) -1-methyl-ethyl] aminocarbonyl! R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A-phenyl-A / -methyl-aminocarbonyl, R 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-l) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-phenylethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenol; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methylene-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N-cyclohexyl-N-methylalcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxymethyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N-hydroxyamidino; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-ethyl-1 / - / - imidazol-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (R) -hydroxymethyl-2-phenyl-et-1-yl) -aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A, A / -diisobutyllamine; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4-methylcarbonylamino-phenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (1 S-methoxymethyl-2-phenyl-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methoxypyridin-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4,5-dihydro-1 H-imidazol-2-ylo; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N- (4-phenyl) -cyclohexyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methyl-4H- [1, 2,4] triazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-dimethylamino-et-1-yl) -A / -methyl-aminocarbonyl; R3 is ethoxycarbonyl; R is H; R5 is H, and Y is O; a compound of formula (I) wherein G is 3-methanesulfonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V-2,2,2, -trifluoroethyl-aminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3 - [(3-methoxy) phenyl] pipe d-n-1-l-carbonyl R 3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / 4-fluorophenyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A - (dimethylaminocarbonylmethyl) -A / -methyl-aminocarbonyl; R3 is H, R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (f?) - h! drox!) pyrrolidin-1-l-carbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (S) -hydroxy) pyrrolidin-1-yl-carbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N- (2-hydroxy-1,1-d-methyl-ethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is fur-3-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is thien-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-4-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-pyrazol-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is methyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is fur-3-ylmethyl; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is N-. { 2-hydroxy-ethyl) -aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A /, A / -diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (R) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4 / - / - [1, 2,4] - oxadiazol-5-oxo-3-yl; R3 is H, R4 is 5-hydroxy; R5 is H; and Y is O.

38.- A compound of formula (I): Formula (I) selected from the group consisting of: a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is ?? - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-methoxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V, A / -diethylamidino; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (3-fluorophenyl) -methyl-aminocarbonyl! R 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 it's H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - [2- (2,6-dimethylphenoxy) -1-methyl-ethyl] aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N-phenyl-W-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-yl) aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-phenylethyl) - / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is Ó; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -cyclohexyl- / V-meth1-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-hydroxymethyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is N-hydroxyamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminophenyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 5-ethyl-1 H-imidazol-2-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (R) -hydroxymethyl-2-phenyl-et-1-yl) -aminocarbonyl R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (2-dimethylamino-et-1-yl) - / V- methyl aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -2,2,2, -trifluoroethyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3 - [(3-methoxy) phenyl] piperidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / 4-fluorophenyl- / V-methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is / V- (dimethylaminocarbonylmethyl) - / V-methylene-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is (3 (S) -hydroxy) pyrrolidin-1-ylcarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-ylR 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazole-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazole-5-thioxo-3-ylR 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-ylR 3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 H-tetrazole-5- ilo; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is fur-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is 1 H-imidazol-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is pyridin-3-yl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is fur-3-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is A /, A / -diethylamidino; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O.

39.- A compound of formula (I): Formula (I) selected from the group consisting of: a compound of formula (I) wherein G is 1 / - / - tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylaminophenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyrrolidin-1-ylcarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-methoxy-ethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is? /, / V-diethylamidino; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is [1, 2,3,5] oxathiadiazol-2-oxo-4-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (3-fluorophenyl) -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - [2- (2,6-d-methylphenoxy) -1-methyl-ethyl] aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / -phenyl-A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (1 (S) -hydroxymethyl-2-phenyl-et-1-yl) aminocarbonyl R 3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methyl-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-phenylethyl) - / V-methylene-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-aminocarbonyl-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-phenylethylaminocarbonyl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 3-methylcarbonylamino-phenyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (2-dimethylamino-et-1-yl) -A / -methyl-aminocarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is A / - (dimethylaminocarbonylmethyl) -A / -methyl-aminocarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is pyridin-3-yl; R3 is H; R4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 1 H-tetrazol-5-yl; R3 is H; R is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-t-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] - Oxadiazol-5-thioxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] thiadiazol-5-oxo-3-yl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is H-tetrazol-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 1 / - / - tetrazole-5-yl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is quinolin-3-yl; R3 is H; R4 is 5-h¡drox¡; R5 is H; and Y is O; a compound of formula (I) wherein G is 2-methylcarbonylamino-phenyl; R3 is pyridin-2-ylmethyl; R4 is H; R5 is H; and Y is S; a compound of formula (I) wherein G is N, N-diethylamidino; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (I) wherein G is 4H- [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-thioxo-3-yl; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; and a compound of formula (I) wherein G is 4 / - / - [1, 2,4] -oxadiazol-5-oxo-3-yl; R3 is H; R 4 is 5-hydroxy; R5 is H; and Y is O.

40.- A compound of formula (Ib): Formula (Ib) selected from the group consisting of: a compound of formula (Ib) where G is carboxy; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is ethoxycarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (Ib) wherein G is cyano; R3 is H; R4 is H; R5 is H; Y Cast; a compound of formula (Ib) wherein G is methoxycarbonyl; R3 is H; R 4 is 6-methoxycarbonyl; R5 is H; and Y is O; a compound of formula (Ib) wherein G is bromine; R3 is H; R 4 is 5-methoxy; R5 is H; and Y is O; a compound of formula (Ib) wherein G is bromine; R3 is H; R4 is H; R5 is H; Y And it's S; a compound of formula (Ib) wherein G is cyano; R3 is H; R4 is H; R5 is H; and Y is S; a compound of formula (Ib) wherein G is cyano; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is cyano; R3 is H; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is cyano; R3 is trifluoromethylcarbonyl; R is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is cyano; R3 is trifluoromethylcarbonyl; R4 is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is carboxy; R3 is t-butoxycarbonyl; R is H; R5 is H; and Y is O; a compound of formula (Ib) wherein G is carboxy; R3 is H; R4 is H; R5 is H; and Y is O; and a compound of formula (Ib) wherein G is carboxy; R3 is H; R4 is H; R5 is H; and Y is O.

41.- A composition comprising the dextrorotatory enantiomer of a compound of formula (I), wherein said composition it is substantially free of the levorotatory isomer of said compound.

42. A composition comprising the levorotatory enantiomer of a compound of formula (I), wherein said composition is substantially free of the dextrorotatory isomer of said compound.

43.- A pharmaceutical composition comprising a compound, salt or solvate as claimed in claim 1, mixed with a pharmaceutically acceptable carrier, excipient or diluent.

44. A veterinary composition comprising a compound, salt or solvate as claimed in claim 1, mixed with a veterinarily acceptable vehicle, excipient or diluent.

45. - The use of a compound, salt or solvate as claimed in claim 1, in the manufacture of a medicament useful for the treatment or prevention of a disease or condition in a mammal, said disease or condition being affected by the modulation of delta-opioid receptors.

46. - The use as claimed in claim 45, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg.

47. The use as claimed in claim 45, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg.

48. The use as claimed in claim 45, wherein the medicament comprises a dose scale of 100 mg to, 000 mg.

49.- The use of a compound, salt or solvate as claimed in claim 1 in the manufacture of a medicament useful for prevention or treatment of mild to severe pain in a mammal.

50. The use as claimed in claim 49, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to injury of soft tissue, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute pain of trauma, acute pain of surgery, chronic pain of headache, chronic pain of neuropathic conditions, chronic pain of conditions after stroke, and Chronic migraine pain.

51. - The use as claimed in claim 49, wherein the pain is caused by a disease or condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, stinging of snake, spider bite, insect sting, neurogenic bladder, benign prostatic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, joint neuralgia mandibular, peripheral neuritis, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot's pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, meralgia paraestésica, burning mouth syndrome , postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache, peripheral neuropathy, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, postfebrile neuritis, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, Morton's neuralgia, nasociliary neuralgia, occipital neuralgia, red neuralgia, Sluder's neuralgia, splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, sinusitis headache, headache by tension, labor, delivery, menstrual cramps and cancer.

52. - The use of a compound, salt or solvate as claimed in claim 1 in the manufacture of a medicament useful for treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, drug abuse, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cardiovascular disease and respiratory diseases in a mammal.

53. The use as claimed in claim 49, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg.

54. The use as claimed in claim 49, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg.

55.- The use as claimed in claim 49, wherein the medicament comprises a dose scale of 100 mg to, 000 mg.

56. - A kit comprising, in one or more containers, an amount of the compound claimed in claim 1, which is effective to treat or prevent mild to severe pain.

57. A pharmaceutical composition comprising a compound, salt or solvate as claimed in claim 26, mixed with a pharmaceutically acceptable carrier, excipient or diluent.

58. A veterinary composition comprising a compound, salt or solvate as claimed in claim 26, mixed with a veterinarily acceptable carrier, excipient or diluent.

59.- The use of a compound, salt or solvate as claimed in claim 26 in the manufacture of a medicament useful in the prevention or treatment of mild to severe pain in a mammal.

60. The use as claimed in claim 59, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to injury of soft tissue, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute pain of trauma, acute pain of surgery, chronic pain of headache, chronic pain of neuropathic conditions, chronic pain of conditions after stroke, and Chronic migraine pain.

61. - The use as claimed in claim 59, wherein the pain is caused by a disease or condition selected from the group that consists of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, snake bite, spider bite, insect bite, neurogenic bladder, benign prostatic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity , itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, mandibular joint neuralgia, peripheral neuritis, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain , Charcot's pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, meralgia paresthetica, burning mouth syndrome, postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache, peripheral neuropathy, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia , trigeminal neuralgia, neuritis optics, postfebrile neuritis, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, Morton neuralgia, nasociliary neuralgia, occipital neuralgia , red neuralgia, Sluder neuralgia, splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, sinusitis headache, tension headache, labor, delivery, menstrual cramps and cancer.

62.- The use of a compound, salt or solvate as claimed in claim 26 in the manufacture of a medicament useful for treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, drug abuse, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cancer pain, cardiovascular disease and respiratory diseases in a mammal .

63. - The use as claimed in claim 59, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg.

64. - The use as claimed in claim 59, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg.

65.- The use as claimed in claim 59, wherein the medicament comprises a dose scale of 100 mg to 1,000 mg.

66.- A team that understands, in one or more containers, an amount of the composition claimed in claim 26, which is effective to treat or prevent mild to severe pain.

67.- A pharmaceutical composition comprising a compound, salt or soivate as claimed in claim 31, mixed with a pharmaceutically acceptable carrier, excipient or diluent.

68. - A veterinary composition comprising a compound, salt or sozoate as claimed in claim 31, mixed with a veterinarily acceptable carrier, excipient or diluent.

69. The use of a compound, salt or soivate as claimed in claim 31 in the manufacture of a medicament useful for the prevention or treatment of mild to severe pain in a mammal.

70. - The use as claimed in claim 69, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to tissue injury soft, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute pain of trauma, acute pain of surgery, chronic pain of headache, chronic pain of neuropathic conditions, chronic pain of post-stroke conditions, and chronic pain of migraine. 71.- The use as claimed in claim 69, wherein the pain is caused by a disease or condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, stinging of snake, spider bite, insect sting, neurogenic bladder, benign prostatic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, joint neuralgia mandibular, peripheral neuritis, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot's pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, meralgia paresthetica, burning mouth syndrome , postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache, neu peripheral clothing, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, postfebrile neuritis, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, neuralgia of Morton, nasociliary neuralgia, occipital neuralgia, red neuralgia, Sluder's neuralgia, splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, sinusitis headache, tension headache, labor, delivery, colic menstrual and cancer. 72.- The use of a compound, salt or solvate as claimed in claim 31 in the manufacture of a medicament useful in treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, abuse of drugs, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cardiovascular disease and respiratory diseases in a mammal. 73. - The use as claimed in claim 69, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg. 74. - The use as claimed in claim 69, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg. 75. - The use as claimed in claim 69, wherein the medicament comprises a dose scale of 100 mg to 1,000 mg. 76. - A team that includes, in one or more containers, a amount of the composition claimed in claim 31, which is effective to treat or prevent mild to severe pain. 77. - A pharmaceutical composition comprising a compound, salt or solvate as claimed in claim 36, mixed with a pharmaceutically acceptable carrier, excipient or diluent. 78. A veterinary composition comprising a compound, salt or solvate as claimed in claim 36, mixed with a veterinarily acceptable carrier, excipient or diluent. 79. The use of a compound, salt or solvate as claimed in claim 36 in the manufacture of a medicament useful for the prevention or treatment of mild to severe pain in a mammal. 80. - Use as claimed in claim 79, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to soft tissue injury, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute pain of trauma, acute pain of surgery, chronic headache pain, chronic pain of neuropathic conditions, chronic pain of post-stroke conditions, and chronic migraine pain. 81. - The use as claimed in claim 79, wherein the pain is caused by a disease or condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, snake bite, spider bite, insect bite, neurogenic bladder, benign prosthetic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, mandibular joint neuralgia, peripheral neuritis, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot pain, reflex sympathetic dystrophy, Guillain syndrome Barre, meralgia paresthetica, burning mouth syndrome, postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache, peripheral neuropathy, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, postfebrile neuritis, migratory neuritis , segmental neuritis, neuritis Gombault, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, Morton neuralgia, nasociliary neuralgia, occipital neuralgia, red neuralgia, Sluder neuralgia, splenopalatine neuralgia, supraorbital neuralgia , vidiana neuralgia, inflammatory bowel disease, irritable bowel syndrome, headache due to sinusitis, tension headache, labor, delivery, menstrual cramps and cancer. 82.- The use of a compound, salt or solvate as claimed in claim 36 in the manufacture of a medicament useful for treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, drug abuse, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cardiovascular disease and respiratory diseases in a mammal. 83. The use as claimed in claim 79, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg. 84. - The use as claimed in claim 79, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg. 85. - The use as claimed in claim 79, wherein the medicament comprises a dose scale of 00 mg to 1,000 mg. 86. - A kit comprising, in one or more containers, an amount of the composition claimed in claim 36, which is effective to treat or prevent mild to severe pain. 87. A pharmaceutical composition comprising a compound, salt or solvate as claimed in claim 37, mixed with a pharmaceutically acceptable carrier, excipient or diluent. 88. A veterinary composition comprising a compound, salt or solvate as claimed in claim 37, mixed with a veterinarily acceptable carrier, excipient or diluent. 89.- The use of a compound, salt or solvate as claimed in claim 37 in the manufacture of a medicament useful for the prevention or treatment of mild to severe pain in a mammal. 90.- The use as claimed in claim 89, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to soft tissue injury, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute trauma pain, acute surgery pain, chronic headache pain, chronic pain of neuropathic conditions, chronic pain of post-stroke conditions, and chronic migraine pain. 91.- The use as claimed in claim 89, wherein the pain is caused by a disease or condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, snake bite, spider bite, insect bite, neurogenic bladder, benign prostatic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis , mandibular joint neuralgia, peripheral neuritis, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot's pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, meralgia paresthetica , Burning mouth syndrome, postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache, peripheral neuropathy, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, neuritis posfebrile, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, Morton neuralgia, nasociliary neuralgia, occipital neuralgia, red neuralgia , Sluder neuralgia, splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, sinusitis headache, tension headache, labor, delivery, menstrual cramps and cancer. 92. - The use of a compound, salt or solvate as claimed in claim 37 in the manufacture of a medicament useful for treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, abuse of drugs, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cardiovascular disease and respiratory diseases in a mammal. 93. The use as claimed in claim 89, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg. 94. The use as claimed in claim 89, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg. 95. The use as claimed in claim 89, wherein the medicament comprises a dose scale of 100 mg to 1,000 mg. 96.- A device comprising, in one or more containers, an amount of the composition claimed in claim 37, which is effective to treat or prevent pain from mild to severe. 97.- A pharmaceutical composition comprising a compound, salt or solvate as claimed in claim 38, mixed with a pharmaceutically acceptable carrier, excipient or diluent. 98.- A veterinary composition comprising a compound, salt or solvate as claimed in claim 38, mixed with a veterinarily acceptable vehicle, excipient or diluent. 99. The use of a compound, salt or solvate as claimed in claim 38 in the manufacture of a medicament useful for the prevention or treatment of mild to severe pain in a mammal. 100. - The use as claimed in claim 99, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to injury of soft tissue, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute pain of trauma, acute pain of surgery, chronic pain of headache, chronic pain of neuropathic conditions, chronic pain of conditions after stroke, and Chronic migraine pain. 101. The use as claimed in claim 99, wherein the pain is caused by a disease or condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, stinging of snake, spider bite, insect bite, neurogenic bladder, benign prosthetic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, mandibular joint neuralgia, neuritis peripheral, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, meralgia paresthetica, burning mouth syndrome, postherpetic neuralgia , trigeminal neuralgia, cluster headache, migraine headache, peripheral neuropathy, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, postfebrile neuritis, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, Morton neuralgia, nasociliary neuralgia, occipital neuralgia, red neuralgia, Sluder neuralgia , splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, headache due to sinusitis, tension headache, labor, delivery, menstrual cramps and cancer. 102.- The use of a compound, salt or solvate as claimed in claim 38 in the manufacture of a medicament useful for treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, abuse from drugs, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cardiovascular disease and respiratory diseases in a mammal. 103. The use as claimed in claim 99, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg. 104. The use as claimed in claim 99, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg. 105. The use as a use is claimed in claim 99, wherein the medicament comprises a dose scale of 100 mg to 1,000 mg. 106. - A kit comprising, in one or more containers, an amount of the composition claimed in claim 38, which is effective to treat or prevent mild to severe pain. 107. A pharmaceutical composition comprising a compound, salt or solvate as claimed in claim 39, mixed with a pharmaceutically acceptable carrier, excipient or diluent. 108. A veterinary composition comprising a compound, salt or solvate as claimed in claim 39, mixed with a veterinarily acceptable carrier, excipient or diluent. 109. The use of a compound, salt or solvate as claimed in claim 39 in the manufacture of a medicament useful for the prevention or treatment of mild to severe pain in a mammal. 110.- The use as claimed in claim 109, wherein the pain is selected from the group consisting of inflammatory pain, centrally mediated pain, peripherally mediated pain, visceral pain, structural related pain, cancer pain, pain related to soft tissue injury, pain related to progressive disease, neuropathic pain and acute pain of acute injury, acute pain of trauma, acute pain of surgery, chronic pain of headache, chronic pain of neuropathic conditions, chronic pain of conditions after stroke, and chronic pain of migraine. 111. The use as claimed in claim 109, wherein the pain is caused by a disease or condition selected from the group consisting of osteoarthritis, rheumatoid arthritis, fibromyalgia, migraine, headache, dental pain, burns, sunburn, stinging of snake, spider bite, insect sting, neurogenic bladder, benign prostatic hypertrophy, interstitial cystitis, rhinitis, contact dermatitis / hypersensitivity, itching, eczema, pharyngitis, mucositis, enteritis, cellulitis, causalgia, sciatic neuritis, joint neuralgia mandibular, peripheral neuritis, polyneuritis, stump pain, phantom limb pain, postoperative ileus, cholecystitis, postmastectomy pain syndrome, oral neuropathic pain, Charcot's pain, reflex sympathetic dystrophy, Guillain-Barre syndrome, paresthetic meralgia, burning mouth syndrome , postherpetic neuralgia, trigeminal neuralgia, cluster headache, migraine headache, peripheral neuropathy, bilateral peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, optic neuritis, neuritis posfebrile, migratory neuritis, segmental neuritis, Gombault neuritis, neuronitis, cervicobrachial neuralgia, cranial neuralgia, geniculate neuralgia, glossopharyngeal neuralgia, migrainous neuralgia, idiopathic neuralgia, intercostal neuralgia, mammary neuralgia, Morton neuralgia, nasociliary neuralgia, occipital neuralgia, red neuralgia , Sluder neuralgia, splenopalatine neuralgia, supraorbital neuralgia, vidial neuralgia, inflammatory bowel disease, irritable bowel syndrome, sinusitis headache, tension headache, labor, delivery, menstrual cramps and cancer. 112. The use of a compound, salt or solvate as claimed in claim 39 in the manufacture of a medicament for treatment or prevention of a disease or condition selected from the group consisting of depression, Parkinson's disease, abuse of drugs, alcohol abuse, gastritis, urinary incontinence, premature ejaculation, diarrhea, cardiovascular disease and respiratory diseases in a mammal. 113. - The use as claimed in claim 109, wherein the medicament comprises a dose scale of 0.1 mg to 1,000 mg. 114. The use as claimed in claim 109, wherein the medicament comprises a dose scale of 50 mg to 1,000 mg. 115. The use as claimed in claim 109, wherein the medicament comprises a dose scale of 100 mg to, 000 mg. 116.- A device comprising, in one or more containers, an amount of the composition claimed in claim 39, which is effective for the treatment or prevention of mild to severe pain. 117.- A compound of formula (Ib): Formula (Ib) wherein: G is bromine, chlorine, cyano, trifluoromethanesulfonyloxy, alkanoyloxy d. 8) carbonyl, carboxy, -C (Z) NR- | R2 > C6-io aryl, C6-io arylthio. or a heterocycle selected from the group consisting of imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiadiazolyl, oxathiadiazolyl, imidazolinyl, tetrahydropyrimidinyl, thienyl, pyrazolyl, pyrimidinyl, triazinyl, furyl, indazolyl, indolyl, indolinyl, isothiazolyl, isoxazolyl, oxazolyl, isoxadiazolyl, benzoxazolyl , quinolinyl, soquinolinyl and pyridinyl; wherein the aryl group of Ce-io of the substituents of G containing C6-io aryl, and the heterocycles of G, are optionally substituted with one to three substituents independently selected from the group consisting of C1-8 alkanyl, alkenyl of C2-8, C2-8 alkynyl, C1-8 alkanoyloxy, C1-8 hydroxyalkanyl, Ci-8 carboxyalkanyl, alkanoyl (Ci-8) carbonylamino, halogen, hydroxy, cyano, nitro, oxo, thioxo, amino , Ci-6-alkylamino, Ci-6-dialkanylamino, Ci-8-alkanylthio, Ci-8-alkylsulfonyl, Ci-8-alkylsulfonylamino, aminocarbonyl, aminothiocarbonyl, aminocarbonylamino, aminothiocarbonylamino, alkanyl (Ci. Nocarbonyl, dialkanyl (Ci-8) aminocarbonyl and alkanoyloxy (Ci-6) carbonylamino; Ri is a substituent selected from the group consisting of hydrogen, Ci-8 alkanyl, C 2-8 alkenyl and C 2-8 alkynyl; R2 is a substituent selected from the group consisting of hydrogen; Ci-8 alkanyl; C2-8 alkenyl; C2-8 alkynyl; C6-io aryl; and C3-8 cycloalkanyl; with the proviso that when Z is O, or S, R2 is different from hydrogen or unsubstituted C1-8 alkanyl; and wherein the Ci-8 alkanyl of R2 is optionally substituted with one to three substituents independently selected from the group consisting of phenyl, arymethylamine, d-6 alkylamino, dialkyl-1-6 alkylamino, Ci-6-alkanoyloxy, Cte, hydroxy, fluorine, chlorine, cyano, aminocarbonyl, alkanyl (Ci-8) aminocarbonyl, dialcani C-aminocarbonyl, alkanoyloxy (Ci.6) carbonyl and aryloxy; wherein the substituents phenyl and aryloxy of the C1-8 alkanyl, and the substituents C6-io aryl and C3-8 cycloalkanyl of R2, are optionally substituted with one to three substituents independently selected from the group consisting of Ci alkanyl -8, C2-8 alkenyl, C2-8 alkynyl, Ci-8 alkynyloxy, trifluoromethyl, trifluoromethoxy, phenyl, halogen, cyano, hydroxy, Ci-8 alkanylthio, Ci (8) alkynyl sulfonyl and Ci (C) alkynyl 8) sulfonylamino; or R 1 and R 2, taken together with the nitrogen to which they are attached, form a 5-7 membered cycloheteroalkyl optionally substituted with phenyl (wherein the phenyl is optionally substituted with one to three substituents of C 1-4 alkanoy or C 1-6 alkanoyloxy) 4), and from one to two additional substituents independently selected from the group consisting of Ci-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, Ci-6 alkylamino, Ci-6 dialkanylamino and halogen; or R-i and R2, taken together with the nitrogen to which they are attached, they form a 5-7 membered cycloheteroalkyl optionally substituted with one to three substituents, independently selected from the group consisting of Ci-8 alkanyl, Ci-8 hydroxyalkanyl, hydroxy, amino, alkylamino C1-6, dialkylamino of Ci-6 and halogen; R3 is a substituent selected from the group consisting of hydrogen, C1-8 alkanyl, halo (i-3) Ci-8 alkanyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkanyl, cycloalkanyl ( Ci-8) alkanyl, alkanoyloxy (C8) alkanyl of Ci-8, alkanyl (Ci-8) thioalkanyl of Ci-8, hydroxyalkanyl of C ^ s, alkanoyloxy (Ci. 8) carbonyl, halo (i-3) alkane (Ci-8) carbonyl, formyl, thioformyl, carbamimidoyl, phenyl-C 1-8 alkynyl, Ci-8 phenyl-alkanyl, C 1-8 phenyl-alkenyl, Ci-8 phenyl-alkynyl, naphthyl- Ci-8 alkanyl and C 1-8 heteroaryl-alkanyl, wherein the heteroaryl is selected from the group consisting of benzo [1,3] dioxolyl, imidazolyl, furanyl, pyridinyl, thienyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl , isothiazolyl, isoxazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrazolyl, thiazolyl; wherein the phenyl, naphthyl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of Ci-6 alkanyl, C 2-6 alkenyl, Ci-6 alkanoyloxy, amino, C-6 alkanoylamino , C 1-6 dialkylamino, alkane (Ci-6) carbonyl, alkanyl (Ci.sub.6) carbonyloxy, (C-6) alkylaminocarbonylamino, C 1-6 alkanthio > alk ^ C ^ 6) sulfonyl, halogen, hydroxy, cyano, fluoroalkanyl of Ci-6, thioureido and fluoro-alkanoyloxy of C1.6; alternatively, when the phenyl and heteroaryl are optionally substituted with alkanyl or alkanoyloxy substituents attached to adjacent carbon atoms, the two substituents can together form a fused alkanyl or cycloheteroalkanyl, selected from the group consisting of - (CH2) 3-5-, -0 (CH2) 2-4-, - (CH2) 2.4O-, and -0 (CH2) i-3O-; R4 is one to three substituents independently selected from the group consisting of hydrogen, C1-6 alkanyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 arylalkynyl, Ci-6 alkanoyloxy, amino, alkylamino of Ci-6, Ci-6 dialkylamino, Ci-6alkylcarbonyl, Ci-6alkylaminocarbonyloxy, Ci-6alkyloxycarbonyl, aminocarbonyl, Ci-6alkylaminocarbonyl, dialkyl (Ci-6) aminocarbonyl, alkanyl (Ci-6) carbonylamino, C 1-6 alkthylthio, (Ci-6) alkylsulphonyl, halogen, hydroxy, mercapto, aminothiocarbonyl, amidino, hydroxyamidino, phenylcarbonyl, -C (= NOH) -phenyl, aminomethyl, hydroxymethyl, methanesulfonylamino, C6-io arylamino (wherein the C6-io aryl is optionally substituted with one to three substituents independently selected from the group consisting of C1-6 alkanyl, C6 alkoxy, halogen, and hydroxy), dihydroimidazolyl, formylamino, thioformylamino, pyridinylamino, cyano, hydroxycarbonyl, aryl of CQ. io, chromanyl, chromenyl, furanyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolinyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinolizinyl, quinoxalinyl, tetrazolyl, thiazolyl, thienyl, fluoroalkanyl and fluoroalkanyloxy; or optionally, when R are two substituents attached to adjacent carbon atoms, the two substituents together form a single fused portion; wherein the fused portion is selected from the group consisting of - (CH2) 3-5-, -0 (CH2) 2-4-, - (CH2) 2-40-, -0 (CH2) i-30- and -SC (NH2) = N-; R5 is one to two substituents independently selected from the group consisting of hydrogen, C6 alkanyl, C2-6 alkenyl, C-, alkanoyloxy. 6, amino, Ci-6alkylamino, Ci-6 dialkylamino, (Ci-6) alkanylcarbonyl, (Ci-6) alkanoyloxy, alkyloxy (Ci-6) carbonyl, alkanyl (Ci-6) aminocarbonyl, alkanyl ( C1-6) carbonylamino, Ci-6 alkanylthio, Ci-6alkylsulfonyl, halogen, hydroxy, cyano, Ci-6 fluoroalkanyl and C1-6 fluoroalkanyloxy; A is absent or is - (CH2) m-, where m is 2 or 3; Y is - (CH2) nX- or -X (CH2) n-; X is O, or S; n is 0 or 1; Z is O, S, NH, N- (C 1-6 alkanyl), N (OH), N- (O-C 1-6 alkanyl), or N- (phenyl); and enantiomers, diastereomers, tautomers, solvates or pharmaceutically acceptable salts thereof. 8. The compound according to claim 117, further characterized in that G is bromine or cyano.