A compound of Formula: wherein E is -COCONHR 6 where R 6 is hydrogen, alkyl, cycloalkyl, aralkyl, or heteroaralkyl wherein the aromatic ring is optionally substituted with one or two halo; R 1 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R 1 are optionally substituted with one or two R b independently selected from hydroxy, alkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic or alicyclic ring in R b is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, carboxy, or carboxyalkyl; X is -O-, -NR 14 - -S-, -SO-, or -SO 2 -; R 3 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R 3 are optionally substituted with one or two R c independently selected from hydroxy, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic or alicyclic ring in R c is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl; Y is -NHC NH-; R 2 is a group of formula (a): where: R d1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino; R d and R d2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and R d3 is a group of formula: optionally substituted with halo, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkoxy, nitro, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkyloxycarbonylamino, amino, alkylamino, dialkylamino, cycloalkylamino, cycloalkylalkylamino or -NHCONRR' where R is hydrogen or alkyl and R' is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl, wherein cycloalkyl and cycloalkylalkyl are optionally substituted with one, two or three alkyl: and R 4 is alkyl; or a pharmaceutically acceptable salt or diastereoisomer thereof. E is -COCONHR 6 where R 6 is hydrogen, alkyl, cycloalkyl, aralkyl, or heteroaralkyl wherein the aromatic ring is optionally substituted with one or two halo; R 1 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R 1 are optionally substituted with one or two R b independently selected from hydroxy, alkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic or alicyclic ring in R b is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, carboxy, or carboxyalkyl; X is -O-, -NR 14 - -S-, -SO-, or -SO 2 -; R 3 is alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl wherein the aliphatic, alicyclic and aromatic groups in R 3 are optionally substituted with one or two R c independently selected from hydroxy, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, alkylthio, arylthio, heteroarylthio, amino, monosubstituted amino, disubstituted amino, alkylsulfonyl, arylsulfonyl, carboxy, alkoxycarbonyl, acylamino, aminocarbonyl, halo, or cyano and further wherein the aromatic or alicyclic ring in R c is optionally substituted with one, two, or three substituents independently selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, carboxy, or carboxyalkyl; Y is -NHC NH-; R 2 is a group of formula (a): where: R d1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino; R d and R d2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and R d3 is a group of formula: optionally substituted with halo, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkoxy, nitro, alkylcarbonylamino, cycloalkylcarbonylamino, cycloalkylalkylcarbonylamino, alkyloxycarbonylamino, amino, alkylamino, dialkylamino, cycloalkylamino, cycloalkylalkylamino or -NHCONRR' where R is hydrogen or alkyl and R' is hydrogen, alkyl, cycloalkyl, or cycloalkylalkyl, wherein cycloalkyl and cycloalkylalkyl are optionally substituted with one, two or three alkyl: and R d1 is hydrogen, hydroxy, alkoxy, amino, alkylamino or dialkylamino; R d and R d2 are independently hydrogen, alkyl, halo, alkoxy, alkylthio, or alkylsulfonyl; and R d3 is a group of formula: R 4 is alkyl; or