MXPA99004590A

MXPA99004590A - Mixes comprising polyurethane termoplast

Info

Publication number: MXPA99004590A
Application number: MXPA/A/1999/004590A
Authority: MX
Inventors: Scholz Gunter; Bruning Ines; Chlosta Andreas
Original assignee: Basf Aktiengesellschaft
Priority date: 1998-05-19
Filing date: 1999-05-18
Publication date: 2000-04-24

Abstract

The blends comprise (a) thermoplastic polyurethane having a Shore hardness of 60 A to 50 D, and (b) ethylene and propylene rubbers (EPM) and / or modified ethylene and propylene rubbers (EPM), wherein the ratio in weight (a) :( b) is from 3: 1 to 999

Description

"MIXES COMPRISING THERMOPLASTIC POLYURETHANE" The present invention relates to mixtures, comprising (a) thermoplastic polyurethane having a Shore hardness of 60 A to 50 D and (b) ethylene and propylene rubbers (EPM), and / or ethylene-propylene rubbers (EPM) modified, wherein the weight ratio of (a): (b) is from 3: 1 to 999: 1, preferably from 6: 1 to 100: 1. Thermoplastic polyurethanes, which are also referred to below as TPU, are generally known. As materials, they are remarkable because of their high strength together, with a good elasticity. In addition to these excellent properties, high abrasion resistance is desirable for many applications. To reduce abrasion, TPU blends with rubbers based on ethylene and propylene polymers are described in the literature. Therefore, Patent Number JP-A 09 255 868 discloses general mixtures comprising TPU and ethylene and propylene rubbers which have been modified with unsaturated aromatic compounds and with unsaturated substances containing polar functional groups. In addition, a further modification is achieved by mixing the aforementioned ethylene and propylene rubbers with styrene and 2-hydroxyethyl methacrylate and various additives. The weight ratio of TPU FUSED PIRROL ANTI-INFLAMMATORY AGENTS, REPLACED WITH ARILUS AND HETEROARIL BACKGROUND OF THE INVENTION The present invention comprises a new class of compounds useful in the treatment of diseases, such as diseases mediated by TNF-α, IL-β, IL-6 and / or IL-8 and other conditions, such as pain and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions that involve inflammation. This invention, in particular, relates to novel fused pyrrole compounds substituted with aryl and heteroaryl, to compositions containing such compounds and to methods of using such compounds. The present invention also relates to processes for the manufacture of such compounds, as well as to intermediates useful in such processes. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-a) are proinflammatory cytokines secreted by a variety of cells including monocytes and macrophages in response to many inflammatory stimuli ( REF .: 30333 The Shore hardnesses disclosed in the present application are measured in accordance with DIN 53 505. As TPU (a) in the blends of the present invention, it is possible to use generally customary TPUs having the specified hardness according to the present invention, and which can be prepared by known methods of (c) isocyanates, (d) compounds that are reactive towards isocyanates and, if desired, (e) chain lengthening agents, in the presence or absence of (f) catalysts, and / or (g) auxiliaries, and / or additives, wherein the ratio of the isocyanate groups of component (c) to the sum of the disocyanate reactive groups of the components (d) and, if is used, (e) is usually from 1: 0.9 to 1: 1.1. The examples of the starting components and the methods of preparation for (a) and (b) will be described below. c) the appropriate organic isocyanates (c) are preferably aliphatic, cycloaliphatic and in particular aromatic diisocyanates. Specific examples are: aliphatic diisocyanates such as 1,6-hexamethylene diisocyanate, 1,5-methylpentaramethylene diisocyanate, 2,4-diisocyanate of 2-ethylbutene or mixtures of at least two of the alkylene diisocyanates of 6 Atoms of elevated IL-1 levels above basal levels have been implicated in the mediation or exacerbation of a number of disease states, including rheumatoid arthritis; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; Ulcerative colitis; anaphylaxis; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption diseases; damage by ischemic reperfusion; atherosclerosis; brain trauma; multiple sclerosis; sepsis; septic shock; and toxic shock syndrome. Viruses sensitive to inhibition by TNF-α, eg, HIV-1, HIV-2, HIV-3, are also affected by IL-1. TNF-a and IL-1 seem to play a role in the destruction of pancreatic β-cells and in diabetes. The ß cells of the pancreas produce insulin, which helps mediate the homeostasis of blood glucose. Deterioration of pancreatic β cells frequently accompanies type I diabetes. Functional abnormalities of β-cells of the pancreas may occur in patients with type II diabetes. Type II diabetes is characterized by functional resistance to diphenylmethane diisocyanate and 1,6-hexamethylene diisocyanate. d) Suitable sub-conditions (d) which are reactive towards isocyanates are, for example, polyhydroxyl compounds having molecular weights of 500 to 8000, preferably polyetherols and polyesterols. However, other suitable isocyanate-reactive substances (d) are hydroxyl-containing polymers, for example, polyacetals, such as polyoxymethylenes and especially water-insoluble formals, e.g. formal polybutanediol and polyhexanediol formal, and aliphatic polycarbonates, particularly those prepared from diphenyl carbonate and 1,6-hexanediol by transesterification and having the aforementioned molecular weights. The mentioned polyhydrioxyl compounds can be used, as individual components or in the form of mixtures. The blends for preparing TPU or TPUs are usually based at least predominantly on bifunctional isocyanate-reactive substances, that is, the average functionality of component (d) is preferably 1.8 to 2.6, particularly preferably 1.9 to 2.2. TPUs in this manner are predominantly not branched, that is, predominantly non-crosslinked. monoclonal antibody specific for TNF-a, cA2, has shown improvement in swollen joints in a human Phase II trial of rheumatoid arthritis (Feldmann et al. Immunological Reviews p-195-223 (1 ^ 90)). The above procedures block the effects of TNF-a and IL-1 either by protein sequestration or receptor antagonism, but an additional procedure for blocking is to intervene in the cell production and secretion of IL-1 and / or TNF. There are numerous points for intervention between the extracellular stimulus and the secretion of IL-1 and TNF-a from the cell, including interference with transcriptional processes, interference with translational processes, blockage of signal transduction, which may alter the translation of proteins and / or the transcription thereof; and blocking the release of proteins from cells. The most reliable effect documented is after the application of a stimulus given to an in vi tro cell (eg, monocytes), of a certain amount of TNF or IL-1 (note: quantified by the enzyme-linked immunosorbent assay , ELISA) is secreted on the basal levels in the hexanediol medium. If desired, it is also possible to use mixtures of the starter molecules. Additional suitable polyetherols are the hydroxyl-containing polymerization products of tetrahydrofuran (polyoxytetramethylene glycols). Preference is given to the use of polyetherols derived from 1,2-propylene oxide and ethylene oxide wherein more than 50 percent, preferably 60 percent to 80 percent, of the OH groups are primary hydroxyl groups, and wherein at least part of the ethylene oxide is placed as a terminal block; specific preference is given to the use of polyoxytetramethylene glycols. These polyetherols can be obtained, for example, by first polymerizing the 1,2-propylene oxide in the initiator molecule and subsequently polymerizing in the ethylene oxide or by first copolymerizing all of the 1,2-propylene oxide with part of the dethylene oxide and subsequently polymerizing in the rest of the ethylene oxide or in stages, first polymerizing part of the ethylene oxide in the initiator molecule and then polymerizing all the 1,2-propylene oxide and then polymerizing in the remainder of the ethylene oxide. Polyetherols, which are essentially linear in the case of TPUs, have molecular weights of 500 to high of other cytokines including IL-1, IL-6 and IL-8, the inhibition of TNF-a production can also reduce levels of other cytokines, including but not limited to IL-1, IL-6 or 11-8. IL-8 is involved in the exacerbation and / or promotion of many disease states in which massive infiltration of neutrophils into sites of inflammation or damage (eg, ischemia) is mediated by the chemotactic nature of IL-8, including but not limited to the following: asthma, inflammatory bowel disease, psoriasis, adult respiratory distress syndrome, cardiac and renal reperfusion injury, thrombosis and glomerulonephritis. In addition to the effect of chemotaxis on neutrophils, IL-8 also has the ability to activate neutrophils. In this way, the reduction of IL-8 levels could lead to decreased infiltration of neutrophils. Evidence has been reported suggesting that P-38 plays a role in the TNF-induced transcriptional activation of IL-6 production (see: Walter Fiers EMBO Journal 1996, vol.15, p.1914-23) and the production of IL-8 (Dinarello, Proc. Nat. Acad. Sci. 1995 Vol. 92, 12230-4). pentanediol, 1,6-hexanediol, 1, 10-decanediol, 2,2-dimethylpropan-1,3-diol and 1,2-propanediol and the dialkylene ether glycols, such as diethylene glycol and dipropylene glycol. Depending on the desired properties, the polyhydric alcohols can be used alone or, if desired, as mixtures with one another. The esters of carbonic acid with the aforementioned diols are also suitable, in particular those having 4 to 6 carbon atoms, e.g. 1,4-butanediol and / or 1,6-hexanediol, the condensation products of the? -hydroxycarboxylic acids, for example,? -hydroxycaproic acid, and preferably the polymerization products of lactones, for example,? -caprolactones replaced or not replaced. The polyesterols which are preferably used are alkanediol polyadipates having from 2 to 6 carbon atoms in the alkylene radical, e.g. ethanediol polyadipates, 1,4-butanediol polyadipates, ethanediol-1,4-butanediol polyadipates, 1,6-hexanediol-neopentyl glycol polyadipates, polycaprolactones and, in particular, polyadipates 1,6-hexanediol-1, 4- butanediol The polyesterols have molecular weights (weight average) of from 500 to 6000, preferably from 800 to 3500. adherence in small blood vessels. TNF-a promotes the infiltration of other cytokines (IL-lb, IL-6), and also chemokines, which promote the infiltration of neutrophils within the infarct area (Feurstein Stroke 25: 1481-1488 (1994)). TNF-a may play a role in promoting certain viral life cycles and disease states associated with them. For example, TNF-α secreted by monocytes induced high levels of HIV expression in a clone of chronically infected T cells (Clouse et al, J. Immunol., 142: 431 (1989)). The role of TNF-a in the states of cachexia and muscle degradation associated with HIV has also been discussed (Lahdevirta et al. The American J. Med 85: 289 (1988)). Elevated levels of IL-1 above baseline levels have been implicated in the mediation or exacerbation of a number of disease states, including rheumatoid arthritis; osteoarthritis; rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; Ulcerative colitis; anaphylaxis; muscle degeneration; antiviral therapy including those viruses sensitive to inhibition by TNF-α, a Preferred chain lengthening agents are alkanediols having from 2 to 6 carbon atoms in the alkylene radical, in particular, 1,4-butanediol and / or dialkiolenglycols having from 4 to 8 carbon atoms. To fix the hardness specified in accordance with the present invention for the TPU and the melting temperatures of the TPU, the molar ratio of the forming components (d) and (e) would usually be given within a scale of (d): ( e) = 1: 0.8 a (d): (e) = 1:10, preferably of (d): (e) = 1: 1 a (d): (e) = 1: 6.4, with hardness and the melting temperature of the TPU increasing with the increased content of the diol. Preference is given to TPUs based on: (c) diphenylmethane, 4,4'-diisocyanate (MDI) and / or hexamethylene diisocyanate, (d) polyoxytetramethylene glycol, polyetherols based on 1, 2-propylene oxide and ethylene oxide, and / or polyesteroles based on alkanediol polyadipate having from 2 to 6 carbon atoms in the alkylene radical, (e) 1,2-ethanediol, 1,4-butanediol and / or 1,6-hexanediol, wherein the The ratio of the isocyanate groups of component (e) to the sum of the isocyanate-reactive groups of components (d) and (e) is preferably 1: 0.9 to 1: 1.1, and Immunol. 136: 40-49 (1986)). The role of IL-1 in cachexia has been discussed (Beutler et al J. Immunol., 135: 3669-3971 (1985)). The role of IL-1 in muscle degeneration has been discussed (Baracos et al. N. Eng. J. Med. 308: 553-558 (1983)). IL-8 has been implicated in the exacerbation and / or promotion of many disease states in which massive infiltration of neutrophils into sites of inflammation or damage (eg, ischemia) is mediated by the chemotactic nature of IL-8. including but not limited to the following diseases: asthma, inflammatory bowel disease, psoriasis, adult respiratory distress syndrome, cardiac and renal reperfusion injury, thrombosis and glomerulonephritis. In addition to the effect of chemotaxis on neutrophils, IL-8 also apparently has the ability to activate neutrophils. Thus, the reduction of IL-8 levels could lead to decreased infiltration of neutrophils. The fused imidazole and substituted imidazole compounds have been described for use in the treatment of cytokine mediated diseases, by the inhibition of proinflammatory cytokines, oxidation, stabilizers, lubricants and mold release agents, dyes and pigments, inhibitors, stabilizers against hydrolysis, light, heat or discoloration, inorganic and / or organic fillers or fillers, reinforcing materials and plasticizers. Additional details related to the auxiliaries and additives mentioned above can be found in the specialized literature. The preparation of the TPU, for example, of the described starting components is generally known and has been described many times. For example, the reaction mixture comprising (c), (d) and, if desired, (e), (f) and / or (g), can be reacted by the process known as a single operation or by the prepolymer process, for example, in a reaction extrusion apparatus and / or in a customary melting unit. TPUs prepared in this manner can be pelletized or granulated and processed together with component (b) to produce the preferably homogeneous mixtures of the present invention. According to the present invention, the mixtures comprise, as component (b), ethylene and propylene rubbers (EPM) or modified ethylene-propylene rubbers. These rubbers based on ethylene and propylene, their preparation and their properties have been described endothelin for the treatment of hypertension, renal insufficiency and cerebrovascular disease (International Patents W094 / 14434 and W095 / 33748, each of which is incorporated by reference in the present in its entirety). A related class of substituted characters has been reported to be useful in the treatment of atherosclerosis (German Patent DE 2909779 A1, which is incorporated by reference herein in its entirety). The variously substituted 7-azaindoles have been prepared and reported for use as antiulcer drugs (Japanese Patent JP 06247966, which is incorporated by reference herein in its entirety). The preparation of the 3- (4-pyridyl) indole compounds has been reported (Patent North American No. 3,551,567; FR French Patent 1587692; German Patent DE 1795061; Ukr. Kim. Zh.

(Russ. Ed.) (1982), 48 (1), 76-9; Khim. Geterotsikl.

Soedin (1980), (7), 959-64; each of which is incorporated by reference herein in its entirety). The preparation of the 2,3-diphenylindole derivatives has been reported (US Patent 3,654,308; US Patent 3,565,912; and French Patent FR 1505197; each precedes, or may be added to component (a) and / or (b) in The production of the mixture As light stabilizers, it is possible to use all the usual light stabilizers, for example benzophenone, benzotriazole, cinnamic acid, organic phosphates and phosphonites based compounds and also amines, stearically hindered. for example, hydrocarbons such as oils, paraffins, PE waxes, PP waxes, fatty alcohols having from 6 to 20 carbon atoms, ketones, carboxylic acids such as fatty acids, montanic acids or oxidized PE wax, carboxamides and esters carboxylic acids, eg comprising ethanol, fatty acids, glycerol, ethanediol or penteritritol, such as alcohol and long-chain carboxylic acids, such as the acid component The stabilizers that can be used are the customary antioxidants, for example, phenolic antioxidants such as alkylated monophenols and ß- (3,5-di-tert-butyl-4-hydroxyphenyl) propionic acid and / or esters and / or amides. / or benzotriazoles Examples of possible antioxidants are mentioned in Patents Number EP-A 698637 and EP-A 669367. Specific examples of phenolic antioxidants are 2,6-di-tert-butyl-4-methylphenol, tetrakis [3- (3, 5 -di-tert-butyl-4-hydroxyphenyl) propionate] of or a pharmaceutically acceptable salt thereof, wherein Xi is N, CH or CRi; X2 is N, CH or CR2; X3 is N, CH or CR3; and X4 is N, CH or CR4; with the proviso that at least one of X_, X2 / X3 and X4 is N or CH, and that no more than two of Xi, X2, X3 and X4 are N; wherein Ri, R2, R3 and R4 are each independently -Z-Y; preferably, Xi is N; X2 is CH or CR2; X3 is CH or CR3; and X4 is CH or CR4; and more preferably X_ is N; X2 is CR2; X3 is CH or CR3; and X4 is CH; wherein R2 is independently -Z-Y; and preferably, R2 is independently Y; and R3 is independently -Z-Y; preferably, R3 is halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, the radicals -C (O) -R20, -C (0) -0R2 ?, -C (O) -NR5R21, - S (O) 2-R20 or -S (O) 2-NRsR2 ?; more preferably, R3 is any of the halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl radicals, shoe soles, industrial molded parts, consumer articles and shaped bodies of all types or calenders to form coatings and films, by known methods usually. Contrary to what was expected on the basis of the results obtained with other mixtures, a significant reduction in abrasion was found in the case of the mixtures of the present invention, without there being any detrimental effect on the attraction resistances. This result is more puzzling because other mixtures with TPU have significant disadvantages in the properties due to the breaking of the hard and soft segments. These advantages become particularly clear, in comparison with pure TPUs or blends comprising TPU, which were of the prior art, for example, blends having a comparatively high proportion of rubber, as described in Patent Number JP-A 09 255 868 or mixtures where a relatively hard TPU is present. The advantages according to the present invention are restricted to TPU having the hardness scale specified according to the present invention and also to the mixing ratios specified according to the present invention. These advantages could not have been reduced from the prior art, and are illustrated in the following examples. methoxycarbonyl, ethoxycarbonyl, amido, N, N-dimethylamido, methylsulfonyl or aminosulfonyl; or alternatively, and preferably, Xi is N; X2 is CH or CR2; X3 is N; and X4 is CH or CR4; and more preferably, X_ is N; X2 is CR2; X3 is N; and X4 is CH or CR4; wherein R2 is independently -Z-Y; and preferably, R2 is independently Y; and R4 is independently -Z-Y; preferably, R4 is any of the halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (0) -OR2, -C (O) -NR5R2 ?, -S (O) 2 radicals -R20 or S (O) 2-NR5R2 ?; more preferably, R 4 is any of the halo, phenyl, trifluoromethyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, N, N-dimethylamido, amido, methylsulfonyl or aminosulfonyl radicals; or alternatively, and preferably, Xi is N; X2 is N; X3 is CH or CR3; and X. is CH or CR4; and more preferably, X_ is N; X2 is N; X3 is CR3; and X4 is CH or CR4; wherein R3 is independently -Z-Y; and preferably, R3 is independently Y; and R4 is EPM type 1: EPM, unmodified, Mooney viscosity (1 + 4) at 125 ° C of 10, MFI (230 ° C / 10 kg) of 35, EPM type 2: EPM-g-MA (0.6% of MA), MFI (230 ° C / 10 kg) of 9, EPM type 3: EPM-g-MA (0.7% MA), MFI (230 ° C / 10 kg) of 22. MFI: flow index of Fusion measured in accordance with DIN ISO 1133.

Table 1 Ex. TPU Type Content Abrasion Resistance Density Hardness EPM mm at the back > ction g / cm Shore N / mm2 1 1 - - 24 39 1.12 86 A / 37 D 2 1 1 10 9 39 1.09 83 A / 35 D 3 1 1 10 7 43 1.09 84 A / 34 D 4 1 1 20 23 28 1.06 81 A / 34 D 1 1 20 24 38 1.06 82 A / 33 D 6 1 2 10 5 38 1.09 84 A / 36 D 7 1 2 10 5 41 1.09 84 A / 36 D 8 1 2 20 13 34 1,065 84 A / 35 D 9 1 2 20 11 35 1.06 84 A / 35 D 1 3 10 7 39 1.085 83 A / 35 D dimethylamido, amido, methylsulfonyl or aminosulfonyl; and R2 is independently -Z-Y; and preferably, R2 is independently Y; or alternatively, and preferably X is CH or CRi; X2 is CH or CR2; X3 is CH or CR3; and X. is CH or CR4, with the proviso that at least one of Xi, X2, X3 and X4 is CH; more preferably, Xi is CH; X2 is CH; X3 is CH or CR3; and X4 is CH or CR "; and even more preferably, Xi is CH; X2 is CH; X3 is CR3; and X4 is CH or CR4; wherein R_ is independently -Z-Y; and preferably, R_ is independently Y; and R2 is independently -Z-Y; and preferably, R2 is independently Y; and R3 is independently -Z-Y; and preferably, R3 is independently Y; and R4 is independently -Z-Y; preferably, R4 is any of the halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (0) -OR__, -C (0) -NR5R2 ?, -S (O) 2- radicals R20 or S (O) 2-NR5R2?; more preferably, R 4 is any of the halo, phenyl, trifluoromethyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, N, N-29 10 34 1.15 83 A radicals 5 2 20 16 31 1.11 82 A 31 6 - - 38 48 1,235 91 A / 42 D 32 6 1 10 10 41 1,185 90 A 33 6 2 10 7 45 1,185 91 A 34 6 3 10 8 45 1,185 90 A 7 - - 36 50 1,195 82 A 36 7 1 10 8 45 1,155 82 A 37 7 2 10 14 32 1.55 83 A Examples 19 to 22 marked with (c) are Comparison examples that were carried out using comparatively hard TPU. The abrasion of these comparison blends shows no improvement compared to pure TPU. However, there is no worsening of the resistance to attraction. The blends of the present invention comprising the soft TPUs and polyolefins have, in comparison with the pure TPU, an unexpectedly significant reduction in abrasion of up to 85 percent (see Examples 12 and 15). Despite these significantly improved, that is, reduced abrasion, the mixtures of R3 and R4 are 0-4, preferably 0-3; each Z is independently one (1) link; (2) alkyl, alkenyl or alkynyl radical optionally substituted by (a) 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano or halo radicals, and (b) 1 to 2 radicals of heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; (3) the heterocyclyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (4) aryl or the heteroaryl radical optionally substituted by 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; preferably, each Z is independently one (1) bond; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 carbon, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms, or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each Z is independently one (1) bond; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- ( alkyl of 1 to 4 carbon atoms) amino; alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, 25 carbon) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; even more preferably, each Z is independently one (1) bond; (2) an alkyl radical of 1 to 8 carbon atoms or alkenyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) carbon) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, halo, or heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4) carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; (3) the heterocyclyl radical 26 optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl having 1 to 4 carbon atoms; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon or haloalkyl atoms of 1 to 2 carbon atoms of 1 to 3 halo radicals; still more preferably, each Z is independently a (1) bond; (2) an alkyl radical of 1 to 4 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 atoms of carbon carbon, halo, or heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (3) the heterocyclyl radical optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms carbon, alkylthio of 1 to 2 carbon atoms or alkyl of 1 to 4 carbon atoms; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) ) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; still more preferably, each Z is independently one (1) bond: (2) a radical 28 alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino , acetamido, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (3) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio having 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; even more preferably, each Z is independently one (1) bond; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms of carbon) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; still more preferably, each Z is independently a (1) bond; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; and more preferably, each Z is a bond; each Y is independently a hydrogen radical, with the proviso that Z is different from a bond; or radical halo, cyano, nitro, -C (O) -R20, -C (0) -OR2 ?, -C (0) -NR5R2 ?; -C (NR5) -NR5R25, -OR2 ?, -0-C (0) -R2 ?, -0-C (0) -NR5R2 ?, -OC (O) -NR22-S (O) 2 -R20, -SR21, -S (O) -R20, -S (O) 2 -R20, -S (0) 2 -NR5R2_, -S (0) 2 -NR22-C (0) -R21, -S (O) 2-NR22-C (O) -OR20, -S (O) 2-NR22-C (O) -NR5R2 ?, -NR5R2 ?, -NR22-C (O) -R2 ?, -NR22-C (O) -OR20, -NR22-C (O) -NR5R2. -NR22-C (NR5) -NR5R2 ?, -NR22-S (O) 2-R20 or -NR22-S (O) 2-NR5R21; preferably, each Y is independently a hydrogen radical, with the proviso that Z is different from a bond; or the radical halo; -C (O) -R20, 30 -C (0) -OR_ ?, -C (0) -NR5R2 ?, -C (NR5) -NR5R21, -OR2 ?, -0-C (0) -R2 ?, -OC (O) -NR5R2 ?, -SR2 ?, -S (O) -R20, -S (O) 2 -R20, -S (0) 2 -NR5R2 ?, -NR5R-1, -NR22-C (O) -R2? , -NR22-C (O) -OR20, -NR22-C (0) -NR5R2 ?, -NR22-C (NR5) -NR5R2? , -NR22-S (O) 2-R20 or - R22-S (O) 2-NR5R2 ?; more preferably, each Y is independently a hydrogen radical, with the proviso that Z is different from a bond; or the radical halo, -C (0) -R2o, -C (0) -OR21, -C (0) -NR5R2 ?, -OR2 ?, -SR21, -S (O) -R20, -S (O) 2-R20, -S (0) 2-NR5R2 ?, -NR5R2 ?, -NR22-C (O) -R2i, -NR22-C (0) -OR2 ?, -NR22-C (O) -OR20, - NR22-C (0) -NR5R2? , -NR22-S (O) 2-R20 or -NR22-S (0) 2-NR5R2 ?; even more preferably, each Y is independently a hydrogen radical, with the proviso that Z is different from a bond; or radical halo, -C (0) -R20, -C (0) -0R2_, -C (O) -NR5R21, -OR2 ?, -SR2i, -S (O) -R20, -S (0) 2- NR5R2 ?, -NR5R2 ?, -S (0) 2-R2Q -NR22-C (0) -R2 ?, -NR22-S (0) 2 -R20 OR -NR22-S (0) 2-NR5R2 ?; still more preferably, each Y is independently a hydrogen radical, with the proviso that Z is different from a bond; or the radical halo, -C (0) -R20, -C (0) -NR5R21, -0R2 ?, -SR2 ?, -S (0) -R20, -NR5R2 ?, -NR22-C (0) -R21 , -NR22-S (0) 2-R20 O -NR22-S (0) 2-NR5R2 ?; and more preferably, each Y is independently a hydrogen radical, with the condition that Z is different from a link; or the radical halo, -NR5R_ ?, -NR22-C (O) -R2i or -NR22-S (O) 2 -R20; wherein each R5 is independently (1) hydrogen radicals; (2) alkyl, alkenyl or alkynyl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkylthio, cyano or halo radicals; or (3) aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; and preferably, each R5 is independently (1) the hydrogen radicals; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 radicals of an amino radical, alkylamino of 1 to 4 carbon atoms, di (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano or halo; or (3) the aryl radical, heteroaryl, aryl- (alkyl of 1 to 4 carbon atoms), heteroaryl- (alkyl of 1 to 4 carbon atoms, heterocyclyl, heterocyclyl- (alkyl of 1 to 32 4 carbon atoms), cycloalkyl of 3 to 8 carbon atoms or (cycloalkyl of 3 to 8 carbon atoms) - (alkyl of 1 to 4 carbon atoms) optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 4 carbon atoms from 1 to 3 halo radicals; more preferably, each R5 is independently (1) hydrogen radicals; (2) alkyl radicals of 1 to 4 carbon atoms, alkenyl of 2 to 5 carbon atoms or alkynyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or halo; or (3) the aryl radical, heteroaryl, aryl- (alkyl of 1 to 4 carbon atoms), heteroaryl- (alkyl of 1 to 4 carbon atoms), heterocyclyl, heterocyclyl- (alkyl of 1 to 4 carbon atoms) cycloalkyl of 3 to 8 carbon atoms or cycloalkyl of 3 to 8 carbon atoms-alkyl of 1 to 4 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms , cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; even more preferably, each R5 is independently (1) hydrogen radicals; (2) alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or halo; or (3) phenyl-alkyl of 1 to 2 carbon atoms, heteroaryl-alkyl of 1 to 2 carbon atoms, heterocyclyl-alkyl of 1 to 2 carbon atoms or cycloalkyl of 3 to 6 carbon atoms-alkyl of 1 to 2 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl from 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; 3. 4 still more preferably, each R5 is independently (1) hydrogen radical; (2) alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms or halo; or (3) phenyl-alkyl radicals of 1 to 2 carbon atoms, heteroaryl-alkyl of 1 to 2 carbon atoms, heterocyclyl-alkyl of 1 to 2 carbon atoms or cycloalkyl of 3 to 6 carbon atoms-alkyl of 1 at 2 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, methoxy, methylthio, cyano, alkyl of 1 to 4 carbon atoms or trifluoromethyl; still more preferably, each R5 is independently (1) hydrogen radical; (2) alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 3 halo radicals; or (3) phenyl-alkyl radicals of 1 to 2 carbon atoms or heteroaryl-alkyl of 1 to 2 carbon atoms, radicals optionally substituted with 1 to 3 amino, dimethylamino, hydroxyl, methoxy radicals, methylthio, methyl or trifluoromethyl; still more preferably, each R5 is independently hydrogen or the alkyl radical of 1 to 4 carbon atoms; and more preferably, each R5 is a hydrogen radical; wherein each R20 is independently (1) the alkyl, alkenyl or alkynyl radical optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, N- (alkoxycarbonyl) -N- (alkyl) amino, aminocarbonylamino , alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkanoyl radicals , alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; (2) heterocyclyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, cyano radicals, alkyl or haloalkyl; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, cyano, halo, azido, alkyl or haloalkyl radicals; preferably, each R20 is independently (1) alkyl radicals of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4, carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((C 1 -C 4 alkoxy) carbonyl) -N- (C 1 -C 4 -alkyl) amino, aminocarbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo or aryl- (alkoxy of 1 to 4 carbon atoms), aryl- (alkylthio of 1) to 4 carbon atoms), aryl- (alkylsulfonyl of 1 to 4 atoms of 37) carbon), cycloalkyl of 3 to 8 carbon atoms, heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino from 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, C 1 -C 5 alkanoyl, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1) to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano , alkyl of 1 to 4 carbon atoms or 38 haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, ( alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each R2 is independently (1) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 5 carbon atoms or alkynyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, 39 hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or aryl- (alkoxy of 1 to 4 carbon atoms) carbon), aryl- (C 1 -C 4 alkylthio), aryl- (C 1 -C 4 alkylsulfonyl), C 3 -C 8 cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 radicals amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, alkanoyl of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms bond or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) the heterocyclyl radial optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 40 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; OR (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, ( alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; even more preferably, each R20 is independently (1) alkyl radicals of 1 to 8 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (C 1-4 alkyl) amino, 41 alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino , aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or aryl- (alkoxy of 1 to 4 carbon atoms), aryl- (C 1 -C 4 -alkylthio), aryl- (C 1 -C 4 -alkylsulfonyl), cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, alkanoyl of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbon ilo, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; (2) the heterocyclyl radical optionally substituted with 1 to 2 amino radicals, 42 alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, (alkoxy of 1 to 4) carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms , cyano, halo, azido, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; still more preferably, each R20 is independently (1) alkyl radicals of 1 to 8 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms , di- (C 1-4 alkyl) amino, 43 alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino , aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or aryl- (alkoxy of 1 to 4 carbon atoms), aryl- (C 1 -C 4 alkylthio), aryl- (C 1 -C 4 alkylsulfonyl), cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, optionally substituted aryl or heteroaryl radicals with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino , alkylsulfonylamino of 1 to 4 carbon atoms, alkanoyl of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) bonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; (2) heterocyclyl radical optionally substituted with 1 to 2 amino radicals, 44 di- (C 1 -C 4 alkyl) amino, (C 1 -C 4 alkoxy) carbonylamino, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, C 1 -C 4 alkoxy, alkylthio from 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, acetamido, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; even more preferably, each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4) carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy from 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl radicals or heteroaryl optionally substituted with 1 to 2 amino radicals, di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkanoylamino, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; 46 even more preferably, each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, NX (t-butoxy) carbonyl) -N - (methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulphinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals of t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; and more preferably, each R2_ is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N (methyl) amino, aminocarbonylamino , hydroxyl, butoxy, 47 methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino, dimethylamino, acetamino, hX.ioxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with t-butoxycarbonyl; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, halo, azido, methyl or trifluoromethyl radicals; every R2? is independently hydrogen or R2o radical; each R22 is independently (1) the hydrogen radical; (2) the alkyl radical optionally substituted with a heterocyclyl, aryl or heteroaryl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; or (3) heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, radicals, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; and preferably, each R22 is independently (1) the hydrogen radical; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a heterocyclyl, aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4) carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 radicals halo; or (3) heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms carbon, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, 49 hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each R22 is independently (1) the hydrogen radical; or (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 2 carbon atoms of 1 to 3 halo radicals; even more preferably, each R2z is independently hydrogen or alkyl of 1 to 4 carbon atoms; and more preferably, each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl, or aryl, heteroaryl, aralkyl or heteroaralkyl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino radicals, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; and preferably, each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or aryl, heteroaryl, aryl- (C1-C4alkyl) or optionally substituted heteroaryl- (C1-C4alkyl) alkyl with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano , halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl, heteroaryl, phenyl- (alkyl of 1 to 2 carbon atoms or heteroaryl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 4 atoms of 51 carbon) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; even more preferably, each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl, heteroaryl, phenyl- (alkyl of 1 to 2 carbon atoms) or heteroaryl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, C 1 -C 5 alkoxylamino, (C 1 -C 4 alkoxy) carbonylamino, hydroxy, C 1 -C 2 alkoxy carbon atoms, alkylthio having 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; even more preferably, each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms or phenyl- (alkyl of 1 to 2 carbon atoms) or heteroaryl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 atoms of 52 carbon) amino, acetamido, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; even more preferably, each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; and more preferably, each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen, R3_, -C (0) -R2_, -C (O) -OR30, -C (O) -NR31R32, -S (0) 2 -R3o or the radical -S (O) 2 -NR3 ? R 2; preferably, Rio is a hydrogen, R30, -C (0) -R2_, -C (O) -NR3? R32, -S (O) 2 -R30 or the radical -S (O) 2 -NR3? R32; more preferably, Rio is a hydrogen, R30, -C (0) -R29 or the radical -C (O) -NR3? R32; and more preferably, Rio is a hydrogen or the methyl radical; R11 and R12 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 3 radicals R30, halo, cyano, -C (O) -R30, -C (0) -OR29, 53 -C (0) -NR3? R32 / -C (NR3?) - NR3? R32, -OR29, -0-C (0) -R29, -O-C (O) -NR31R32. -OC (O) -NR33-S (O) 2-R30, -SR29, -S (0) -R3o, -S (0) 2 -R3o, -S (0) 2 -NR3? R32, -S ( O) 2-NR33-C (O) -R30, ~ S (O) 2-NR33-C (O) -OR30, -S (0) 2-NR33-C (0) -NR3? R32, -NR31R32, -NR33-C (O) -R29, -NR33-C (O) -OR30, -NR33-C (O) -NR3? R32, -NR33-C (NR31) -NR31R32, -NR33-S (O) 2 -R30 or the radicals preferably, Ru and R12 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 2 radicals of R30, halo, cyano, -C (0) -R30, -C (0) -OR29, - C (O) -NR31R32, -C (NR31) -NR3? R32, -OR29, -SR29 / -S (O) -R30, -S (O) 2 -R30 / -S (0) 2 -NR3? R32 , -NR3? R32 -NR33-C (0) -R29 or radicals -NR33-C (0) -OR30; more preferably, Ru and Ri2 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 2 radicals R3o, halo, cyano, -C (0) -R30, -C (0) -OR29, -C (0) - NR3? R32, -C (NR31) -NR3? R32, -OR29, -SR29, -S (0) -R30, -S (0) 2 ~ R30, -S (0) 2 -NR3? R32 -NR31R32 or -NR33-C (0) -R29; even more preferably, Ru and R? 2 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 2 radicals R30, halo, cyano, -C (0) -NR3? R32, -OR29, -SR29, -S ( 0) -R3o, 54 -S (0) 2-R30, -S (0) 2-NR3? R32, -NR31R32 or -NR33-C (0) -R29; still more preferably, Ru is a heteroaryl radical optionally substituted with 1 to 2 radicals R3Q, halo, cyano, -C (0) -NR3? R32, -OR29, -SR29-NR31R32 or -NR33-C (0) -R29; and R12 is an aryl radical optionally substituted with 1 to 2 radicals R30, halo, cyano, -C (0) -NR31R32, -OR29, -SR29, -S (0) -R30, -S (0) 2 -R3o, -S (0) 2-NR3? R32, -NR3? R32 or -NR33-C (0) -R29; still more preferably, Ru is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; and R12 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; still more preferably, Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; and R 2 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, radicals. methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl; and more preferably, Ru is a 4-pyridyl radical optionally substituted with an amino radical, dimethylamine, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl; and R12 is an unsubstituted phenyl radical or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfonyl, methyl or trifluoromethyl radicals; and with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Ru and R12 is 0-1; and with the proviso that when each Xi, X2, X3 and X4 represent carbon atoms, then Ru is a substituted aryl radical and Ri2 is a heteroaryl radical, or Ru is a heteroaryl radical and Ri2 is a substituted aryl radical; wherein each R30 is independently (1) alkyl, alkenyl or alkynyl radicals optionally substituted with 1 to 3 radicals NR31R31, -C02R23, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, heterocyclyl, aryl or heteroaryl optionally 56 substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl radicals; [2] the heterocyclyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; preferably, each R3o is independently (1) the alkyl radicals of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms or alkynyl of 2 to 4 carbon atoms optionally substituted with 1 to 3 radicals -NR3? R3 ?, -C? 2R23, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo or aryl- ( C 1 -C 4 -alkoxy), aryl- (C 1 -C 4 -alkylthio), aryl- (C 1 -C 4 -alkylsulfonyl), 57 heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy 1 a. Carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) the heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 58) 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each R3o is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 3 radicals of (a) -NR3iR3 ?; (b) (C 1 -C 4 alkoxy) carbonyl or phenoxycarbonyl or phenylmethoxycarbonyl optionally substituted with 1 to 3 amino, alkylamino, di- (C 1 -C 4 alkyl) amino, alkanoylamino radicals of 1 to 5 carbon atoms carbon, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; or (c) hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, or phenyl- (alkoxy of 1 to 4 carbon atoms), phenyl- (alkylthio of 1 to 4 carbon atoms) carbon), the heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; even more preferably, each R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with (a) amino, alkylamino of 1 to 4 carbon atoms or di- (alkyl of 1 to 4 carbon atoms) Not me; or (b) 60 hydroxyl, alkoxy of 1 to 4 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino from 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 atoms carbon or trifluoromethyl; (2) haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, ( C 1-4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; still more preferably, each R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 4 atoms) carbon) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the trifluoromethyl radical; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; still more preferably, each R3o is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl; (2) the trifluoromethyl radical; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; and more preferably, R3o is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; (2) 62 trifluoromethyl radical; or (3) the aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; each R29 is independently a hydrogen or R30 radical; and preferably R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; each R3i is independently (1) the hydrogen radicals; (2) the alkyl radical optionally substituted with a cycloalkyl, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; preferably, each R3? is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a 63 cycloalkyl radical of 3 to 8 carbon atoms, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 at 5 atoms d < carbon, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon or haloalkyl atoms of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl, heteroaryl, heterocyclyl or the cycloalkyl radical of 3 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each R3? is independently (1) the hydrogen radicals, or (2) the alkyl radical 64 from 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, C 1 -C 4 alkyl or trifluoromethyl; even more preferably, each R3? is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; and more preferably, R3? it is independently the hydrogen, methyl or ethyl radicals; each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical optionally substituted with a cycloalkyl, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino radicals, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl; preferably, each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a cycloalkyl radical of 3 to 8 carbon atoms, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkoxylamino, (C 1 -C 4 alkoxy) carbonylamino, C 1 -C 4 alkylsulfonylamino, hydroxyl, C 1 -C alkoxy 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl, heteroaryl, heterocyclyl or the cycloalkyl radical of 3 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) mino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, 66 alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; more preferably, each R32 is independently (1) the hydro radicals, or (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a cycloalkyl radical of 3 to 6 carbon atoms, aryl, heterocyclyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) ) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms carbon of 1 to 3 halo radicals; or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl radical of 3 to 6 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino , alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, 67 hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; even more preferably, R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with phenyl or the heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) ) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or the trifluoromethyl radicals; or (3) phenyl or the heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or trifluoromethyl; still more preferably, each R32 is independently (1) the hydrogen radicals; (2) 68 the alkyl radical of 1 to 4 carbon atoms or the alkyl radical of 1 to 2 carbon atoms substituted with phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, acetamido, hydroxylc, alkoxy of 1 to 2 carbon atoms, alkyl of 1 to 4 carbon atoms or trifluoromethyl; or (3) phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkyl of 1 to 4 atoms carbon or trifluoromethyl; still more preferably, each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms or alkyl of 1 to 2 carbon atoms substituted with phenyl or the heteroaryl radical optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals; or (3) phenyl or heteroaryl radical optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals; and more preferably, each R32 is independently (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms. carbon; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals; and each R33 is independently (1) the hydrogen radical; (2) the alkyl radical optionally substituted with a heterocyclyl, aryl, or heteroaryl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; preferably each R33 is independently (1) the hydrogen radical; or (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a heterocyclyl, aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4) carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 70 halo radicals; more preferably, each R33 is independently hydrogen or the alkyl radical of 1 to 4 carbon atoms; and more preferably, each R33 is independently hydrogen or the methyl radical.

The compounds of interest include the following: 3- (4-pyridyl) -2- (4-fluorophenyl) indole; 3- (4-fluorophenyl) -2- (4-pyridyl) indole; 6-amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-3- (4-fluorophenyl) -2- (4-pyridyl) -7-aza-indole; 6- (4'-t-Butoxycarbonylamino-1'-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-amino-1 '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-ureido-l '-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 71 6-5, -ureido-l'-oxo-2 '-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-t-Butoxycarbonylamino-1 '-oxo-2'-t-butoxycarbonylaminohexy-iiino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6 * -amino-1 '-oxo-2'-aminohexylamino) -3- (4-pyridyl) 2- (4-fluorophenyl) -7-aza-indole; 6- (5'-t-Butoxycarbonylamino-1 '-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-amino-1 '-oxo-2'-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (4-iodophenyl) -1 '-oxo-2'-t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (4-iodophenyl) -1 '-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 72 6- (3 '-methyl-1 * -oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-methyl-1' -oxo-2 '-aminobutylamino) -? - (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 A 4 '-dimeti1-1' -oxo-2 * -t-butoxycarbonylamino-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4A4l-dimethyl-1-oxo-2'-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5"-t-Butoxycarbonylamino-1 '-oxo-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-amino-1 '-oxo-pentilamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-t-Butoxycarbonylamino-1 '-oxo-heylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-amino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 73 6- (3, -cyclohexyl-1-oxo-2'-t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-cyclohexyl-l, -oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-t-Butoxycarbonyl-1'-oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (4'-carboxy-1-oxo-2I-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-0-t-Butoxy-1-oxo-2, -t-butoxycarbonyl-butynylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-hydroxy-1-oxo-2'-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1-oxo-2'-t-butoxycarbonylaminopropyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 74 6- (3'-phenyl-11-oxo-2'-D, L-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (31- (-t-Butoxyphenyl) -1' -oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (4-hydroxyphenyl) -l'-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-1-butoxycarbonylamino-1 '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-amino-l '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-1-Butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-amino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (methylsulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 75 6- (1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole; 6- (2 '- (5-chlorothienyl) sulfonylamino) -3- (4-pyridyl) -2- (4-fluoroyenyl) -7-aza-indole; 6- (phenylsulfonylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2'-N-phthaloyl-1'-oxo-ethylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-N-phthaloyl-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 3- (4-pyridyl-2- (4-fluoro-phenyl) -4,7-aza-indole; 6- (2'-N-t-butoxycarbonyl-L-prolylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2'-L-prolylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2S '-dimethylamino-1' -oxo-propylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 76 6- (2 * -dimethylamino-1 * -oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-N-methyl-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) 2- (4-fluorophenyl) -7-aza-indole; 6- (2'-N-methyl-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 '-N-t-butoxycarbonyl isonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-isonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 '-methylsulfoxo-1' -oxo-2 'S-t -toxycarbonylaminobutylami o) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 * -methylsulfoxo-1 '-oxo-2' S-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (3-pyridyl) -1 '-oxo-2' S-t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 77 6- (3'- (3-pyridyl) -l'-oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (N, N-Di-t-butoxycarbonyl-L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indc1; 6- (L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (N-1-butoxycarbonyl-3 (S) -r, 2 ', 3', 4 • -tetrahydro-3 '-isoquinoliniloxo-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) - 7-aza-indole; 6- (3 (S) -l ', 2', 3 ', 4l-tetrahydro-3' -isoquinoliniloxo-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 * -phenyl-1-oxo-2l R-N-t-butoxycarbonylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-pheny1-1 '-oxo-2' R-aminoethylamino) -3- (4-pyridyl) 2- (4-fluorophenyl) -7-aza-indole; 78 6- (2 * -phenyl-l '-oxo-2' -S-N-t-butoxycarbonylamino-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-1-oxo-2I-S-aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-pheny1-1 '-oxo-2' R-N-t-butoxycarbonyl-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-1-oxo-2 'R-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1-oxo-2 '- (L) -t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 79 6- (3'-phenyl-1-oxo-2'- (L) -a-inopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-t-butoxycarbonyl-N-methylaminopropyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-N-methylaminopropylamino) -3- (4-pyridyl) • 2- (4-fluorophenyl) -7-aza-indo1; 6- (1-oxo-2 'St-butoxycarbonyl-N-methyl-4-methyl-2-aminopentyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-N-methy1-4-methy1-2-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'R-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'R-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (2-thienyl) -l'-oxo-2'- (L) -t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 80 6- (3 '- (2-thienyl) -1' -oxo-2 * - (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '- (4-azidophenyl) -l'-oxo-2'S-t-butoxycarbonyl-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '- (4-azidophenyl) -l' -oxo-2' S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- { 3l- (3-benzothienyl) -l'-oxo-2l S-t-butoxycarbonyl-1-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (3-benzothienyl) -l'-oxo-2'-S-aminopropylamino) • 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-phenyl-1-oxo-2'- (L) -t-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-pheny1-1 '-oxo-2' - (L) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 81 6- (4'-phenyl-1-oxo-2'- (D) -t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-phenyl-1, -oxo-2, -) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-amino-l '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutoxycarbonyl-7-aza-indole; 6- (phenylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (diethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 * (R, S) -phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 '(R, S) -eti-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 82 6-amino-5-chloro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-5-fluoro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-5-bromo-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (di-isoamylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) • 7-aza-indole; 6- (2 ', 2'-dimethyl-1-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (i Silylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-ethylbutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-thieni lmeti lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 83 6- (3 A-3'-di-phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1'-oxo-2 '- (R, S) -methylpropylane) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -1-methy1-7-aza-indole; 6- (3A3'-dimethyl-l '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (ethoxycarbonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 'S-ami o-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-methyl-7-aza-indole; 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutyl-7-aza-indole; and 84 6- (2'S-amino-1 '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-cyclohexylmethyl-7-aza-indole.

As used herein, the following terms shall have the following meanings: "Alkyl", alone or in combination, means a straight chain or branched chain alkyl radical preferably containing 1 to 15 carbon atoms (C1-C15), more preferably 1 to 8 carbon atoms (Ci-Cß), yet more preferably 1 to 6 carbon atoms (Ci-Cß), still more preferably 1 to 4 carbon atoms (C 1 -C 4), even more preferably 1 to 3 carbon atoms (C 1 -C 3), and more preferably 1 to 2 carbon atoms (C1-C2). Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isoamyl, hexyl, octyl and the like.

"Hydroxyalkyl", alone or in combination means an alkyl radical as defined above in which at least one hydrogen radical is replaced with a hydroxyl radical, preferably 1 to 3 radicals hydrogen are replaced with hydroxyl radicals, more preferably 1 to 2 hydrogen radicals are replaced with hydroxyl radicals, and more preferably a hydrogen radical is replaced with a hydroxyl radical. Examples of such radicals include hydroxymethyl, 1-, 2-hydroxyethyl, 1-, 2-, 3-hydroxypropyl, 1,3-dihydroxy-2-propyl, 1,3-dihydroxybutyl, 1, 2,3,4,5. , 6-hexahydroxy-2-hexyl and the like.

"Alkenyl", alone or in combination means a straight chain or branched chain hydrocarbon radical having one or more double bonds, preferably 1 to 2 double bonds and more preferably a double bond, and preferably containing 2 to 15 carbon atoms (C2-C5), more preferably 2 to 8 carbon atoms (C2-C8), even more preferably 2 to 6 carbon atoms (C2-Cß), even more preferably 2 to 4 carbon atoms (C2-C4) ), and still more preferably 2 to 3 carbon atoms (C2-C3). Examples of such alkenyl radicals include ethenyl, propenyl, 2-methylpropenyl, 1,4-butadienyl and the like. «6"Alkynyl", alone or in combination means a straight chain or branched chain hydrocarbon radical having one or more triple bonds, preferably 1 to 2 triple bonds and more preferably a triple bond, and preferably containing from 2 to 15 carbon atoms. carbon (C2-C15), more preferably 2 to 8 carbon atoms (C_-Cß), still more preferably 2 to 6 carbon atoms (C2-C6), still more preferably 2 to 4 carbon atoms (C2-C4) , and still more preferably 2 to 3 carbon atoms (C2-C3) "Examples of such alkynyl radicals include ethynyl, propynyl, (propargyl), butynyl and the like, "Alkoxy", alone or in combination means a radical of the type "R-0-" wherein "R" is an alkyl radical as defined above and "O" is an oxygen atom. Examples of such alkoxy radicals include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy and the like.

"Alkoxycarbonyl", alone or in combination means a radical of the type "R-O-C (O) -" wherein "R-0-" is an 87 alkoxy radical as defined above and "C (O)" is a carbonyl radical.

"Alkoxycarbonylamino", alone or in combination, means a radical of the type "RO- (0) -NH-" wherein "ROC (O)" is an alkoxycarbonyl radical as defined above, wherein the amino radical may be optionally substituted , such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

"Alkylthio", alone or in combination, means a radical of the type "R-S-" wherein "R" is an alkyl radical as defined above and "S" is a sulfur atom. Examples of such alkylthio radicals include methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, iso-butylthio, sec-butylthio, tert-butylthio and the like.

"Alkylsulfinyl", alone or in combination, means a radical of the type "R-S (O) -" wherein "R" is an alkyl radical as defined above and "S (0)" is a monooxygenated sulfur atom. Examples of such alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, n-propylsulphinyl, isopropylsulfinyl, n-butylsulfinyl, iso-butylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl and the like.

"Alkylsulfonyl", alone or in combination, means a radical of the type "R-S (0) 2-" where "R" is an alkyl radical as defined above and "S (0) 2" is a monooxygenated sulfur atom. Examples of such alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, iso-butylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, and the like.

"Alkylsulfonylamino", alone or in combination, means a radical of the type "RS (O) 2-NH-" wherein "RS (0) 2-" is an alkylsulfonyl radical as defined above, wherein the amino radical may be optionally substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

"Aryl", alone or in combination, means a phenyl or naphthyl radical which is optionally substituted with one or more selected substituents. alkyl, alkoxy, halogen, hydroxyl, amino, azido, nitro, cyano, haloalkyl, carboxyl, alkoxycarbonyl, cycloalkyl, heterocycle, alkanoylamino, amido, amidino, alkoxycarbonylamino, N-alkylamidino, alkylamino, dialkylamino, N-alkylamido, N, N -dialkylamido, aralkoxycarbonylamino, alkylthio, alkylsulfinyl, alkylsulfonyl and the like. Examples of the aryl radicals are phenyl, p-tolyl, 4-methoxyphenyl, 4- (tert-butoxy) phenyl, 3-methyl-4-methoxyphenyl, 4-CF3-phenyl, 4-fluorophenyl, 4-chlorophenyl, 3- nitrophenyl, 3-aminophenyl, 3-acetamidophenyl, 4-acetamidophenyl, 2-methyl-3-acetamidophenyl, 2-methyl-3-aminophenyl, 3-methyl-4-aminophenyl, 2-amino-3-methylphenyl, 2,4- dimethyl-3-aminophenyl, 4-hydroxyphenyl, 3-methyl-4-hydroxyphenyl, 1-naphthyl, 2-naphthyl, 3-amino-1-naphthyl, 2-methyl-3-amino-1-naphthyl, 6-amino- 2-naphthyl, 4,6-dimethoxy-2-naphthyl, piperazinylphenyl and the like.

"Aralkyl", alone or in combination means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced with an aryl radical as defined above, such as benzyl, 1-, 2 - 90 phenylethyl, dibenzylmethyl, hydroxyphenylmethyl, methylphenylmethyl, diphenylmethyl, dichlorophenylmethyl, 4-methoxyphenylmethyl and the like.

"AralcoxX, alone or in combination, means an alkoxy radical as defined above in which at least one hydrogen atom, preferably 1-2, is replaced with an aryl radical as defined above, such as benzyloxy, 1-, 2 phenylethoxy, dibenzylmethoxy, hydroxyphenylmethoxy, methylphenylmethoxy, dichlorophenylmethoxy, 4-methoxyphenylmethoxy and the like.

"Aralkoxycarbonyl", alone or in combination, means a radical of the type "ROC (O) -" wherein "R-0-" is an aralkoxy radical as defined above and "-C (O) -" is a carbonyl radical .

"Aryloxy", alone or in combination, means a radical of the type "R-0-" wherein "R" is an aryl radical as defined above.

"Alkanoyl", alone or in combination, means a radical of the type "R-C (O) -" wherein "R" is an alkyl radical as defined above and "-C (O) -" is an radical carbonyl. Examples of such alkanoyl radicals include acetyl, trifluoroacetyl, hydroxyacetyl, propionyl, butyryl, valeryl, 4-methylvaleryl, and the like.

"Alkanoylamino", alone or in combination, means a radical of the type "RC (0) -NH-" wherein "RC (O) -" is an alkanoyl radical as defined above, wherein the amino radical may be optionally substituted , such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl and the like.

"Aminocarbonyl", alone or in combination, means a carbonyl radical substituted with amino (carbamoyl), wherein the amino radical may be optionally mono- or di-substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkanoyl, alkoxycarbonyl, aralkoxycarbonyl and the like. "Aminocarbonylamino", alone or in combination, means a carbonyl substituted with amino, substituted on a second amino (ureido) radical, wherein each amino radical may be optionally mono- or di-substituted, such as with alkyl, aryl, aralkyl, cycloalkyl, 92 cycloalkylalkyl, alkanoyl, alkoxycarbonyl, aralkoxycarbonyl and the like.

"Aminoalkanoyl", alone or in combination, means an alkanoyl radical as defined above, derivative in which at least one, preferably 1 to 2, hydrogen atoms are replaced by an amino radical, wherein each amino radical may be optionally mono - or di-substituted such as with alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, alkanoyl, alkoxycarbonyl, aralkoxycarbonyl and the like.

"Benzo", alone or in combination, means the divalent radical C6H4 = benzene derivative.

"Bicyclic" as used herein is intended to include fused ring systems, such as naphthyl and β-carbolinyl, and substituted ring systems, such as biphenyl, phenylpyridyl, naphthyl and diphenylpiperazinyl.

"Cycloalkyl", alone or in combination, means a saturated or partially saturated alkyl radical, preferably with a double bond, monocyclic or bicyclic, preferably monocyclic, preferably containing 3 to 10 carbon atoms (C3-C10), more preferably 3 to 8 carbon atoms (C3-Cs), even more preferably 3 to 6 carbon atoms (C3-C6), which is optionally benzo fused, and which is optionally substituted as defined herein with respect to the definition of aryl. Examples of such cycloalkyl radicals include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, dihydroxycyclohexyl, cycloheptyl, octahydronaphthyl, tetrahydronaphthyl, dimethoxytetrahydronaphthyl, 2,3-dihydro-1H-indenyl, and the like.

"Cycloalkylalkyl", alone or in combination, means an alkyl radical as defined above which is substituted with a cycloalkyl radical as defined above. Examples of such cycloalkylalkyl radicals include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 1-cyclopentylethyl, 1-cyclohexylethyl, 2-cyclopentylethyl, 2-cyclohexylethyl, hydroxycyclopentylpropyl, tetrahydronaphthylpropyl, cyclohexylbutyl, and the like. 94"Cycloalkylcarbonyl" means an acyl radical of the formula cycloalkyl-C (0) - wherein the term "cycloalkyl" has the meaning given above, such as cyclopropylcarbonyl, cyclohexylcarbonyl, adamantylcarbonyl, 1,2,3,4-tetrahydro-2 -naphthoyl, 2-acetamido-l, 2,3,4-tetrahydro-2-naphthoyl, 1-hydroxy-1,2,3,4-tetrahydro-6-naphthoyl and the like.

"Heteroatoms" means nitrogen, oxygen and sulfur heteroatoms.

"Heterocyclyl", alone or in combination, means a saturated or partially unsaturated heterocyclic radical, preferably with a double bond, monocyclic or bicyclic, preferably monocyclic, containing at least one, preferably 1 to 4, more preferably 1 to 3, furthermore preferably 1 to 2, nitrogen, oxygen or sulfur atoms in the ring member, and preferably having 3 to 8 ring members in each ring, more preferably 5 to 8 ring members in each ring, and even more preferably 5 to 6 ring members in each ring. "Heterocyclyl" is intended to include the sulfone and sulfoxide derivatives of the members rings of sulfur and N-oxides of tertiary nitrogen ring members, and fused carbocyclics, preferably 3 to 6 carbon atoms and more preferably 5 to 6 carbon atoms, and ring systems fused with benzo. The "heterocyclyl" radicals may be optionally substituted on at least one, preferably 1 to 4, more preferably 1 to 3, even more preferably 1 to 2, carbon atoms by halogen, alkyl, alkoxy, hydroxyl, oxo, thioxo, aryl, aralkyl, heteroaryl, heteroaralkyl, amidino, N-alkylamidino, alkoxycarbonylamino, alkylsulfonylamino and the like, and / or on a secondary nitrogen atom by hydroxy, alkyl, aralkoxycarbonyl, alkanoyl, alkoxycarbonyl, heteroaralkyl, aryl or aralkyl. More preferably, "heterocyclyl", alone or in combination, it is a radical of a system saturated monocyclic or bicyclic heterocyclic ring having 5 to 8 ring members per ring, wherein 1 to 3 ring members are oxygen, sulfur or nitrogen, which is optionally unsaturated or fused to a benzo, and optionally substituted with 1 to 2 oxo or thioxo radicals. Examples of such heterocyclyl radicals include 96 pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 4-benzyl-piperazin-l-yl, pyrimidinyl, tetrahydrofuryl, pyrazolidinyl, pyrazolinyl, pyridazinonyl, pyrrolidonyl, tetrahydrothienyl and its sulfoxide and sulfone derivatives, 2, 3-dihydroindolyl, tetrahydroquinolinyl, 1, 2, 3, 4-tetrahydroisoquinolinyl, 1, 2, 3, 4-tetrahydro-1-oxo-isoquinolinyl, 2,3-dihydrobenzofuryl, benzopyranyl, methylenedioxyphenyl, ethylenedioxyphenyl and the like.

"Heterocyclylalkyl", alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1 to 2, is replaced with a heterocyclyl radical as defined above, such as pyrrolidinylmethyl, tetrahydrothienylmethyl, piperidinylethyl and similar.

"Heteroaryl", alone or in combination, means an aromatic, monocyclic or bicyclic, preferably monocyclic, heterocycle radical having at least one, preferably 1 to 4, more preferably 1 to 3, even more preferably 1 to 2, ring members of atoms of nitrogen, oxygen or sulfur and 97 which preferably has 5 to 6 ring members in each ring, which is optionally fused to a benzo or fused to a saturated carbocyclic, preferably 3 to 4 carbon atoms (C3-C) and which is optionally substituted. defined above with respect to the definitions of aryl and heterocyclyl. More preferably, "heteroaryl", alone or in combination, is a radical of an aromatic, monocyclic or bicyclic heterocyclic ring system, having 5 to 6 ring members per ring, wherein 1 to 3 ring members are oxygen heteroatoms, sulfur or nitrogen, which is optionally fused to a benzp or fused to a carbocycle of 3 to 4 saturated carbon atoms. Examples of such heteroaryl groups include imidazolyl, l-benzyloxycarbonylimidazol-4-yl, pyrrolyl, pyrazolyl, pyridyl, 2- (l-piperidinyl) pyridyl, 2- (4-Benzyl-piperazin-l-yl) -1-pyridinyl, pyrazinyl, triazolyl, furyl, thienyl, oxazolyl, thiazolyl, indolyl, quinolinyl, 1-oxido-2-quinolinyl, isoquinolinyl, 5,6,7,8-tetrahydroquinolyl, 5,6,7,8-tetrahydroisoquinolinyl, quinoxalinyl, benzothiazolyl, ß- carbolinyl, benzofuryl, benzimidazolyl, benzoxazolyl and the like. 98"Heteroaralkyl", alone or in combination, means an alkyl radical as defined above in which at least one hydrogen atom, preferably 1 to 2, is replaced with a heteroaryl radical as defined above, such as 3-furylpropyl, pyrrolylpropyl, chloroquinolinylmethyl, 2-thienylethyl, pyridylmethyl, 1-imidazolylethyl and the like.

"Halogen" and "halo", alone or in combination, means the fluorine, chlorine, bromine or iodine radicals.

"Haloalkyl", alone or in combination, means an alkyl radical as defined above, in which at least one hydrogen atom, preferably 1 to 3, is replaced with a halogen radical, more preferably the fluoro or chloro radicals. Examples of such haloalkyl radicals include 1,1-trifluoroethyl, chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, bis (trifluoromethyl) methyl and the like.

"Leaving group" refers generally to groups easily displaceable by a nucleophile, such as an amine, a thiol or a nucleophile of alcohol. Tales 99 Outgoing groups are well known in the art. Examples of such leaving groups include, but are not limited to, N-hydroxysuccinimide, N-hydroxybenzotriazole, halides, triflates, tosylates, and the like. Preferred leaving groups are indicated herein where appropriate.

"Protective group" refers generally to groups well known in the art which are used to prevent reactive groups selected, such as carboxyl, amino, hydroxyl, mercapto and the like, so that they do not suffer undesired reactions, such as nucleophilic reaction, electrophilic, oxidation, reduction and the like. Preferred protecting groups are indicated herein where appropriate. Examples of amino protecting groups include, but are not limited to, aralkyl, substituted aralkyl, cycloalkenylalkyl and substituted cycloalkenylalkyl, allyl, substituted allyl, acyl, alkoxycarbonyl, aralkoxycarbonyl, silyl, and the like. Examples of aralkyl include, but are not limited to, benzyl, ortho-methylbenzyl, trifly and benzhydryl, which may be optionally substituted with halogen, alkyl, alkoxy, hydroxyl, nitro, acylamino, acyl and the like, and salts, such as phosphonium and ammonium salts. Examples of aryl groups include phenyl, naphthyl, indanyl, anthracenyl, 9- (9-phei-J-xfluorenyl), phenanthrenyl, durenyl and the like. Examples of cycloalkenylalkyl or substituted cycloalkylenylalkyl radicals preferably have 6 to 10 carbon atoms, and include, but are not limited to, cyclohexenylmethyl and the like. The acyl, alkoxycarbonyl and aralkoxycarbonyl groups include the benzyloxycarbonyl, t-butoxycarbonyl, iso-butoxycarbonyl, benzoyl, substituted benzoyl, butyryl, acetyl, tri-fluoroacetyl, tri-chloroacetyl, phthaloyl radicals and the like. A mixture of protecting groups can be used to protect the same amino group, such as a primary amino group which can be protected by both an aralkyl group and an aralkoxycarbonyl group. Amino protecting groups can also form a heterocyclic ring with the nitrogen to which they are attached, for example, 1,2-bis (methylene) benzene, phthalimidyl, succinimidyl, maleimidyl and the like and where these heterocyclic groups can also include the binding of aryl and cycloalkyl rings. 101 In addition, the heterocyclic groups can be mono-, di- or tri-substituted, such as nitrophthalimidyl. Amino groups can also be protected against undesired reactions, such as oxidation, through the formation of an addition salt, such as hydrochloride, toluene sulfonate, trifluoroacetate and the like. Many of the amino protecting groups are also suitable for the protection of the carboxyl, hydroxyl and mercapto groups. For example, aralkyl groups. Alkyl groups are also suitable groups for the protection of the hydroxyl and mercapto groups, such as tert-butyl. The silyl protecting groups are silicon atoms optionally substituted with one or more alkyl, aryl and aralkyl groups. Suitable silyl protecting groups include, but are not limited to, trimethylsilyl, triethylsilyl, tri-isopropylsilyl, tert-butyldimethylsilyl, dimethylphenylsilyl, 1,2-bis (dimethylsilyl) benzene, 1,2-bis (dimethylsilyl) ethane and diphenylmethylsilyl. Silylation of the amino groups provides the mono- or di-silylamino groups. Silylation of the aminoalcohol compounds can lead to a N, N, O-tri-silyl derivative. The removal of the silyl functional group from a silyl ether functional group 102 it is easily achieved by treatment with, for example, a metal hydroxide or ammonium fluoride reagent, either as a discrete reaction step or during a reaction with the alcohol group. Suitable silylating agents are, for example, trimethylsilyl chloride, tert-butyldimethylsilyl chloride, phenyldimethylsilyl chloride, diphenylmethylsilyl chloride or their combination products with imidazole or dimethylformamide. Methods for the silylation of amines and the removal of the silyl protecting groups are well known to those of skill in the art. Methods for the preparation of these amine derivatives from the corresponding amino acids, amino acid amides or amino acid esters, are also well known to those skilled in the art of organic chemistry, including the amino acid / amino acid ester or chemistry of aminoalcohols. The protecting groups are removed under conditions that will not accept the remaining portion of the molecule. These methods are well known in the art and include acid hydrolysis, hydrogenolysis and the like. A preferred method involves the removal of a protecting group, such as as the removal of a benzyloxycarbonyl group by hydrogenolysis using palladium on carbon in a suitable solvent system such as an alcohol, acetic acid, and the like or mixtures thereof. A t-butoxycarbonyl protecting group can be removed using an inorganic or organic acid, such as HCl or trifluoroacetic acid, in a suitable solvent system, such as dioxane or methylene chloride. The resulting amino salt can be easily neutralized to produce the free amine. The carboxyl protecting group, such as methyl, ethyl, benzyl, tert-butyl, 4-methoxyphenylmethyl and the like, can be removed under hydrolysis or hydrogenolysis conditions well known to those skilled in the art. The procedures for the preparation of the compounds of this invention are described below. It should be noted that the general procedures are shown as they relate to the preparation of compounds having unspecified stereochemistry. However, such methods are generally applicable to those compounds of a specific stereochemistry, for example, where the stereochemistry with respect to a group is (S) or (R). In addition, compounds that have a stereochemistry 104 (e.g., (R)) can be frequently used to produce those having opposite stereochemistry (e.g., (S)) using well-known methods, e.g., by inversion.

Preparation of the Compounds of Formula I The compounds of the present invention represented by Formula I above can be prepared using the following general procedures as shown schematically in the Schemes I and II.

Scheme I 105 Scheme II Via W = H VIb W = (t-But) (Me) 2Si Various types of synthesis of indole and azaindole can be used to prepare the compounds of this invention, which are included by reference (for reviews of the synthesis of indole see G. Gribble Recent Developments in Nature Ring Synthesis-Methodology and Applications in Contemporary Organic Synthesis pp. 145-172, R. Sundberg and PV Nguyen Five Membered Ring Systems: Pyrroles and Benzo Derivatives, Chapter 5, Comprehensive Heterocyclic Chemistry) and Schemes shown later. 106 A general synthesis of indoles and azaindoles useful for the preparation of the novel compounds of this invention is illustrated in Scheme I by which an appropriately substituted acetylene (II) is coupled with a c-Ito-iodoaniline (I) or a 1, 2-iodoaminoheterocycle (for example, 2-amino-3-iodopyridine) using palladium (0) -mediated coupling under the conditions of Larock et al. (Tetrabutylammonium chloride 1 equivalent), potassium acetate 5 equivalents, and triphenylphosphine (5 mol%), Tet. Lett. 1993, 2823-2826) to provide a mixture of regioisomeric indoles or azaindoles (III and IV) that can be separated by chromatography. Preferably, when the general synthesis of Scheme I is used in the preparation of the novel compounds of this invention, Ri, R2, R3 and R will not contain aryl substituted with halogen or heteroaryl and other radicals well known to those skilled in the art, which have the potential to interfere with, compete with or inhibit the ring formation reaction. A second general synthesis of Índoles and azaindoles, useful for the preparation of novel compounds of this invention, is illustrated in 107 Scheme II, whereby an appropriately substituted alpha-hydroxyketone (VI) or alpha-silyloxyketone (Via) is coupled with an appropriately substituted aniline or an amino-substituted heterocycle (V) (eg, 2-aminopyridine, 3-aminopyridine) , 1-aminopyridine, 3-amino-6-chloropyridazine, 3-phenyl-6-aminopyridazine, 4-aminopyridazine, 3-methoxy-4-amino-6-chloropyridazine, 4-amino-2,6-dichloropyridine, 4-amino -2-chloropyridine, 4-amino-5-cyano-2-methoxypyridine, 4-amino-2-methylpyridine, 4-amino-5-cyano-2-methoxypyridine, 2-amino-4-methylpyridine, 2-amino-4 , 6-dimethylpyridine, 2-amino-5-bromopyridine, 6-aminonicotinamide, 3-amino-2-chloro-pyridine, 5-amino-2-chloropyridine, 5-amino-2-methoxypyridine, 3-amino-2, 6 -dimethoxypyridine, 2,6-diaminopyridine, 2-aminopyrazine and 2,4-diaminopyrimidine, which are commercially available) under acid catalysis (in concentrated sulfuric acid at 190 ° C see: Herbert et al. J. Chem. Soc. C 1969 , P. 1505 or preferably under catálisi s by p-toluenesulfonic acid in xylene with heat, see J. Szmuskovicz U.S. Patent No. 3,565,912) to provide the regioisomeric indoles (III and IV) which can be separated by chromatography. Preferably, when synthesis 108 is used of Scheme II in the preparation of the novel compounds of this invention, Rx, R2, R3 and R4 will not contain an amino-substituted aryl or heteroaryl, and other radicals well known to those of skill in the art, which have the potential to to interfere with, compete with or inhibit the formation reaction of the ring. The yields for the general reaction of Scheme II are more favorable when the substituted aniline or the heterocycle (V) substituted with amino is rich in electrons. Preferably, when Ri, R2, R3 or R represent an electron withdrawing group directly coupled to the aromatic ring, the electron withdrawing substituent must be introduced after ring formation of Scheme II. In a third general synthesis of indoles and azaindoles, useful for the preparation of novel compounds of this invention, it is illustrated in Scheme III, by which the appropriate Grignard reagent is added to the cyano functional group of a 2-amino-1 cyanoaryl or heteroaryl (for example, 3-amino-4-cyanopyridine, 2-amino-5-nitrobenzonitrile, 2-amino-6-fluorobenzonitri lo Scheme lia Scheme 11b Scheme II I 110 and 2-amino-5-chlorobenzonitrile, which are commercially available) the system (VII) to provide the corresponding imine, which after hydrolysis provides the ketone (VIII). Alternatively, an ortho-nitrobenzonitrile (e.g., 2-methyl-6-nitrobenzonitrile, 5-chloro-2-nitrobenzonitrile, 4-cyano-3-nitrobenzotri fluoride, 4,5-dimethoxy-2-nitrobenzonitrile, 4-chloro-2) -nitrobenzonitrile, 6-nitro-o-anisonitrile and 6-bromo-2-cyano-4-nitroaniline, which are commercially available) can be converted to a 2-aminobenzonitrile as described by Jacini et al. (Gazz. Chim. Ital 1947, Vol. 77, 308). Acylation of the aminoaryl or amioheterocycle with the appropriate acid chloride (IX) (for example, benzoyl chloride, 3,5-bis (trifluoromethyl) benzoyl chloride, 2-bromobenzoyl chloride, 2-fluorobenzoyl chloride, pentafluorobenzoyl chloride , 2,4-difluorobenzoyl chloride, 2,6-difluorobenzoyl chloride, 2,6-dichlorobenzoyl chloride, o-toluoyl chloride, m-anisoyl chloride, 3,4,5-trimethoxybenzoyl chloride, 4-chlorobenzoyl chloride, -biphenylcarbonyl, 4-tert-butylbenzoyl chloride, 4-n-butylbenzoyl chloride, 4-cyanobenzoyl chloride, 2-naphthoyl, 2,5-difluorobenzoyl chloride, 5- (dimethylsulfamoyl) -2-methoxybenzoyl chloride, 2,3-dichlorobenzoyl chloride, 1-naphthoyl chloride, 2-ethoxy-1-naphthoyl chloride, and 2-naphthoyl, which are commercially available.) As shown in Scheme III, provides the bicycled fused (III) after treatment with titanium (0) as described in the literature (Furstner et al. Tet. Lett. 1991, 6695-6696). Such substituted benzoyl chlorides can be prepared from the corresponding benzoic acids, commercially available, by treatment with oxalyl chloride or thionyl chloride (Tet Lett, 1993, 3543-3546; and Julia et al. J. Chem. Soc. Perkin Trans. I 1991, Vol. 5, 1101-1105, respectively).

Scheme IV 112 A general preparation of the acetylenes for use in the coupling of Scheme I is illustrated in Scheme IV. The appropriate aryl- or heteroaryl aldehyde (XI) is reacted with diphenyl phosphite (XII) to provide the carbinol derivative (XIII) which is subsequently converted to the chlorinated derivative (XIV) by treatment with phosphorus oxychloride. Treatment of the chloromethane phosphonate with two equivalents of potassium t-butoxide, followed by the addition of the appropriate aldehyde (XV) provides the desired acetylene derivative (II) for use in Scheme I. For purposes of illustration, examples of commercially available aryl aldehydes (XI) include 3-phenoxybenzaldehyde, 6-bromoveratraldehyde, 2-bromobenzaldehyde, 2-fluorobenzaldehyde, 4-fluorobenzaldehyde, 2-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, 2-chloro -6-fluorobenzaldehyde, o-anisaldehyde, 2, 3-dimethoxybenzaldehyde, 3-cyanobenzaldehyde, 3-fluoro-p-anisaldehyde, 3- (3,4-dichlorophenoxy) benzaldehyde, 3- (3- (trifluoromethyl) phenoxy) benzaldehyde, 3- (4-methoxyphenoxy) benzaldehyde, 3-methyl-p-anisaldehyde, 4,4'-ethylbiphenyl-4-carboxaldehyde, 2-chloro-4- 113 dimethylaminobenzaldehyde, 2,4-triethoxybenzaldehyde, 1-naphthaldehyde, 2-methoxy-1-naphthaldehyde, 4-methoxy-1-naphthaldehyde, 4-dimethylamino-1-naphthaldehyde, 4-methyl-1-naphthaldehyde, 2-benzyloxy- l-naphthaldehyde, 2- (2,4-dichlorobenzyloxy) -1-naphthaldehyde, 2-naphthaldehyde, 1-bromo-2-naphthaldehyde, 6-methoxy-2-naphthaldehyde and 7-methyl 1-2-naphthaldehyde. For purposes of illustration, examples of commercially available heteroarylaldehyde (XI) include 2,6-diphenyl-4-pyridinecarboxaldehyde, quinoline-3-carboxaldehyde, 2-chloro-3-quinolinecarboxaldehyde, 2-chloro-6-methoxy-3-quinolinecarboxaldehyde , 2-imidazolecarboxaldehyde, Nl-benzyl-2-imidazolecarboxaldehyde, 2-methyl-3-imidazolecarboxaldehyde, 3-imidazolecarboxaldehyde, 2-ethyl-4-methyl-3-imidazolecarboxaldehyde, 4-methyl-5-imidazolecarboxaldehyde and 2-phenyl-4 -imidazolecarboxaldehyde. In addition, commercially available heteroarylcarboxylic acids or derivatives thereof can be converted to heteroaryl aldehydes by standard synthetic transformations well known to those skilled in the art. For example, the heteroaryl ester can be reduced to the aldehyde by treatment with diisobutylaluminum hydride. For purposes of illustration, commercially available heteroarylcarboxylic acids or derivatives thereof which can be converted to heteroaxylaldehydes (XI) include methyl 2-chloro-6-methyl-4-pyrimidinecarboxylate; 4-carboxypyrimidine; 2,6-dimethylamino-4-pyrimidinecarboxylate methyl; and methyl 4,6-diphenyl-2-pyrimidinecarboxylate. Alternatively, heteroaryl halides can be converted to heteroarylaldehydes (XI) by lithium-halogen exchange and quenching of the anion with dimethylformamide. For purposes of illustration, commercially available heteroaryl halides that can be converted to heteroaryl aldehydes (XI) include 6-chloro-2, -dimethoxypyrimidine; 4-chloro-2-methylthiopyrimidine; 2-amino-4-chloro-6-methylpyrimidine; 4-chloro-2-phenylquinazoline; 4-chloro-2-methylquinoline; 4-chloro-2-methylquinoline; 4-chloro-7- (trifluoromethyl) quinoline; 4-chloro-6-methoxyquinoline; 4-chloro-2-picoline; 2,5-dimethyl-4-bromopyridine; 2-ethoxy-4-bromopyridine; 3-amino-4-chloroquinoline; and 3-amino-4-chloropyridine (note: the amino group of the substituted heteroaryl halide derivatives could be first adequately protected). 115 The alphahydroxyketone (Via) or the alfasilyloxyketone (VIb) of Scheme II can be prepared, for example when Ru is 4-pyridyl or 4-quinolinyl, by generating the anion of the protected silyl ether (XVI) and reacting it with the N -methyl-N-methoxyamide (XVII) as shown in Scheme Va (Gallagher et al Biorg, Med. Chem. Lett, 1995, 1171-1176). The N-methyl-N-methoxyamide (XVII) can be obtained through the reaction of R? 2-C (0) Cl (for example, the 3,5-bis (trifluoromethyl) benzoyl chloride; 2-bromobenzoyl chloride; 2-fluorobenzoyl chloride; pentafluorobenzoyl chloride; 2,4-difluorobenzoyl chloride; 2,6-difluorobenzoyl chloride; 2,6-dichlorobenzoyl chloride; or o-toluoyl chloride; m-anisoyl chloride; 3,4,5-trimethoxybenzoyl chloride; 4-biphenylcarbonyl chloride; 4-tert-butylbenzoyl chloride; 4-n-butylbenzoyl chloride; 4-cyanobenzoyl chloride; 2-naphthoyl chloride; 2, 5-difluorobenzoyl chloride; 5- (dimethylsulfamoyl) -2-methoxybenzoyl chloride; 2,3-dichlorobenzoyl chloride; 1-naphthoyl chloride, 2-ethoxy-1-naphthoyl chloride; and 2-naphthoyl chloride, which are commercially available) with N, 0- 116 dimethylhydroxylamine in the presence of triethylamine. Such acid chlorides can be prepared from the corresponding R 2 -C (0) 0H by treatment with oxalyl chloride or thionyl chloride (Tet Lett, 1993, 3543-3546 and Julia et al. J. Chem. Soc. Perkin Trans. I 1991, Vol. 5, 1101-1105, respectively).

Outline It burns Vb XX XV 117 Alternatively, the dimethylketal XX, prepared according to Scheme Vb, can be used in the Scheme II process in place of the alphahydroxyketone (Via) and the alphasilyloxyketone (VIb). The dimethylketal XX can be prepared at birth by reacting the anion of dimethoxyacetal XIX with the aldehyde XV. The dimethoxyacetal XIX can be easily prepared from the corresponding aldehyde XI (for example, 2,6-diphenyl-4-pyridinecarboxaldehyde, quinoline-3-carboxaldehyde, 2-chloro-3-quinolinecarboxaldehyde, 2-chloro-6-methoxy-3). -quinolinecarboxaldehyde; 2-imidazolecarboxaldehyde; Nl-benzyl-2-imidazolecarboxaldehyde; 2-methyl-3-imidazolecarboxaldehyde; 3-imidazolecarboxaldehyde; 2-ethyl-4-methyl-3-imidazolecarboxaldehyde; 4-methyl-5-imidazolecarboxaldehyde; phenyl-4-imidazolecarboxaldehyde, which are commercially available) using methods well known to those skilled in the art. Alternatively, the Índoles or azaindoles (III) can be prepared (Scheme VI) by the reaction of the 2-substituted indoles or azaindoles (XIX) (e.g., 2- (4-fluorophenyl) indole; 2X2-naphthyl) indole; and 2- (4-chlorophenyl) indole, which are commercially available) with Ru-L, where L is a 118 leaving group such as chlorine, bromine, iodine and similar radicals (for example, 4-chloropyridine, 4-chloroquinoline or 4-chloropyrimidine, which are commercially available). The indole or 2-substituted azaindole (XIX) can be treated with methylmagnesium bromide in ether followed by the addition of Ru-L and heated in a metal pump at 160 ° C for 20 hours, to provide the indole or the azaindole (III ) (US Patent No. 3,551,567) Scheme VI XIX III The following is included to further illustrate the synthetic procedures useful in the preparation of the novel compounds of this invention. A specific example of a palladium mediated coupling as described in Scheme I is illustrated in Scheme VII wherein l- (4-pyridyl) -2- (4-fluorophenyl) ethyne (1) and 2- 119 Iodoaniline (2) provides the 2,3-disubstituted regioisomeric (3) and (4) as a 1: 4 mixture, respectively. The compound (4) can be separated from the compound (3) by means of flash chromatography.

It burns VI I Alternatively, the substituted acetylenes and iodoanilines can be coupled via a palladium-mediated process as described in Scheme I. The substituted 2-iodoanilines can be either purchased or prepared by conventional methods. standards well known to those of skill in the art. For example, monoiodination of a substituted aniline derivative could provide the 2-iodoaniline derivative using a variety of iodination reagents, such as N-iodosuccinimide. The substituted acetylenes can be obtained as described in Scheme IV as illustrated in Scheme VIII for 1- (4-pyridyl) -2- (4-fluorophenyl) ethyne (1). The adduct or addition complex (6) of diphenylphosphite and 4-pyridinecarboxaldehyde (5) is treated with phosphorus oxychloride to provide the chlorinated derivative (7). The condensation and elimination to the alkyne (1) is effected by treatment of the chlorinated derivative (7) and the 4-fluorobenzaldehyde (8) with 2.1 equivalents of potassium t-butoxide.

Scheme VIII (5) (6) 121 Scheme IX illustrates the preparation of the substituted characters according to the method of Scheme III, a coupling mediated by titanium oxide. The Grignard reagent 4-bromopyridine (10) is prepared by treatment at low temperature (-78 ° C) with n-butyllithium, followed by treatment with magnesium bromide etherate. A cooled solution of Grignard (10) is added to anthranilonitrile (9) at low temperature (-5Q ° C) followed by heating to room temperature. The resulting imine (11) is hydrolyzed by treatment with sulfuric acid to the anilinoketone (12). Acylation of the anilinoketone (12) with 4-fluorobenzoyl chloride (13) gives the ketoamide (14). The regiospecific synthesis of 122 Indole (3) is completed by treatment of the ketoamide (14) with titanium oxide.

It's burning IX eleven 123 Scheme X illustrates the preparation of the indoles and the azaindoles according to the method of Scheme II, the acid-mediated condensation of an aminoaryl or aminoheteroaryl and a substituted benzoin. The condensation of 2,6-diaminopyridine (15) with 1- (4-fluorophenyl) -2-t-butyldimethylsiloxy-2- (4-pyridyl) ethanone (16) is effected by treatment with an excess of p-acid. toluenesulfonic in xylene at high temperatures, to provide the azaindoles (17) and (18) which can be separated by flash chromatography. Further functionalization of the 2, 3-disubstituted indoles or azaindoles can be easily achieved by reaction in an appropriately placed group, such as an amino, carboxyl, halo, substituted alkyl and the like group, on the azoindoles or azaindoles 2, 3- disubstituted Scheme XI illustrates the functionalization of a 6-amino derivative (17) of a 2, 3-disubstituted azaindole. The reaction of the 6-amino group of (17) with the mixed anhydride of N-4-t-butoxycarbonylaminobutyric acid (20) provides the compound N-4-t-butoxycarbonylaminobutanoyl (21), which can be easily converted to the aminobutanoyl compound. (22) by exposure to 90% trifluoroacetic acid and water for 1 hour. Similarly, the aminoalkylsulfonyl compound (26) can be prepared according to the method shown in Scheme XII.

Escruema X Scheme XI BOCNH 125 Further functionalization of the 2, 3-disubstituted indoles or azaindoles can easily be achieved by site-specific electrophilic substitution, and subsequent processing at the coupling point of a newly introduced electrophile. For example, in Scheme XIII, N-bromosuccinimide (NBS) is reacted with compound (17) to introduce a bromo radical at position 5 of (17), yielding the brominated derivative (27). The brominated compound (27) can also be used to introduce other substituents at position 5, using methods and reagents well known to those of skill in the art. Similarly, a fluoro radical can be introduced at position 5 of (17) through the use of N-fluorobenzenesulfonimide to provide the fluorinated derivative (28). Alternatively, a brominated compound such as (27), or an appropriately NH-protected derivative of 6-amino and indole, can be converted to the fluorinated derivative by lithium-halogen exchange followed by quenching the lithium anion with N-fluorobenzenesulfonimide (Synlett, 187 (1991) and Tetrahedron Lett. 1631 (1992)).

These reactions exemplify in a 126 azaindole after the indole has been formed by electrophilic substitution. In a more general sense, these demonstrate how other electrophilic agents (eg, iodine, Vilsmeier reagent, nitric acid and the like) can be used to substitute azaindoles and indoles in a specific manner.

Scheme XII Scheme XIII 127 Essuema XIV Scheme XV In addition, the functionalization of the azan.doles or 2, 3-disubstituted Índoles can easily be achieved in the indole nitrogen by the use of Mitsunobu conditions, wherein an appropriate alcohol is activated by treatment with triphenylphosphine and diethylazodicarboxylate (DEAD) and then reacted with the indol or azaindole compound. For example, in Scheme XV, the indole nitrogen of (29) is N-methylated under the conditions of Mitsunobu and then reacted with NBS to provide the 5-bromo-N-methyl derivative, followed by the deprotection that provides (32) Scheme XVI Scheme XVII 129 Scheme XVIII 34 36 In addition, functionalization of azaindoles or 2, 3-disubstituted indoles can be easily achieved by site-specific electrophilic halogenation., followed by palladium mediated coupling to introduce the aryl substituent. Alternatively, an aryl halide can be converted to an aryl stannane by lithium-halogen exchange followed by quenching with a trialkylstannyl chloride (for example, tributylstannyl chloride or trimethylstannyl chloride). The aryl stannane can then be reacted in the presence of palladium (0) in a coupling process. Those of skill in the art are well versed in the various conditions and methods available for palladium (0) aided couplings (Palladium Reagents and Catalysts - Innovations in Organic 130 Synthesis by Jiro Tsuji, Wiley (1995); and Palladium Reagents in Organic Syntheses by Heck, Academic Press (1985)).

Scheme XIX Scheme XX 31 41 Schemes XVI-XXIII illustrate the use of palladium-mediated couplings to prepare the compounds of this invention. For example, the brominated compound (31) can be coupled to aniline (other amines also work, see Buch ald 131 et al., J. Am. Chem. Soc. 7901 (1994); Buchwald et al., Angew. Chem. Int. Ed. Engl. 1348 (1995); Hartwig et al., J. Am. Chem. Soc. 5969 (1994)) in a palladium (0) mediated coupling to provide the compound (33) as illustrated in Scheme XVI. Alternatively, compound (31) can be coupled with an arylboronic acid to provide a derivative (43) substituted with phenyl, as illustrated in Scheme XVII Scheme XXI 42 Scheme XXII 46 132 Scheme XXIII (See Chem. Lett., 1405 (1989), Bull, Chem. Soc. Jpn 3008 (1988), Synthesis 184 (1989), Tetrahedron Lett 1523 (1990)). The brominated compound (34) can be coupled to a heterocycle such as imidazole, as exemplified in Scheme XVIII, which has been demonstrated in the literature for similar systems ((35) plus 2-bromopyridine using tetrakistriphenylphosphine-palladium (0) , AS Bell et al, Tetrahedron Lett, 5013 (1988) and Synthesis 843 (1987)). The compound (37) (Scheme XIX) can be prepared from the 4-aminp-2-mercapto-6-methylpyrimidine by conversion to the corresponding 2-iodo derivative (iodine and hydrogen iodide in analogy to the bromide conditions and HBr found in Zh. Org. Khim. (1991) 2235-2236) then converted to (37) in the manner illustrated in Scheme X. The Reformatsky reagent (38) may be 133 coupled to the iodine derivative (37) using the tetrakistri phenyl fos-palladium (0) Scheme XXIV in a manner similar to the previously described coupling with 4,6-dimethyl-2-iodopyrimidine (see: Yamanaka et al., Chem. Phar. Bull. 4309 (1985)). An unnatural amino acid can be prepared directly from the compound (41) of Scheme XX by reduction (e.g., hydrogen gas in the presence of Rh (DIPAMP)). The compound (41) can itself be obtained through a palladium (0) -mediated coupling of the enamide (40) directly with the brominated derivative (41) 134 using the conditions previously used for similar transformations (Pd2 (dba) 3, (o-tol) 3P, Et3N, acetonitrile, see J. Org. Chem. 2584 (1991); Synthesis 414 (1989); J. Org. Chem. 1289 (1991); Tetrahedron 7151 (1990)). The brominated derivative (31) can be converted to the carboxymethyl derivative (42) as illustrated in Scheme XXI using the conditions previously employed for similar transformations (Pd2 (dba) 3, triphenylphosphine, methanol, carbon monoxide used with 2, 6 -dichloropyrazine, see Synthesis 923 (1990)). An acetylene group can be directly coupled to azaindole or indole as illustrated in Scheme XXII using the conditions previously used for similar transformations (tetrakistriphenylphosphine palladium (0), Cul, Et3N see: Synthesis 728 (1984)). Compound (44) can be obtained using commercially available 3-methoxy-4-amino-6-clpro-pyridazine, in the same manner as Scheme X. Vinyl functionalization of azaindoles or 2,3-disubstituted Índoles, appropriate , can be easily achieved as illustrated in Scheme XXIII. 135 It's burning XXV The conversion of the brominated derivative (47) of Scheme XXIII to the tributylstannyl derivative as described above, can be followed by a palladium mediated coupling (0) to a vinyl triflate using the conditions previously employed for similar transformations (Pd2 (dba) 3, Ph3As, NMP, see Tetrahedron Lett 4243 (1991)). Compound (47) p __, e be obtained from 3-amino-2-bromoaniline in a manner similar to Scheme X.

Scheme XXVI 62 137 Further functionalization of the appropriate 2, 3-disubstituted azaindoles or indoles can easily be achieved by the introduction of a sulfide group as illustrated in Scheme XXIV or alternatively the thiol can be introduced prior to indole formation. Examples of introduction of thiol include alkyl thiol (Rumler et al., Pharmazie (1990) 657-659) and thiol itself (Pascual et al., Bull, Soc. Chim, Belg, 101: 297-302 (1992)). For example, the chloro group of compound (50) can be displaced by a thiol reagent. The sulfide (51) can be oxidized to the sulfoxide (52) by treatment with t-butyl hydroperoxide in the presence of pyridine (Kagan et al., Tetrahedron asymmetry (1990) 597-610) or subsequently oxidized to the sulfone (53) (Trost and collaborators, Tetrahedron Lett (1981) 1287). A sulfonamide radical can be introduced before the indole formation process (Schemes I or II) and then further functionalized as illustrated in Scheme XXV. Reaction of the sulfonamide (56) with the excess chloroformates, results in the formation of the compound (57) wherein CR3 = -S (O) 2 -NR22-C (O) -OR20 (J. Med. Chem. (1990) 2393-2407). The reaction of sulfonamide (56) with 138 acid chlorides after deprotonation of the sulfonamide with sodium hydride, results in the formation of the compound (58) wherein CR3 = -S (0) 2 -NR22-C (0) -R2? (Curran, J. Org. Chem. (1990) 4584-4595). Reaction of the sulfonamide (56) with isocyanates results in the formation of compound (59) wherein CR3 = -S (0) 2-NR22-C (0) -NR5R21 where R5 = hydrogen (Howbert et al., J Med. Chem. (1990) 2393-2407). The introduction of the substituent CR3 = -NR 2S (0) 2NR5R21 can be achieved as illustrated in Scheme XXVI. First, the amino group of the compound (60) can be alkylated in a reductive amination to provide the compound (61). Then, the alkylated amino substituent of compound (61) can be reacted with an o-phenylene sulfate to provide (62), followed by further reaction with a second amine as illustrated in Scheme XXVI to provide the compound (63). ) where CR3 = -NR22-S (0) 2-NR5R2? (Lee et al., Bull, Korean Chem. Soc. (1992), 357). Additional methods of indole and azaindol preparation are included by reference: G. Gribble Recent Developments in Nature Ring Synthesis-Methodology and Applications in Contemporary Organic 139 Synthesis p. 145-172; R. Sundberg and P. V. Nguyen five Membered Ring Systems: Pirroles and Benzo Derivatives, Chapter 5, Comprehensive Heterocyclic Chemistry. It will be understood that these novel compounds are not limited to the methods described for the preparation thereof. The sulfonyl halides can be prepared by the reaction of a suitable alkyl, aryl, heteroaryl, heterocyclyl and similar Grignard, or lithium reagents with sulfuryl chloride, or sulfur dioxide followed by oxidation with a halogen, preferably chlorine. Alkyl, aryl, heteroaryl, heterocyclyl, and similar Grignard or lithium reagents can be prepared from their corresponding halide compounds (such as chlorine or bromine) which are commercially available or readily prepared from commercially available starting materials, using methods known in the art. Alternatively, mercaptans can be oxidized to sulfonyl chlorides using chlorine in the presence of water under carefully controlled conditions. In addition, sulphonic acids can be converted to sulfonyl halides using reagents such as PC15, S0C12, C1C (0) C (0) C1 and 140 similar, and also a. anhydrides using appropriate dehydration reagents. Sulfonic acids are either commercially available or can be prepared using techniques well known in the art from commercially available starting materials. Instead of the sulfonyl halides, sulfinyl halides or sulfenyl halides can be used to prepare the compounds wherein the sulfonyl portion is replaced by a sulfinyl or thio portion, respectively. Arylsulfonic acids, heterocyclylsulfonic acids fused to a benzo or heteroarylsulfonic acids, can be prepared by sulfonation of the aromatic ring by methods well known in the art, such as by reaction with sulfuric acid, SO3, S03 complexes, such as DMF (S03) ), pyridine (S03), N, N-dimethylacetamide (S03), and the like. Preferably, such sulfonyl halides are prepared from such aromatic compounds by reaction with DMF (S03) and S0C12 or C1C (O) C (O) Cl. The reactions can be carried out step by step or in a single container. Alkylsulfonic acids, arylsulfonic acids, heterocyclylsulfonic acids, acids 141 heteroarylsulfonic, alkarycarboxynes, arylmercaptans, heterocyclylmercaptans, heteroarylmercaptans, alkyl halides, aryl halides, heterocyclyl halides, heteroaryl halides and the like, a commercially available or can be readily prepared from commercially available starting materials, using well known standard methods in the technique. The thioether derivatives can be converted to the corresponding sulfone or sulfoxide by oxidation of the thioether derivative, with a suitable oxidation agent in a suitable solvent. Suitable oxidizing agents include, for example, hydrogen peroxide, sodium meta-perborate, oxone (potassium peroxy monosulfate), meta-chloroperoxybenzoic acid, periodic acid and the like, including mixtures thereof. Suitable solvents include acetic acid (for sodium meta-perborate) and, for other peracids, ethers such as THF and dioxane, and acetonitrile, dimethylformamide and the like, including mixtures thereof. The chemical reactions described above are generally described in terms of 142 its widest application to the preparation of the compounds of this invention. Occasionally, the reactions may not be applicable as described for each compound included within the scope described. The compounds for which this occurs will be readily recognized by those of skill in the art. In such cases, any of the reactions can be successfully carried out by conventional modifications known to those of skill in the art, for example, by appropriate protection of the interference groups, by switching to alternative conventional reagents, by routine modification of the reaction conditions, and the like, or other reactions described herein or otherwise conventional, will be applicable to the preparation of the corresponding compounds of this invention. In all preparation methods, all the initial materials are known or easily prepared from initial materials. Prodrugs of the compounds of this invention are also contemplated by this invention. A prodrug is an active or inactive compound that is chemically modified through an in vivo physiological action, such as hydrolysis, metabolism and the like, to a compound of this invention after administration of the prodrugs to a patient. The adequacy and techniques involved in the preparation and use of prodrugs are well known to those with experience in the field. For a general discussion of prodrugs involving esters see Svensson and Tunek Drug Metabolism Reviews 165 (1988) and Bundgaard Design of Prodrugs, Elsevier (1985). Examples of a masked carboxylate anion include a variety of esters, such as alkyl (e.g., methyl, ethyl), cycloalkyl (e.g., cyclohexyl), aralkyl (e.g., benzyl, p-methoxybenzyl) esters, and alkylcarbonyloxyalkyl (for example, pivaloyloxymethyl). The amines have been masked as substituted arylcarbonyloxymethyl derivatives, which are cleaved by esterases in vi liberating the free drug and formaldehyde (Bungaard J. Med. Chem. 2503 (1989)). Also, drugs containing an acidic NH group such as imidazole, imide, indole and the like, have been masked with the N-acyloxymethyl groups (Bundgaard Design of Prodrugs, Elsevier (1985)). The 144 Hydroxyl groups have been masked as esters and ethers. Without further elaboration, it is believed that one of skill in the art can, using the foregoing description, utilize the present invention to its fullest extent. The following specific, preferred embodiments have therefore to be considered as merely illustrative, and not as limiting the rest of the description, in any way. All reagents were used as received, without purification. All the proton and carbon NMR spectra were obtained either from a nuclear magnetic resonance spectrometer VXR-300 or VXR-400. The following Examples illustrate the preparation of the compounds of the present invention and the intermediates useful in the preparation of the compounds of the present invention. 145 Example 1 Section A 1- (4-pyridyl-2- (4-fluorophenyl) ethyne (1 The 4-pyridinecarboxladehyde (5) (25.0 g, 0.232 mol) was added dropwise in 1 hour to a cooled (0 ° C) solution of diphenylphosphite (54.0 g, 0.23 mol) and tetrahydrofuran (100 ml). After complete addition, the reaction was allowed to warm to 23 ° C. After 16 hours, the reaction was concentrated in vacuo and purified by direct application to flash chromatography (100% ethyl acetate) which gave 4-pyridyl-hydroxymethyldiphenylphosphonate (6): Mass Spectrum (Cl) 342 (MH +) . The 4-pyridyl-hydroxymethyldiphenylphosphonate (6) (15.3 g, 46 mmol), diethylaniline (4 ml) and 146 Phosphorus oxychloride (50 ml) were heated at 90 ° C for 16 hours. The reaction was quenched by pouring the reaction mixture onto ice (400 g). Potassium carbonate was added until a pH of 8 was obtained for the solution, followed by extraction with methylene chloride (3 x 200 ml). After drying over magnesium sulfate, the reaction was concentrated to give the crude 4-pyridyl-chloromethyldiphenylphosphonate (7) as a solid which was used in the next step without further purification: Mass Spectrum (Cl) 36 (MH +). Potassium t-butoxide (3.30 g, 29.2 mmol) was added as a solid to 4-pyridyl-chloromethyldiphenylphosphonate (7) (5.00 g, 13.9 mmol), 4-fluorobenzaldehyde (8) (2.00 g, 15.3 mmol), and tetrahydrofuran (70 ml) at 23 ° C under an argon atmosphere. After 16 hours, the reaction was quenched by addition to water (200 ml) in 3 minutes. After adjusting the pH of the solution to 7 with 1N HCl, the mixture was extracted with ethyl acetate (3 x 350 ml), and dried over magnesium sulfate. After concentration in vacuo, the residue was purified by flash chromatography (ethyl acetate: methylene chloride 1: 1) to give 1-147 (4-pyridyl) -2- (4-fluorophenyl) ethyne (1) as a solid: Mass Spec (Cl) 198 (MH +). 3- (4-pyridyl) -2-4-fluorophenyl) indole (3) 2-Iodoaniline (2) (525 mg, 2.40 mmol) was added to palladium acetate (26.9 mg, 0.120 mmol), triphenylphosphine (31.5 mg, 0.120 mmol), potassium acetate (1.18 g, 12.0 mmol), tetrabutylammonium chloride (547 mg, 2.40 mmol), 1- (4-pyridyl) -2- (4-fluorophenyl) ethyne (1) (1.0 g, 4.8 mmol) and dimethylformamide (20 ml). The reaction was heated at 100 ° C for 17 hours under argon atmosphere. After cooling to 23 ° C, the reaction was poured into water (200 ml), extracted with ethyl acetate (3 x 100 ml), and dried over magnesium sulfate. After concentration in vacuo, the residue was purified by flash chromatography on silica gel (methanol: ethyl acetate 1:19) to give the indoles (3) and (4) as a mixture of regioisomers (4: 1): Mass Spectrum (Cl) 289 (MH +). 148 Section b 4- (2-aminobenzoyl) pyridine (12) 4-Bromopyridine (10) (49.38 g, 0.254 mol, free base of the hydrochloride by division between ether and saturated bicarbonate) and diethyl ether (200 ml), were added in 1 hour to a cooled solution (-78 ° C) of n-butyl-lithium (0.381 mol of a 2.5 M solution in hexane) under an argon atmosphere. After 30 minutes at (-78 ° C), magnesium bromide diethyl etherate (98.37 g, 0.381 mole) was added via a dry powder addition funnel. After 1 hour at -78 ° C, the reaction mixture was transferred to an addition funnel lined at -50 ° C, the solution was added to a cold solution (-50 ° C) of anthranilonitrile (15.0 g, 0.127). mol) and benzene (400 ml) in 10 minutes. The reaction was allowed to warm to 23 ° C. after 16 hours, the reaction was emptied into 18% sulfuric acid (100 ml), and digested for 1 hour. The resulting mixture was extracted with ethyl acetate (400 ml), washed with water (3 x 400 ml), and dried over magnesium sulfate. After concentration in vacuo, the residue was purified by flash chromatography of a gradient way gradient (one liter of methylene chloride; one liter of ethyl acetate: methylene chloride 1: 9; one liter of ethyl acetate: methylene chloride 2: 8; one liter of ethyl acetate: methylene chloride 3: 7; one liter of ethyl acetate: methylene chloride 4: 6) which afforded 4- (2-aminobenzoyl) pyridine (12) as a solid: Mass Spectrum (Cl) 199 (MH +). Alternatively, to a solution of 1-iodo-2-nitrobenzene (3.76 g, 15.1 mmol) in dry tetrahydrofuran (80 ml) at -78 ° C was added n-butyllithium (7.54 ml, 18.9 mmol) in 5 minutes. After 40 minutes at -78 ° C, ethyl isonicotinate was added in one portion to anhydrous tetrahydrofuran (70 ml). After 10 minutes, the reaction was allowed to warm to 0 ° C for 10 minutes, then quenched with 20 ml of glacial acetic acid: 30 ml of water. After adjusting the pH to 8 with saturated bicarbonate solution, the mixture was extracted with ethyl acetate (1 x 500 ml), washed with brine (2 x 500 ml), dried over sodium sulfate. After concentration in vacuo, the reaction mixture was treated with 120 ml of 5 N NaOH: methanol: water (1: 1: 1). After removal of the methanol under vacuum, the reaction mixture was extracted 150 with ethyl acetate (1 x 500 ml), then dried over sodium sulfate. After concentration in vacuo, the residue was purified by flash chromatography (graduax methylene chloride 100%, ethyl acetate 20%: methylene chloride: then 40% ethyl acetate: methylene chloride) provide 4- (2-nitrobenzoyl) pyridine. The 4- (2-nitrobenzyl) pyridine (100 mg, 0.44 mmol), stannous chloride dihydrate (297 mg, 1.32 mmol) and 1.1 ml of concentrated hydrochloric acid were heated at 100 ° C for 10 minutes. After cooling to 23 ° C, the reaction was emptied into 10 ml of water and 5N sodium hydroxide (14 ml) followed by extraction with ethyl acetate (2 x 50 ml). The ethyl acetate layer was washed with brine (1 x 20 ml), dried over sodium sulfate, and concentrated in vacuo to provide 4- (2-aminobenzoyl) pyridine (12). 4- (2- (4-fluoro-N-benzoylamino) benzoyl) pyridine (14) 4-Fluorobenzoyl chloride (78.0 mg, 0.55 mmol) was added to 4- (2-aminobenzoyl) pyridine (12) (100 mg, 0.50 mmol), triethylamine (0.35 mL, 2.52 mL), and chloroform (5.0 mL) at 23 ° C under an argon atmosphere. 151 After 24 hours at 23 ° C, the reaction was poured into water (50 ml), extracted with ethyl acetate (3 x 50 ml), and dried over magnesium sulfate. After concentration in vacuo, the residue was purified by instantaneous chromatography (ethyl acetate: methylene chloride 1: 1) to give 4- (2- (4-fluoro-N-benzoylamino) benzoyl) pyridine (14): Mass Spectrum (Cl) 321 (MH +). 3- (4-pyridyl) -2-4- fluorophenyl) indole (3) Graphite (272 mg, 3.63 mmol) and potassium (100 mg, 0.33 mmol) were heated at 150 ° C under argon atmosphere in a 250 ml round bottom flask, with stirring for 25 minutes. 30 ml of tetrahydrofuran was added via syringe to the hot bronze colored solid, followed by a suspension of titanium (III) chloride (254 mg, 1.65 mmol) in 20 ml of tetrahydrofuran. The resulting black solution was allowed to warm to reflux for 1 hour. The 4- (2- (4-fluoro-N-benzoylamino) benzoyl) pyridine (14) (100 mg, 0.33 mmol) and tetrahydrofuran (20 ml) were then added to the hot (65 ° C) reaction mixture in the reaction mixture. minutes After 1 hour at 65 ° C, the reaction was cooled to 23 ° C and filtered through a pad 152 silica gel (20 g), After concentration in vacuo, the residue was purified by flash chromatography (ethyl acetate: methylene chloride 1: 1) to give 3- (4-pyridyl) -2- (4 g). -fluorophenyl) indole (3): Mass Spectrum (Cl) 289 (MH +). The following compounds were made using the ring closure mediated by titanium (O) above, with the appropriate acid chlorides to provide the amide (X) which was closed to the indole XI. It should be noted that in the case of 2- (3-bromothiophene) carbonyl chloride the amide X contains the bromine atom on the thiophene, but the process of ring closure (Ti) removed the bromine from the thiophene, resulting in the hydride replacement.

R 12 MS MS 3-trifluoromethylphenyl 371 (MH +) 339 (MH +) 4-chlorophenyl 335 (M-H) 303 (M-H) 153 3-methylphenyl 315 (MH) 285 (MH +) 4-pyridyl 304 (MH +) 272 (MH +) 1-naphthyl 353 (MH +) 321 (MH +) 2-benzofuranyl 341 (MH) 311 (MH +) 4-methylsulfinyl phenyl 347 ( MH) 2- (3-bromothiophene) 385 (MH) 2-thiophene 275 (MH) Example 2 3- (4-fluorophenyl) -2- (4-pyridyl) indole (4) A portion of the 4: 1 regioisomers of Section A of Example 1, compounds (4): (3), was subjected to purification by flash chromatography (100% ethyl acetate) to provide (4) in a pure state: Mass Spectrum (Cl) 289 (MH +). 154 Example 3 17 6-amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) 1- (4-fluorophenyl) -2-t-butyldimethylsiloxy-2- (4-pyridyl) ethanone (16) (3.45 g, 10.0 mmol), 2,6-diaminopyridine (1.09 g, 10.0 mmol), p-acid toluenesulfonic monohydrate (13.3 g, 70.0 mmol), and xylene (140 ml) were heated to 60 ° C under an argon atmosphere (note: all condensation reactions of this type were conducted behind an explosion protection). After 1 hour at 60 ° C, the reaction was heated at 135 ° C for 3 hours. After allowing the reaction to cool to 23 ° C, the top layer of xylene and p-toluenesulfonic acid was decanted from the bottom layer of the rubber-like residual product. The lower layer of product was divided between saturated bicarbshato (100 ml), and 155 ethyl acetate (250 ml). The ethyl acetate layer was washed with brine (1 x 100 ml), and dried over sodium sulfate. After concentration in vacuo, the residue was purified by the application of flash chromatography (2 liters of ethyl acetate: hexane 7: 3 followed by 100% ethyl acetate) to give the regioisomer (17) cleanly separated: Mass (Cl) 305 (MH +).

Example 4 6-amino-3- (4-fluorophenyl) -2- (4-pyridyl) -7-aza-indole (18) A lower RF product from Example 3 was re-purified by flash chromatography (100% ethyl acetate) 156 to provide (18) as a solid: Mass Spectrum (Cl) 305 (MH +).

Example 5 6- (4'-t-Butoxycarbonyla ino-1'-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole (20) The general procedure for the coupling of mixed anhydride was followed. Isobutyl chloroformate (32 ml, 0.24 mmol) was added dropwise to a solution at -20-30 ° C of 4-t-butoxycarbonylaminobutyric acid (19) (50.1 mg, 0.247 mmol), 4-methylmorpholine (124 ml, 1.23 mmol), and tetrahydrofuran (2 ml). After 20 minutes at -20-30 ° C, 6-amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) (75 mg, 0.24 mmol) and tetrahydrofuran (3 ml) were added. in a single portion. The reaction was allowed to warm to 23 ° C. After 16 hours at 23 ° C, the reaction was evacuated in bicarbonate 157 Saturated (80 ml), extracted with ethyl acetate (2 x 100 ml), washed with brine (1 x 100 ml), and dried over sodium sulfate. After concentration in vacuo, the residue was purified by application to two preparative chromatography plates (silica gel, 2 mm thick, 100% ethyl acetate) to give 6- (4'-t-butoxycarbonylamino-1) '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (20) as a solid: Mass Spectrum (Cl) 489 (MH +). Ethyl chloroformate can be used in place of isobutyl chloroformate in this process.

Example 6 6- (4'-amino-1'-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (21) A solution of trifluoroacetic acid: water: anisole (900 ml: 100 ml: 39 ml) was added. added to 6- (4'-t-butoxycarbonylamino-2'-oxo-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (20) (38 mg, 0.078 mmol ) at 23 ° C. After 1 hour at 23 ° C, the reaction was concentrated under a stream of nitrogen in a ventilated hood. The residue was triturated with 2 ml of ether, the resulting solid was filtered and washed with ether (3 x 2 ml). The TFA salt of (21) was dissolved in 2 ml of water containing 3 equivalents of 1 N HCl and subsequently lyophilized to give the HCl salt of 6- (4'-amino-1'-oxo-amino) - 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (21). The HCl salt was used in the biological test or alternatively the free base can be used in the biological test which was obtained by dividing the hydrochloride salt between ethyl acetate and saturated bicarbonate. The ethyl acetate layer was dried over sodium sulfate, and concentrated in vacuo to provide 6- (4'-amino-1'-oxo-butylamino) -3- (4-pyridyl) -2- (4- fluorophenyl) -7-aza-indole (21) as a solid: Mass Spectrum (Cl) 389 (MH +). 159 Example 7 6- (5'-solid-l '-oxo-2'-t-butoxycarboni lamino-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (26) Compound (26) was prepared in the same manner as Example 5 with the following substitution: Nat-Boc-citrulline was used in place of Nt-Boc-g-aminobutyric acid, which afforded 6- (5'-ureido- 1-oxo-2'-t-butoxycarbonylamino-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (26) after preparative plate chromatography: Mass Spectrum (Cl ) 562 (MH +). 160 Example 8 6- (5'-ur € ldo-l * -oxo-2 '-aminopentylamino) -3- (4-pyridyl) -2- (-fluorophenyl) -7-aza-indole (27) Compound (27) was prepared from compound (26) in the same manner as in Example 6, which afforded 6- (5'-solid-2'-oxo-3 '-aminopentylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (27): Mass Spectrum (Cl) 462 (MH +).

Example - 9 161 6- (6'-t-Butoxycarbonylamino) -l'-oxo-2'-t-butoxycarbonylaminohexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (28) Compound (28) s_ was prepared in the same manner as in Example 5 with the following substitution: Nat-Boc-e-Boc-lysine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (6 '-t-butoxycarbonylamino) -l'-oxo-2'-t-butoxycarbonylaminohexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (28) after plate chromatography preparation: Mass Spectrum (Cl) 633 (MH +).

Example 10 6- (, '-amino-1' -oxo-2 '-aminohexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (29) 162 Compound (29) was prepared from compound (28) in the same manner as in Example 6, which afforded 6- (6'-amino-1'-oxo-2'-aminohexylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (29): Mass Spectrum (Cl) 433 (Mill.

Example 11 6- (5'-t-Butoxy-ributylamino-1-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (30) The compound (30) was prepared in the same manner as in Example 5 with the following substitution: N-a-t-Boc-d-Boc-ornithine was used instead of the acid Nt-Boc-g-aminobutyric, which provided 6- (5'-t-butoxycarboni lamino-1'-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (30) after 163 preparative plate chromatography: Mass Spectrum (Cl) 619 (MH +).

Example 12 6- (5'-amino-1-oxo-2 '-aminopenti lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (31) Compound (31) was prepared from compound (30) in the same manner as in Example 6, which afforded 6- (5'-amino-1'-oxo-2'-aminopentylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (31): Mass Spectrum (Cl) 419 (MH +).

Example 13 164 6- (3'- (4-iodophenyl) -1 '-oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (32) Compound (32) was prepared in the same manner as Example 5 with the following substitution: Nat-Boc-p-iodo-phenylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (3 * - (4-iodophenyl) -1 '-oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (32) after chromatography on preparative plate: Mass Spectrum (Cl) 678 (MH +).

Example 14 6- (3 '~ (4-iodophenyl) -1' -oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (33) 165 Compound (33) was prepared from compound (32) in the same manner as in Example 6, which gave 6- (3 '- (4-iodophenyl) -1' -oxo-2'-aminopropylamino) -3 - (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (33): .__. Pectro mass (Cl) 578 (MH +).

Example 15 6- (3'-methyl-1 '-oxo-2'-t-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (34) Compound (34) was prepared in the same manner as in Example 5 with the following substitution: Nat-Boc-valine was used in place of Nt-β-g-aminobutyric acid, which gave 6- (3'-methyl-) 1 '-oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (34) after 166 of preparative plate chromatography: Mass Spectrum (Cl) 504 (MH +).

Example 16 6- (3 '-methyl-1' -oxo-2 '-aminobutylamino) -3- (4-pyridyl) -2- (-fluorophenyl) -7-aza-indole (35) The compound (35) was prepared from the compound (34) in the same manner as in Example 6, which afforded 6- (3 '-methyl-1 * -oxo-2'-aminobutylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (35): Mass Spectrum (Cl) 404 (MH +). 167 Example 17 6- (4 ', 4'-dimethyl-1' -oxo-2'-1-butoxycarbonylamino-pentylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -1- a zaindol (36) Compound (36) was prepared in the same manner as Example 5 with the following substitution: Nat-Boc-bt-butylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (4X4 '- dimethyl-1'-oxo-2'-t-butoxycarbonylamino-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (36) after preparative plate chromatography: Spectrum of Mass (Cl) 532 (MH +). 168 Example 18 6- (4 ', 4' -dimethyl-1 '-oxo-2' -a in-opentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (37) The compound (37) was prepared from the compound (36) in the same manner as in Example 6, which afforded 6- (4 ', 4'-dimethyl-1 * -oxo-2'-aminopenti lamino) -3 - (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (37): Mass Spectrum (Cl) 432 (MH +).

Example 19 169 6- (5'-1-Butoxycarbonylamino-1 '-oxo-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (38) Compound (38) was prepared in the same manner as Example 5 with the following substitution: Nt-Boc-5-aminovaleric acid was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (5 ') -1-butoxycarbonylamino-1 '-oxo-pentylamino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (38) after preparative plate chromatography: Mass Spectrum (Cl) 504 (MH +).

Example 20 6- (5'-amino-1 '-oxo-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (39) The compound (39) was prepared from the compound (38) in the same manner as in Example 6, 170 which afforded 6- (5'-amino-1'-oxo-pentylamino) 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (39) Mass Spectrum (Cl) 404 ( MH +).

Example 21 6- (6'-t-Butoxycarbonylamino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (40) Compound (40) was prepared in the same manner as Example 5 with the following substitution: Nt-Boc-6-aminocarproic acid was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (6 ') -toboncarbonylamino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (40) after preparative plate chromatography: Mass Spectrum (Cl) 518 (MH +). 171 Example 22 6- (6'-amino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (41) Compound (41) was prepared from compound (40) in the same manner as in Example 6, which afforded 6- (6'-amino-1'-oxo-hexylamino) -3- (4-pyridyl) - 2- (4-fluorophenyl) -7-aza-indole (41): Mass Spectrum (Cl) 418 (MH +).

Example 23 172 6- (3'-cyclohexyl-1'-oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (42) Compound (42) was prepared in the same manner as Example 5 with the following substitution: Nat-Boc-b-cyclohexylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave the 6- (3'-) cyclohexyl-l '-oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (42) after preparative plate chromatography: Mass Spectrum (Cl) 558 (MH +).

Example 24 6- (3'-cyclohexyl-1-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (43) 173 Compound (43) was prepared from compound (42) in the same manner as in Example 6, which afforded 6- (3'-cyclohexyl-1'-oxo-2'-aminopropyl amino) -3- (4 -pyridyl) -2- (-fluorophenyl) -7-aza-indole (43): Mass Spectrum (Cl) 458 (MH +).

Example 25 6- (4'-t-Butoxycarbonyl-1-oxo-2'-t-butoxycarbonyl-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (44) Compound (44) was prepared in the same manner as in Example 5 with the following substitution: Nat-Boc-bt-butylglutamic acid was used in place of Nt-Boc-g-aminobutyric acid, which afforded 6- (4 ') -t-butoxycarbonyl-1'-oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (44) after the preparative plate chromatography: Mass Spectrum (Cl) 590 (MH +).

Example 26 6- (4'-carboxy-1-oxo-2'-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (45) Compound (45) was prepared from compound (44) in the same manner as in Example 6, which afforded 6- (4'-carboxy-1'-oxo-2'-aminobutylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (45): Mass Spectrum (Cl) 434 (MH +). 175 Example 27 6- (3'-0-t-Butoxy-l '-oxo-2'-t-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (46 ) Compound (46) was prepared in the same manner as in Example 5 with the following substitution: Nat-Boc-Ot-butyltreonine was used instead of Nt-Boc-g-aminobutyric acid, which gave 6- (3 '- Ot-butoxy-1 * -oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-azaindole (46) after preparative plate chromatography: Spectrum of Mass (Cl) 562 (MH +). 176 Example 28 6- (3'-hydroxy-l '-oxo-2 * -aminobutylamino) -3- (4-pyridyl) -2- (-fluorophenyl) -7-aza-indole (47) Compound (47) was prepared from compound (46) in the same manner as in Example 6, which afforded 6- (3'-hydroxy-1 * -oxo-2'-aminobutylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (47): Mass Spectrum (Cl) 406 (MH +).

Example 29 177 6- (3'-phenyl-1-oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (48) Compound (48) was prepared in the same manner as Example 5 with the following substitution: Nat-Boc-D, L-phenylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave the 6- (3 '-0-t-butoxy-1-oxo-2' -t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (48) after preparative plate chromatography: Mass Spectrum (Cl) 552 (MH +).

Example 30 6- (3'-phenyl-1-oxo-2'-D, L-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (49) 178 Compound (49) was prepared from compound (48) in the same manner as in Example 6, which afforded 6- (3'-phenyl-1'-oxo-2'-aminopropylamino) -3- (4-pyridyl) ) -2- (4-fluorophenyl) -7-aza-indole (49): Mass Spectrum (Cl) 452 (MH +).

Example 31 6- (3 '- (4-t-butoxyphenyl) -1' -oxo-2'-t-butoxycarbonyl-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza- indole (50) Compound (50) was prepared in the same manner as Example 5 with the following substitution: N-α-t-Boc-O-t-butyltyrosine was used in place of N-t-Boc-g-aminobutyric acid, which provided the 6- (3'- (4-t-Butoxy phenyl) -1' -oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole ( 50) after the 179 preparative plate chromatography: Mass Spectrum (Cl) 624 (MH +). Example 32 6- (3'- (4-hydroxyphenyl) -l'-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (51) Compound (51) was prepared from compound (50) in the same manner as in Example 6, which afforded 6- (3 '- (4-hydroxyphenyl) -1' -oxo-2'-aminopropylamino) -3 - (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (51): Mass Spec (Cl) 468 (MH +).

Example 33 6- (3'-t-Butoxycarbonylamino-l '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (52) 180 Compound (52) was prepared in the same manner as example 5, with the following substitution: N-Boc-b-alanine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (3 '-t-butoxica ._-___ &nt; nilamino-l' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (52) after chromatography on preparative plate: Mass Spectrum (Cl) 476 (MH +).

Example 34 6- (3'-t-amino-1 '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (53) Compound (53) was prepared from compound (52) in the same manner as example 6, which afforded 6- (3'-amino-1'-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (53): Mass Spectrum (Cl) 376 (MH +). 181 Example 35 6- (2'-t-Butoxycarbonylamino-1 '-oxo-et i-lamino) -3- (4-pyridyl) -2- (4-f luorofenyl) -7-aza-indole (54) Compound (54) was prepared in the same manner as Example 5, with the following substitution: N-Boc-glycine was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (2 '- t-butoxycarbonylamino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (54) after preparative plate chromatography: Mass Spectr (Cl) 461 (MH +). 182 Example 36 6- (2'-amino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (55) A solution of HCl-dioxane (4N, anhydrous, 0.27 ml) was added to 6- (2'-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) ) -7-aza-indole (54) (50.0 mg, 0.11 mmol), anisole (59 ml, 0.55 mmol), and dioxane (4 ml) in one portion. After 30 minutes at 23 ° C, the reaction was concentrated under a stream of nitrogen in a hood. The residue was diluted with saturated bicarbonate (30 ml), extracted with ethyl acetate (3 x 50 ml), and dried over sodium sulfate. After concentrating in vacuo, the residue was purified by preparative plate chromatography (two 2-mm silica gel plates, 19: 1 ethyl acetate-methanol) to provide 6- (2'-amino-1 '- oxo-ethylamino) -3- (4- 183 pyridyl) -2- (4-fluorophenyl) -7-aza-indole (55): Mass Spectrum (Cl) 362 (MH +).

Example 37 6- (Methylsulfonylamino) -3- (4-pyridyl) -2- (4-flus-phenyl) -7-aza-indole (56) Methanesulfonyl chloride (5 ml, 0. 07 mmol) dropwise to 6-amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) (20 mg, 0.066 mmol) dimethylaminopyridine (1 mg, 0.007 mmol) , and chloroform (3 ml). After 3 hours at 24 ° C, 4 additional equivalents of methanesulfonyl chloride were added. After 4 hours at 23 ° C, sodium hydroxide (10 N, 3 ml) was added. After 3 hours, the mixture was extracted with (50 ml) of ethyl acetate, washed with water (3 x 15 ml), and dried over sodium sulfate. After concentration in vacuo, the 184 residue was purified by preparative plate chromatography (two 2 mm silica gel plates, ethyl acetate) to provide 6- (methylsulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7 -a __.- indole (56): Mass Spectrum (Cl) 383 (MH +).

Example 38 6- (lf -oxo-etilamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (57) 6-Amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) (50 mg, 0.164 mmol) and acetic anhydride (0.5 ml) were heated at 60 ° C for 1 hour. After cooling to 23 ° C, the reaction was diluted with ethyl acetate (50 ml), washed with sodium hydroxide (1 N, 50 ml), and dried over sodium sulfate. Concentration in vacuo afforded 6- (1-oxo-185) ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (57) after preparative plate chromatography: Mass Spectrum (Cl) 347 (MH +).

Example 39 6- (2 '- (5-chlorothienyl) sulfonylamino) -3- (4-pyridyl) -2- (4-luo-phenyl) -7-aza-indole (58) Compound (58) was prepared in the same manner as example 37 with the following substitution: 5-chlorothienyl-2-sulfonyl chloride (4 equivalents) was used in place of methanesulfonyl chloride which gave 6- (2'-) (5-chlorothienyl) sulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (58) after preparative plate chromatography: Mass Spectrum (Cl) 485 (MH +) . 186 Example 40 6- (Phenylsulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (59) Compound (59) was prepared in the same manner as example 37 with the following substitution: phenylsulfonyl chloride (4 equivalents) was used in place of methanesulfonyl chloride which gave 6- (2 '- (5-chlorothienyl) sulfonylamino ) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (58): Mass Spectrum (Cl) 445 (MH +). 187 Example 41 6- (2'-N-phthaloyl-l '-oxo-ethylamino) -3- (-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (60) Compound (60) was prepared in the same manner as example 5, with the following substitution: N-phthaloylglycine was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (2'-N-) phthaloyl-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (60) after preparative layer chromatography: Mass Spectrum (Cl) 492 ( MH +). 18 8 Example 42 6- (3 r -N-f-aloyl-1 '-oxo-propylamino) -3- (-pyridyl) -2 - (4-fluorophenyl) -7-aza-indole (61) Compound (60) was prepared in the same manner as example 5, with the following substitution: N-phthaloyl-b-alanine was used in place of Nt-Boc-g-aminobutyric acid, which gave the 6- (2 '-N-phthaloyl-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (61) after preparative plate chromatography: Mass Spectrum ( Cl) 506 (MH +). 189 Example 43 3- (4-pyridyl) -2- (4-fluorophenyl) -4,7-diaza-indole (62) 1- (4-fluorophenyl) -2-t-butyldimethylsiloxy-2- (4-pyridyl) ethanone (16) (5.44 g, 15.77 mmol), 2-aminopyrazine (1.00 g, 10.5 mmol), and concentrated HCl (30 g. ml) were heated in a sealed tube at 190 ° C behind an explosion protection. After 3 hours at 190 ° C, the reaction was allowed to cool to 23 ° C and then diluted with water (100 ml). After further dilution with concentrated ammonium hydroxide to pH 12, the reaction was extracted with methylene chloride (3 x 200 ml), and dried over magnesium sulfate. After concentration in vacuo, the residue was purified by flash chromatography (100% ethyl acetate) to provide 3- (4-pyridyl) -2- (4-fluorophenyl) -4,7-diaza-indole ( 62): Mass Spectrum (Cl) 291 (MH +). 190 Example 44 6- (2 '-N-t-Butoxycarbonyl-L-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (63) The compound (63) was prepared in the same manner as example 5, with the following substitution: Nt-Boc-proline was used in place of the Nt-Boc-g-aminobutyric acid, which provided the 6- (2 '- Nt-Butoxycarbonyl-L-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (63) after preparative plate chromatography: Mass Spectrum (Cl) 502 (MH + ). 191 Example 45 6- (2 '-L-propylamino) -3- (-pyridyl) -2- (4-fluorophenyl-7-aza-indole (64) Compound (64) was prepared from compound (63) in the same manner as example 6, whereby 6- (2'-L-propylamino) -3- (4-pyridyl) -2- was provided. (4-fluorophenyl) -7-aza-indole (64): Mass Spectrum (Cl) 402 (MH +).

Example 46 192 6- (2S '-dimethylamino-lf -oxo-propylamino) -3- (A-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (65) Compound (65) was prepared in the same manner as Example 5, with the following substitution: N, N-dimethylalanine was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (2 '- dimethylamino-1 '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (65) after preparative plate chromatography: Mass Spectrum (Cl) 404 ( MH +).

Example 47 6- (2'-dimethylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (66) The compound (66) was prepared in the same manner as example 5, with the following 193 substitution: N, N-dimethylglycine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (2'-dimethylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2 - (4-fluorophenyl) -7-aza-indole (66) after preparative plate chromatography: Mass Spectrum (Cl) 389 (MH +).

Example 48 6- (2'-N-methyl-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (67) The compound (67) was prepared in the same manner as example 5, with the following substitution: N-Boc-N-methyl-glycine was used in place of the Nt-Boc-g-aminobutyric acid, which gave the (2 '-N-methyl-t-butoxycarbonylamino-1' -oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7- 194 aza-indole (67) after preparative plate chromatography: Mass Spectrum (Cl) 476 (MH +). 49 6- (2'-N-methyl-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (68) The compound (68) prepared from compound (67) in the same manner as example 6, which afforded 6- (2'-N-methyl-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2 - (4-fluorophenyl) -7-aza-indole (68): Mass Spectrum (Cl) 376 (MH +). 195 Example 50 6- (4'-N-t-Butoxycarbonyl-1-bispecite-lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (69) Compound (69) was prepared in the same manner as example 5, with the following substitution: N-Boc-isonipecotic acid was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (4 ') -Nt-Butoxycarbonylisonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (69) after preparative plate chromatography: Mass Spectrum (Cl) 516 (MH +).

Example 51 6- (4 '-isonipecoti lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (70) 196 Compound (70) was prepared from compound (69) in the same manner as example 6, whereby 6- (4'-bis-isopi-ethylamino) -3- (4-pyridyl) -2- (4- fluorophenyl) -7-aza-indole (70): Mass Spectrum (Cl) 416 (MH +).

Example 52 6- (4 '-methylsulfoxo-l -oxo-2? S ^ -toxycarbonylamino) 3- (4-pyridyl) -2- (4-phlorophenyl) -7-aza-indole (71) The compound (69) was prepared in the same manner as example 5, with the following substitution: N-Boc-L-methionine sulfoxide (diastereoisomeric mixture) was used instead of Nt-Boc-g-aminobutyric acid, which provided 6- (4 '-methylsulfoxo-1' -oxo-2 'St-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fl orophenyl) -7-aza- 197 indole (71) after preparative plate chromatography: Mass Spectrum (Cl) 552 (MH +).

Example 53 6- (A '-methylsulfoxo-1' -0x0-2 'S-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (72) The compound (72) was prepared from the compound (71) in the same manner as example 6, which gave 6- (4'-methylsulfoxo-1'-oxo-2 'S-aminobutylamino) -3- (4-pyridyl) -2- (4-f luorofenyl) -7-aza-indole (72): Mass Spectrum (Cl) 452 (MH *).

Example 54 6- (3 '- (3-pyridyl) -l -oxo-2' S-t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (73) 198 Compound (73) was prepared in the same manner as example 5, with the following substitution: N-Boc-Lb- (3-pyridyl) -alanine was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (3 '- (3-pyridyl) -1' -oxo-2' St-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (73 ) after preparative plate chromatography: Mass Spectrum (Cl) 553 (MH +).

Example 55 6- (3 '- (3-pyridyl) -1' -oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (74) The compound (74) was prepared in the same manner as the compound (73) in the same manner as example 6, which afforded 6- (3 '- (3-pyridylJ-1'-oxo-2' S-aminopropylamino) -3- (4-pyridyl) -2- (4-199) f luorofenil) -7-aza-indole (74): Mass Spectrum (Cl) 453 (MH +).

Example 56 6- (N, N-Di-t-Butoxycarbonyl-L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (75) Compound (73) was prepared in the same manner as example 5, with the following substitution: 2'-N, N-Di-t-butoxycarbonyl-L-histidine was used in place of Nt-Boc-g-aminobutyric acid , which afforded 6- (2'-N, N-Di-t-Butoxycarbonyl-L-histidinyl) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (74) after preparative plate chromatography: Mass Spectrum (Cl) 642 (MH +). 200 Example 57 6- (L-hi idini lamino) -3- (4-pyridyl) -2- (4'-fluorophenyl) -7-aza-indole (76) Compound (76) was prepared from compound (75) in the same manner as example 6, which afforded 6- (L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) - 7-aza-indole (76): Mass Spectrum (Cl) 542 (MH +).

Example 58 201 6- (Nt-Butoxycarbonyl-3 (S) -l ', 2', 3f, 4 '-tetrahydro-3 • -isoquinoliniloxo-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7 -aza-indole (114) Compound (114) was prepared in the same way as Example 5, with the following substitution: Nt-Butoxycarbonyl-3 (S) 1,2,3,4-tetrahydro-3-isoquinolinylcarboxylic acid was used instead of Nt-Boc-g-aminobutyric acid, which provided 6- (Nt-But-x-carbonyl-3 () 1 ', 2', 3 ', A' - ehydro-3 '-isoquinoliniloxo-amino) -3- ( 4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (114) after preparative plate chromatography: Mass Spectrum (Ci) 564 (MH +).

Example 59 202 6- (3 (S) -l, 2 ', 3,, 4' -tetrahydro-3 '-isoquinoliniloxo-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza- Indole (115) Compound (115) was prepared from compound (114) in the same manner as example 6, which afforded 6- (3 [S) -l ', 2', 3 ', 4'-tetrahydro-3' -isoquinoliniloxoamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indo? (115): Mass Spectrum (Cl) 464 (MH +).

Example 60 6- (2'-phenyl-1-oxo-2 'R-N-t-butoxycarbonylamino-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (116) 203 Compound (116) was prepared in the same manner as example 5, with the following substitution: N-Boc-R-phenylglycine was used in place of Nt-Boc-g-aminobutyric acid, which gave the 6- (2 '-phenyl-1' -oxo-2 'RNt-butoxycarbonylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (116) after preparative plate chromatography: Spectrum of Mass (Cl) 538 (MH +).

Example 61 6- (2'-phenyl-1'-oxo-2'R-aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (117) Compound (117) was prepared from compound (116) in the same manner as example 6, which afforded 6- (2'-phenyl-1'-oxo-2 'R-204 aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7 aza-indole (117): Mass Spectrum (Cl) 438 (MH +).

Example 62 6- (2'-phenyl-1-oxo-2-S-N-t-butoxycarbonylamino-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (118) The compound (118) was prepared in the same manner as example 5, with the following substitution: N-Boc-S-phenylglycine acid was used in place of the Nt-Bo? -g-aminobutyric acid, which gave the (2'-phenyl-1'-oxo-2 'SNt-butoxycarbonylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (118) after preparative plate chromatography: Mass Spectrum (Cl) 538 (MH +). 205 Example 63 6- (2'-phenyl-1-oxo-2 'S-aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (119) Compound (119) was prepared from compound (118) in the same manner as example 6, which afforded 6- (2'-phenyl-1 Xoxo-2 'S-aminoethylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (119): Mass Spectrum (Cl) 438 (MH +).

Example 64 206 6- (2-phenyl-1 '-oxo-2' R-N-t-butoxycarbonyl-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluoro-enyl) -7-aza-indole (120) Compound (120) was prepared in the same manner as example 5, with the following substitution: N-Boc-R-methylphenylglycine was used in place of Nt-Boc-g-aminobutyric acid, which provided the 6- (2 '-phenyl-1' -oxo-2 'RNt-butoxycarbonyl-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (120) after plate chromatography preparation: Mass Spectrum (Cl) 552 (MH +).

Example 65 _- (2'-phenyl-l '-oxo-2' R-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (121) 207 Compound (121) was prepared from compound (120) in the same manner as example 6, which afforded 6- (2'-phenyl-1'-oxo-2 'RN-methylaminoethylamino) -3- ( 4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (121): Mass Spectrum (Cl) 452 (MH +).

Example 66 6- (1'-oxo-2 'S-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (122) Compound (122) was prepared in the same manner as example 5, with the following substitution N-Boc-L-alanine was used instead of Nt-Boc-g-aminobutyric acid, which provided 6- (1 ') -oxo-2'-St-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (122) after preparative plate chromatography: Mass Spectrum (Cl) 476 ( MH +). 208 Example 67 6- (1'-oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (123) Compound (123) was prepared from compound (122) in the same manner as Example 6, which provided 6- (1-oxo-2'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (123): Mass Spectrum (Cl) 376 (MH +).

Example 68 6- (3'-phenyl-lf -oxo-2 '- (L) -t-butoxycarbonylamino-pramino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (124 ) The compound (124) was prepared in the same manner as example 5, with the following 209 substitution; N-Boc-L-phenylalanine was used instead of Nt-Boc-g-aminobutyric acid, which gave 6- (3'-phenyl-1'-oxo-2 '- (L) -t-butoxycarbonylaminopramino) - 3- (4-pyridyl) -2- (4-fluorophenyl) -7-azanedol (124) after preparative plate chromatography: Mass Spectrum (Cl) 552 (MH +) - Example 69 6- (3'-phenyl-1-oxo-2f- (L) -aminopramino) -3- (4-pyridyl) -2- (4-oxo-phenyl) -7-aza-indole (125) Compound (125) was prepared from compound (124) in the same manner as example 6, which afforded 6- (3'-phenyl-1'-oxo-2 '- (L) -aminopramino) - 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (125); Mass Spectrum (Cl) 452 (MH +). 210 Example 70 6- (l -oxo-2 'S-t-butoxycarbonyl-N-methylaminopr-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (126) The compound (126) was prepared in the same manner as example 5, with the following substitution; N-Boc-LN-methylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (3'-phenyl-1'-oxo-2 '- (L) -t-butoxycarbonylaminopramino) -3 - (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (126) after preparative plate chromatography: Mass Spectrum (Cl) 489 (MH +). 21 1 Example 71 6- (1-oxo-2 'S-N-methylaminopramino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (127) Compound (127) was prepared from compound (126) in the same manner as example 6, which afforded 6- (1'-oxo-2'-N-methylaminopramino) -3- (4-pyridyl) ) -2- (4-fluorophenyl) -7-aza-indole (127): Mass Spectrum (Cl) 389 (MH +).

Example 72 212 6- (1'-oxo-2 'St-butoxycarbonyl-N-methyl-4-methyl) -2-aminopentyl-amino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole (128) The compound (128) was prepared in the same manner as example 5, with the following substitution: N-Boc-LN-methyl-leucine was used in place of the Nt-Boc-g-aminobutyric acid, which gave the (1 '-oxo-2' St-butoxycarbonyl-N-methyl-4-methyl) -2-aminopentylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole (128) after of preparative plate chromatography: Mass Spectrum (Cl) 532 (MH +).

Example 73 6- (1'-oxo-2 'S-N-methyl-4-methy1-2-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (129) 213 Compound (129) was prepared from compound (128) in the same manner as example 6, which afforded 6- (1'-oxo-2 'SN-methyl-4-methyl-2-aminopentylamino) - 3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole (129): Mass Spectrum (Cl) 432 (MH +).

Example 74 6- (1-oxo-2 'R-t-butoxycarbonylaminopramino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole (130) Compound (130) was prepared in the same manner as Example 5, with the following substitution: N-Boc-D-alanine was used in place of Nt-Boc-g-aminobutyric acid, which gave the 6- (1 '-oxo-2' Rt-butoxycarbonylamino-pramino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-214 indole (130) after preparative plate chromatography: Mass Spectrum (Cl) 476 (MH +).

Example 75 6- (1'-oxo-2 'R-aminopramino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (131) Compound (131) was prepared from compound (130) in the same manner as example 6, which afforded 6- (1'-oxo-2 'R-aminopramino) -3- (4-pyridyl-2) - (4-fluorophenyl) -7-aza-indole (131): Mass Spectrum (Cl) 376 (MH +). 215 Example 76 6- (3f- (2-thienyl) -l'-oxo-2 '(L) -t-butoxycarbonyl-aminoprane) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza- indole (132) Compound (132) was prepared in the same manner as Example 5, with the following substitution: N-Boc-Lb- (2-thienyl) -alanine was used in place of Nt-Boc-g-aminobutyric acid, which provided 6- (3 '- (2-thienyl) -1' -oxo-2' (L) -t-butoxycarbonylaminopramino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza- indole (132) after preparative plate chromatography: Mass Spectrum (Cl) 558 (MH +). 216 Example 77 6- (3 '- (2-thienyl) -l' -oxo-2' - (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (133 ) Compound (133) was prepared from compound (132) in the same manner as Example 6, which afforded 6- (3'- (2-thienyl) -l'-oxo-2'- (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (133): Mass Spectrum (Cl) 458 (MH +).

Example 78 6- (3 '- (4-Azidophenyl) -1' -oxo-2 'St-butoxycarbonyl-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (134) 217 The compound (134) was prepared in the same manner as example 5, with the following substitution: (3 '- (4-azidophenyl) -1'-oxo-2' St-butoxycarbonylaminopropionic acid was used instead of Nt- Boc-g-aminobutyric, which provided 6- (3 '- (4-azidophenyl) -1' -oxo-2 'St-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) - 7-aza-indole (134) after preparative plate chromatography: Mass Spectrum (Cl) 609 (MH +).

Example 79 6- (3 * - (4-azidophenyl) -1"-0X0-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (135) The compound (135) was prepared from the compound (134) in the same manner as example 218 6, which afforded 6- (3 '- (4-azidophenyl) -1' -oxo-2' S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza- indole (135): Mass Spectrum (Cl) 509 (MH +).

Example 80 6- (3f - (3-benzothienyl) -1' -oxo-2 'S-t-butoxycarbonyl-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (136) The compound (136) was prepared in the same manner as example 5, with the following substitution: 3- (3'-benzothienyl) -1-oxo-2S-t-butoxycarbonylaminopropionic acid was used in place of the Nt-Boc acid. g-aminobutyric, which provided 6- (3 '- (3-benzothienyl) -1' -oxo-2 'St-butoxycarbonyl-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) - 7- 219 aza-indole (136) after preparative plate chromatography: Mass Spectrum (Cl) 608 (MH +).

Example 81 6- (3 '- (3-benzothienyl) -lf -0x0-2' S-aminopropylamino) -3- (4-pyridyl) -2- (-fluorophenyl) -7-aza-indole (137) Compound (137) was prepared from compound (136) in the same manner as example 6, which afforded 6- (3 '- (3-benzothienyl) -1' -oxo-2' S-aminopropylamino) -3- (4-Pyridyl) -2- (4-fluorophenyl) -7-aza-indole (137): Mass Spectrum (Cl) 508 (MH +). 220 Example 82 6- (4'-phenyl-1-oxo-2'- (L) -t-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (138) Compound (138) was prepared in the same manner as example 5, with the following substitution: Nat-Boc-L-homophenylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (4 '-phenyl-1' oxo-2 '- (L) -t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (138) after plate chromatography Preparation: Mass Spectrum (Cl) 566 (MH +). 221 Example 83 6- (4'-pheny1-1 'oxo-2' - (L) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (139) Compound (139) was prepared from compound (138) in the same manner as example 6, which afforded 6- (4'-phenyl-1 'oxo-2' - (L) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (139): Mass Spec (Cl) 466 (MH +).

Example 83B 222 -bromo-3- (4-pyridyl) -2- (3-trifluoromethylphenyl) indole 3- (4-pyridyl) -2- (3-trifluoromethylphenyl) -indole was treated with NBS in the same manner as 6-amino-5-bromo-3- (4-pyridyl) -2- (-fluorophenyl) -7-aza-indole to provide the title compound Mass Spectrum (Cl) 417 (MBr81-H).

Example 84 6- (4'-phenyl-1 'oxo-2' - (D) -t-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (140) Compound (140) was prepared in the same manner as example 5, with the following substitution: Nat-Boc-D-homophenylalanine was used in place of Nt-Boc-g-aminobutyric acid, which gave 6- (4 '-phenyl-1' oxo-2 '- (D) -t- 223 butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (140) after preparative plate chromatography: Mass Spectrum (Cl) 566 (MH +).

Example 85 6- (4'-phenyl-1 '-oxo-2' - (, D) -aminobutylamino) -3- (4-pyridyl) -2- (4-flnorofeni 1) -7-aza-indole (141) Compound (141) was prepared from compound (140) in the same manner as example 6, which afforded 6- (4'-phenyl-1'-oxo-2 '- (D) -aminobutylamino) - 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (141): Mass Spec (Cl) 466 (MH +). 224 Example 86 6- (2 * -amino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -1-isobutoxycarbonyl-7-aza-indole (143) 6- (2'-Butoxycarbonylamino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -1-isobutoxycarbonyl-7-aza-indole (29) (50 mg, 0.108 mmol), isobutyl chloroformate (42 ml, 0.325 mmol), N-methylmorpholine (119 ml, 1.08 mmol), potassium carbonate (74.9 mg, 0.542 mmol), and DMF (4 ml), were heated to 80 ° C by 16 hours. After cooling to 23 '> C, the reaction was diluted with 20 ml of water, extracted with ethyl acetate (2 x 20 ml) and dried over sodium sulfate. After concentration in vacuo, the residue was purified by preparative plate chromatography to 225 provide 6- (2'-t-butoxycarbonylamino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -1-isobutoxycarbonyl-7-aza-indole (142). Compound (104) was converted to 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutoxycarbonyl-7-aza-indole ( 143) in the same manner as in Example 6: Mass Spectrum (Cl) 462 (MH +).

Example 87 6- (Phenylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (144) 6-Amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) (100 mg, 0.329 mmol), benzaldehyde (100 mL, 0.987 mmol), and 1.2 Dichloroethane (20 ml) was allowed to stir for 15 minutes followed by the addition of sodium triacetoxyborohydride (139 mg, 0.658 mmol) as a solid. After 16 hours at 226 23 ° C, the reaction was partitioned between ethyl acetate (200 ml) and saturated bicarbonate (80 ml). The organic layer was washed with 80 ml of brine, and dried over sodium sulfate. After concentration in vacuo, a portion of the residue was purified by preparative chromatography to provide 6- (phenylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (144): Spectrum of Mass (Cl) 395 (MH +).

Example 88 6- (diethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (145) Compound (145) was prepared in the same manner as example 87, with the following substitution: acetaldehyde was used in place of benzaldehyde thereby affording 6- (diethylamino) -3- (4-pyridyl) -2- ( 4-fluorophenyl) -7-aza- 227 indole (145) after preparative plate chromatography: Mass Spectrum (Cl) 361 (MH +).

Example 89 6- (3'-phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (146) Compound (146) was prepared in the same manner as example 87, with the following substitution: phenylhydrocinnamaldehyde was used in place of benzaldehyde thereby providing 6- (3'-phenylpropylamino) -3- (4-pyridyl) -2 - (4-fluorophenyl) -7-aza-indole (146) after preparative plate chromatography: Mass Spectrum (Cl) 423 (MH +). 228 Example. 90 6- (2 '(R, S) -phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (147) Compound (147) was prepared in the same manner as example 87, with the following substitution: 2'-phenylpropionaldehyde was used in place of benzaldehyde thereby providing 6- (2 '(R, S) -phenylpropylamino) - 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (147) after preparative plate chromatography: Mass Spectrum (Cl) 423 (MH +). 229 Example 91 6- (2 '(R, S) -eti-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (148) Compound (148) was prepared in the same manner as example 87, with the following substitution: 2'-ethylhexanaldehyde was used in place of benzaldehyde, thereby providing 6- (2 '(R, S) -ethylhexy lamino ) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (148) after preparative plate chromatography: Mass Spectrum (Cl) 417 (MH +). 230 Example 92 6-Amino-5-chloro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indol (149) Compound (149) was prepared in the same manner as Example 3, with the following substitution: 3-chloro-2,6-diaminopyridine was used instead of 2,6-diaminopyridine, thereby providing 6-Amino- 5-Chloro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (149) after flash chromatography: Mass Spectrum (Cl) 439 (MH +). 231 Example 93 6-Amino-5-fluoro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (28) 6-Amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) (250 mg, 0.822 mmol), N-fluorobenzenesulfonamide (259 mg, 0.822 mmol) and DMF ( 4 ml) were heated to 90 ° C behind an explosion protection. After 48 hours, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (ethyl acetate: hexane 1: 1) to give 6-Amino-5-fluoro-3- (4-pyridyl) -2- ( 4-fluorophenyl) -7-aza-indole (28): Mass Spectrum (Cl) 323 (MH +). 232 Example 94 6-Amino-5-bromo-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (27) 6-Amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17) (250 mg, 0.822 mmol), N-bromosuccinamide (146 mg, 0.822 mmol) and DMF ( 4 ml) were heated to 90 ° C behind an explosion protection. After 24 hours, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (ethyl acetate: hexane 1: 1) to give 6-Amino-5-bromo-3- (4-pyridyl) -2- ( 4-fluorophenyl) -7-aza-indole (27): Mass Spectrum (Cl) 385 (MH + Br? L). 233 Example 95 6- (di-isoamylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (150) Compound (150) was prepared in the same manner as example 87, with the following substitution: 3-methylbutyraldehyde was used in place of benzaldehyde, which provided 6- (di-isoamylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole (150) after preparative plate chromatography: Mass Spectrum (Cl) 445 (MH +). 2. 3. 4 Example 96 6- (2 ', 2'-dimethyl-1-propylamino) -3- (4-pyridyl) -2- (4-fluorsphenyl) -7-aza-indol (151) Compound (151) was prepared in the same manner as Example 87, with the following substitution: pivaldehyde was used in place of benzaldehyde, thereby providing 6- (2 ', 2'-dimethylpropylamino) -3- (4 -pyridyl) -2- (4-fluorophenyl) -7-aza-indole (151) after preparative plate chromatography: Mass Spectrum (Cl) 475 (MH +). 235 Example 97 6- (isoamylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (152) Compound (152) was prepared in the same manner as example 87, with the following substitution: 3-methylbutyraldehyde was used instead of benzaldehyde, which provided 6- (isoamylamino) -3- (4-pyridyl) -2 - (4-fluorophenyl) -7-aza-indole (152) after preparative plate chromatography: Mass Spectrum (Cl) 375 (MH +).

Example 98 236 6- (2'-Ethylbutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indoI (15) Compound (153) was prepared in the same manner as example 87, with the following substitution: 2-ethylbutyraldehyde was used instead of benzaldehyde, thereby providing 6- (2'-ethylbutylamino) -3- (4- pyridyl) -2- (4-fluorophenyl) -7-aza-indole (153) after preparative plate chromatography: Mass Spectrum (Cl) 389 (MH +).

Example 99 6- (2'-thieni lmeti lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (154) The compound (154) was prepared in the same manner as example 87, with the following substitution: 2-thiophene-carboxaldehyde was used in 237 place of the benzaldehyde, thereby affording 6- (2'-thienylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (154) after preparative plate chromatography: Mass Spectrum (Cl) 401 (MH +).

Example 100 6- (3 ', 3' -diphenylpropylamino) -3- (4-pyridyl) -2- (4'-fluorophenyl) -7-aza-indole (155) Compound (155) was prepared in the same manner as example 87, with the following substitution: phenylhydrocinnamaldehyde was used, instead of benzaldehyde, which provided 6- (3 ', 3'-di-phenylpropylamino) -3- ( 4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (155) after preparative plate chromatography: Mass Spectrum (Cl) 541 (MH +). 238 Example 101 6- (Ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (156) Compound (156) was prepared in the same manner as example 87, with the following substitution: acetaldehyde was used in place of benzaldehyde, thereby providing 6- (diethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (156) after preparative plate chromatography: Mass Spectrum (Cl) 361 (MH +).

Example 102 239 6- (3'-phenyl-1 '-oxo-2' - (R, S) -methylpropilamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (157) Compound (157) was prepared in the same manner as Example 5, with the following substitution: 3-phenyl-2-methylpropionic acid was used in place of Nt-Boc-g-aminobutyric acid, thereby providing the 6- (3'-pheny1-1 '-oxo-2' - (R, S) -methylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (157) after preparative plate chromatography: Mass Spectrum (Cl) 451 (MH +).

Example 103 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4'-fluorophenyl) -7-aza-indole (158) 240 To a solution of 6- (2'-t-butoxycarbonylamino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (29) (50.0 mg, 0.108 mmol), triphenylphosphine (85 mg, 0.325 mmol), methanol (13 ml, 0.791 mmol) and methylene chloride (5 ml) were added diethyl azodicarboxylate (51 ml, 0.325 mmol) at 0 ° C. The reaction was allowed to warm to 23 ° C. After 2.5 hours, 2 additional equivalents of methanol, triphenylphosphine and diethyl azodicarboxylate were added. After 16 hours, the reaction was concentrated in vacuo and the residue was purified by preparative plate chromatography to provide 6- (2'-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) - 2- (4-fluorophenyl) -1-methyl-7-aza-indole (30) which was converted to 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2 - (4-fluorophenyl) -7-aza-indole (158), as described in Example 6: Mass Spectrum (Cl) 376 (MH +).

Example 104 241 6- (3 ', 3' -dimethyl-1 '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (159) The compound (159) was prepared in the same manner as example 5, with the following substitution: 3, 3-dimethylbutyric acid was used in place of the Nt-Boc-g-aminobutyric acid, thereby providing the 6- (3 ', 3' -dimethyl-1 '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (159) after preparative plate chromatography: Mass Spectrum (Cl) 403 (MH +).

Example 105 6- (ethoxycarbonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (160) The compound (160) was obtained as a collateral product of example 104, wherein a 242 small amount of the unreacted ethyl chloroformate resulted in the acylation of the 6-amino functional group to provide 6- (ethoxycarbonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (160 ) after preparative plate chromatography: Mass Spectrum (Cl) 377 (MH +).

Example 106 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4'-fluorophenyl) -l-methyl-7-aza-indole (161) Compound (161) was prepared in the same manner as example 87, with the following substitution: 6- (2 'St-butoxycarbonyl-amino-1'-oxo-propylamino) -3- (4-pyridyl) - 2-4-fluorophenyl) -7-aza-indole instead of 6- (2'-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7 -aza-indole, with which 243 provided 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (161) after preparative plate chromatography : Mass Spectrum (Cl) 390 (MH +).

Example 107 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutyl-7-aza-indole (162) The compound (162) was prepared in the same manner as example 87, with the following substitutions: 6- (2'S-t-butoxycarbonylamino-1'-oxo-propylamino) -3- (4-pyridyl) -2- was used (4-fluorophenyl) -7-aza-indole instead of 6- (2'-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7- aza-indole and isobutanol was used in place of methanol, which gave 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- 244 (4-fluorophenyl) -l-isobutyl-7-aza-indole (162) after preparative plate chromatography: Mass Spectrum (Cl) 432 (MH +).

Example 108 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-cyclohexylmethyl-7-aza-indole (163) Compound (163) was prepared in the same manner as example 87, with the following substitutions: 6- (2'S-t-butoxycarbonylamino-1'-oxo-propylamino) -3- (4-pyridyl) -2- was used (4-fluorophenyl) -7-aza-indole instead of 6- (2'-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza -indole and cyclohexylmethanol was used instead of methanol, which gave 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutyl-7-aza-indole (163) after the preparative plate chromatography: Mass Spectrum (Cl) 472 (MH +).

Example 109 Using the procedures of the above general description and the above examples, the compounds of Tables 1-7 can be prepared. Table 1 R 4] 4-Butyl CH methyl C-CH 3 Ethyl N ethyl C-CH (OH) CH 3 Propyl CH propyl C-CH.OH Isopropyl N isopropyl C-N (CH 3) _ Hydroxymethyl N-hydroxymethyl C-OCH 3 Hydroxyetik > CH hydroxyethyl C-CH3 Benzyl N-benzyl C-OCF3 246 4-methoxybenzyl N 4-methoxybenzyl - C-OH 4-iodobenzyl CH 4 -iodobenzyl C-CH3 4-pyridylmethyl N 4 -pyridylmethyl C-CH 3 3-pyridylmethyl CH 3 -pyridimethyl C-OH 2-pyridylmethyl N 2 -pyridylmethyl C-? CH3 Methylthioethyl N-methylthioethyl C-CF3 Methylsulfonylethyl CH methylsulphonylethyl C-F methylsulililethyl N methylsulinthylethyl C-CH (OH) CH3 imidazolylmethyl C-CH3 Imidazolylmethyl C-OCH3 Table 2 4-pyridyl C-F 4- (2-aminoimidazoyl) C-CH3 4-pyridyl N 4- (2-aminoimidazoik >) C-CH (OH) CH 3 4-pyridyl C-Br 4-quinolinyl C-CH2OH 4-quinolinyl N 4 -pyridyl C-N (CH 3) 2 4- (2-aminopyridyl) C-F 4-pyridyl C-OCH3 4- (2-aminopyridyl) C-CF3 4-quinolinyl C-CH3 4- (2-aminopyridyl) N 4 -pyridyl C-OCF3 4-quinolinyl C-F 4 -pyridyl C-OH 247 -quinolinyl C-CF3 4- (2-aminopyridyl) C-CH 3 -pyridyl > C-Ph 4-pyridyl C-CH 3 -quinolinyl C-Ph 4-quinolipyl C-OH - (2-aminopyridyl) C-Ph 4-quinolinyl C-OCH 3 -quinolinyl C-Cl 4-pyridyl C-CF 3 - (2- aminopyridyl) C-Cl 4- (2 -acetamyldopyridyl) CF - (2-aminoimidazoyl) CF 4 -pyridyl? C-CH (OH) CH 3 - (2-aminoimidazo_Lo) C-Br 4- (2-aminoimidazoik-) C-OCH 3 -pyrimidinyl C-CF 3 4-pyrimidinyl C-CH 3 -pyrimidini. N 4-pyrimidinyl C-OH-pyrimidinyl C-F 4-pyrimidinyl C-OCH 3 -pyrimidinyl C-Cl 4-pyrimidinyl C-CH (OH) CH 3 -pyrimidinyl C-Ph 4-pyrimidinyl C-Br Table 3 -pihdyl-NH2 4- (2-aminoimidazoyl) -CH 3 -pyridyl-NHPh 4- (2-aminoimidazoyl) -Ph -pyridyl-NHCH 3 4-quinolinyl -Ph -quinolinyl-NH (4-MeOPh) 4-pyridyl -Ph 248 - (2-aminopyridyl) -NH2 4-pyridyl 2-thienyl- (2-aminopirtidyl) -NHPh 4-quiniluyl -CH2NH2 - (2-aminopyridyl) -NHCH3 4-pyridyl n-Bu -quinolinyl -NH2 4-pyridyl -CH2N (CH3) 2-u? Nilinyl-NHPh 4- (2-aminopyridyl) -CH3-pyridyl-NH (4-MeOpH) 4-pyridyl-CH3-quinnyl-CH2N (CH3) -2-quinolinyl-CH3 - ( 2-aminopyridyl) -CH 2 N (CH 3) 2 4-quino-nyl-n-propyl -quinilinyl -CH 2 CH 2 N (CH 3) 2 4-pyridyl-CH 2 CH 2 N (CH 3) 2 - (2 -arainopyridyl) -CH_NH 2 4- (2-acetamidopyridyl) CH 2 CH 2 N ( CH3) 2 - < 2-aminoimidazoyl) -CH 2 CH 2 N (CH 3) 2 4-pyridyl-CH 2 NH 2 - (2-aminoimidazoyl) -CH 2 N (CH 3) 2 4- (2-aminopyridyl) -CH 2 NH 2 -pyridiminyl. NH2 4-pyridyminyl 2-thienyl-pyridiminyl-NHPh 4-pyridinimyl-CH2NH2-pyridiminyl-HCH3 4-pyridinyl-n-Bu-pyridiminyl-NH (4-MeOPh) 4-pyridinimino-CH2N (CH3) 2-pyridiminyl -Ph 4 -pyridiminyl -CH3 Table 4 "-10 R 10 249 Methyl CH-methyl-CH3 Ethyl N ethyl C-CH (OH) CH3 Propyl CH propyl C-CH2OH Isopropyl N isopropyl C-N (CH3) 2 -C (0) Ph N benzyl C-OCH3 -C (0) NH2 CH -C (0) NH2 C-CH3 Benzyl N 4-methoxybenzyl C-OCF3 4-methoxybenzyl N 4-iodobenzyl C-OH -C (0) NHPh CH 4-pyridrlmethyl C-CH3 -C (0) NHEt N 3-pyridylmethyl C-CH3 -C (0) Ph CH C (0) Ph C-OH -C (0) NH2 N -C (0) NHEt C-OCH3 Methyl N ethyl C-CF3 Ethyl CH methyl C-F Isobutyl N -C (0) NH2 C-CH (OH) CH3 Methyl C-CH3 methyl-OCH3 Table 5 > -12 «• 12 250 phenyl CH 3 -chlorophenyl -CH 3 phenyl N 3-chlorophenyl C-CH (OH) CH 3 3-chlorophenyl CH 4-fluorophenyl C-CH 2 OH 3-ck > Rophenyl N 4-fluorophenyl • C-N (CH 3) 2 4-fluorophenyl N 4 -methylthioyl- C 7 OCH 3 4-fluorophenyl CH 3-methylthiophenyl C-CH 3 1 - . 1 - . 1-naphthyl N 3 -methylsulfinylphenyl C-OCF3 - N-4-cyanophenyl C-OH naphthyl 3-methylthiophenyl CH 4 -carboxamidophenyl C-CH 3 3-Methylthiaphenyl N 4-fluorophenyl C-CH 3 t -naphthyl CH 3,4-dichlorophenyl C-OH 3,4-dichlorophenyl N 3-methylthiophenyl C-OCH 3 3 - . 3-trifluoromethylphenolyl N-3,4-dichlorophenyl C-CF3 3,4-dichlorophenyl CH 4-fluorophenyl C-F 4-methoxyphenyl N 4-methoxyphenyl C-CH (OH) CH 3 4-methoxyphenyl C-CH3 4-methoxyphenyl C-OCH3 Table 6 R »? R41 251 Methyl CF Methyl C-CH3 -CHz Hz - N -CH2NH2 C-CH (OH) CH3 2- (5-chlorothie_) C-Br 2- (5-chlorothienyl) C-CH 2 OH -CH2NMe2 N -CH2NMe2 C-N (CH3) 2 phenyl C-F Phenyl C-OCH3 methyl C-CF3 Methyl C-CH3 1 -naphthyl N 1 -naphthyl C-OCF. 2- (5-chlorothienyl) C-F 2- (5-chlorothienyl) C-OH -CH2CH2NH2 C-CF3 -CH2CH2NH2 C-CH3 phenyl C-Ph 4-carboxymethylphenyl C-CH3 methyl C-Ph 4-n-butoxyphenyl C-OH -CH2NH2 C-Ph, 1-naphthyl C-OCH3 phenyl C-Cl Methyl C-CF3 methyl C-Cl -CH2NH2 C-F. methyl C-F Methyl C-CH (OH) CH3 -CH2NH2 C-Br -CH2CH2NH2 C-OCH3 n-butyl C-CF3 3- (1-piperidinyl) propyl C-CH3 4-methoxyphenyl N 3 - (1-piperizinyl) pcopyl C-OH 4-Cyanophenyl C-F 2- (5-chlorothienyl) C-OCH 3 4-n-butoxyphenyl c-a. -CH2NH2 C-CH (OH) CH3 methyl C-Ph n-butyl C-Br 252 Table 7? 2? 3? 3 -C-C (0) Ph C-F N • C-CH3 -C-C (0) NHMe N C-F C-CH (OH) CH3 -C-C (0) NHMe C-Br C-CF3 C-CH.OH -C-S- (02) -Et N N C-N (CH3) 2 -C-C (0) -Bu C-F C-Br C-OCH3 -CH C-CF3 N C-CH3 -C-S (02) -NHEt N -CH C-OCF3 -C-NH-S (02) -NHCH3 C-F -CH C-OH -C-C (02) Me C-CF3 C-C (02) Me C-CH3 -CH C-Ph -CH C-CH3 -C-S (02) -Et C-Ph. -CH C-OH -C-C (0) Ph C-Ph C-NHEt C-OCH3 CH C-Cl -CH C-CF3 -C-NHEt C-Cl -CH C-F -C-NHPr C-F -CH C-CH (OH) CH3 -CH C-Br -CH C-OCH3 -C-NHMe C-CF3 -CH C-CH3 253 -C-C (0) NHPh. N C-C (0_) Me C-OH -C-N (Me) -C (0) -Me C-F C-F-C-OCH3 -C-N-S (02) Me C-Cl C-CF3 C-CH (OH) CH3 -C-NHEt C-Ph C-S (02) -Et C-Br Table 8 3 254 Table 9? 2? 3? 3 -C-NH-C (0) -Me C-F N C-CH3 -C-C (0) NHMe N C-F -CH (OH) CH3 -C-C (0) NHMe C-Br C-CF3 C-CH2OH -C-NH-S (02) Me N N C-N (CH3) 2 -C-C (0) -Bu C-F C-Br C-OCH3 -CH C-CF3 N C-CH3 -C-NH (CO) CH2NH2 N -CH C-OCF3 255 C-NH-C (0) CH (Me) NH 2 C-F -CH C-OH C-C (C_) Me. C-CF3 C-C (C_) Me C-CH3 CH C-Ph -CH C-C (0) H C-S (02) -Et C-Ph -CH C-OH C-C (0) Ph C-Ph C-NHEt C-OCH3 CH C-Cl -CH C-CF3 C-NHEt C-Cl-CH. C-F C-NHPr C-F -CH C-CH (OH) CH3 CH C-Br -CH C-OCH3 C-NHMe C-CF3 -CH C-CH3 C-C (0) NHPh N C-C (02) Me C-OH C-NH-S (C_) Me C-F C-F C-OCH3 C-N-S (02) Me C-Cl C-CF3 C-CH (OH) CH3 C-NHEt C-Ph C-S (02) -Et C-Br Table 10 -C-NH-C (0) Me C-F N C-CH3 256 C-C (0) NHMe N C-F C-CH (OH) CH3 -C-C (Q) NHMfi C-Br C-CF3 C-CH 2 OH -C-NH-S- (02) Me N N C-N (CH 3) 2 -CC (0) -Bu CF C-Br C-OCH3 -CH C-CF3 N »-.- CH3 -C-NH (C0) CH2NH2 N -CH C-OCF3 -C-NH-C (0) CH ( Me) NH2 CF -CH C-OH-CC (02) Me C-CF3 CC (02) Mfi C-CH3 -CH C-Ph -CH CC (0) H -CS (02) -Et C-Ph -CH C-OH-CC (0) Ph C-Ph C-NHEt C-OCH 3 -CH C-Cl -CH C-CF 3 -C-NHEt C-Cl -CH CF -C-NHPr CF -CH C-CH (OH ) CH3 -CH C-Br -CH-C-OCH3 -C-NHMe C-CF3 -CH C-CH3 -CC (0) NHPh N CC (02) Me C-OH -C-NH-S (02) Me CF CF C-OCH3 -CNS (02) Me C-Cl C-CF3 C-CH (OH) CH3 -C-NHEt C-Ph C-S (02) -Et C-Br Example 110 The following tests were used to characterize the ability of 257 compounds the invention to inhibit the production of TNF-a and IL-1-β. The second assay measured the inhibition of TNF-α and / or IL-1β in mice after oral administration of the test compounds. The third assay, an in vitro assay of glucagon binding inhibition, can be used to characterize the ability of the compounds of the invention to inhibit glucagon binding. The fourth assay, an in vitro assay of inhibition activity of the enzyme Cyclooxygenase (COX-1 and COX-2), can be used to characterize the ability of the compounds of the invention to inhibit COX-1 and / or COX-2 .

Assay of production of TNF in monocytes activated by lipopolysaccharides.

Isolation of monocytes The test compounds were evaluated in vitro for the ability to inhibit the production of tumor necrosis factor (TNF) by monocytes activated with bacterial lipopolysaccharide (LPS). Fresh leukocytes from residual source (a by-product of plaquetoferesis) were obtained 258 from a local blood bank and peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation on Ficol-Paque Plus (Pharmacia). The PBMCs were suspended at 2 x 106 / ml in DMEM supplemented to contain 2% FCS (10 mM); 0.3 mg / ml glutamate, 100 U / ml penicillin G and 100 mg / ml streptomycin sulfate (complete medium). Cells were placed in flat bottom Falcon 96-well culture plates (200 μl / well) and cultured overnight at 37 ° C and 6% C02. The non-adherent cells were removed by washing with 200 μl / well of fresh medium. Wells containing adherent cells (~ 70% monocytes) were again filled with 100 μl of fresh medium.

Preparation of reserve solutions of the test compound The test compounds were dissolved in DMZ Reserve solutions of the compound were prepared at an initial concentration of 10-50 μM.

The stocks were initially diluted to 20-200 μM in complete medium. Then nine 259 were prepared serial dilutions, of each compound, in complete medium.

Treatment of cells with the test compounds and production activation in TNF with lipopolysaccharide One hundred microliters of each dilution of the test compound were added to microtiter wells containing adherent monocytes and 100 μl of complete medium. The monocytes were cultured with the test compounds for 60 minutes, at which time 25 μl of complete medium containing 30 ng / ml lipolisaccharide from E. coli K532 was added to each well. The cells were cultured in an additional period of 4 hours. The culture supernatants were then removed and the TNF present in the supernatants was quantified using an ELISA assay.

TNF ELISA High Bond ELISA plates, Corning 96 wells, flat bottom, were coated overnight (4 ° C) with 150 μl / well of 3 μg / ml of murine human anti-TNFα monoclonal antibody (R & D Systems 260 # MAB210). The wells were then blocked 1 h at room temperature with 200 μl / well of buffer for CaCl2-free ELISA, supplemented to contain 20 mg / ml of BSA (standard buffer for ELISA: 20 mM, 150 mM NaCl, 2 ml. CaCl2, 0.15 mM thimerosal, pH 7.4). Plates were washed and re-filled with 100 μl of test supernatants (diluted 1: 3) or standard. The standards consisted of eleven serial dilutions at 1.5 times from a stock of 1 ng / ml recombinant human TNF (R &D Systems). The plates were incubated at room temperature for 1 hour on an orbital shaker (300 rpm), washed and refilled with 100 μl / well of goat anti-human TNFa antibody at 0.5 μg / ml (R &D systems # AB-210-NAJ biotinylated at a 4: 1 ratio Plates were incubated for 40 minutes, washed and refilled with 100 μl / well of conjugated streptavidin alkaline phosphatase (Jackson Im One Research # 016-050-084 ) at 0.02 μg / ml Plates were incubated 30 minutes, washed and refilled with 200 μl / well of 1 mg / ml p-nitrophenyl phosphate.After 30 minutes, the plates were read at 405 nm on a Vmax plate reader. 261 Analysis of data The data from the standard curve were adjusted to a second-order polyand the unknown concentrations of TNF-a were determined from their optical density by solving this equation for the concentration. The concentrations of TNF were then plotted versus the concentration of the test compound using a second order polynomial. This equation was then used to calculate the concentration of the test compounds causing a 50% reduction in TNF production. The following compounds had an IC50 less than 20 μM: 3- (4-pyridyl) -2- (4-fluorophenyl) indole (3); 6-amino-3- (4-fluorophenyl) -2- (4-pyridyl) -7-aza-indole (18); 6- (4'-t-Butoxycarbonylamino-1 '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (21); 6- (4'-amino-1'-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (22); 6- (5'-ureido-1 '-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (64); 6- (5'-ureido-1-oxo-2 '-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (65); 6- (6'-t-butoxycarbonylamino) -1 '-oxo-2' -t- 262 butoxycarbonylaminohexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (66); 6- (6'-amino-1 '-oxo-2'-aminohexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (67); 6- (4'-amino-1'-oxo-butylamino) -3- (4-pyridyl) -2- (4-flu-phenyl) -7-aza-indole (22); 6- (5'-t-Butoxycarbonylamino-1 '-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (68); 6- (5'-amino-1 '-oxo-2'-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (69); 6- (3 '-methyl-1' -oxo-2'-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (73); 6- (4 ', 4'-dimethyl-1' -oxo-2'-aminopentylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole (75); 6- (5'-amino-1'-oxo-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (77); 6- (6'-amino-1-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (79); 6- (3'-Cyclohexyl-1 '-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (81); 6- (4 '-carboxy-1' -oxo-2'-aminobutylamino) -3- (4-pyridyl) -2- (4-flurophenyl) -7-aza-indole (83); 6- (3f-hydroxy-1'-oxo-2-r-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (85); 6- (3'-phenyl-1 '-oxo-2'-D, L-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (87); 6- (3 '-amino-1' -oxo-propylamino) -3- (4-263 pyridyl) -2- (4-fluorophenyl) -7-aza-indole (91); 6- (2'-t-Butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (29); 6- (methylsulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (93); 6- (1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (94); 6- (2 '- (5-chlorothienyl) sulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (95); 6- (3 '-N-phthaloyl-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (98); 3- (4-pyridyl) -2- (4-fluorophenyl) -4,7-diaza-indole (99); 6- (2'-N-t-butoxycarbonyl-L-prolylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (100); 6- (2 '-L-propylamino) -3- (4-pyridyl) -2- (-fluorophenyl) -7-aza-indole (101); 6- (2'-dimethylamino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (103); 6- (4 '-methylsulfoxo-1' -oxo-2 'S-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (108); 6- (4 '-methylsulfoxo-1' -oxo-2 'S-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (109); 6- (3 '- (3-pyridyl) -1' -oxo-2 'S-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (110); 6- (3'- (3-pyridyl) -l'-oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (111); 6- (N, N-Di-t-butoxycarbonyl-L-histidinylamino) -3- (4-pyridyl) - 264 2- (4-fluorophenyl) -7-aza-indole (112); 6- (L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (113); 6- (3 (S) -1 ', 2', 3 ', A' -tetrahydro-3 '-isoquinoliniloxoamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole ( 115); 6- (3 '-fenii-1' -oxo-2 '- (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (125); 6- (1'-oxo-2 'S-N-methy1-2-2-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (129); 6- (3 '- (2-thienyl) -1' -oxo-2 '- (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (133 ); 6- (3 '- (4-azidophenyl) -1' -oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (135); 6- (3 '- (3-benzothienyl) -1' -oxo-2' S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (137); 6- (4'-phenyl-1 '-oxo-2' - (L) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (139); 6- (4'-phenyl-1'-oxo-2 '- (D) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (141); 6- (2'-amino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutoxycarbonyl-7-aza-indole (143); 6- (2 '(R, S) -phenylpropylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole (147); 6- (2 '(R, S) -ethylhexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (148); 6-amino-5-fluoro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-265 indole (28); 6-amino-5-bromo-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (27); 6- (2 ', 2'-dimethylpropyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (151); 6- (isoamylamino) -3- (-pyridyl) -2- (4-fluorophenyl) -7-aza indole (152); 6- (2'-ethylbutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (153); 6- (2'-thienylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (154); 6- (ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (156); and 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (-fluorophenyl) -l-methyl-7-aza-indole (158). The following compounds had an IC 50 of less than 1 μM: 6-amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (17); 6- (3 '- (4-iodophenyl) -l'-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (71); 6- (3 '- (4-hydroxyphenyl) -1' -oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (89); 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole (92); 6- (2S '-dimethylamino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (102); 6- (2'-N-methyl-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (104); 6- (2'-N-methyl-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (105); 6- 266 (4'-N-t-butoxycarbonylisonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (106); 6- (4'-isonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (107); 6- (2'-phenyl-1'-oxo-2'-R-aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (117); 6- (2'-phenyl-1 '-oxo-2' S-a-inoeti-lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (119); 6- (2'-phenyl-1 '-oxo-2' R-N-methylaminoethylamino) -2- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (121); 6- (1'-oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (123); 6- (1'-oxo-2 'S-N-methylaminopropylamino) -3- (-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (127); and 6- (1'-oxo-2 'R-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole (131). In a manner similar to the assay described above involving the release of TNF-α induced by LPS from monocytes, the compounds of this invention may also show that they inhibit the release of IL-1β, IL-6 and / or IL- 8 induced by LPS, from monocytes by measuring the concentrations of IL-lβ IL-6 and / or IL-8 by methods well known to those of skill in the art. 267 The selected compounds of this invention have demonstrated anti-inflammatory properties in models of inflammation including the model in foot edema by carrageenan (CA Winter et al., Soc. Exp. Biol. Med. Med. (1962) vol 111, p544; KF Swingle, in RA Scherrer and MW Whitehouse, Eds., Antiinflammatory Agents, Chemistry and Pharmacology, Vol. 13-11, Academic, New York, 1974, p.33) and collagen-induced arthritis DE Trentham et al J. Exp. Med. (1977) vol. 146, p. 857; J. S. Courtenay, Nature (New Biol.) (1980), Vol. 283, p. 666). Also, compounds selected from the class have shown in vivo activity in a mouse model with LPS in which levels of TNF-α were reduced in the presence of the compounds of this invention.

Inhibition of TNF-a production induced by LPS, in mice Male DBA / 1LACJ mice were dosed with vehicle or test compounds in a vehicle (the vehicle consisting of 0.5% tragacanth in 0.03 N HCl) 30 minutes before the injection of lipopolysaccharide (2 mg / kg, intravenous). 268 Ninety minutes after the injection of LPS, blood was collected and serum was analyzed by ELISA for TNF levels.

Selection of Link of x u-lucagón with CHQ / hGLUR cells The assay is described in the International Patent NO. WO 97/16442, which is incorporated by reference herein in its entirety.

Reagents The reagents can be prepared as follows: (a) prepare fresh 1M Phenanthroline (Aldrich.) (198.2 mg / ml ethanol); (b) prepare fresh 0.5 M DTT (Sigma); (c) Protease Inhibitor Mixture (1000X): 5 mg of leupeptin, 10 mg of benzamidine, 40 mg of bacitracin and 5 mg of trypsin inhibitor of soy per ml of DMSO, and store aliquots at -20 ° C; (d) human glucagon 250 μm (Peninsula): solubilize 0. 5 mg of the vial in 575 μl of 0.1 N acetic acid (1 μl produces a final concentration of 1 μM in the assay for the non-specific binding) and store in aliquots at -20 ° C; (e) Trial Shock Absorber: Tris 269 mM (pH 7.8), 1 mM DTT and 3 mM o-phenanthroline; (f) Test Buffer with 0.1% BSSA (for marker dilution only, 0.01% final in the assay): 10 μl of 10% BSA (heat inactivated) and 990 μl of Test Buffer; (g) 125i Clucagón (NEN, receiving grade, 2200 Ci / mmol): dilute to 50,000 cpm / 25 μl in assay buffer with BSA (final concentration of approximately 50 pM in the assay).

Harvest of the CHO-hGLUR cells for the assay 1. Remove the medium from the confluent flask and then rinse once in each with PBS (free of calcium and magnesium) and enzyme-free dissociation fluid (Specialty Media, Inc.). 2. Add 10 ml of enzyme-free dissociation fluid and keep for approximately 4 minutes at 37 ° C. 3. Gently tap the cell, crush, take an aliquot for counting and centrifuge the rest for 5 minutes at 1000 rpm. 270 4. Resuspend the cell button in the Assay Buffer at 75,000 cells per 100 μl.

Membrane preparations of CHO / hGLUR cells can be used in place of whole cells in the same assay volume. The final protein concentration of a membrane preparation is determined on a per batch basis.

Test The determination of the glucagon binding inhibition can be carried out by measuring the reduction of the I 125 -glucagon bond in the presence of compounds of the formula I. The reagents are combined in 120 μl of assay buffer as follows: Compound / Glucagon, 25I-Glucagon Cells Vehicle 250 μM CHO / hGLUR Total Link -15 μl ~ 25 μl 100 μl + 5 μl / - ~ 25 μl 100 μl Non-Specific Linkage ~ / 5 μl l μl 25 μl 100 μl Compound 271 The mixture is incubated for 60 minutes at 22 ° C on a shaker at 275 rpm. The mixture is filtered on a pre-wetted GF / C filter mesh (0.5% polyethylene (PEI), using an Innotech Harvester or a Tomtec Harvester with four washes of ice-cooled 20 mM Tris buffer (pH 7.8). The filters are determined by a gamma scintillation counter In a manner similar to the assay described above involving the release of TNF-α induced by TPS from monocytes, the compounds of this invention can also be inhibitors of IL-1 release. lß, IL-6 and / or IL-8 from monocytes induced by LPS, by measuring the concentrations of IL-lß, IL-6 and / or IL-8 by methods well known to those of experience in the technique.

Enzyme Activity Cyclooxygenase Assay The line of human monocytic leukemia cells, THP-1, differentiated by exposure to phorbol esters expresses only COX-1; the human osteosarcoma cell line 143B predominantly expresses COX-2. THP-1 cells are 272 routinely cultured in complete medium RPMl supplemented with 10% FBS and human osteosarcoma cells (HOSC) are cultured in minimal essential medium supplemented with 10% fetal bovine serum (MEM-10% FBS); all cell incubations are at 37 ° C in a humidified environment containing 5% C02- COX-1 test In preparation for the COX-1 assay, THP-1 cells are grown to confluence, divided 1: 3 in RPMl containing 2% FBS and 10 mM phorbol 12-myristate-13-acetate (TPA) and incubated for 48 hours on a shaker to prevent coupling. The cells are concentrated and resuspended in Hank's buffered saline solution (HBS) at a concentration of 2.5 x 10 6 cells / ml and seeded in 96 culture plates at a density of 5 x 10 5 cells / mole. The test compounds are diluted in HBS and added to the desired final concentration and the cells are incubated for a further 4 hours. Arachidonic acid is added to a final concentration of 30 mM, the cells are incubated 273 for 20 minutes at 37 ° C / and the enzymatic activity is determined as described below.

COX-2 test For the COX-2 assay, the subconfluent HOSCs are trypsinized and resuspended at 3 x 106 cells / ml in MEM-FBS containing a nanogram of human IL-ib / ml, placed in 96-well tissue culture plates to a density of 3 x 104 cells per well, incubate in an agitator for 1 hour to evenly distribute the cells, followed by an additional static incubation of 2 hours to allow the coupling. The medium is then replaced with MEM containing 2% FBS (MEM 2% FBS) and 1 ng IL-lb / ml, and the cells are incubated for 18-22 hours. After replacing the medium with 190 ml of MEM, 10 ml of the test compound diluted in HBS is added to achieve the desired concentration and the cells are incubated for 4 hours. The supernatants are removed and replaced with MEM containing 30 mM arachidonic acid, the cells are incubated for 20 minutes at 37 ° C, and the enzyme activity is determined as described below. 274 Cox Activity Determined After incubation with arachidonic acid, the reactions are stopped by the addition of 1 N HCl, followed by neutralization with 1 N NaOH and centrifugation to concentrate the cell debris. The activity of cyclooxygenase enzyme in the supernatants of the HOSC and THF-1 cells is determined by measuring the PGE2 concentration, using a commercially available ELISA (Neagen # 404110). A standard curve of PGE2 is used for calibration and commercially available COX-1 and COX-2 inhibitors are included as standard controls. The following compounds show activities in the cyclooxygenase assay as IC5o values of 20 μM or less: 6- (6'-amino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; and 6- (1'-oxo-2 'SN-methylamino (propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole. The following compounds show activities in the cyclooxygenase assay with IC5_ values of 5 μM or less: 6- (3'-phenyl-1'-oxo-2'-D, L-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7- aza-indole; 6- (methylsulfonylamino) -3- 275 (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; and 3- (4-pyridyl) -2- (4-fluorophenyl) indole. This invention further relates to the use of a compound of this invention in the manufacture of a medicament for the prophylaxis and treatment, either acutely or chronically, of disease states mediated by TNF-a. In addition, the compounds of this invention are useful in the manufacture of a medicament for the treatment of disease states in which IL-1, IL-6 and / or IL-8 play a role. Also the compounds of this invention are useful in the manufacture of an analgesic medicament and a medicament for the treatment of pain disorders, such as hyperalgesia. The compounds of the present invention are also useful in the manufacture of a medicament for preventing the production of prostaglandins by inhibiting the enzymes in the human arachidonic acid / prostaglandin pathway. This invention also relates to a pharmaceutical composition comprising a compound of this invention and a pharmaceutically acceptable carrier, and if desired, other active ingredients. The compounds of this invention are administered by any suitable route, preferably in 276 the form of a pharmaceutical composition adapted for such a route, and in an effective dose for the intended treatment. Therapeutically effective doses of the compounds of the present invention required to retain the progress or prevent tissue damage associated with the disease are readily evaluated by one of skill in the art. All compounds of this invention are useful in the prophylaxis and treatment of disease states mediated by TNF-α. The compounds are also useful in the prophylaxis and treatment of disease states in which IL-1, IL-6 and IL-8 play a role. Preferably, the compounds of this invention are useful in the prophylaxis and ep treatment of rheumatoid arthritis; osteoarthritis, rheumatoid spondylitis; gouty arthritis; inflammatory bowel disease; adult respiratory distress syndrome (ARDS); psoriasis; Crohn's disease; allergic rhinitis; Ulcerative colitis; anaphylaxis; contact dermatitis; asthma; antiviral therapy including those viruses sensitive to inhibition by TNF-α, namely HIV-1, HIV-2, HIV-3, cytomegalovirus (CMV), influenza virus, adenovirus, and herpesviruses including HSV-1, HSV- 277 2, and herpes zoster; muscle degeneration; cachexia; Reiter's syndrome; type II diabetes; bone resorption diseases; graft versus host reaction; damage by ischemic reperfusion; brain trauma; atherosclerosis; Alzheimer disease; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever and myalgias due to infection. In addition to inhibiting the production of TNF-α, the compounds of this invention can also reduce the levels of other cytokines including, but not limited to IL-1, IL-6 or IL-8. The reduction of elevated levels of these inflammatory cytokines to basal or lower levels is favorable in control, decreased progression, or possibly relief of many disease states. The present invention provides a method for the treatment of a disease state in which cytokine levels are elevated, which comprises administering an effective amount of a compound of this invention. The compounds of this invention are for use in the prophylaxis and in the acute or chronic therapy of any disease state in a human or other mammal, which is exacerbated or mediated by the high or unregulated production of IL-1, IL-6, IL-8 and / or TNF-α by the cells of such a mammal, such as, but not limited to monocytes, macrophages, and gual cells. More preferably, this invention relates to a method for decreasing the levels of TNF-α and / or IL / 1 in a mammal in need thereof, which comprises administering an effective dose of a compound of this invention or a pharmaceutical composition thereof. Furthermore, this invention relates to a method for decreasing the levels of IL-6 and / or IL-8 in a mammal in need thereof, which comprises administering an effective dose of a compound of this invention or a pharmaceutical composition of the invention. same. Accordingly, the compounds of this invention or a pharmaceutical composition thereof are useful in the treatment or prophylaxis of a number of disease states including rheumatoid arthritis; Pagets disease; osteoporosis; multiple myeloma; uveitis; acute and chronic myelogenous leukemia; destruction of B cells of the pancreas; osteoarthritis, rheumatoid spondylitis, gouty arthritis; inflammatory bowel disease; respiratory insufficiency syndrome of 279 adult (ARDS); psoriasis; Crohn's disease; allergic rhinitis; Ulcerative colitis; anaphylaxis; contact dermatitis; asthma; muscle degeneration; cachexia; Reiter's syndrome; type I and type II diabetes; bone resorption disease; graft reaction vs. Guest; damage by ischemic reperfusion; atherosclerosis; brain trauma; Alzheimer disease; apoplectic shock; myocardial infarction; multiple sclerosis; cerebral malaria; sepsis; septic shock; toxic shock syndrome; fever; and myalgias due to infection by HIV-1, HIV-3, cytomegalovirus (CMV), influenza, adenovirus, herpesviruses (including HSV-1, HSV-2, and herpes zoster, all of which are sensitive to inhibition by TNF-a and / or IL-1 or glucagon antagonism, will also be positively effected by the compounds and methods of the invention The compounds of the present invention may also possess analgesic properties and may be useful for the treatment of disorders of the pain, such as hyperalgesia due to excessive IL-1 The compounds of the present invention can also prevent the production of prostaglandins by the inhibition of enzyme in the human route of arachidonic acid / prostaglandin 280 including cyclooxygenase (WO 96/03387, incorporated by reference herein in its entirety). Due to their ability to lower TNF-α and IL-1 concentrations or inhibit glucagon binding to their receptor, the compounds of the invention are also useful as research tools to study the physiology associated with blocking these effects. In another aspect more, this invention comprises the use of a compound of the invention, or pharmaceutically acceptable salts thereof, the manufacture of a medicament for the treatment of either acute or chronic disease state mediated by TNF-a, IL-lß, IL -6, and / or IL-8, including those previously described. In yet another aspect, this invention provides a pharmaceutical composition comprising an amount effective to decrease TNF-α, IL-β, IL-6, and / or IL-8 and / or an amount effective to decrease the level of plasma glucose , of a compound of the invention and a pharmaceutically acceptable diluent carrier, and if other active ingredients are desired. The compounds of the invention are administered by any suitable route, 281 preferably in the form of a pharmaceutical composition adapted for such a route, and in an effective dose for the treatment in question. Therapeutically effective doses of the compounds of the present invention, required to arrest the progress or prevent tissue damage associated with the disease, are readily ascertained by one of ordinary skill in the art, using standard methods. For the treatment of disease states mediated by TNF-a, IL-lß, IL-6, and IL-8 and / or hyperglycemia, the compounds of the present invention can be administered orally, parenterally, by inhalation spray, rectally, or topically in unit dose formulations containing conventional pharmaceutically acceptable carriers, adjuvants and vehicles. The term "parenteral" as used herein includes subcutaneous, intravenous, intramuscular, intrasternal, infusion or intraperitoneally. For the prophylaxis and treatment of disease states, the compounds of the present invention can be administered orally, parenterally or by spray for inhalation, 282 rectally, or topically in unit dose formulations containing conventional, pharmaceutically acceptable carriers, adjuvants and vehicles. The term parenteral as used in the present ii-uye, subcutaneous intravenous, intramuscular, intrasternal administration, infusion techniques or intraperitoneally. The amount of active ingredient that can be combined with the carrier materials to produce a single dose form will vary depending on the host treated and the particular mode of administration. The dose regimen for the treatment of a disease state with the compounds of this invention and / or the compositions of this invention is based on a variety of factors, including the type of disease, age, weight, sex and the medical condition of the patient, the severity of the condition, the route of administration, pharmacological considerations such as the activity, efficacy, pharmacokinetic and toxicological profiles of the particular compound employed, whether a drug distribution system is used and if the compound is administered as part of a drug combination. In this way, the 283 Dosage regimen can vary widely. Dosage levels in the range of about 0.01 mg to 80 mg per kilogram of body weight per day, preferably from about 0.5 mg to 30 mg / kg, more preferably from about 1 mg to 15 mg / kg are useful for all methods of use described herein. The pharmaceutically acceptable compounds of this invention can be processed according to conventional pharmacy methods to produce medicinal agents for administration to patients, to mammals including humans. For oral administration, the pharmaceutical composition may be in the form of, for example, a capsule, a tablet, a suspension, or liquid. The pharmaceutical composition is preferably made in the form of a unit dose containing a given amount of the active ingredient. For example, these may contain an amount of active ingredient of about 1 to 250 mg, preferably about 25 to 150 mg. A suitable daily dose for a human or other mammal can vary widely depending on the condition of the patient and other factors. 284 The compounds of this invention can also be administered by injection as a composition with suitable carriers including saline, dextrose, or water. The daily parenteral dosage regimen will be from about 0.1 to about 80 mg / kg of total body weight, preferably from about 0.5 to about 30 mg / kg, and more preferably from about 1 mg to 15 mg / kg. Injectable preparations, for example, injectable, sterile aqueous or oily suspensions can be formulated according to the known technique using suitable spraying or wetting agents, and suitable suspending agents. The sterile injectable preparation can also be a sterile injectable solution or suspension in a non-toxic, parenterally-acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents that may be employed are water, Ringer's solution, and isotonic sodium chloride solution. In addition, fixed, sterile oils are conventionally employed as a solvent or suspending medium. For this purpose any fixed, soft oil can be used 285including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid find use in the preparation of injectables. Suppositories for rectal administration of the drug can be prepared by mixing the drug with a suitable non-irritating excipient, such as cocoa butter and polyethylene glycols which are solid at ordinary temperatures, but liquid at the rectal temperature and will therefore melt at the straight and they will release the drug. A suitable topical dose of the compounds of this invention is from 0.1 mg to 150 mg administered one to four, preferably two to three times daily. For topical administration, the active ingredient may comprise from 0.001% to 10% w / w, for example from 1% to 2% by weight of the formulation, although this may comprise as much as 10% w / w, but preferably no more of 5% w / w, and more preferably from 0.1% to 1% of the formulation. Formulations suitable for topical administration include liquid or semi-liquid preparations suitable for penetration through the skin such as liniments, lotions, ointments, creams, or pastes and drops suitable for administration to the eye, ear or nose. 286 For administration, the compounds of this invention are ordinarily combined with one or more adjuvants appropriate for the indicated route of administration. The compounds can be admixed with lactose, sucrose, powdered starch, cellulose esters of alkanoic acids, stearic acid, talc, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, acacia, gelatin , sodium alginate, polyvinylpyrrolidine and / or polyvinyl alcohol, and formed into tablets or capsules for conventional administration. Alternatively, the compounds of this invention can be dissolved in saline, in water, in polyethylene glycol, in propylene glycol, in ethanol, in corn oil, in peanut oil, in cottonseed oil, in sesame oil, in gum tragacanth, in benzyl alcohol, and / or in various buffers. Other adjuvants and modes of administration are well known in the pharmaceutical art. The carrier or diluent may include the time delay material, such as glyceryl monostearate or glyceryl distearate, alone or with a wax, or other materials well known in the art. 287 The pharmaceutical compositions can be constituted in a solid form including granules, powders or suppositories or in a liquid form such as solutions, suspensions or emulsions. The pharmaceutical compositions may be subjected to conventional pharmaceutical operations such as sterilization and / or may contain conventional adjuvants, such as preservatives, stabilizers, wetting agents, emulsifiers, buffers, etc. Solid dosage forms for oral administration may include capsules, tablets, pills, powders and granules. In such solid dosage forms, the compound can be mixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms may also comprise, as in normal practice, additional substances other than inert diluents, for example, lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can also be prepared with enteric coatings. 288 Liquid dosage forms for oral administration may include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs, containing common inert diluents used in the art, such as water. Such compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, and sweetening, flavoring and flavoring agents. The compounds of the present invention may possess one or more asymmetric carbon atoms, and in this way they are able to exist in the form of optical isomers, as well as in the form of racemic or non-racemic mixtures thereof. The optical isomers can be obtained by resolution of racemic mixtures according to conventional processes, for example by formation of the diastereomeric salts by treatment with an optically active acid or base. Examples of suitable acids are tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, ditoluoyltartaric acid, and camphorsulfonic acid, and then separation of the diastereomeric mixture by crystallization followed by release of the optically active bases from these salts. A 289 Different process for the separation of the optical isomers involves the use of an optimally chosen chiral chromatography column to maximize the separation of the enantiomers. Another available method involves the synthesis of covalent diastereoisomeric molecules by reacting the compounds of this invention with an optically pure acid in an activated form or an optically pure isocyanate. The synthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolysates to distribute the enantiomerically pure compound. The optically active compounds of this invention can likewise be obtained by the use of optically active starting materials. These isomers may be in the form of a free acid, a free base, an ester or a salt. The compounds of the present invention can be used in the form of salts derived from inorganic or organic acids. These salts include, but are not limited to the following: acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorrate, camphorsulfonate, digluconate, 290 cyclopentanpropionate, dodecyl sulfate, ethanesulfonate, glycoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxy-ethanesulfonate, lactate, maleate, methanesulfonate, nicotinate 2-naphthalenesulfonate, oxalate, palmoate, pectinate, persulfate 3- phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, mesylate, and undecanoate. Also, groups containing basic hydrogen can be quaternized with agents such as lower alkyl halides, such as methyl, ethyl, propyl and butyl chlorides, bromides and iodides; dialkyl sulfates such as dimethyl, diethyl, dibutyl and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides such as benzyl and phenethyl bromides, and others. This results in soluble or dispersible products in water or oil. Examples of acids that can be employed to form the pharmaceutically acceptable acid addition salts include inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and organic acids such as these. such as oxalic acid, maleic acid, succinic acid and citric acid. Other examples include salts with alkali metals or alkaline earth metals, such as sodium, potassium, calcium or magnesium or with organic bases. While the compounds of the invention can be administered as the sole active pharmaceutical agent, they can also be used in combination with one or more other agents. When administered as a combination, the therapeutic agents can be formulated as separate compositions which are administered at the same time at different times, or the therapeutic agents can be administered as a simple composition. The foregoing is merely illustrative of the invention and is not intended to limit the invention to the disclosed compounds. Variations and changes that are obvious to someone of experience in the art are intended to be within the scope and nature of the invention, which will be defined in the appended claims. From the above description, one skilled in the art can easily evaluate the essential characteristics of this invention, and 292 without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various uses and conditions.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following:

Claims

- 2. 3 R E I V I N D I C A C I O N S

1. A mixture comprising (a) thermoplastic polyurethane having a Shore hardness of 60 A to 50 D, and (b) ethylene and propylene rubbers (EPM) and / or modified ethylene and propylene rubbers (EPM), wherein the ratio in weight (a): (b) is from 3: 1 to 999: 1. 2. A mixture according to claim 1, wherein the weight ratio is from 6: 1 to 100: 1. 3. A mixture according to claim 1, wherein (b) is present in unmodified form in the mixture. 4. A mixture according to claim 1, wherein (b) has been grafted with acrylic acid, methacrylic acid, its derivatives and / or maleic anhydride. 5. The use of a mixture according to claim 1, for producing cable sheathing, films, hoses, fibers, profiles or blow molded articles by extrusion, for producing shoe shovels, shoe soles, industrial molded parts, articles of the consumer or bodies - 25 - SUMMARY OF THE INVENTION The blends comprise (a) thermoplastic polyurethane having a Shore hardness of 60 A to 50 D, and (b) ethylene and propylene rubbers (EPM) and / or modified ethylene and propylene rubbers (EPM), wherein the ratio in weight (a): (b) is from 3: 1 to 999: 1. CLAIMS l.A compound of formula or a pharmaceutically acceptable salt thereof, characterized in that X! is N, CH or CR_; X2 is N, CH or CR2; X3 is N, CH or CR3; and X4 is N, CH or CR4; with the proviso that at least one of Xi, X2, X3 and X4 is N or CH, and that no more than two of Xi, X2, X3 and X4 are N; wherein Ri, R2, R3 and R are each independently -Z-Y; with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R_, R2, R3 and R is 0-4, wherein each Z is independently a (1) bond; (2) alkyl, alkenyl or alkynyl radical optionally substituted by (a) 1 to 3 amino, alkylamino, dialkylamino, alkynylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano or halo radicals, and (b) 1 to 2 radicals of heterocyclyl, aryl or heteraryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; (3) the heterocyclyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (4) aryl or the heteroaryl radical optionally substituted by 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; each Y is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) radical halo, cyano, nitro; (3) -C (0) -R20, -C (0) -OR2 ?, -C (0) -NR5R2i; or -C (NR5) -NR5R21; (4) -0R2i, -0-C (0) -R2i, -0-C (0) -NR5R2 ?, or -0-C (0) -NR22-S (O) 2-R20; (5) -SR2 ?, -S (0) -R20, -S (O) 2 -R20, -S (0) 2-NR5R2? , -S (0) 2-NR22-C (0) -R2 ?, -S (O) 2-NR22-C (O) -OR20, or -S (0) 2-NR22-C (0) -NR5R2 ? or (6) -NR5R2 ?, -NR22-C (0) -R2i, -NR22-C (0) -OR20, -NR22-C (0) -NR5R2 ?, -NR22-C (NR5) -NR5R2 ?, -NR22-S (O) 2-R20 or -NR22-S (0) 2-NR5R2 ?; wherein each R5 is independently (1) hydrogen radicals; (2) alkyl, alkenyl or alkynyl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkylthio, cyano or halo radicals; or (3) aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, heterocyclylalkyl, cycloalkyl or cycloalkylalkyl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; and wherein each R2o is independently (x) the alkyl, alkenyl or alkynyl radical optionally substituted with 1 to 3 radicals C02R23, amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, N- (alkoxycarbonyl) -N- (alkyl) amino, aminocarbonylamino , alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkanoyl radicals , alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; (2) heterocyclyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, alkoxycarbonyl, hydroxyl, alkoxy, alkylthio, cyano, halo, azido, alkyl or haloalkyl radicals; every R2? is independently hydrogen or R2o radical; each R22 is independently (1) the hydrogen radical; (2) the alkyl radical optionally substituted with a heterocyclyl, aryl or heteroaryl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; or (3) heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl radicals; each R23 is independently hydrogen or alkyl, or aryl, heteroaryl, aralkyl or heteroaralkyl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkyl_; uiphenylamino, hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo , alkyl or haloalkyl; Y Rio is a hydrogen radical, R3c -C (0) -R29, -C (O) -OR30, -C (O-NR31R32, -S (O) 2 -R30 or -S (0) 2 -NR3? R32; R11 and R12 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 3 radicals (2) halo, cyano; (3) -C (0) -R3o, -C (0) -OR29, -C (O) -NR31R32, or -C (NR3?) - NR31R32, (4) -OR29, -0-C (0) -R29, -OC (O) -NR3? R32, -OC (O) -NR33-S (O) 2-R3o, (5) -SR29, -S (O) -R30, -S (O) 2- R30, -S (0) 2-NR31R32, -S (0) 2-NR33-C (0) -R3o ,. -S (O) 2-NR33-C (0) -OR30, or -S (O) 2-NR33-C (O) -NR31R32; (6) -NR3.R3-, -NR33-C (0) -R29, -NR33-C (O) -OR30, -NR33-C (O) -NR3? R32, -NR33-C (NR31) -NR3 R32, -NR33-S (O) 2-R30 or -NR33-S (O) 2-NR31R32; with the proviso that the total number of aryl, heteroaryl, cycloalkyl and substituted alkylcyclic radicals on each Ru and R12 is 0-1; wherein each R30 is independently (1) alkyl, alkenyl or alkynyl radicals optionally substituted with 1 to 3 radicals -NR31R31, -C02R23, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo or aralkoxy, aralkylthio, aralkylsulfonyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, halo, alkyl or haloalkyl; (2) the heterocyclyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, halo, alkyl or haloalkyl radicals; each R29 is independently a hydrogen radical or e) R31 and R32 are each independently (1) the hydrogen radicals; (2) the alkyl radical optionally substituted with a cycloalkyl, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; or (3) aryl, heteroaryl, heterocyclyl or cycloalkyl radical optionally substituted with 1 to 3 amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; Y each R33 is independently (1) the hydrogen radical; or (2) the alkyl radical optionally substituted with a heterocyclyl, aryl, or heteroaryl radical optionally substituted with 1 to 3 t-amino, alkylamino, dialkylamino, alkanoylamino, alkoxycarbonylamino, alkylsulfonylamino, hydroxyl, alkoxy, alkylthio, cyano, alkyl or haloalkyl radicals; with the proviso that when each Xi, X2, X3 and X4 represent carbon atoms, then Ru is a substituted aryl radical and R_2 is a heteroaryl radical, or Ru is a heteroaryl radical and Ri2 is a substituted aryl radical;

2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N, CH or CR_; X2 is N, CH or CR2; X3 is N, CH or CR3; and X4 is N, CH or CR4; with the proviso that at least one of Xir X2, X3 and X4 is N or CH, and that no more than two of Xi, X2, X3 and X are N; where Ri, R2, R3 and R4 are each independent .__ nte -Z-Y; with the condition of (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri, R2, R3 and R4 is 0-4, each Z is independently one (1) link; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di (alkyl) from 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms , alkylthio of 1 to 4 carbon atoms, cyano, halo, or heterocyclyl, aryl or heteroaryl optionally substituted by 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms bonus of 1 to 3 halo radicals; (3) the heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 4 carbon atoms of 1 to 3 halo radicals; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonyiamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms, or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; each Y is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) radical halo, cyano, nitro; (3) -C (O) -R20, -C (0) -OR2i, -C (0) -NR5R21; or -C (NR5) -NR5R2 ?; (4) -OR2 ?, -0-C (0) -R2 ?, -O-C (O) -NR5R2_, or -O-C (O) -NR22-S (O) 2-R20; (5) -SR21, -S (O) -R20, -S (O) 2 -R20, -S (O) 2-NR5R2. , -S (0) 2-NR22-C (0) -R2 ?, -S (O) 2-NR22-C (O) -OR20, OR -S (O) 2 -NR22-C (O) -NR5R2 ? or (6) -NR5R2 ?, -NR22-C (0) -R2i, -NR22-C (O) -OR20,? JR22-C (O) -NR5R2 ?, -NR22-C (NR5) -NR5R2 ?, -NR22-S (O) 2-R20 or -NR22-S (O) 2-NR5R2 ?; each R5 is independently: (1) the hydrogen radicals; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 radicals of an amino radical, alkylamino of 1 to 4 carbon atoms, di (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano or halo; or (3) the aryl, heteroaryl, aryl- (alkyl of 1 to 4 carbon atoms), heteroaryl- (alkyl of 1 to 4 carbon atoms, heterocyclyl, heterocyclyl- (alkyl of 1 to 4 carbon atoms), cycloalkyl of 3 to 8 carbon atoms or (cycloalkyl of 3 to 8 carbon atoms) - (alkyl of 1 to 4 carbon atoms) optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, (C 1-4 alkyl) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms. carbon of 1 to 3 halo radicals; each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4, carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 atoms of carbon, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo or aryl- (alkoxy of 1 to 4 carbon atoms), aryl- (alkylthio of 1 to 4 carbon atoms) , aryl- (alkylsulfonyl of 1 to 4 carbon atoms), cycloalkyl of 3 to 8 carbon atoms, heterocyclyl, aryl or heteroaryl optional nally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) ) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, alkanoyl of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 atoms carbon, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1) to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano , alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkylamino of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, ( alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; every R2? is independently the hydrogen radical or R2_; each R22 is independently (1) the hydrogen radical; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a heterocyclyl, aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4) carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy- of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxy, alkoxy of 1 to 4 carbon atoms, alkylthio _ to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, carbon, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms carbon, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or aryl, heteroaryl, aryl- (alkyl of 1 to 4 carbon atoms) or heteroaryl- (alkyl of 1 to 4 carbon atoms) optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkoxylamino, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms , hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms carbon or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; Rio is a hydrogen radical, R30, -C (0) -R29, -C (0) -OR3o, -C (0) -NR3? R32, -S (O) 2 -R30 or -S (O) 2- NR31R32; Ru and R12 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 3 radicals (1) R30, (2) halo or cyano; (3) -C (O) -R30, -C (0) -OR29, -C (0) -NR3? R32, or (4) -OR29, -0-C (0) -R29, -0-C (0) -NR3? R32, -OC (Q) -NR33-S (O) 2-R30, (5) -SR29, -S (0) -R3o, -S (0) 2 -R3o, -S ( O) 2-NR3? R32, -S (O) 2-NR33-C (O) -R30, -S (O) 2-NR33-C (O) -OR30 / O -S (O) 2-NR33- C (O) -NR31R32; (6) -NR3? R32, -NR33-C (0) -R29, -NR33-C (O) -OR30, -NR33-C (O) -NR3? R32, -NR33-C (NR31) -NR3? R32, -NR33-S (0) 2-R3o or -NR33-S (0) 2-NR3? R32; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Ru and R? 2 is 0-1; each R30 is independently (1) the alkyl radicals of 1 to 4 carbon atoms, alkenyl of 2 to 4 carbon atoms or alkynyl of 2 to 4 carbon atoms optionally substituted with 1 to 3 radicals -NR3? R3 ?, -C02R23 , hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo or aryl- (alkoxy of 1 to 4 carbon atoms), aryl- (C 1 -C 4 -alkylthio), aryl- (C 1 -C 4 -alkylsulfonyl), heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 or amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl , alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl from 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) the heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy) 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms carbon or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; each R29 is independently a hydrogen radical or R30; each R31 and R3_ are each independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a cycloalkyl radical of 3 to 8 carbon atoms, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or halaalkyl of 1 to 4 carbon atoms from 1 to 3 halo radicals; or (3) aryl, heteroaryl, heterocyclyl or the cycloalkyl radical of 3 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; and each R33 is independently (1) the hydrogen radical; or (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a heterocyclyl, aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4) carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; Y wherein heterocyclyl is a radical of a saturated, monocyclic or bicyclic heterocyclic ring system having 5 to 8 ring members per ring, wherein 1 to 3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally partially unsaturated or fused to a benzo, and optionally substituted with 1 to 2 oxo or thioxo radicals; aryl is a phenyl or naphthyl radical; and heteroaryl is a radical of an aromatic, monocyclic or bicyclic heterocyclic ring system having 5 to 6 ring members per ring, wherein 1 to 3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally fused to a benzo or fused to a carbocycle of one to three carbon atoms saturated.

3. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, characterized in that: each Z is independently one (1) link; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di (alkyl) from 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms , alkylthio of 1 to 4 carbon atoms, cyano, halo, or heterocyclyl, aryl or heteroaryl optionally substituted by 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) to o, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 atoms of carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms bonus of 1 to 3 halo radicals; (3) the heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 4 carbon atoms of 1 to 3 halo radicals; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms, or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; each Rs is independently: (1) the hydrogen radicals; (2) alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 radicals of an amino radical, alkylamino of 1 to 4 carbon atoms, di (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano or halo; or (3) the aryl radical, heteroaryl, aryl- (alkyl of 1 to 4 carbon atoms), heteroaryl- (alkyl of 1 to 4 carbon atoms), heterocyclyl, heterocyclyl- (alkyl of 1 to 4 carbon atoms) , cycloalkyl of 3 to 8 carbon atoms or (cycloalkyl of 3 to 8 carbon atoms) - (alkyl of 1 to 4 carbon atoms) optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, - (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 atoms carbon of 1 to 3 halo radicals; each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms or alkynyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 radicals - C02R23, amino, alkylamino of 1 to 4, carbon atoms, di- (C 1-4 -alkyl) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1-4 -alkoxy) carbonylamino, N- ((C 1-6 -alkoxy) 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 atoms of carbon, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo or aryl-. { C 1 -C 4 -alkoxy), aryl- (C 1 -C 4 -alkylthio), aryl- (C 1 -C 4 -alkylsulfonyl), C 3 -C 8 -cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) ) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, alkanoyl of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 atoms carbon, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) heterocyclyl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1) to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano , alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, ( alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; every R2? is independently the radical hydrogen or R20; each R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 3 radicals of (a) (b) (C 1 -C 4 alkoxy) carbonyl or phenoxycarbonyl or phenylmethoxycarbonyl optionally substituted with 1 to 3 amino, alkylamino, di- (C 1 -C 4 alkyl) amino, alkanoylamino radicals of 1 to 5 carbon atoms carbon, (C 1 -C 4 alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; or (c) hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, or phenyl- (alkoxy of 1 to 4 carbon atoms), phenyl- (alkylthio of 1 to 4 carbon atoms) , heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; (2) haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R29 is independently a hydrogen radical or R30; each R31 is independently (1) the hydrogen radicals, or (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms , di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkanoylamino, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, C 1 -C 4 alkoxy, C 1 alkylthio to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a cycloalkyl radical of 3 to 8 carbon atoms, aryl, heterocyclyl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkoxylamino, (C 1 -C 4 alkoxy) carbonylamino, C 1 -C 4 alkylsulfonylamino, hydroxyl, C 1 -C alkoxy 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; or (3) aryl, heteroaryl, heterocyclyl or the cycloalkyl radical of 3 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms carbon, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 4 carbon atoms of 1 to 3 halo radicals; Y each R33 is independently hydrogen or the alkyl radical of 1 to 4 carbon atoms.

4. The compound according to claim 3 or a pharmaceutically acceptable salt thereof, characterized in that: Ri, R2, R3 and R4 are each independently -Z-Y; with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri, R2, R3 and R4 is 0-3; each Z is independently one (1) link; (2) an alkyl radical of 1 to 8 carbon atoms or alkenyl of 2 to 8 carbon atoms optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) carbon) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, halo, or heterocyclyl, aryl or heteroaryl optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4) carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; (3) the heterocyclyl radical optionally substituted with 1 to 2 amino radicals, di- (C 1 -C 4) alkyl amino, (C 1 -C 4 alkoxy) carbonylamino, hydroxy, alkoxy of 1 to 4 carbon atoms carbon, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon or haloalkyl atoms of 1 to 2 carbon atoms of 1 to 3 halo radicals; each Y is independently a radical (1) hydrogen, with the proviso that Z is different from a bond; (2) the halo radical; (3) -C (O) -R20, -C (0) -OR2 ?, -C (0) -NR5R2 ?, or -C (NR5) -NR5R2 ?, (4) -OR2i, -0-C ( 0) -R2 ?, -0-C (0) -NR5R2 ?, (5) -SRzi, -S (O) -R20, -S (0) 2 -R2O, O -S (O) 2 -NR5R2?; or (6) -NR5R2 ?, -NR22-C (0) -R2 ?, -NR22-C (O) -OR20, -NR22-C (O) -NR5R2, -NR22-C (NR5) -NR5R2 ?, -NR22-S (O) 2-R20 or -NR22-S (O) 2-NR5R2i; each R5 is independently (1) hydrogen radicals; (2) alkyl of 1 to 4 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or halo; or (3) phenyl-alkyl of 1 to 2 carbon atoms, heteroaryl-alkyl of 1 to 2 carbon atoms, heterocyclyl-alkyl of 1 to 2 ato.; G_ > carbon or cycloalkyl of 3 to 6 carbon atoms - alkyl of 1 to 2 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 radicals - C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl) from 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- ( alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms , halo or aryl- (C 1 -C 4 alkoxy), aryl- (C 1 -C 4 alkylthio), aryl- (C 1 -C 4 alkylsulfonyl), cycloalkyl of 3 to 6 C atoms , heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, alkanoyl of 1 to 5 atoms of carbon, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; (2) the heterocyclyl radical optionally substituted with 1 to 2 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamine of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms , cyano, halo, azido, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; each R2i is independently hydrogen or R20 radical; each R22 is independently (1) the hydrogen radical; or (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicaxes, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl from 1 to 2 carbon atoms of 1 to 3 halo radicals; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl, heteroaryl, phenyl- (alkyl of 1 to 2 carbon atoms or heteroaryl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 3 amino, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; Rio is a hydrogen radical, R3o > -C (0) -R29, -C (O) -NR31R32, -S (O) 2"R30 or -S (0) 2 -NR3? R32; Rn and R12 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 2 radicals of (1) Rao; (2) halo or cyano; (3) -C (O) -R30, -C (0) -OR29, -C (0) -NR3? R32, or -C (NR3?) -NR31R32, (4) -OR29, -SR29, -S (O) -R30, -S (0) 2-R30, -S (0) 2 -NR3? R32, -NR3? R32, -NR33-C (O) -R29 or -NR33-C (0) -OR3o; with the proviso that the total number of aryl, heteroaryl, radicals. substituted cycloalkylq and heterocyclyl on each Rn and Ri2 is 0-1; each R3o is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with (a) amino, alkylamino of 1 to 4 carbon atoms or di- (C1 to C4 alkyl) amino; or (b) hydroxyl, alkoxy of 1 to 4 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) haloalkyl of 1 to 2 carbon atoms of 1 to 3 halo radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) mino, alkanoylamino of 1 to 5 carbon atoms, ( C 1-4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R29 is independently hydrogen or R30 radical; each R31 is independently hydrogen or alkyl of 1 to 4 carbon atoms; each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms optionally substituted with phenyl or the heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkyl amino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 atoms) carbon) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or the trifluoromethyl radicals; or (3) phenyl or the heteroaryl radical optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms or trifluoromethyl; and each R33 is independently the hydrogen or methyl radical; Y wherein heterocyclyl is a radical of a saturated, monocyclic heterocyclic ring system, having 5 to 6 ring members per ring, wherein 1 to 3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally fused to a benzo , and optionally substituted with 1 to 2 oxo or thioxo radicals; aryl is a phenyl or naphthyl radical; and heteroaryl is a radical of a monocyclic aromatic heterocyclic ring system, having 5 to 6 ring members per ring, wherein 1 to 3 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally fused to a benzo or fused to a carbocycle of one to three saturated carbon atoms.

5. The compound according to claim 4 or a pharmaceutically acceptable salt thereof, characterized in that: each Z is independently one (1) link; (2) an alkyl radical of 1 to 4 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or heterocyclyl, aryl or heteroaryl optionally substituted by 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy from 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (3) the heterocyclyl radical optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms carbon, alkylthio of 1 to 2 carbon atoms or alkyl of 1 to 4 carbon atoms; or (4) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio having 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently (1) hydrogen radical; (2) alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms or halo; or (3) phenyl-alkyl radicals of 1 to 2 carbon atoms, heteroaryl-alkyl of 1 to 2 carbon atoms, heterocyclyl-alkyl of 1 to 2 carbon atoms or cycloalkyl of 3 to 6 carbon atoms-alkyl of 1 at 2 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, methoxy, methylthio, cyano, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R22 is independently the hydrogen radical or alkyl of 1 to 4 carbon atoms; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl, heteroaryl, phenyl- (alkyl of 1 to 2 carbon atoms) or heteraryl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, C 1 -C 5 alkanoylamino, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, C 1 -C 2 alkoxy, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Ru and R 2 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 2 radicals (1) R 30; (2) halo or cyano; (3) -C (O) -R30, -C (0) -OR29, -C (0) -NR3? R32, or -C (NR3i) -NR3? R32, (4) -OR29, -SR29, - S (O) -R30, -S (O) 2-R30, -S (O) 2-NR3aR32-NR31R32 or -NR33-C (O) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Ru and Ri2 is 0-1; each R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 4 alkyl) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the trifluoromethyl radical; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R29 is independently a hydrogen radical or R30; Y each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms or the alkyl radical of 1 to 2 carbon atoms. carbon substituted with phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkyl of 1 to 4 atp carbon or trifluoromethyl; or (3) phenyl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (C 1 -C 2 alkyl) amino, acetamido, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkyl of 1 to 4 atoms carbon or trifluoromethyl; Y wherein heterocyclyl is a radical of "a saturated, monocyclic heterocyclic ring system, having 5 to 6 ring members per ring, wherein 1 to 2 ring members are oxygen, sulfur or nitrogen heteroatoms, which is optionally fused to a benzo, and optionally substituted with 1 to 2 oxo or thioxo radicals, aryl is a phenyl or naphthyl radical, and heteroaryl is a radical of a monocyclic aromatic heterocyclic ring system, having 5 to 6 ring members per ring, wherein to 2 ring members are heteroatoms of oxygen, sulfur or nitrogen, which is optionally fused to a benzo.

6. The compound according to claim 5 or a pharmaceutically acceptable salt thereof, characterized in that: each Z is independently one (1) bond: (2) an alkyl radical of 1 to 4 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 atoms carbon) amino, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 radicals amino, di- (alkyl of 1 to 2 carbon atoms) amino, acetamido, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of "1 to 2 carbon atoms -juno, cyano, halo, alkyl 1 to 4 carbon atoms or trifluoromethyl; or (3) the aryl or heteroaryl radical optionally substituted with 1 to 3 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio having 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each Y is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) the radical halo, (3) -C (O) -R20, -C (0) -OR2 ?, -C (O) -NR5R21, (4) -OR2i, -SR2 ?, -S (O) -R20, -S (O) 2 -R20, or -S (O) 2-NR5R2i; or (5) -NR5R2 ?, -NR22-C (O) -R2_, -NR22-C (O) -OR20, -NR22-C (O) -NR5R2 ?, -NR22-S (O) 2 -R20 O -NR22-S (0) 2-NR5R2 ?; each R5 is independently (1) hydrogen radical; (2) alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 3 halo radicals; or (3) phenyl-alkyl radicals of 1 to 2 carbon atoms or heteroaryl-alkyla of 1 to 2 carbon atoms, radicals optionally substituted with 1 to 3 amino, dimethylamino, hydroxyl, methoxy, methylthio, methyl or trifluoromethyl radicals; each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms or alkenyl of 2 to 5 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- ( alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (C 1 -C 4 alkyl) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or aryl- (alkoxy 1 to 4 carbon atoms), aryl- (alkylthio of 1 to 4 carbon atoms), aryl- (alkylsulfonyl of 1 to 4 carbon atoms), cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 3 amino radicals, alkylamino of 1 to 4 carbon atoms, (C 1 -C 4 alkyl) amino, C 1 -C 5 alkoxylamino, C 1 -C 4 alkoxy, carbonylamino, C 1 -C 4 alkylsulfonylamino, C 1-5 alkanoyl (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkyl of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or haloalkyl of 1 to 2 carbon atoms from 1 to 3 halo radicals; (2) heterocyclyl radical optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, acetamido, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms carbon or trifluoromethyl; each R2X is independently hydrogen or R20; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms or phenyl- (alkyl of 1 to 2 carbon atoms) or heteroaryl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 3 amino radicals, di - (C 1 -C 2 alkyl) amino, acetamido, (C 1 -C 4 alkoxy) carbonylamino, hydroxyl, C 1 -C 2 alkoxy, C 1 -C 2 alkylthio, cyano, halo , alkyl of 1 to 4 carbon atoms or trifluoromethyl; Ru and R12 are each independently an aryl or heteroaryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; (3) -C (0) -NR3? R32, -OR29, -SR29, -S (O) -R30, -S (O) 2 -R30, -S (0) 2 -NR3? R32, -NR3? R32 or -NR33-C (0) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Ru and R? 2 is 0-1; each R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; (2) the trifluoromethyl radical; or (3) the aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; each R29 is independently a hydrogen radical or R3o, " csdaB is independently the hydrogen, methyl or ethyl radicals; Y each R32 is independently (1) the hydrogen radicals; (2) the alkyl radical of 1 to 4 carbon atoms or alkyl of 1 to 2 carbon atoms substituted with phenyl or the heteroaryl radical optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals; or (3) phenyl or heteroaryl radical optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals;

7. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is CH or CR2; X3 is CH or CR3; and X4 is CH or CR4; wherein R2, R3 and R4 are each inc ~ edentially -Z-Y; with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri, R2, R3 and R4 is 0-3,

8. The compound according to claim 7 or a pharmaceutically acceptable salt thereof, characterized in that: R3 is halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, and the radicals -C (O) -R20, -C (0) -0R2 ?, -C (0) -NR5R2 ?, - S (O) 2-R20 O -S (0) 2-NR5R2?; Y R2 and R4 are each independently -Z-Y; with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2, R3 and R4 is 0-3.

9. The compound according to claim 8 or a pharmaceutically acceptable salt thereof, characterized in that: is N; X2 is CR2; X3 is CH or CR3; and X4 is CH; Y wherein R2 is -Z-Y; with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 is 0-3. R3 is any of the halo, trifluoromethyl, phenyl, methyl, acetyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, methoxycarbonyl, ethoxycarbonyl, amido, N, N-dimethylamido, methylsulfonyl or aminosulfonyl radicals; Ru is a heteroaryl radical optionally substituted with 1 to 2 radicals (1) R30, (2) halo or cyano; or (3) -C (0) -NR3? R32, -OR29, -SR29, -NR31R32 or -NR33-C (0) -R29; Y R12 is an aryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; or (3) -C (0) -NR3? R32, -OR29, -SR29, -S (O) -R30, -S (O) 2 -R30f -S (0) 2 -NR3? R32, -NR3? R32 O-NR33-C (0) -R29; with the proviso that he total number of aryl, heteroaryl, cycloalkyl radicals. and substituted heterocyclyl on each Ru and R? 2 is 0-1.

10. The compound according to claim 9 or a pharmaceutically acceptable salt thereof, characterized in that: each Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently hydrogen or alkyl of 1 to 4 carbon atoms; each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 atoms, carbon, di- (alkyl of 1 to 4 carbon atoms) ) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) carbon) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 atoms) carbon) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms,. { C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals. { C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R2i is independently hydrogen radical or each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Rio is a hydrogen radical, R3o, -C (0) -R29 or -C (O) -NR3? R32; Ru is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Ri2 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R3Q is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; (2) the trifluoromethyl radical; or (3) the aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R3? it is independently the hydrogen, methyl or ethyl radicals; R 32 is independently (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals.

11. The compound according to claim 10 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) the halo radical; (3) -C (O) -R20, -C (0) -OR2 ?, or -C (0) -NR5R2 ?, (4) -OR2 ?, -SR2 ?, -S (O) -R20, - S (O) 2-R20, or -S (O) 2-NR5R2 ?; or (5) -NR5R2 ?, -NR22-C (0) -R2 ?, -NR22-S (O) 2 -R20 or -NR22-S (0) 2-NR5R2?; R5 is a hydrogen radical; each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetates , hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; every R2? is independently radical hydrogen or R2o; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; "• 10 is a hydrogen or methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; and R 2 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals;

12. The compound according to claim 11 or a pharmaceutically acceptable salt thereof, characterized in that: R2 is independently Y; with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 is 0-3; R3 is any of the halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, amido or N, N-di ethylamido radicals; And it is independently one (1) halo radical; (2) -C (O) -R20 or -C (0) -NR5R2 ?; (3) -OR2i, -SR21, or -S (O) -R20; or (4) -NR R2 ?, -NR22-C (0) -R2i, -NR22-S (O) 2 -R20 or -NR22-S (0) 2-NR5R2i;

13. The compound according to claim 12 or a pharmaceutically acceptable salt thereof, characterized in that: R3 is the halo or trifluoromethyl radicals; And it is independently a halo radical, -NR5R2 ?, -NR22-C. { 0) -R21 or -NR22-S. { 0) 2-R20; each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N. { methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulphinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with t-butoxycarbonyl; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, halo, azido, methyl or trifluoromethyl radicals; every R2? is independently radical hydrogen or R20; Ru is a 4-pyridyl radical optionally substituted with a radical to ina, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl; Y R 12 is an unsubstituted phenyl radical or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfonyl, methyl or trifluoromethyl radicals;

14. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is CH or CR2; X3 is CH or CR3; and X. is N; wherein R2 and R3 are each independently -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R3 is 0-3.

15. The compound according to claim 14 or a pharmaceutically acceptable salt thereof, characterized in that: R3 is halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, the radicals -C (0) -R2o, -C (0) -OR2 ?, -C (0) -NR5R2 ?, -S (O) 2-R20 or -S (O) 2-NR5R21; R2 is -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R3 is 0-3. Rn is a heteroaryl radical optionally substituted with 1 to 2 radicals (2) halo or cyan; (3) -C (O) -NR3? R32, -OR29, -SR29, -NR3? R32 O R 2 is an aryl radical optionally substituted with 1 to 2 radicals (1) R 30; (2) halo or cyano; (3) -C (0) -NR3? R32, -OR29, -SR29, -S (O) -R30, -S (O) 2 -R30, -S. { 0) 2-NR3? R32, -NR31R32 or -NR33-C (0) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Ru and R? 2 is 0-1;

16. The compound according to claim 15 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is CR2; X3 is CH or CR3; and X4 is N; Y wherein R2 is -Z-Y, with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 is 0-3. R is halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, amido, N, N-dimethylamido, methylsulfonyl or aminosulfonyl; Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino,. { C 1-4 alkoxy) carbonylamino, hydroxyl, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio having 1 to 2 carbon atoms, cyano, halo, alkyl of 1 4 carbon atoms or trifluoromethyl; each R5 is independently the hydrogen or alkyl radical of 1 to 4 carbon atoms, each R20 is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino , alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 atoms carbon, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkanoylamino, (C 1 -alkoxy) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; every R2? is independently radical hydrogen or R20; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Rio is a hydrogen radical, R3o, -C (0) -R29 or -C (O) -NR3iR32; Ru is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Y R12 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; Y R is independently 32 (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals.

17. The compound according to claim 16 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) halo radical; (3) -C (Q) -R20, -C (0) -QR2 ?, -C (0) -NR5R2 ?, (4) -0R2 ?, -SR21, -S (0) -R20, -S ( 0) 2-R2o, or -S (0) 2-NR5R21; or (5) -NR5R2 ?, -NR22-C (0) -R2 ?, -NR22-S (0) 2 -R20 or -NR22-S (0) 2-NR5R2i; R5 is a hydrogen radical; each R20 is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals - CO2R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; Y each R2i is independently hydrogen radical or R20; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen or the methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl, or trifluoromethyl radical; and R 2 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, ... cilsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl.

18. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is CH or CR2; X3 is N; and X4 is CH or CR4; wherein R2 and R are each independently -Z-Y, with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; Y (3) the total combined number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R4 is 0-3.

19. The compound according to claim 18 is a pharmaceutically acceptable salt thereof, characterized in that: R4 is halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (0) -OR20, -C (0) -OR2 ?, -C (0) -NR5R21, -S (O) 2-R20 or S (0) 2-NR5R2 ?; R2 is -Z-Y, with the proviso that (1) R2 and R4 is not. i both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloaikyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R4 is 0-3. Rn is a heteroaryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; or (3) -C (0) -NR3? R32, -OR29, -SR29, -NR3? R32 or -NR33-C (0) -R29; Y R 12 is an optionally substituted aryl radical with 1 to 2 radicals of (1) R 30; (2) Halo or cyano radicals; or (3) the radicals -C (O) -NR3? R32, -OR29, -SR29, -S (O) -R30, -S (0) 2 -R3o, -S (0) 2 -NR3? R32, -NR3? R32 0 -NR33-C (O) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Ru and R12 is 0-1.

20. The compound according to claim 19 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is CR2; X3 is N; and X4 is CH or CR4; wherein R2 is -Z-Y, with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 is 0-3. R4 halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, amido, N, N-dimethylamido, methylsulfonyl or aminosulfonyl; Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkyi of 1 to 2 atoms of carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently hydrogen or alkyl of 1 to 4 carbon atoms; each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (C 1 -C 4 alkyl) amino, C 1 -C 5 alkylamino, (C 1 -C alkoxy) 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) arbono) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoramethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; every R2? is independently hydrogen or R2o radical; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (ax.uyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Rio is a hydrogen radical, R30, -C (O) -R29 or -C (0) -NR3? R32; Rii is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Y R 2 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; (2) the trifluoromethyl radical; or (3) the aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R 32 is independently (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals.

21. The compound according to claim 20 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) halo radical; (3) -C (O) -R20, -C (0) -OR2 ?, -C (0) -NR5R2 ?, (4) -OR2 ?, -SR21, -S (O) -R20, -S ( O) 2-R20, or -S (0) 2-NR5R2 ?; or (5) -NR5R21, -NR22-C (0) -R2 ?, -NR22-S (O) 2 -R20 or -NR22-S (0) 2-NR5R2?; R5 is a hydrogen radical; each R20 is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; Y every R2? is independently radical hydrogen or R20; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen or the methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; Y R 2 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals.

22. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is N; X3 is CH or CR3; and X4 is CH or CR4; wherein R3 and R4 are each independently -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, Xcloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R4 is 0-3.

23. The compound according to claim 22 or a pharmaceutically acceptable salt thereof, characterized in that: R4 is any of the radicals halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (0) -OR2 ?, -C (0) -NR5R2 ?, -S (O) 2 -R20 or S (0) 2-NR5R2 ?; R3 is -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R3 and R4 is 0-3; Rn is a heteroaryl radical optionally substituted with 1 to 2 radicals (1) Rao; (2) halo or cyano; or (3) -C (0) -NR3iR32, -OR29, -SR29, -NR3iR32 or -NR33-C (0) -R29; Y R12 is an aryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; or (3) -C (0) -NR3? R32, -OR29, -SR29, -S (0) -R30, -S (O) 2 -R30, -S (0) 2 -NR3? R32, -NR3 ? R32 or -NR33-C (0) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Rn and R? 2 is 0-1.

24. The compound according to claim 23 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is N; X2 is N; X3 is CR3; and X4 is CH or CR4; wherein R3 is -Z-Y, with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R3 is 0-3; R 4 is any of the halo, phenyl, trifluoromethyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, N, N-dimethylamido, amido, methylsulfonyl or aminosulfonyl radicals; Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently the hydrogen or alkyl radical of 1 to 4 carbon atoms, each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N-. { alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms , halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 atoms of carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; every R2? is independently radical hydrogen or R20; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Rio is a hydrogen radical, R30, -C (0) -R29 or -C (0) -NR3? R32; Rn is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Y R12 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radical; (2) the trifluoromethyl radical; or (3) the aryl or heteraryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; Y R is independently 32 (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals.

25. The compound according to claim 24 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino-, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) halo radical; (3) -C (O) -R20, -C (0) -OR2 ?, -C (0) -NR5R2 ?, (4) -OR2 ?, -SR2 ?, -S (O) -R20, -S (0) 2-R2o, or -S (O) 2-NR5R21; or (5) -NR5R2 ?, -NR22-C (0) -R2 ?, -NR22-S (O) 2 -R20 or -NR22-S (0) 2-NR5R2i; R5 is a hydrogen radical; each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; Y every R2? is independently radical hydrogen or R20; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen or the methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; Y R12 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals.

26. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH or CRi, X2 is CH or CR 2 X3 is N; and X4 is N; wherein Ri and R2 are each independently -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri and R2 is 0-3.

27. The compound according to claim 26 or a pharmaceutically acceptable salt thereof, characterized in that: R is halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (O) -OR20, -C (0) -OR2 ?, -C (O) -NR5R21, -S (O) 2-R20 OS (O) 2-NR5R2 ?; R2 is -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri and R2 is 0-3. Rn is a heteroaryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; (3) -C (0) -NR3? R32, -OR29, -SR29, -NR3? R32 OR -NR33-C (O) -R29; Y R12 is an aryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano, (3) -C (0) -NR3? R32, -OR29, -SR29, -S (O) -R30, -S (O) 2 -R30, -S (0) 2- NR3? R32, -NR3? R32 or -NR33-C (0) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Rn and Ri2 is 0-1.

28. The compound according to claim 27 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH or CRi; X2 is CR2; X3 is N; and X4 is N; wherein Ri is the halo, trifluoromethyl, phenyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, amido, N, N-dimethylamido, methylsulfonyl or aminosulfonyl radicals; R2 is -Z-Y, with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 is 0-3; z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthia of 1 to 2 carbon atoms carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently the hydrogen or alkyl radical of 1 to 4 carbon atoms, each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbon) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbons) ono) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) the radicals api? or heteroaryl optionally substituted with 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; every R2? is independently radical hydrogen or R20; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Rio is a hydrogen radical, R 30, -C (0) -R 9 or -C (0) -NR 31 R 32; Rn is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Y RX2 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; Y R 32 is independently (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals.

29. The compound according to claim 28 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) halo radical; (3) -C (O) -R20, -C (0) -OR2 ?, -C (0) -NR5R2 ?, (4) -0R2X, -SR2i, -S (O) -R20, -S (O ) 2-R20f or -S (O) 2-NR5R21; or (5) -NR5R2 ?, -NR22-C (0) -R2_, -NR22-S (O) 2 -R20 or -NR22-S (0) 2-NR5R2?; Rs is a hydrogen radical; each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, metaxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; each R21 is independently hydrogen radical or R20; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen or the methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; Y R12 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals.

30. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH or CRi; X2 is CH or CR2; X3 is CH or CR3; and X4 is CH or CR4, with the proviso that at least one of Xi, X2, X3 and X4 is CH; wherein Ri, R2, R3 and R are each independently -Z-Y, with the proviso that (1) R2 and R4 are not both substituted or unsubstituted amino radicals; (2) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (3) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri, R2, R3 and R4 is 0-3.

31. The compound according to claim 30 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH; X2 is CH; X3 is CH or CR3; and X4 is CH or CR4; wherein R3 and R4 are each independently -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R is 0-3.

32. The compound according to claim 31 or a pharmaceutically acceptable salt thereof, characterized in that: R4 is any of the radicals halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (0) -OR2 ?, -C (0) -NR5R2 ?, -S (0) 2 -R2O or S (0) 2-NR5R2 ?; wherein R3 is -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R3 and R4 is 0-3; Rn is an optional heteroaryl radical substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; or (3) -C (O) -NR3? R32, -OR29, -SR29, -NR31R32 or -NR33-C (0) -R29; and R12 is an aryl radical optionally substituted with 1 to 2 radicals (1) Rao; (2) halo or cyano; or (3) -C (0) -NR3? R32, -OR29, -SR29, -S (O) -R30, -S (0) 2 -R3o, -S (0) 2 -NR3? R2, -NR3 ? R32 or -NR33-C (O) -R29; with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Rn and R? 2 is 0-1:

33. The compound according to claim 32 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH; X2 is CH; X3 is CR3; and X4 is CH or CR4 wherein R3 is -Z-Y, with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R3 is 0-3. R4 is halo, phenyl, trifluoromethyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, N, N-dimethylamido, amido, methylsulfonyl or aminosulfonyl Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently the hydrogen or alkyl radical of 1 to 4 carbon atoms, each R2o is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, alkylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbon) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 atom-s of carbon) arbono) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; every R2? is independently radical hydrogen or R20? each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Rio is a hydrogen radical, R30, -C (0) -R29 or -C (0) -NR3iR32; Ru is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Y R12 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R30 is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; (2) the trifluoromethyl radical; or (3) the aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R 32 is independently (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals;

34. The compound according to claim 33 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) halo radical; (3) -C (O) -R20, -C (0) -OR2 ?, -C (0) -NR5R2 ?, (4) -OR2i, -SR2 ?, -S (O) -R20, -S ( O) 2-R20, OR -S (O) 2-NR5R2; or (5) -NR5R21, -NR22-C (0) -R2 ?, -NR22-S (O) 2 -R20 or -NR22-S (O) 2-NR5R21, " R5 is a hydrogen radical; each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; Y every R_? is independently radical hydrogen or R2o; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen or the methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; and R12 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals.

35. The compound according to claim 30 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH; X2 is CH or CR2; X3 is CH or CR3; and X4 is CH; wherein R2 and R3 are each independently -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in Ri, R2 and R3 is 0-3.

36. The compound according to claim 35 or a pharmaceutically acceptable salt thereof, characterized in that: R3 is any of the halo, trifluoromethyl, phenyl, methyl, hydroxyethyl, hydroxymethyl, dimethylamino, methoxy, trifluoromethoxy, -C (0) -OR20, -C (0) -OR2i, -C (0) -NR5R21, -S radicals (O) 2-R20 or S (O2-NR5R-, R2 is -Z-Y, with the proviso that (1) the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in each -Z-Y is 0-3; and (2) the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 and R3 is 0-3; Ru is a heteroaryl radical optionally substituted with 1 to 2 radicals (1) R30; (2) halo or cyano; or (3) -C (0) -NR3? R32, -OR29, -SR29, -NR3? R32 or -NR33-C (0) -R29; Y R 2 is an aryl radical optionally substituted with 1 to 2 radicals (1) R 30; (2) halo or cyano; or (3) -C (0) -NR3? R32, "OR29, -SR29, -S (O) -R30, -S (O) 2 -R30, -S (OA-NR31R32, -NR3? R32 O- NR33-C (0) -R29, with the proviso that the total number of substituted aryl, heteroaryl, cycloalkyl and heterocyclyl radicals on each Rn and Rx2 is 0-1:

37. The compound according to claim 36 or a pharmaceutically acceptable salt thereof, characterized in that: Xi is CH; X2 is CR2; X3 is CH or CR3; and X4 is CH; Y wherein R2 is -Z-Y, with the proviso that the combined total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R2 is 0-3; R3 is any of the halo, phenyl, trifluoromethyl, methyl, hydroxymethyl, hydroxyethyl, dimethylamino, methoxy, trifluoromethoxy, acetyl, methoxycarbonyl, ethoxycarbonyl, N, N-dimethylamido, amido, methylsulfonyl or aminosulfonyl radicals; Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 2 carbon atoms) amino, (alkoxy of 1 to 4 carbon atoms) carbonylamino, hydroxyl alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, halo, or aryl or heteroaryl optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms carbon, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; each R5 is independently the hydrogen or alkyl radical of 1 to 4 carbon atoms, each R20 is independently (1) alkyl radicals of 1 to 8 carbon atoms optionally substituted with 1 to 3 radicals -C02R23, amino, alkylamino of 1 to 4 carbon atoms, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbonylamino, N- ((alkoxy of 1 to 4 carbon atoms) carbonyl) -N- (alkyl of 1 to 4 carbon atoms) amino, aminocarbonylamino, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, alkylsulfinyl of 1 to 4 carbon atoms, axylsulfonyl of 1 to 4 carbon atoms, halo or cycloalkyl of 3 to 6 carbon atoms, heterocyclyl, aryl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, di- (alkyl of 1 to 4 carbon atoms) amino, alkanoylamino of 1 to 5 carbon atoms, (alkoxy of 1 to 4 carbon atoms) carbon) carbonylamino, alkylsulfonylamino of 1 to 4 carbon atoms, (alkoxy of 1 to 4 carbon atoms) arbono) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 radicals (alkoxy of 1 to 4 carbon atoms) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms; or (3) aryl or heteroaryl radicals optionally substituted by 1 to 2 radicals (C 1 -C 4 alkoxy) carbonyl, hydroxyl, alkoxy of 1 to 4 carbon atoms, alkylthio of 1 to 4 carbon atoms, cyano, halo, azido, alkyl of 1 to 4 carbon atoms or trifluoromethyl; every R2? is independently radical hydrogen or R20; each R23 is independently hydrogen or alkyl of 1 to 4 carbon atoms, or phenyl- (alkyl of 1 to 2 carbon atoms) optionally substituted with 1 to 2 hydroxyl radicals, alkoxy of 1 to 2 carbon atoms, alkylthio of 1 to 2 carbon atoms, cyano, halo, alkyl of 1 to 4 carbon atoms or trifluoromethyl; Ru is a heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radicals; Y R 2 is an aryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals; R3o is independently (1) the alkyl radical of 1 to 4 carbon atoms optionally substituted with a phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; (2) the trifluoromethyl radical; or (3) the aryl or heteroaryl radicals optionally substituted with 1 to 3 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; R29 is an aryl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, methoxy, methyl or trifluoromethyl radicals; Y R 32 is independently (1) hydrogen or the alkyl radical of 1 to 4 carbon atoms; or (2) phenyl or heteroaryl radical optionally substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, methoxy, methyl or trifluoromethyl radicals.

38. The compound according to claim 37 or a pharmaceutically acceptable salt thereof, characterized in that: Z is independently one (1) link; or (2) an alkyl radical of 1 to 4 carbon atoms optionally substituted with 1 to 2 amino, t-butoxycarbonylamino, dimethylamino, hydroxyl, methoxy, methylthio or halo radicals; And it is independently one (1) hydrogen radical, with the proviso that Z is different from a bond; (2) halo radical; (3) -C (O) -R20, -C (0) -OR2i, -C (0) -NR5R21, (4) -OR2 ?, -SR21, -S (O) -R20, -S (O) 2-R20, or -S (O) 2-NR5R21; or (5) -NR5R2 ?, -NR22-C (0) -R2i, -NR22-S (O) 2 -R20 or -NR22-S (O) 2-NR5R2?; R5 is a hydrogen radical; each R2o is independently (1) alkyl radicals of 1 to 6 carbon atoms optionally substituted with 1 to 3 radicals - CO2R23, amino, methylamino, dimethylamino, t-butoxycarbonylamino, N- ((t-butoxy) carbonyl) -N- ( methyl) amino, aminocarbonylamino, hydroxyl, butoxy, methoxy, butylthio, methylthio, methylsulfinyl, methylsulfonyl, halo or cycloalkyl of 5 to 6 carbon atoms, heterocyclyl, phenyl or heteroaryl radicals optionally substituted with 1 to 2 amino radicals, dimethylamino, acetamino, hydroxyl, methoxy, methylthio, halo, methyl or trifluoromethyl; (2) the heterocyclyl radical optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, or alkyl of 1 to 4 carbon atoms radicals; or (3) aryl or heteroaryl radicals optionally substituted with 1 to 2 t-butoxycarbonyl, hydroxyl, methoxy, methylthio, cyano, halo, azido, methyl or trifluoromethyl radicals; every R2? is independently radical hydrogen or R20; each R22 is independently hydrogen or methyl radical; each R23 is independently hydrogen or alkyl radicals of 1 to 4 carbon atoms; Rio is a hydrogen or the methyl radical; Ru is a 4-pyridyl, 4-quinolinyl, 4-imidazolyl or 4-pyrimidinyl radical optionally substituted with an amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methyl or trifluoromethyl radical; Y R12 is an unsubstituted phenyl or naphthyl radical, or a phenyl radical substituted with 1 to 2 amino, dimethylamino, acetamido, hydroxyl, halo, cyano, methoxy, methylthio, methylsulfinyl, methylsulfonyl, aminocarbonyl, methyl or trifluoromethyl radicals.

39. The compound according to claim 1, characterized in that it is: 3- (4-pyridyl) -2- (4-fluorophenyl) indole; 3- (4-fluorophenyl) -2- (4-pyridyl) indole; 6-amino-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-3- (4-fluorophenyl) -2- (4-pyridyl) -7-aza-indole; 6- (4'-t-Butoxica bonylamino-1 '-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 '-amino-1 * -oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-ureido-l '-oxo-2'-t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-5'-ureido-1-oxo-2 '-aminopenti lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-t-Butoxycarbonylamino-1 '-oxo-2'-t-butoxycarbonylaminohexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-amino-1-oxo-2'-aminohexylaii-o) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-t-Butoxycarbonylamino-1 '-oxo-2 * -t-butoxycarbonylaminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-amino-l, -oxo-2I-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (4-iodophenyl) -1 '-oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (31- (4-iodophenyl) -1 '-oxo-2'-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-methyl-1' -oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-methyl-1 * -oxo-2'-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 •, 4 '-dimethyl-1' -oxo-2'-t-butoxycarbonylamino-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aze-indole; 6- (4 *, 4'-dimethyl-1 '-oxo-2'-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5 * -t-Butoxycarbonylamino-1 '-oxo-pentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (5'-amino-1 '-oxo-pentylamino) -3- (4-pixidyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-1-Butoxycarbonylamino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (6'-amino-1 '-oxo-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-cyclohexyl-1-oxo-2l-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-cyclohexyl-l, -oxo-2I-aminopropylamino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole; 6- (4'-t-Butoxycarbonyl-1-oxo-2'-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (4 I-carboxy-1-oxo-2 '-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-O-t-Butoxy-1-oxo-2'-1-butoxycarbonylaminobutyl) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-hydroxy-1-oxo-2'-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1'-oxo-2 * -t-butoxycarbonylaminopropyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1-oxo-2'-D, L-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (31- (4-t-butoxyphenyl) -1' -oxo-2'-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-? 4-hydroxyphenyl) -l'-oxo-2'-aminopropylamino) • 3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-t-Butoxycarbonylamino-1 '-oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-t-Butoxycarbonyla ino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-amino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (methylsulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 '- (5-chlorothienyl) sulfonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (phenylsulfonylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2'-N-phthaloyl-1 * -oxo-ethylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (3 '-N-phthaloyl-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 3- (4-pyridyl-2- (4-fluorophenyl) -4,7-aza-indole; 6- (2'-N-t-butoxycarbonyl-L-prolylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2'-L-prolylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2S '-dimethylamino-1' -oxo-propylamino) -3- (4-pyridyl-2- (4-fluorophenyl) -7-aza-indole; 6- (2'-dimethylamino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-N-methyl-t-butoxycarbonylamino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-N-methyl-1-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 '-N-t-butoxycarbonylisonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-isonipecotylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 '-methylsulfoxo-1' -oxo-2 'S-t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4 '-methylsulfoxo-1' -oxo-2 'S-aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (31- (3-pyridyl) -l' -oxo-2 * S-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (3-pyridyl) -lf -oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (N, N-Di-t-butoxycarbonyl-L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (L-histidinylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (Nt-butoxycarbonyl-3 (S) -l ', 2', 3 ', 4' -tetrahydro-3'-isoquinoliniloxo-amino) -3- (4-pyridyl) -2- (4-fluoro-phenyl) -7-aza-indole; 6- (3 (S) -l ', 2', 3 ', 4' -tetrahydro-3 '-isoquinoliniloxo-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza- indole; 6- (2 * -phenyl-1-oxo-2 'R-N-t-butoxycarbonylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-l '-oxo-2' R-aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-l '-oxo-2' -S-N-t-butoxycarbonylamino-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-1-oxo-2'-S-aminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-l '-oxo-2' R-N-t-butoxycarbonyl-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-phenyl-1-oxo-2 'R-N-methylaminoethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1'-oxo-2 '- (L) -t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1 '-oxo-2' - (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1 * -oxo-2 'S-t-butoxycarbonyl-N-methylaminopropyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-N-methylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- { 1 '-oxo-2' S-t-butoxycarbonyl-N-methyl-4-methyl-2-aminopentyl-amino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'S-N-methy1-4-methy1-2-aminopentylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1'-oxo-2 'R-t-butoxycarbonylaminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (1-oxo-2 'R-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (2-thienyl) -1' -oxo-2'- (L) -t-butoxycarbonylamino-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza -indol; 6- (3 '- (2-thienyl) -l'-oxo-2' - (L) -aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '- (4-azidophenyl-l'-oxo-2'S-t-butoxycarbonyl-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '- (4-azidophenyl) -1' -oxo-2 'S-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'- (3-benzothienyl) -1' -oxo-2 'S-t-butoxycarboni 1-aminopropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 '- (3-benzothienyl) -1' -oxo-2'-S-aminopropylamine) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-phenyl-1-oxo-2'- (LJ-t-butoxycarbonylamino-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-phenyl-1-oxo-2'- (L) -aminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-phenyl-1'-oxo-2 '- (D) -t-butoxycarbonylaminobutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (4'-phenyl-1-oxo-2 * - (D) -aminob._t -lamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-amino-1'-oxo-ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutoxycarbonyl-7-aza-indole; 6- (phenylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (diethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 '(R, S) -phenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 '(R, S) -eti-hexylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-5-chloro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-5-fluoro-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6-amino-5-bromo-3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (di-isoamylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 ', 2'-dimethyl-1-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (isoamylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-ethylbutylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-thienylmethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3 ', 3' -diphenylpropylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (ethylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (3'-phenyl-1-oxo-2 '- (R, S) -methylpropylamino) -3-r (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2'-amino-1 '-oxo-ethylamino) -3- (4-pyridyl) -2r- (4-fluorophenyl) -1-methyl-1-7-aza-indo1; 6- (3 ', 3'-dimethyl-1-oxo-butylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (ethoxycarbonylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -7-aza-indole; 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-methyl-7-aza-indole; 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-isobutyl-7-aza-indole; and 6- (2 'S-amino-1' -oxo-propylamino) -3- (4-pyridyl) -2- (4-fluorophenyl) -l-cyclohexylmethyl-7-aza-indole.

40. A pharmaceutical composition, characterized in that it comprises a compound according to claims 1 to 39, and a pharmaceutically acceptable carrier.

41. A method of prophylaxis or treatment of inflammation, characterized in that it comprises the administration of an effective amount of a compound according to claims 1 to 39.

42. A method of prophylaxis or treatment of inflammation, characterized in that it comprises the administration of an effective amount of a composition according to claim 40.

43. A method of prophylaxis or treatment of rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveitis, acute or chronic leukemia, destruction of ß-cells of the pancreas, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, syndrome of adult respiratory failure (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, utuscular degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases , graft reaction vs. host, Alzheimer's disease, stroke, myocardial infarction, damage due to ischemic stroke, atherosclerosis, cerebral trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever or myalgia due to infection, or the viruses HIV-1, HIV-2, HIV-3, cytomegalovirus, influenza virus, adenovirus, herpes virus or herpes zoster in a mammal, characterized in the method because it comprises the administration of an effective amount of a compound in accordance with Claims 1 to 39.

44. A method of prophylaxis or treatment of rheumatoid arthritis, Pagets disease, osteoporosis, multiple myeloma, uveitis, acute or chronic myelogenous leukemia, destruction of ß-cells of the pancreas, osteoarthritis, rheumatoid spondylitis, gouty arthritis, inflammatory bowel disease, syndrome of adult respiratory failure (ARDS), psoriasis, Crohn's disease, allergic rhinitis, ulcerative colitis, anaphylaxis, contact dermatitis, asthma, muscle degeneration, cachexia, Reiter's syndrome, type I diabetes, type II diabetes, bone resorption diseases , graft reaction vs. host, Alzheimer's disease, stroke, myocardial infarction, ischemic stroke damage, atherosclerosis, brain trauma, multiple sclerosis, cerebral malaria, sepsis, septic shock, toxic shock syndrome, fever or myalgia due to infection, or the viruses HIV-1, HIV-2, HIV-3, cytomegalovirus, influenza virus, adenovirus, herpes virus or herpes zoster in a mammal, characterized in the method because it comprises the administration of an effective amount of a compound in accordance with the Claim 40

45. A method for decreasing plasma concentrations of either TNF-a and IL-1, characterized in that it comprises the administration of an effective amount of a compound according to claims 1 to 39.

46. A method for decreasing plasma concentrations of either TNF-a and T-1, characterized in that it comprises the administration of an effective amount of a composition according to claim 40.

47. A method for decreasing plasma concentrations of either IL-6 and IL-8, characterized in that it comprises the administration of an effective amount of a compound according to claims 1 to 39.

48. A method for decreasing plasma concentrations of either IL-6 and IL-8, characterized in that it comprises the administration of an effective amount of a composition according to claim 40.

49. A method of prophylaxis or treatment of diabetes disease in a mammal, characterized in that it comprises administering an effective amount of a compound according to claims 1 to 39, to produce a glucagon antagonist effect.

50. A method of prophylaxis or treatment of diabetes disease in a mammal, characterized in that it comprises the administration of an effective amount of a pharmaceutical composition in accordance with the claim 40, to produce a glucagon antagonist effect.

51. A method of prophylaxis or treatment of a pain disorder in a mammal, characterized in that it comprises the administration of an effective amount of a compound according to claims 1 to 39.

52. A method of prophylaxis or treatment of a pain disorder in a mammal, characterized in that it comprises the administration of an effective amount of a pharmaceutical composition according to claim 40.

53. A method for decreasing the production of prostaglandins in a mammal, characterized in that it comprises the administration of an effective amount of a compound according to claims 1 to 39.

54. A method for decreasing the production of prostaglandins in a mammal, characterized in that it comprises the administration of an effective amount of a pharmaceutical composition according to claim 40.

55. A method for decreasing the activity of the enzyme cyclooxygenase in a mammal, characterized in that it comprises the administration of an effective amount of a compound according to claims 1 to 39.

56. The method according to claim 55, characterized in that the enzyme cyclooxygenase is COX-2.

57. A method for decreasing the activity of the enzyme cyclooxygenase in a mammal, characterized in that it comprises the administration of an effective amount of a pharmaceutical composition according to claim 40.

58. The method according to claim 57, characterized in that the enzyme cyclooxygenase is COX-2.