WE CLAIM :

1.

A compound of Formula I: in which: X1 is C(R1)(R2)X2 or X3; X2 is cyano,CHO,C (R7)(R8)R5, C(R7)(R8) CF3,C (R7)(R8)CF2CF2R9 CHCHS(O)2R5, C(R7)(R8)CF2C(O)NR5R6, C(R7)(R8)C(R7)(R8)NR5R6, C(R7)(R8)C(R7)(R8)OR5, C(R7)(R8)CH2OR5, C(R7)(R8)CH2N(R6)SO2R5, C(R7)(R8)C(R7)(R8)N(R6)(CH2)2OR6, C(R7)(R8) C (R7) (R8) N (R6) (CH2) 2NR6 or C(R7)(R8)C(R7)(R8)R5; wherein R5 is (C14) alkyl, (C6lo) aryl (Co6) alkyl, hetero (C410)aryl(C06) alkyl, (C4. 10) cycloalkyl (Co6) alkyl or hetero (C41o) cycloalkyl (Co6) alkyl; R6 is hydrogen or (C16) alkyl; R7 is hydrogen or (C14) alkyl and R8 is hydroxy or R7 and R8 together form oxo; R9 is hydrogen, halo, (C14) alkyl, (C510)aryl(C06)alkyl or hetero (C510) aryl (Co6) alkyl ; X3 represents a group of Formula (a): (a) in which n is 1 or 2, z is 0 or 1, X5 is selected from NR10, S or 0, wherein Rlo is hydrogen or (Cl6) alkyl, and X6 is 0, S or NRtI, wherein Rll is selected from hydrogen, (C16) alkyl, X4C(O)OR12, X4C(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4S(O)2R14, R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4C(O)NR12R15 and X4S(O)2NR12R15, in which X4 is a bond or (C16)alkylene ; Rl2 at each occurrence independently is hydrogen or (Cl6) alkyl; R"is hydrogen, (C16)alkyl or halosubstituted(C16)alkyl, R14 is (C16) alkyl or halosubstituted (Ci6) alkyl and Rl5 is (C3_io) cYcloalkyl (Co6) alkyl, hetero (C3 io) cycloalkyl (Co3) alkyl, (C610)aryl(C06)alkyl, hetero(C510)aryl(C06)alkyl, (C9l2) bicycloaryl (Co6) alkyl or hetero(C812) bicycloaryl (Co6) alkyl; wherein within Xl any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R20 selected from R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, XRN412C(O)R15, X4NR12C(O)OR15, X4C(O)NR15R12, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12 ; and wherein Xl and R20 may be substituted further with 1 to 5 radicals independently selected from (C16) alkyl, cyano, halo, halosubstituted (Cl4) alkyl, nitro, X4NR12R2,XRNR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14 and X4S(O)2R14 wherein X4, R12, R13, R14 and R15 are as defined above; R1 and R2 are both fluoro; or R1 is hydrogen or (Cl6) alkyl and R2 is selected from the group consisting of hydrogen, (C16)alkyl, cyano, X4NR12R12, XRNR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR19)NR19R12, X4OR13, X4SR13, X4C(O)OR12, <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13,<BR> X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14, X4S(O)2R14, R15, XROR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR15RE12, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12, wherein X4, R12, R13, R14 and R15 are as defined above; or R'and R2taken together with the carbon atom to which both R1 and R2 are attached form (C38) cycloalkylene or hetero (C38) cycloalkylene; wherein R2, said cycloalkylene and said heterocycloalkylene may be substituted further with 1 to 3 radicals independently selected from (Cl6) alkyl, cyano, halo, halosubstituted (C14) alkyl, nitro, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(ONR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, XRC(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12,X4S(O)R14 and X4S(O2)R14, wherein X4,R12, R13 and R14 are as defined above; R3 and R4 are independentlyC (Rl6) (R17)X7, wherein R16 and R17 are hydrogen, (C16) alkyl or fluoro, or R16 is hydrogen and R17 is hydroxy and X7 is selected from X4NR12R12, XRN412C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13,X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O(NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14, X4S(O)2R14, R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR15R12, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(ONR15R12 and X4NR12C(NR12)NR15R12, wherein X4, R12, R13, Rl4 and R are as defined above; wherein within one of R3 or R4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R21 selected from R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR12R15, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12, wherein X4, R 12 and R15 are as defined above; and wherein each of R3, R4 and R21 may be substituted further with 1 to 5 radicals independently selected from (C16) alkyl, cyano, halo, halosubstituted (C14) alkyl, nitro, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, 0X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X40P (O) (ORl') ORl',X4S (O) R14 andX4S (0) 2R14, wherein X4, R12, R13 and R14 are as defined above; provided that only one bicyclic ring structure is present within each of R3 or R4 ; and provided that when X2 is cyano and X7 within one of R3 or R4 isX4C (O) R13 or X4C (O) R, wherein X4 is a bond, then X7 within the other of R3 or R4 is limited to X4S415, X4S(O)R15 and X4S(O02R15, wherein R'5 is (C6io) aryl (C16) alkyl substituted with 1 to 5 radicals or hetero (C510) aryl (C06) alkyl optionally substituted with 1 to 5 radicals, wherein said radicals are independently selected from (C16) alkyl, cyano, halo, halosubstituted (C14)alkyl, niro, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR2C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14 and X4S(O)2R14, wherein X4, R12, R13 and R14 are as defined above, provided that the radical is not selected from only halo when R15 is (C610)aryl(C16) alkyl; and provided that when X2 is cyano then X7 within R3 and R4 is not X4C(O)NR12R12, X4C(O)NR15R12 or X4C(O)NR18R19, wherein X4 is a bond and Rlg and R19 together with the nitrogen atom to which they are attached form hetero (C310)cycloalkyl or hetero (C510)aryl; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

2.

The compound of Claim 1 in which: X1 is C(R1)(R2)X2 or X3; X2 is cyano,CHO,C (O) R5,C (O) CF3,C (O) CF2CF2R9 CHCHS (0) 2R5, C(O)CF2C(O)NR5R6, C(O)C(O)NR5R6, C(O) C (O) OR5,C (O) CH20RS, C(O)CH2N(R6)SO2R5, C(O) C (O) N (R6) (CH2) 20R6,C (O) C (O) N (R6) (CH2) 2NR6 or C (O) C (O) R5, wherein R5 is (Cl_4) alkyl, (C6lo) aryl (Co6) alkyl, hetero (C410)aryl(C06)alkyl, (C410)cycloalkyl(C06) alkyl or hetero (C410)cycloalkyl(C06) alkyl, R6 is hydrogen or (C16) alkyl and R9 is halo ; X3 represents a group of Formula (b): in which n is 1 or 2, z is 0 or 1, X6 is O or NR11, wherein Rll is selected from hydrogen, (C16)alkyl, X4OC(O)R13, X4C(O)OR12, X4C(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4S(O)2R14, R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4C(O)NR12R15 and X4S(O)2NR12R15, in which X4 is a bond or (C16)alkylene ; R12 at each occurrence independently is hydrogen or (C16) alkyl; R13 is hydrogen, (C16)alkyl or halosubstituted (C16)alkyl, R14 is (Cl6) alkyl or halosubstituted (C16)alkyl and R15 is (C310)cycloalkyl(C06) alkyl, hetero (C3 io) cYcloalkyl (Co3) alkyl, (C610)aryl(C06)alkyl, hetero 9C510) aryl (Co6) alkyl, (C912) bicycloaryl C06)alkyl or hetero (C812) bicycloaryl (C06) alkyl; wherein within Xl any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from R15 and X4C(O)R15 ; and wherein Xl may be substituted further with 1 to 3 radicals independently selected from (C16) alkyl, halosubstituted (C14)alkyl, X4NR12R12, X4OR13 and X4S(O)2R14, wherein X4, Rl2, Rl3, R14 and R15 are as defined above; R1 and R2 are both fluoro ; or Rl is hydrogen or (Cl6) alkyl and R2 is selected from the group consisting of hydrogen, (C16)alkyl, X4OR13 and R15 ; or R'and R 2taken together with the carbon atom to which both R1 and R2 are attached form (C3s) cycloalkylene or hetero (C38)cycloalkylene ; wherein R2 may be substituted further with (C16)alkyl ; wherein X4, R13 and R15 are as defined above; R3 and R4 are independently C(R16)(R17)X7, wherein R16 and R17 are hydrogen, (C16) alkyl or fluoro, or R16 is hydrogen and R17 is hydroxy and X7 is selected from X4SR13, X4C(O)R13, X4C(O)NR12R12,R15,X4OR15,X4SR15, X4S(O)2R15, X4C(O)R15 and X4C(O)NR15R12, wherein X4, R12, R13 and R15 are as defined above; wherein within one of R3 or R4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR12R15, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12, wherein X4, R12 and R15 are as defined above; and wherein each of R3 and R4 may be substituted further with 1 to 5 radicals independently selected from (Cl 6) alkyl, cyano, halo, halosubstituted (C14)alkyl, nitro, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, 40P (O) (OR12) ORl2,X4S (O) R14 andX4S (0) 2R14, wherein X4, Rl2, R13 and R14 are as defined above; wherein within one of R3 and R4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected fromR15 andX40R15 ; and wherein each of R3 or R4 may be substituted further by 15 radicals independently selected from (C16) alkyl, cyano, halo, halosubstituted (C14)alkyl, X4NR12C(O)OR12, X4OR13, X4C(O)OR12, X4C(O)R13, X4C(O)NR12R12, X4NR12S(O)2R13 and X4S(O)2R14, wherein X4, R12, R13, R14 and R15 are as defined above; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

3.

A compound of claim 2 in which R3 and R4 are independentlyCH, X7, wherein X7 is selected from X4SR13, X4C(O)R13, X4C(O)NR12R12, R15, X4OR15, X4SR15, X4S(O)2R15, X4C(O)R15 and X4C(O)NR15R12, wherein X4 is a bond or (C16) alkylene, Ru'art each occurrence independently is hydrogen or (Cl6) alkyl, R13 is hydrogen, (C16) alkyl or halosubstituted (C16)alkyl, R14 is (C16)alkyl or halosubstituted (C16) alkyl and R15 is (C310)cycloalkyl(C06) alkyl, (C3io) cYcloalkyl (Co6) alkyl, hetero (C3_lo) cycloalkyl (Co3) alkyl, (C6io) arYl (Co6) alkyl, hetero (C510)aryl(C06)alkyl, (C912) bicycloaryl (Co6) alkyl or hetero (C812) bicycloaryl (Co6) alkyl; wherein within R3 and R4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical selected from R15 andX40RI5, wherein X4 and Rl5 are as defined above; and wherein R3 and R4 may be substituted further by 1 to 5 radicals independently selected from (Cl6) alkyl, cyano, halo, halosubstituted (C14)alyl, X4NR12C(O)OR12, X4OR13, X4C(O)OR12, X4C(O)R13, X4C (o) NRI2Rl2,X4NRt2S (0) 2RI3 andX4S (0) 2RI4, wherein X4 Rl2, Rl3 and Rl4 are as defined above; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

4.

A compound of claim 3 in which R3 is selected from 5bromothiophen2 ylmethyl, 3cyclohexylpropyl, 2cyclohexylpropyl, 2cyclopentylpropyl, 3phenylpropyl, 3 (2difluoromethoxy) phenylpropyl, 2phenylcyclopropylmethyl, 2,2difluoro 3phenylpropyl, 1benzylcyclopropylmethy, 2tetrahydropyran4ylethyl, 1isobutylcyclopropylmethyl, thiophen2ylmethyl, tetrahydropyran4ylmethyl, cyclopropylmethylsulfanylmethyl, 2,2dimethyl3phenylpropyl, 4methyl [1,2,5] thiadiazol3ylmethylsulfonylmethyl, 3methyl [1, 2,4] thiadiazol3 ylmethylsulfonylmethyl, thiophen3ylmethylsulfonylmethyl, 3methoxy5methyl isoxazol4ylmethylsulfonylmethyl, 2,4dimethylthiazol5ylmethylsulfonylmethyl, 2 methyloxazol4ylmethylsulfonylmethyl, 2methylthiazol4ylmethylsulfonylmethyl,, 1, 2,3] thiadiazol4ylmethylsulfonylmethyl, 3methyl [1, 2,4] thiadiazol5 ylmethylsulfonylmethyl, 4methyl [1, 2,5] thiadiazol3ylmethylsulfonylmethyl, thiophen3 ylmethylsulfonylmethyl, tetrahydropyran4yloxymethyl, piperidin1ylcarbonyl, thiophene2sulfonylmethyl, 3chloro2fluorobenzylsulfonylmethyl, benzenesulfonylmethyl, benzylsulfonylmethyl, 2 (1, 1difluoromethoxy)benzylsulfonylmetliyl, 2benzenesulfonylethyl, 2 (pyridine2sulfonyl)ethyl, 2 (pyridine4sulfonyl)ethyl, 2benzylsulfonylethyl, oxypyridin2ylmethylsulfonylmethyl, prop2ene1sulfonylmethyl, 4methoxybenzylsulfonylmethyl, ptolylmethylsulfonylmethyl, 4chlorobenzylsulfonylmethyl, otolylmethylsulfonylmethyl, 3,5dimethylbenzylsulfonylmethyl, 4trifluoromethylbenzylsulfonylmethyl, 4trifluoromethoxybenzylsulfonylmethyl, 2bromobenzylsulfonylmethyl, pyridin2ylmethylsulfonylmethyl, pyridin3ylmethylsulfonylmethyl, pyridin4ylmethylsulfonylmethyl, naphthalen2ylmethylsulfonylmethyl, 3methylbenzylsulfonylmethyl, 3trifluoromethylbenzylsulfonylmethyl, 3trifluoromethoxybenzylsulfonylmethyl, 4fluoro2trifluoromethoxybenzylsulfonylmethyl, <BR> <BR> <BR> 2fluoro6trifluoromethylbenzylsulfonylmethyl, 3chlorobenzylsulfonylmethyl, 2fluorobenzylsulfonylmethyl, 2trifluorobenzylsulfonylmethyl, 2cyanobenzylsulfonylmethyl, 4tertbutylbenzylsulfonylmethyl, 2fluoro3methylbenzylsulfonylmethyl, 3fluorobenzylsulfonylmethyl, 4fluorobenzylsulfonylmethyl, 2chlorobenzylsulfonylmethyl, 2,5difluorobenzylsulfonylmethyl, 2,6difluorobenzylsulfonylmethyl, 2,5dichlorobenzylsulfonylmethyl, 3,4dichlorobenzylsulfonylmethyl, <BR> <BR> <BR> <BR> 2 (l, 1difluoromethoxy)benzylsulfonylmethyl, 2cyanobenzylsulfonylmethyl, 3cyanobenzylsulfonylmethyl, 2trifluoromethoxybenzylsulfonylmethyl, 2,3difluorobenzylsulfonylmethyl, 2,5difluorobenzylsulfonylmethyl, biphenyl2ylmethylsulfonylmethyl, cyclohexylmethyl, 3fluorobenzylsulfonylmethyl, 3,4difluorobenzylsulfonylmethyl, 2,4difluorobenzylsulfonylmethyl, 2,4,6trifluorobenzylsulfonylmethyl, 2,4,5trifluorobenzylsulfonylmethyl, 2,3,4trifluorobenzylsulfonylmethyl, 2,3,5trifluorobenzylsulfonylmethyl, 2,5,6trifluorobenzylsulfonylmethyl, 2chloro5trifluoromethylbenzylsulfonylmethyl, 2methylpropanelsulfonyl, 2fluoro3trifluoromethylbenzylsulfonylmethyl, 2fluoro4trifluoromethylbenzylsulfonylmethyl, 2fluoro5trifluoromethylbenzylsulfonylmethyl, 4fluoro3trifluoromethylbenzylsulfonylmethyl, 2methoxybenzylsulfonylmethyl, 3,5 bistrifluoromethylbenzylsulfonylmethyl, 4difluoromethoxybenzylsulfonylmethyl, 2difluoromethoxybenzylsulfonylmethyl, 3difluoromethoxybenzylsulfonylmethyl, 2,6dichlorobenzylsulfonylmethyl, biphenyl4ylmethylsulfonylmethyl, 3,5dimethylisoxazol4ylmethylsulfonylmethyl, 5chlorothiophen2ylmethylsulfonylmethyl, <BR> <BR> <BR> <BR> 2 [4 (I, 1Difluoromethoxy)benzenesulfonyl]ethyl,<BR> <BR> <BR> <BR> <BR> <BR> 2 [2 (1, 1Difluoromethoxy)benzenesulfonyl]ethyl, 2 [3 (1, 1Difluoromethoxy)benzenesulfonyl]ethyl, 2 (4trifluoromethoxybenzenesulfonyl)ethyl, 2 (3trifluoromethoxybenzenesulfonyl)ethyl, 2 (2trifluoromethoxybenzenesulfonyl)ethyl, (cyanomethylmethylcarbamoyl)methyl, biphenyl3ylmethyl, 2oxo2pyrrolidin1ylethyl, 2benzenesulfonylethyl, isobutylsulfanylmethyl, 2phenylsulfanylethyl, cyclohexylmethylsulfonylmethyl, 2cyclohexylethanesulfonyl, benzyl, naphthalen2yl, benzylsulfanylmethyl, 2trifluoromethylbenzylsulfanylmethyl, phenylsulfanylethyl and cyclopropylmethylsulfonylmethyl; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

5.

A compound of claim 4 in which R4 is selected from 2trifluorobenzylsulfonylmethyl, 3phenylsulfanylpropyl, 4chlorobenzylsulfonylmethyl, thiophen2ylsulfonylmethyl, benzylsulfonylmethyl, 4methylbenzylsulfonylmethyl, 2phenylsulfonylethyl, 2pyridin2ylsulfonylethyl, 2pyridin4ylsulfonylethyl, 2benzylsulfonylethyl, 2 (3difluoromethoxyphenylsulfonyl) ethyl, naphthalen2ylmethylsulfonylmethyl, pyridin2ylmethylsulfonylmethyl, 3methylbenzylsulfonylmethyl, 3trifluoromethylbenzylsulfonylmethyl, 3difluoromethoxybenzylsulfonylmethyl, 3chlorobenzylsulfonylmethyl, 3fluorobenzylsulfonylmethyl, 4fluorobenzylsulfonylmethyl, 3cyanobenzylsulfonylmethyl, 4cyanobenzylsulfonylmethyl, 3,4difluorobenzylsulfonylmethyl, benzylsulfonylmethyl, NcyanomethylNmethylcarbamoylmethyl, 3bromobenzyl, 4phenylbutyl, 2,2difluoro 3phenylpropyl, 4'methylsulfonylaminobiphenyl3ylmethyl, 4'ethoxycarbonylaminobiphenyl3ylmethyl, 4methylpiperazin1ylcarbonylmethyl, 1fluoro2 (4methylpiperazin1yl)2oxoethyl, 1hydroxy4methylpiperazin1yl 2oxoethyl, 1hydroxy2morpholin4yl2oxoethyl, 1hydroxy2oxo2pyrrolidin1yl ethyl, 1fluoro2oxo2pyrrolidin1yletliyl, 1fluoro2isopropylamino2oxoethyl, 1hydroxy2isopropylamino2oxoethyl, 1fluoro2oxo2piperazin1ylethyl, thiophen3ylmethylsulfonylmethyl, 4methyl [1, 2,5] thiadiazol3ylmethylsulfonylmethyl, 3methoxy5methylisoxazol4ylmethylsulfonylmethyl, 2,4dimethylthiazol5 ylmethylsulfonylmethyl, 2methyloxazol4ylmethylsulfonylmethyl, 2methyl thiazol4ylmethylsulfonylmethyl, 2 ( [1, 2,3] thiadiazol4ylmethylsulfonyl)ethyl, 2 (3 methyl [1, 2,4] thiadiazol5ylmethylsulfonyl)ethyl, 2oxo2phenylethyl, 2morpholin4yl2oxoethyl, 2benzenesulfonylethyl, 2naphthalen2yl2oxoethyl, 2benzo [1,3] dioxol5yl2oxoethyl, 2benzo [b] thiophen2yl2oxoethyl, 2biphenyl4yl2oxoethyl, 4benzylsulfonylmethyl, <BR> <BR> <BR> <BR> 2 (3trifluoromethoxybenzenesulfonyl)ethyl, 2oxo2 (4phenoxyphenyl)ethyl, 2 (4hydroxyphenyl)2oxoethyl, benzylcarbamoylmethyl, 4acetylpiperazine1carboxylic acid ethyl ester, cyclohexylcarbamoylmethyl, <BR> <BR> <BR> <BR> 2(3Chlorobenzo [b] thiophen2yl)2oxoethyl,'benzenesulfonylmethyl, 2oxo2thiophen2ylethyl, 2oxo2thiophen3ylethyl, naphthalene2sulfonylmethyl, <BR> <BR> <BR> <BR> 2 (5methylthiophen2yl)2oxoethyl, 2 (3chlorothiophen2yl)2oxoethyl,<BR> <BR> <BR> <BR> <BR> <BR> 5methylthiophene2sulfonylmethyl, phenylcarbamoylmethyl, (5,6,7,8tetrahydronaphthalen1ylcarbamoyl)methyl, (4carbamoylphenylcarbamoyl)methyl, (3carbamoylphenylcarbamoyl)methyl, (butylmethylcarbamoyl)methyl, biphenyl4ylmethyl, 2oxo2ptolylethyl, <BR> <BR> <BR> <BR> 2 (3fluoro4methoxyphenyl)2oxoethyl, 2 (4chlorophenyl)2oxoethyl,<BR> <BR> <BR> <BR> <BR> 2 (4methoxyphenyl)2oxoethyl, 2oxo2 (4trifluoromethoxyphenyl)ethyl, 2 (3, 4difluorophenyl)2oxoethyl, 2 (3, 4dimethoxyphenyl)2oxoethyl, 2 (4fluorophenyl)2oxoethyl, 5methyl2oxohexyl, 3,5dimethylbenzylsulfonylmethyl, 4trifluoromethylbenzylsulfonylmethyl ; 4trifluoromethoxybenzylsulfonylmethyl, isopropylcarbamoylmethyl, 4dimethylcarbamoylmethyl, pyridin4ylcarbamoylmethyl, pyridin4ylmethylsulfonylmethyl, pyridin3ylmethylsulfonylmethyl, 3,4dichlorobenzylsulfonylmethyl, pyridin3ylcarbamoylmethyl, 4methoxybenzylsulfonylmethyl, 4chlorobenzylsulfonylmethyl, thiophene2sulfonylmethyl, benzylsulfonylmethyl, ptolylmethylsulfonylmethyl, 2benzenesulfonylethyl, 2 (pyridine2sulfonyl)ethyl, 2 (pyridine4sulfonyl)ethyl, 2benzylsulfonylethyl, 2 [3 (1, lDifluoromethoxy)benzenesulfonyl]ethyl, naphthalen2ylmethylsulfonylmethyl, pyridin2ylmethylsulfonylmethyl, mtolylmethylsulfonylmethyl, 3trifluoromethylbenzylsulfonylmethyl, 3trifluoromethoxybenzylsulfonylmethyl, 3chlorobenzylsulfonylmethyl, 3fluorobenzylsulfonylmethyl, 4fluorobenzylsulfonylmethyl, 3cyanobenzylsulfonylmethyl, 4cyanobenzylsulfonylmethyl, 3,4difluorobenzylsulfonylmethyl, (cyanomethylmethylcarbamoyl)methyl, 3bromobenzyl, 2oxo2pyrrolidin1ylethyl, 2 (4'chlorobiphenyl4yl)2oxoethyl, biphenyl3ylmethyl, 2 (1, 1difluoromethoxy)benzylsulfonylmethyl, 2 (4methylsulfonylaminophenyl)2oxoethyl, 2oxo2piperidin1ylethyl, 2 (4methylsulfonylpiperazin1yl)2oxoethyl, 2trifluoromethylbenzylsulfonylmethyl, 4fluoro3trifluoromethylbenzylsulfonylmethyl, 4carboxybenzylsulfonylmethyl, 3,5bistrifluoromethylbenzylsulfonylmethyl, 4 (1, 1difluoromethoxy)benzylsulfonylmethyl, 3 (1, 1difluoromethoxy)benzylsulfonylmethyl, 5chlorothiophen2ylmethylsulfonylmethyl, 2 [4 (l, ldiGuoromethoxy)benzenesulfonyI]ethyt, 2 (4trifluoromethoxybenzenesulfonyl)ethyl, 2phenylsulfanylethyl, benzylsulfanylmethyl, 2trifluoromethylbenzylsulfanylmethyl, 2trifluoromethoxybenzylsulfanylmethyl, 2cyclohexylethyl and isobutylsulfanylmethyl ; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

6.

The compound of claim 5 in which R1 is hydrogen or (Cl 6) alkyl and R2 is hydrogen,X4OR13, hetero (C5_lo) aryl (Co6) alkYl, (C5io) aryl (Co6) alkyl or (Cl_6) alkyl ; or il and R2 taken together with the carbon atom to which both R1 and R2 are attached form (C38) cycloalkylene or hetero (C38) cycloalkylene ; wherein the cycloalkylene or heterocycloalkylene are optionally substituted with 1 to 3 (Cl 6) alkyl radicals; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

7.

The compound of claim 6 in which R1 is hydrogen or methyl and R2 is methoxymethyl, methoxyethyl, methyl, ethyl, propyl, butyl, phenethyl, hiophen2yl or 5 methylfuran2yl; or R1 and R2 taken together with the carbon atom to which both R1 and R2 are attached form cyclopropyl, tetrahydropyran4yl or 1methylpiperidin4yl ; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

8.

The compound of claim 7 of Formula I (a): I (a) and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

9.

The compound of claim 8 selected from the group consisting of 3biphenyl 3ylNcyanomethyl2benzylsulfonylmethylpropionamide ; 3biphenyl4ylN cyanomethyl2benzylsulfonylmethylpropionamide; 3 (3bromophenyl)Ncyanomethyl 2benzylsulfonylmethylpropionamide; Ncyanomethyl3 (3cyanobenzylsulfonyl)2 benzylsulfonylmethylpropionamide; Ncyanomethyl2 [21, 1difluoromethoxy) benzylsulfanylmethyl]3benzylsulfanylpropionamide ; Ncyanomethyl3 (2 trifluoromethylbenzylsulfanyl)2 (2trifluoromethylbenzylsulfanylmethyl) propionamide; Ncyanomethyl3isobutylsulfanyl2isobutylsulfanylmethylpropionamide ; Ncyanomethyl4phenylsulfanyl2 (2phenylsulfanylethyl)butyramide ; Ncyanomethyl 3[2(1, 1difluoromethoxy)benzylsulfanyl]2[2(1, 1difluoromethoxy) benzylsulfanylmethyl]propionamide; 3benzylsulfanyl2benzylsulfanylmethylN cyanomethylpropionamide ; Ncyanomethyl2 [21, 1difluoromethoxy) benzylsulfonylmethyl]3benzylsulfonylpropionamide ; Ncyanomethyl3(2 <BR> <BR> <BR> <BR> trifluoromethylbenzylSulfonyl)2(2trifluoromethylbenzylsulfonyolmethyl)propionamide; 4benenesulfonyl2(2benzenesulfonylethyl)Ncyanomethylbutyramide ; N <BR> <BR> <BR> <BR> cyanomethyl3 [2 ( 1, 1difluoromethoxy)benzylsulfonyl]2 [2 ( I, 1difluoromethoxy) benzylsulfonylmethyl]propionamide; Ncyanomethyl3benzylsulfonyl2 benzylsulfonylmethylpropionamide; Ncyanomethyl3(2methylpropane1sulfonyl)2 (2methylpropane1sulfonylmethyl)propionamide ; Ncyanomethyl3(2methylthiazol 4ylmethylsulfonyl)2benzylsulfonylmethylpropionamide ; 3biphenyl3ylN <BR> <BR> <BR> <BR> cyanomethyl2[2(1, 1difluoromethoxy)benzylsulfonylmethyl]propionamide; (3' {2 (cyanomethylcarbamoyl)3[2(1,1difluoromethoxy)benzylsulfonyl]propyl}biphenyl 4yl)carbamic acid ethyl ester; Ncyanomethyl2 [2 (1, 1difluoromethoxy) benzylsulfonylmethyl]3(4'methylsulfonylaminobiphenyl3yl)propionamide ; 3 (3 bromophenyl)Ncyanomethyl2 [2 (1, 1difluoromethoxy)phenyl methylsulfonylmethyl]propionamide ; Ncyanomethyl2((E)3phenylallyl)3 benzylsulfonylpropionamide; andNcyanomethyl3benzylsulfonyl2(3phenylpropyl) propionamide; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

10.

The compound of Claim 7 of Formula I (b): I (b) and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

11.

The compound of claim 10 in which R5 is lHbenzoimidazol2yl, benzooxazol2yl, oxazolo [4,5b] pyridin2yl, benzothiazol2yl, 5phenyl [1, 3,4] oxadiazol2yl, 4 (5pyridin4yl [1, 3,4] oxadiazol2yl, 5pyridin3yl [1, 3,4] oxadiazol2yl, 5pyridazin3yl [1, 3,4] oxadiazol2yl, pyrimidin2yl, pyridazin3 yl, 3penyl [1, 2,4] oxadiazol5yl, 5methoxymethyl [1, 3,4] oxadiazol2yl, 5ethyl [1, 3,4] oxadiazol2yl,, 1, 3,4] thiadiazol2yl, benzyloxycarbonyl, benzyloxydicarbonyl, phenyldicarbonyl, 5methyl [1, 3,4] thiadiazol2yl, 5trifluoromethyl [1, 3,4] oxadiazol2yl, 5methyl [1, 3,4] oxadiazol2yl, 5methyl [1, 2,4] oxadiazol3yl, 5phenyl [1, 2,4] oxadiazol 3yl, 5thiophen3yl [1, 2,4] oxadiazol3yl, 5trifluoromethyl [1, 2,4] oxadiazol3yl, 3 methyl [1, 2,4] oxadiazol5yl or 3pyrazin2yl; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

12.

The compound of claim 11 selected from the group consisting of N[(S)1 (1Benzooxazol2ylmethanoyl)butyl]3benzylsulfonyl2benzylsulfonylmethyl propionamide; N[(S)1(1Benzooxazol2ylmethanoyl)butyl]3(2trifluoromethyl benzylsulfonyl)2(2trifluoromethylbenzylsulfonylmethyl)propionamide ; N[(S)1(1 Benzooxazol2ylmethanoyl)pentyl]4 (2methoxybenzenesulfonyl)2 [2 (2methoxy benzenesulfonyl)ethyl]butyramide ; 4Benzenesulfonyl2(2benzenesulfonylethyl)N [ (S)l (lbenzooxazol2ylmethanoyl)butyl]butyramide ; (R)N[(S)1(1benzooxazol2 ylmethanoyl)butyl]2cyclohexylmethyl3benzylsulfonylpropionamide ; N [ (S)l (I benzothiazol2ylmethanoyl)propyl]4morpholin4yl4oxo2benzylsulfonylmethyl butyramide; N [ (S)l (lbenzooxazol2ylmethanoyl)butyl]3cyclohexyl2 cyclohexylmethylpropionamide; N[(S)1(1Benzooxazol2ylmethanoyl)butyl]3 isobutylsulfanyl2isobutylsulfanylmethylpropionamide ; N[(S)1(1benzooxazol2yl methanoyl)butyl]3benzylsulfanyl2benzylsulfanylmethylpropionamide ; N[(S)1(1 benzooxazol2ylmethanoyl)butyl]4phenylsulfanyl2 (2phenylsulfanylethyl) butyramide; N[(S)l(lbenzooxazol2ylmethanoyl)propyl]4morpholin4yl4oXo2 benzylsulfonylmethylbutyramide ; N[(S)l(lBenzooxazol2ylmethanoyl)pentyl]4 morpholin4yl4oxo2benzylsulfonylmethylbutyramide ; 4Morpholin4yl4oxo2 benzylsulfonylmethylN { (S)1 [1 (3phenyl [1, 2,4] oxadiazol5yl)methanoyl]propyl} butyramide; N[ (S)l (lBenzooxazol2ylmethanoyl)butyl]2 [2 (1, 1difluoromethoxy) benzylsulfonylmethyl]3benzylsulfonylpropionarnide ; 4Morpholin4yl4oxoN[1(2 oxo2phenylacetyl)pentyl]2benzylsulfonylmethylbutyramide ; N (l, lDimethyl2 oxazolo [4,5b] pyridin2yl2oxoethyl)4morpholm4yl4oxo2benzylsulfony ! methyl butyramide ; N [1 (5Ethyl [1, 3,4] oxadiazole2carbonyl)butyl]4morpholin4yl4oxo2 benzylsulfonylmethylbutyramide ; N[1(5Ethyl[1, 3,4] oxadiazole2carbonyl)butyl]4 oxo2benzylsulfonylmethyl4piperidin1ylbutyramide ; N [1 (5Ethyl [1,3,4] oxadiazole2carbonyl)butyl]4oxo2benzylsulfonylmethyl4pyrrolidin1yl butyramide; N [1 (5Methoxymethyl [1, 3,4] oxadiazole2carbonyl)propyl]4morpholin 4yl4oxo2benzylsulfonylmethylbutyramide; N [1 (5Methoxymethyl [1, 3,4] oxadiazole2carbonyl)propyl]4oxo2benzylsulfonylmethyl4piperidin1yl butyramide; N [l (5Methoxymethyl [1, 3,4] oxadiazole2carbonyl)propyl]4oxo2 benzylsulfonylmethyl4pyrrolidin1ylbutyramide ; 4Morpholin4yl4oxo2 benzylsulfonylmethylN[l(Sphenyl[l, 3,4] oxadiazole2carbonyl)propyl]butyramide ; 4Oxo2benzylsulfonylmethylN [l (5phenyl [1, 3,4] oxadiazole2carbonyl)propyl]4 piperidin1ylbutyramide ; 4Oxo2benzylsulfonylmethylN[1(5phenyl [1, 3,4] oxadiazole2carbonyl)propyl]4pyrrolidin1ylbutyramide ; 4Morpholin4ylN [1 (oxazolo [4,5b] pyridine2carbonyl)propyl]4oxo2benzylsulfonylmethylbutyramide ; N[1(Oxazolo [4,5b] pyridine2carbonyl)propyl]4oxo2benzylsulfonylmetliyl4 piperidin1ylbutyramide ; N[l(Oxazolo [4,5b] pyridine2carbonyl)propyl]4oxo2 benzylsulfonylmethyl4pyrrolidin1ylbutyramide ; 4Morpholin4yl4oxo2 benzylsulfonylmethylN [1 (5pyridin4yl [1, 3, 4] oxadiazole2carbonyl)propyl] butyramide; 4Oxo2benzylsulfonylmethyl4piperidin1ylN [l (5pyridin4yl [1, 3,4] oxadiazole2carbonyl)propyl]butyramide ; 4Oxo2benzylsulfonylmethylN[1 (5pyridin4yl [1, 3,4] oxadiazole2carbonyl)propyl]4pyrrolidin1ylbutyramide ; 4 Morpholin4yl4oxo2benzylsulfonylmethylN [l (5pyridin3yl [2, 3,4] oxadiazole2 carbonyl)propyl]butyramide ; N[l(Benzooxazole2carbonyl)propyl]4oxo2 benzylsulfonylmethyl4piperidin1ylbutyramide ; N[l(Benzooxazole2carbonyl) propyl]4oxo2benzylsulfonylmethyl4pyrrolidin1ylbutyramide ; N[l(Benzooxazole 2carbonyl)propyl]2cyclohexylmethyl4morpholin4yl4oxobutyramide ; 2 Cyclohexylmethyl4morpholin4ylN[1(oxazolo [4,5b] pyridine2carbonyl)propyl]4 oxobutyramide; 2CyclohexylmethylN [l (5ethyl [1, 3,4] oxadiazole2carbonyl)butyl] 4morpholin4yl4oxobutyramide; N(2Benzooxazol2yl1methoxymethyl2oxo ethyl)2 (2difluoromethoxybenzylsulfonylmethyl)4morpholin4yl4oxobutyramide ; <BR> <BR> <BR> <BR> N[1(Benzooxazole2carbonyl)propyl]2(2cyclohexylethyl)4morpholin4yl4oxo butyramide; 2(2Cyclohexylethyl)4morpholin4ylN[1(oxazolo [4,5b] pyridine2 carbonyl)propyl]4oxobutyramide; 2(2Cyclohexylethyl)4morpholin4yl4oxoN [1(5phenyl[1, 3,4] oxadiazole2carbonyl)propyl]butyramide; 2(2Difluoromethoxy benzylsulfonylmethyl)4morpholin4yl4oxoN [1 (5phenyl [1,3,4] oxadiazole2 carbonyl)propyl]butyramide ; 2(2Difluoromethoxybenzylsulfonylmethyl)N[1(5ethyl [1,3,4] oxadiazole2carbonyl)butyl]4morpholin4yl4oxobutyramide ; N [I <BR> <BR> <BR> <BR> (Benzooxazole2carbonyl)propyl]2(2difluoromethoxybenzylsulfonylmethyl)4 morpholin4yl4oxobutyramide; 2 (2Morpholin4yl2oxoethyl)5phenylpentanoic acid, 1(benzooxazole2 carbonyl)propyl]amide ; (R)2Cyclohexylmethyl4morpholin4yl4oxoN[(S)l(S phenyl1, 2,4oxadiazole3carbonyl)propyl]butyramide; 2(2Morpholin4yl2oxo ethyl)5phenylpentanoic acid, (S)l (5phenyl [1, 2,4] oxadiazole3carbonyl)propyl] amide; 4Morpholin4yl4oXo2benzylsulfonylmethylN[(S)l(Sphenyl1, 2,4 oxadiazole3carbonyl)propyl]butyramide; (R)2Cyclohexyhnethyl4morpholin4yl4 oxoN [ (S)1 (3phenyl1, 2,4oxadiazole5carbonyl)propyl]butyramide; 4Morpholin4 <BR> <BR> <BR> <BR> ylN[l (oxazole2carbonyl)3phenylpropyl]4oxo2benzylsulfonylmethylbutyramide;<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> N (1, 1Dimethyl2oxazol2yl2oxoethyl)4morpholin4yl4oxo2 benzylsulfonylmethylbutyramide ; N4IsopropylN1 [1(oxazole2carbonyl)3phenyl propyl]2benzylsulfonylmethylsuccinamide ; 2(2Difluoroemthoxy benzylsulfonylmethyl)4morpholin4ylN [1(oxazole2carbonyl)3phenylpropyl]4 oxobutyramide ; 2(2Methylpropane1sulfonylmethyl)4morpholin4ylN[1(oxazole 2carbonyl)3phenylpropyl]4oxobutyramide ; 2Cyclopropylmethylsulfonylmethyl4 morpholin4ylN [1 (oxazole2carbonyl)3phenylpropyl]4oxobutyramide ; N [1 <BR> <BR> <BR> <BR> (Benzooxazole2carbonyl)butyl]2benzylsulfonyl3 (tetrahydropyran4yloxymethyl) propionamide; N[l(Benzooxazole2carbonyl)butyl]3ethanesulfonyl2(tetrahydro pyran4yloxymethyl)propionamide; N(2Benzenesulfonyl3oxoazepan4yl)2 cyclopropylmethylsulfonylmethyl4morpholin4yl4oxobutyramide ; 2 CyclopropylmethylsulfonylmethylN{(S)1[(R)hydroxy(3phenyl1, 2,4oxadiazol5yl) methyl]propyl}4morpholin4yl4oxobutyramide ; N { (S)l [ (R)hydroxy (3phenyl 1,2,4oxadiazol5yl)methyl]propyl}2 (2methylpropanelsulfonylmethyl)4 morpholin4yl4oxobutyramide; 2 (2Morpholin4yl2oxoethyl)5phenylpentanoic acid { (S)I [ (R)hydroxy (3pheTiyl1, 2,4oxadiazol5yl)methyl]propyl}amide; 2 Cyclopropylmethylsulfonylmethyl4morpholin4yl4oxoN [ (S)1 (3phenyl1,2,4 oxadiazole5carbonyl)propyl]butyramide ; 2 (2methylpropanelsulfonylmethyl)4 morpholin4yl4oxoN[(S)1(3phenyl1, 2,4oxadiazole5carbonyl)propyl] butyramide; 2(2Morpholin4yl2oxoethyl)5phenylpentanoic acid, (S)1 (3phenyl 1, 2,4oxadiazole5carbonyl)propyl}amide; N[(1S)1(Benzooxazol2ylhydroxy <BR> <BR> <BR> <BR> methyl)3phenylpropyl]2cyclopropylmethylsulfonylmethyl4morpholin4yl4oxo butyramide ; (R)2((S)1Hydroxy2morpholin4yl2oxoethyl)5phenylpentanoic acid, 1(benzoxazole2carbonyl)propy]amide ; (R)5(2Difluoromethoxyphenyl)2((S)l hydroxy2morpholin4yl2oxoethyl)pentanoic acid, 1 (benzoxazole2carbonyl) propyl]amide ; and 4Morpholin4ylN [1 (oxazole2carbonyl)cyclopropyl]4oxo2 benzylsulfonyl methylbutyramide ; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

13.

The compound of claim 7 of Formula I (c): I (c) and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

14.

The compound of claim 13 in which R5 is phenyl; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

15.

The compound of claim 14 selected from the group consisting of N[(S)1 ( (E)2benzenesulfonylvinyl)pentyl]3benzylsulfonyl2benzylsulfonylmethyl propionamide and N (3benzenesulfonyllphenethylallyl)3benzylsulfonyl2 benzylsulfonylmethylpropionamide; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

16.

The compound of claim 7 of Formula I (d): I (d) and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

17.

The compound of claim 16 in which Rs is phenyl and R6 is hydrogen; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

18.

The compound of claim 17 namely N(3benzenesulfonylamino2oxo propyl)4morpholin4yl4oxo2benzylsulfonylmethylbutyramide; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

19.

The compound of claim 7 of Formula I (e): and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

20.

The compound of claim 19 in which Rs and R6 is methyl ; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

21.

The compound of claim 20 in which one X7 is morpholine4carbonyl and the other is benzylsulfonyl, R1 is hydrogen and R2 is ethyl, namely (S)2,2difluoro4 (4 morpholin4yl4oxo2benzylsulfonylmethylbutanoylamino)3oxohexanoic acid dimethylamide; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

22.

The compound of claim 7 of Formula I (f) : I(f) and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

23.

The compound of claim 22 in which Rs is methyl, benzyl, phenethyl, cyclohexyl, methoxyethyl, dimethylaminoethyl, tetrahydropyran4yl, 1methylsulfonyl piperidin4yl, 4methylpiperazin1yl, morpholin4ylethyl, pyridin2yl, pyridin2 ylmethyl or oxazol2ylmethyl; R6 is hydrogen or methyl; or Rs and R6 together with the nitrogen atom to which both Rs and R6 are attached form morpholine4yl, pyrrolidin1yl, 4dimethylaminopiperazin1yl, 4hydroxypiperazin1yl, 4pyridin2ylpiperazin1yl, 4benzoylpiperazin1yl or 3oxopiperazin1yl ; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

24.

The compound of claim 23 selected from the group consisting of N[(S)1 (1Benzylcarbamoylmethanoyl)propyl]3benzylsulfonyl2benzylsulfonylmethyl propionamide andN [ (S)1 (1Benzylcarbamoylmethanoyl)propyl]4morpholin4yl4 oxo2benzylsulfonylmethylbutyramide; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

25.

The compound of claim 7 of Formula I (g): and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

26.

The compound of claim 25 in which X3 is 1benzoyl4oxopyrrolidin3yl, 4oxopyrrolidin3yl1carboxylic acid tertbutyl ester, 2methyl4oxotetrahydrofuran 3yl, 2ethyl4oxotetrahydrofuran3yl, 4oxotetrahydrofuran3yl, 2acetoxy4oxo azetidin3yl, 1isopropyl3oxoazepan4yl, 3oxoazepan4yl1carboxylic acid benzyl ester, 3oxoazepan4yl1carboxylic acidtertbutyl ester, 1benzoyl3oxoazepan4yl, 1 isobutyryl3oxoazepan4yl, 3oxo1 (propane2sulfonyl)azepan4yl, 1 benzenesulfonyl3oxoazepan4yl, 1benzenesulfonyl3oxopiperidin4yl, 1 benzenesulfonyl4oxopyrrolidin3yl, 1benzoyl3oxopiperidin4yl or 3oxo tetrahydropyran4yl; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof ; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

27.

The compound of claim 23 selected from the group consisting of 3 Hydroxy4 (4morpholin4yl4oxo2benzylsulfonylmethyl'butyrylamino)azepanel carboxylic acid tertbutyl ester; 4 (2Cyclopropylmethylsulfonylmethyl4morpholin4yl 4oxobutyrylamino)3hydroxyazepane1carboxylic acid tertbutyl ester; 3Hydroxy4 [2(2methylpropane1sulfonylmethyl)4morpholin4yl4oxobutyrylamino]azepane lcarboxylic acid tertbutyl ester; 4 (4Morpholin4yl4oxo2benzylsulfonylmethyl butyrylamino)3oxoazepane1carboxylic acid tertbutyl ester; 4 (2 <BR> <BR> <BR> <BR> Cyclopropyhnethylsulfonylmethyl4morpholin4yl4oxobutyrylamino)3oxoazepane 1carboxylic acid tertbutyl ester; 4 [2 (2Methylpropanelsulfonylmethyl)4morpholin 4yl4oxobutyrylamino]3oxoazepane1carboxylic acid tertbutyl ester; N(1 Benzenesulfonyl3oxoazepan4yl)4morpholin4yl4oxo2benzylsulfonylmethyl butyramide; N (lBenzenesulfonyl3oxoazepan4yl)2 (2methylpropanel sulfonylmethyl)4morpholin4yl4oxobutyramide; 3 (4Morpholin4yl4oxo2 benzylsulfonylmethylbutyrylamino)4oxopyrrolidine1carboxylic acid tertbutyl ester; <BR> <BR> <BR> <BR> 4 (4Morpholin4yl4oxo2benzylsulfonylmethylbutyrylamino)3oxoazepane1 carboxylic acid benzyl ester; and acetic acid (2S, 3S)3 (4morpholin4yl4oxo2 benzylsulfonylmethylbutanoylamino)4oxoazetidin2yl ester; and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

28.	A pharmaceutical composition comprising a therapeutically effective amount of a compound of Claim 1 in combination with a pharmaceutically acceptable excipient.

29.

A method for treating a disease in an animal in which inhibition of Cathepsin S can prevent, inhibit or ameliorate the pathology and/or symptomology of the disease, which method comprises administering to the animal a therapeutically effective amount of compound of Claim 1 or a Noxide derivative or individual isomer or mixture of isomers thereof; or a pharmaceutically acceptable salt or solvate of such compounds and the Noxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixtures of isomers thereof.

30.	The use of a compound of Claim 1 in the manufacture of a medicament for treating a disease in an animal in which Cathepsin S activity contributes to the pathology and/or symptomology of the disease.

31.

A process for preparing a compound of Formula I : I in which: X1 is C(R1)(R2)X2 or X3 ; X2 is cyano,CHO,C (R7) (R) R5, C (R7) (R8) CF3,C (R7) (R8) CF2CF2R9 CH=CHS(O)2R5, C(R7)(R8)CF2C(O)NR5R6, C(R7)(R8) C (R7) (R8)NR5R6, C(R7)(R8)C(R7)(R8)OR5, C(R7)(R8)CH2OR5, C(R7)(R8)CH2N(R6)SO2R5, C (R7) (R8) C (R7) (R8) N (R6) (CH2) 20R6,C (R7) (R8)C(R7)(R8)N(R6)(CH2)2NR6 or C(R7)(R8)C(R7)(R8)R5 ; wherein R5 is (Cl4) alkyl, (C610)aryl(C06) alkyl, hetero (C410)aryl(C06)alkyl, (C410)cycloalkyl(C06)alkyl or hetero (C4io) cycloalkyl (C06) alkyl; R6 is hydrogen or (C16) alkyl; R7 is hydrogen or (C14) alkyl and R8 is hydroxy or R7 and R8 together form oxo; R9 is hydrogen, halo, (C14) alkyl, (C510)aryl(C06) alkyl or hetero (C510) aryl (Co6) alkyl ; X3 represents a group of Formula (a): in which n is 1 or 2, z is 0 or 1, X5 is selected from NR10, S or 0, wherein Rlo is hydrogen or (Cl6) alkyl, and X6 is 0, S or NR", wherein Rll is selected from hydrogen, (C16) alkyl, X4C(O)OR12, X4C(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4S(O)2R14, R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4C(O)NR12R15 and X4S(O)2NR12R15, in which X4 is a bond or (C16) alkylene; R12 at each occurrence independently is hydrogen or (C16) alkyl; R13 is hydrogen, (C16) alkyl or halosubstituted (C16) alkyl, R14 is (C16) alkyl or halosubstituted (C16) alkyl and Rls is (C3lo) cycloalkyl (Co6) alkyl, hetero (C310)cycloalkyl(C03) alkyl, (C610)aryl(C06) alkyl, hetero (CS_io) aryl (Co6) alkyl, (C912)bicycloaryl(C06)alkyl or hetero(C812) bicycloaryl (Co6) alkyl; wherein within Xl any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R20 selected from R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR15R12, X4S(O)2NR15R12, X4NR12S(O)R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12; and wherein Xl and R20 may be substituted further with 1 to 5 radicals independently selected from (C16)alkyl, cyano, halo, <BR> <BR> <BR> <BR> halosubstituted (Cl4) alkyl, nitro,X4NR1'R12,X4NR12C (O) R12,X4NR12C (o) OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, <BR> <BR> <BR> <BR> <BR> X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14 and X4S(O)2R14 wherein X4, R12, R13, R14 and R15 are as defined above; R1 and R2 are both fluoro; or R1 is hydrogen or (C16) alkyl and R2 is selected from the group consisting of hydrogen, (C16)alkyl, cyano, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, XRP(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14, X4S(O)2R14, R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR15R12, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12, wherein X4, R12, R13, R14 and Rls are as defined above; or R1 and R2 taken together with the carbon atom to which both R1 and R2 are attached form (C38) cycloalkylene or hetero (C38) cycloalkylene; wherein R2, said cycloalkylene and said heterocycloalkylene may be substituted further with 1 to 3 radicals independently selected from (C16) alkyl, cyano, halo, halosubstituted (C14) alkyl, nitro, X4RN12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14 and X4S(O)2R14, WHEREIN X4, R12, R13 and R14 are as defined above; R3 and R4 are independentlyC (Rl6) (Rl7) X7, wherein R16 and R17 are hydrogen, (C16) alkyl or fluoro, or R16 is hydrogen and R17 is hydroxy and X7 is selected from X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14, X4S(O)2R14, R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR15R12, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12, wherein X4, Rl2, Rl3, Rl4 and R15 are as defined above; wherein within one of R3 or R4 any cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted with 1 radical R21 selected from R15, X4OR15, X4SR15, X4S(O)R15, X4S(O)2R15, X4C(O)R15, X4C(O)OR15, X4OC(O)R15, X4NR15R12, X4NR12C(O)R15, X4NR12C(O)OR15, X4C(O)NR12R15, X4S(O)2NR15R12, X4NR12S(O)2R15, X4NR12C(O)NR15R12 and X4NR12C(NR12)NR15R12, wherein X4, R12 and Rl5 are as defined above; and wherein each of R3, R4 and R21 may be substituted further with 1 to 5 radicals independently selected from (C16) alkyl, cyano, halo, halosubstituted (C14) alkyl, nitro, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12, X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14 and X4S(O)2R14, wherein X4, Rl2, R13 and Rl4 are as defined above; provided that only one bicyclic ring structure is present within each of R3 or R4 ; and provided that when X2 is cyano and X7 within one of R3 or R4 isX4C (O) R13 or X4C(O)R15, wherein X4 is a bond, then X7 within the other of R3 or R4 is limited to X4SR15, X4S(O)R15 and X4S(O)2R15, wherein R15 is (C6lo) aryl (Cl6) alkyl substituted with 1 to 5 radicals or hetero (C510)aryl(C06) alkyl optionally substituted with 1 to 5 radicals, wherein said radicals are independently selected from (Cl6) alkyl, cyano, halo, halosubstituted (Cl4) alkyl, nitro, X4NR12R12, X4NR12C(O)R12, X4NR12C(O)OR12, X4NR12C(O)NR12R12, X4NR12C(NR12)NR12R12, X4OR13, X4SR13, X4C(O)OR12, X4C(O)R13, X4OC(O)R13, X4C(O)NR12R12 X4S(O)2NR12R12, X4NR12S(O)2R13, X4P(O)(OR12)OR12, X4OP(O)(OR12)OR12, X4S(O)R14 and X4S(O)2R14, wherein X4, R12, R13 and R14 are as defined above, provided that the radical is not selected from only halo when Rls is (C610)aryl(C16) alkyl; and provided that when X2 is cyano then X7 within R3 and RUZ is not X4C(O)NR12R12, X4C(O)NR15R12 or X4C(O)NR18R19, wherein X4 is a bond and R'8 and R'9 together with the nitrogen atom to which they are attached form hetero (C3 lo) cycloalkyl or hetero (cslo) aryl; and the corresponding Noxides, and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof; and the pharmaceutically acceptable salts and solvates of such compounds of formula I and their Noxides and their prodrugs, and their protected derivatives, individual isomers and mixtures of isomers thereof ; which process comprises : (A) reacting a compound of Formula 2: 2 with a compound of the formula NH2CR1R2X2, in which X', R', R2, R3 and R4 are as defined in the Summary of the Invention for Formula I; or (B) reacting a compound of Formula 2 with a compound of the formula NH2X3, in which X3, R3 and R4 are as defined in the Summary of the Invention for Formula I; or (C) optionally converting a compound of Formula I into a pharmaceutically acceptablesalt; (D) optionally converting a salt form of a compound of Formula I to nonsalt form; (E) optionally converting an unoxidized form of a compound of Formula I into a pharmaceutically acceptable Noxide ; (F) optionally converting an Noxide form of a compound of Formula I its unoxidized form ; (G) optionally resolving an individual isomer of a compound of Formula I from a mixture of isomers; (H) optionally converting a nonderivatized compound of Formula I into a pharmaceutically prodrug derivative; and optionally converting a prodrug derivative of a compound of Formula I to its nonderivatized form.