Sulfonamides having antiangiogenic and anticancer activity

A compound of formula (II)

• 31
• or a therapeutically acceptable salt thereof, wherein
• R1, R2 and R3 are independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyloxy, alkylidene, alkylsulfanyl, alkylsulfanylalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, aminoalkyl, aminoalkenyl, aminoalkoxy, aminocarbonylalkenyl, aryl, carboxyalkenyl, carboxyalkyl, cyano, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, (heterocycle)alkyl, hydroxy, hydroxyalkyl, nitro;
• or
• R1 and R2 together with the carbon atoms to which they are attached, form a five-, six-, or seven-membered saturated or unsaturated carbocyclic ring which can be optionally substituted with 1 or 2 substituents independently selected from the group consisting of alkoxy, alkyl, amino, halo, and haloalkyl;
• or
• R2 and R3 together with the carbon atoms to which they are attached, form a five-, six-, or seven-membered saturated or unsaturated carbocyclic ring which can be optionally substituted with 1 or 2 substituents independently selected from the group consisting of alkoxy, alkyl, amino, halo, and haloalkyl;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rd4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rd4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Re4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Re5)Ncarbonyl, Re5Rf5Nalkyl(Rc5)Ncarbonylalkenyl, Re4Rf5Nalkylcarbonyl(Rc5)N—, Re5Rf5Nalkoxycarbonyl(Rc5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl;
• and
• provided that at least one of R1, R2, R3 and R4 is other than hydrogen, C1 alkyl or halo.

A compound of formula (III)

• 32
• or a therapeutically acceptable salt thereof, wherein
• R1 is selected from the group consisting of hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 alkoxy, halo, haloalkyl, haloakoxy, RaRbN— and RaRbNalkoxy, wherein Ra and Rb are each independently selected from the group consisting of hydrogen and alkyl;
• R2 is selected from the group consisting of alkoxy, alkoxyalkyl, C1-C10 alkyl, alkylsulfanyl, alkylsulfanylalkyl, alkylsulfonyl, alkylsulfonylalkyl, amino, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, and haloalkyl;
• R3 is selected from the group consisting of hydrogen, alkyl and halogen;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rd4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rd4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Rc4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Rc5)Ncarbonyl, Re5Rf5Nalkyl(Re5)Ncarbonylalkenyl, Re4Rf5Nalkylcarbonyl(Rc5)N—, Re4Rf5Nalkoxycarbonyl(Rc5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl.

A compound of formula (IV)

• 33
• or a therapeutically acceptable salt thereof, wherein
• R1 and R2, together with the carbon atoms to which they are attached, form a five-, six-, or seven-membered saturated or unsaturated carbocyclic ring which can be optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, alkyl, amino, halo, and haloalkyl;
• R3 is selected from the group consisting of hydrogen, alkyl and halogen;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rd4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rd4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Re4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Rc5)Ncarbonyl, Re5Rf5Nalkyl(Rc5)Ncarbonylalkenyl, Re5Rf5Nalkylcarbonyl(Rc5)N—, Re5Rf5Nalkoxycarbonyl(Rc5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl.

A compound of formula (IV)

• 34
• or a therapeutically acceptable salt thereof, wherein
• R1 and R2, together with the carbon atoms to which they are attached, form a six membered monounsaturated carbocyclic ring which can be optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, alkyl, amino, halo, and haloalkyl;
• R3 is selected from the group consisting of hydrogen, alkyl and halogen;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rd4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rf4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Re4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Rc5)Ncarbonyl, Re5Rf5Nalkyl(Rc5)Ncarbonylalkenyl, Re5Rf5Nalkylcarbonyl(Rc5)N—, Re5Rf5Nalkoxycarbonyl(Rc5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl.

A compound of formula (V)

• 35
• or a therapeutically acceptable salt thereof, wherein
• R3 is selected from the group consisting of hydrogen, alkyl and halogen;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rd4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rd4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Re4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Rc5)Ncarbonyl, Re5Rf5Nalkyl(Rc5)Ncarbonylalkenyl, Re5Rf5Nalkylcarbonyl(Rc5)N—, Re5Rf5Nalkoxycarbonyl(Re5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl;
• and
• R7 is selected from the group consisting of hydrogen, C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkoxy, halo, haloalkyl, haloakoxy, RaRbN— and RaRbNalkoxy, wherein Ra and Rb are each independently selected from the group consisting of hydrogen and alkyl.

A compound of formula (VI)

• 36
• or a therapeutically acceptable salt thereof, wherein
• R3 is selected from the group consisting of hydrogen, alkyl and halogen;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rd4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rd4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Re4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Rc5)Ncarbonyl, Re5Rf5Nalkyl(Rc5)Ncarbonylalkenyl, Re5Rf5Nalkylcarbonyl(Rc5)N—, Re5Rf5Nalkoxycarbonyl(Rc5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl;
• and
• R7 is selected from the group consisting of hydrogen, C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkoxy, halo, haloalkyl, haloakoxy, RaRbN— and RaRbNalkoxy, wherein Ra and Rb are each independently selected from the group consisting of hydrogen and alkyl.

A compound of formula (VII)

• 37
• or a therapeutically acceptable salt thereof, wherein
• R1 is selected from the group consisting of hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkoxy, halo, haloalkyl, haloakoxy, RaRbN— and RaRbNalkoxy, wherein Ra and Rb are each independently selected from the group consisting of hydrogen and alkyl;
• R2 and R3, together with the carbon atoms to which they are attached, form a five-, six-, or seven-membered saturated or unsaturated carbocyclic ring which can be optionally substituted with one or two substituents independently selected from the group consisting of alkoxy, alkyl, amino, halo, and haloalkyl;
• R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkylsulfanyl, alkylsulfanylalkyl, carboxy, cyano, cyanoalkyl, cycloalkyl, (cycloalkyl)alkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, hydroxyalkyl, nitro, phenyl, phenylsulfonyl, Rc4Rd4N—, Rc4Rf4Nalkyl, Rc4Rd4Nalkenyl, Rc4Rd4Nalkynyl, Rc4Rd4Nalkoxy, Rc4Rd4Nalkoxycarbonyl, Rc4Rd4Ncarbonyl, Rc4Rd4Ncycloalkyl, Rc4Rd4Nalkylcycloalkyl, Rc4Rd4N(cycloalkyl)alkyl, Rc4Rd4Nsulfinyl, Re4Rf4Nalkyl(Rc4)N—, Re4Rf4Nalkyl(Rc4)Ncarbonyl, Re4Rf4Nalkyl(Rc4)Ncarbonylalkenyl, Re4Rf4Nalkylcarbonyl(Rc4)N—, Re4Rf4Nalkoxycarbonyl(Rc4)N—, Rc4Rd4Nalkylsulfanyl, Rc4Rd4Nalkylsulfinyl, Rc4Rd4Nalkylsulfonyl, Rg4Rj4Nalkyl(Re4)Ncarbonyl(Rc4)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc4, Rd4, Re4, Rf4, Rg4 and Rj4 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl, or each individual pair of Rc4 and Rd4, or Re4 and Rf4, or Rg4 and Rj4 taken together with the nitrogen atom they are each attached form a heterocycle;
• R5 is selected from the group consisting of alkyl, amino, aminoalkyl, aryl, arylalkenyl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkyl and heterocyclealkenyl, wherein aryl, the aryl group of arylalkenyl, the aryl group of arylalkyl, the heteroaryl, the heteroaryl of heteroarylalkenyl, the heteroaryl of heteroarylalkyl, and the heterocycle of R5 may be optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, aminoalkyl, phenyl, phenylsulfonyl, carboxy, cyano, cyanoalkyl, halo, haloalkoxy, haloalkyl, heteroaryl, heterocycle, heterocyclealkyl, heterocyclealkenyl, hydroxy, nitro, Rc5Rd5N—, Rc5Rd5Nalkyl, Rc5Rd5Nalkenyl, Rc5Rd5Nalkynyl, Rc5Rd5Nalkoxy, Rc5Rd5Nalkoxycarbonyl, Rc5Rd5Ncarbonyl, Rc5Rd5Ncycloalkyl, Rc5Rd5Nalkylcycloalkyl, Rc5Rd5Ncycloalkylalkyl, Rc5Rd5Nsulfinyl, Re5Rf5Nalkyl(Rc5)N—, Re5Rf5Nalkyl(Rc5)Ncarbonyl, Re5Rf5Nalkyl(Rc5)Ncarbonylalkenyl, Re5Rf5Nalkylcarbonyl(Rc5)N—, Re5Rf5Nalkoxycarbonyl(Rc5)N—, Rc5Rd5Nalkylsulfanyl, Rc5Rd5Nalkylsulfinyl, Rc5Rd5Nalkylsulfonyl, Rg5Rj5Nalkyl(Re5)Ncarbonyl(Rc5)N—;
• wherein the phenyl group, the phenyl group of phenylsulfonyl, the heteroaryl, the heterocycle, the heterocycle of heterocyclealkyl, the heterocycle of heterocyclealkenyl may be optionally substituted with 1, 2 or 3 substituents selected from the group consisting of alkoxy, alkyl, cyano, halo, haloalkoxy, haloalkyl, and nitro;
• and wherein Rc5, Rd5, Re5, Rf5, Rg5 and Rj5 are each independently selected from the group consisting of hydrogen, alkoxyalkyl, alkyl, alkylcarbonyl, aminoalkyl, cycloalkyl, (cycloalkyl)alkyl, heterocycle and phenyl;
• and
• R6 is selected from the group consisting of hydrogen, alkyl, alkylsulfanylalkyl, aryl, and arylalkyl.