Anti-infective agents

A process for the preparation of a compound of formula (I)

• 433
• or a pharmaceutically acceptable salt form, stereoisomer or tautomer thereof, wherein:
• A is a monocyclic or bicyclic ring selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocycle;
• R1 is selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, alkylcarbonylalkyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkynyl, aryl, arylalkenyl, arylalkyl, arylsulfanylalkyl, arylsulfonylalkyl, carboxyalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, formylalkyl, haloalkoxyalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heteroarylsulfonylalkyl, heterocycle, heterocyclealkenyl, heterocyclealkyl, hydroxyalkyl, nitroalkyl, RaRbN—, RaRbNalkyl-, RaRbNC(O)alkyl-, RaRbNC(O)Oalkyl-, RaRbNC(O)NRcalkyl-, RfRgC═N— and RkO—, wherein R1 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRe), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Re), —C(O)Rc, —C(O)ORc and —C(O)NRcRe;
• R2 and R3 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, alkyl, aryl, arylalkyl, heteroaryl, heterocycle, heteroarylalkyl, cyano, halo, —N(Ra)(Rb), RaRbNC(O)—, —SRa, —S(O)Ra, —S(O)2Ra and RaC(O)—;
• wherein R2 and R3 are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of Ra, alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, -(alkyl)(ORk), -(alkyl)(NRaRb), —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb;
• alternatively, R2 and R3, together with the carbon atoms to which they are attached form a five- or six-membered ring selected from the group consisting of aryl, cycloalkyl, heteroaryl and heterocycle, wherein said aryl, cycloalkyl, heteroaryl and heterocycle is optionally substituted with (R6)m;
• R4 is selected from the group consisting of alkoxy, arylalkoxy, aryloxy, halo, hydroxy, RaRbN—, N3—, RcS—, wherein R4 is independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, nitro, cyano, —OH, —NH2, and —COOH;
• R5 is independently selected at each occurrence from the group consisting of alkenyl, alkoxy, alkyl, alkynyl, aryl, arylalkyl, arylcarbonyl, aryloxy, azidoalkyl, formyl, halo, haloalkyl, halocarbonyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, hydoxyalkyl, cycloalkyl, cyano, cyanoalkyl, nitro, RaRbN—, RaC(O)—, RaS—, Ra(O)S—, Ra(O)2S—, RaRbNalkyl-, Ra(O)SN(Rf)—, RaSO2N(Rf)—, Ra(O)SN(Rf)alkyl-, RaSO2N(Rf)alkyl-, RaRbNSO2N(Rf)—, RaRbNSO2N(Rf)alkyl-, RaRbNC(O)—, RkOC(O)—, RkOC(O)alkyl-, RkOalkyl-, RaRbNSO2—, RaRbNSO2alkyl-, (RbO)(Ra)P(O)O— and —ORk, wherein each R5 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• R6 is independently selected at each occurrence from the group consisting of alkyl, alkenyl, alkynyl, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclealkyl, -(alkyl)(ORk), -(alkyl)(NRaRb), —SRa, —S(O)Ra, —S(O)2Rc, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb;
• wherein each R6 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, haloalkyl, cyano, nitro, —ORa, —NRaRb, —SRa, —SORa, —SO2Ra, —C(O)ORa, —C(O)NRaRb and —NC(O)Ra;
• Ra and Rb, at each occurrence, are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkylsulfanylalkyl, aryl, arylalkenyl, arylalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, formylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkenyl, heterocyclealkyl, hydroxyalkylcarbonyl, nitroalkyl, RRdN—, RkO—. RkOalkyl-, RcRdNalkyl-, RcRdNC(O)alkyl-, RcSO2—, RcSO2alkyl-, RcC(O)—, RcC(O)alkyl-, RcOC(O)—, RcOC(O)alkyl-, RcRdNalkylC(O)—, RcRdNC(O)—, RcRdNC(O)Oalkyl-, RcRdNC(O)N(Re)alkyl-, wherein Ra and Rb are substituted with 0, 1 or 2 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), —SRa, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• alternatively, Ra and Rb, together with the nitrogen atom to which they are attached form a three- to six-membered ring selected from the group consisting of heteroaryl and heterocycle, wherein the heteroaryl and heterocycle are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), -(alkyl)SO2NRcRd, -alkylC(O)NRcRd, —SRc, —S(O)Rc, —S(O)2Ra, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• Rc and Rd, at each occurrence, are independently selected from the group consisting of hydrogen, —NRfRh, —ORf, —CO(Rf), —SRf, —SORf, —SO2Rf, —C(O)NRfRh, —SO2NRfRh, —C(O)ORf, alkenyl, alkyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl;
• wherein each Rc and Rd is independently substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORf), -(alkyl)(NRfRh), —SRf, —S(O)Rf, —S(O)2Rf, —ORf, —N(Rf)(Rh), —C(O)Rf, —C(O)ORf, —C(O)NRfRh, —C(O)N(H)NRfRh, —N(Re)C(O)ORf, —N(Re)SO2NRfRh, —N(Re)C(O)NRfRh, -alkylIN(Re)C(O)ORf, -alkylIN(Re)SO2NRfRh, and -alkylIN(Re)C(O)NRfRh;
• alternatively, Rc and Ra, together with the nitrogen atom to which they are attached form a three- to six-membered ring selected from the group consisting of heteroaryl and heterocycle, wherein the heteroaryl and heterocycle are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORf), -(alkyl)(NRfRh), —SRf, —S(O)Rf, —S(O)2Rf, —ORf, —N(Rf)(Rh), —C(O)Rf, —C(O)ORf and —C(O)NRfRh;
• Re is selected from the group consisting of hydrogen, alkenyl, alkyl and cycloalkyl;
• Rf, Rg and Rh, at each occurrence, are independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, heteroaryl and heteroarylalkyl;
• wherein each Rf, Rg and Rh is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, oxo, nitro, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, heteroarylalkyl, —OH, —O(alkyl), —NH2, —N(H)(alkyl), —N(alkyl)2, —S(alkyl), —S(O)(alkyl), —SO2alkyl, -(alkyl)-OH, -(alkyl)-O-alkyl, -(alkyl)NH2, -(alkyl)N(H)(alkyl), -(alkyl)N(alkyl)2, -alkylS(alkyl), -(alkyl)S(O)(alkyl), -(alkyl)SO2alkyl, —N(H)C(O)NH2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)NH2, —C(O)N(H)(alkyl), and —C(O)N(alkyl)2;
• alternatively, Rf and Rg together with the carbon atom to which they are attached form a three- to seven-membered ring selected from the group consisting of cycloalkyl, cycloalkenyl and heterocycle;
• alternatively, Rf and Rh together with the nitrogen atom to which they are attached form a three- to seven-membered ring selected from the group consisting of heterocycle and heteroaryl;
• wherein each of the heterocycle and heteroaryl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, oxo, nitro, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, heteroarylalkyl, —OH, —O(alkyl), —NH2, —N(H)(alkyl), —N(alkyl)2, —S(alkyl), —S(alkyl), —S(O)(alkyl), -(alkyl)-OH, -(alkyl)-O-alkyl, -(alkyl)NH2, -(alkyl)N(H)(alkyl), -alkylS(alkyl), -(alkyl)S(O)(alkyl), -(alkyl)SO2alkyl, -(alkyl)N(alkyl)2, —N(H)C(O)NH2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)NH2, —C(O)N(H)(alkyl), and —C(O)N(alkyl)2;
• Rk is selected from the group consisting of hydrogen, alkenyl, alkyl, aryl, arylalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, formylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, nitroalkyl, RaRbNalkyl-, RaOalkyl-, RaRbNC(O)—, RaRbNC(O)alkyl, RaS—, RaS(O)—, RaSO2—, RaSalkyl-, Ra(O)Salkyl-, RaSO2alkyl-, RaOC(O)—, RaOC(O)alkyl-, RaC(O)—, RaC(O)alkyl-, wherein each Rk is substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• m is 0, 1, 2,3, or 4;
• and
• n is 0, 1, 2,3, or 4;
• with the proviso that when A is a monocyclic ring other than
• 434
• and R4 is alkoxy, aryloxy, hydroxy or ReS—, and R5 is hydrogen, alkenyl, alkoxy, alkyl, alkynyl, aryl, halo, heteroaryl, heterocyclealkyl, cycloalkyl, cyano, nitro, RaRbN—, RaC(O)—, RaS—, Ra(O)S—, Ra(O)2S—, RaSO2N(Rf)—, RaRbNC(O)—, RkOC(O)—, RaRbNSO2— or —ORk, and R6 is hydrogen, alkyl, alkenyl, alkynyl, halo, cyano, nitro, aryl, heteroaryl, heterocyclealkyl, —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb, then R1 is not hydrogen, alkenyl, alkyl, alkynyl, aryl, arylalkenyl, arylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocyclealkenyl or heterocyclealkyl;
• and with the further proviso that when A is
• 435
• and R4 is hydroxy or ReS—, and R5 is hydrogen, unsubstituted alkyl, halo or —ORk, and R6 is hydrogen, alkyl, alkenyl, alkynyl, halo, cyano, nitro, aryl, heteroaryl, heterocyclealkyl, —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb, then R1 is not hydrogen, alkenyl, alkyl, alkynyl, aryl, arylalkenyl, arylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocyclealkenyl or heterocyclealkyl;
• comprising:
• (a) contacting a compound of formula (26)
• 436
• with carbon disulfide and a methylating agent in the presence of a base to provide a compound of formula (27)
• 437
• and
• (b) contacting the compound of formula (27) with a compound of formula (13)
• 438

A process for the preparation of a compound of formula (I),

• 439
• or a pharmaceutically acceptable salt form, stereoisomer or tautomer thereof, wherein:
• A is a monocyclic or bicyclic ring selected from the group consisting of aryl, cycloalkyl, cycloalkenyl, heteroaryl and heterocycle;
• R1 is selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, alkylcarbonylalkyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkynyl, aryl, arylalkenyl, arylalkyl, arylsulfanylalkyl, arylsulfonylalkyl, carboxyalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, formylalkyl, haloalkoxyalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heteroarylsulfonylalkyl, heterocycle, heterocyclealkenyl, heterocyclealkyl, hydroxyalkyl, nitroalkyl, RaRbN—, RaRbNalkyl-, RaRbNC(O)alkyl-, RaRbNC(O)Oalkyl-, RaRbNC(O)NRcalkyl-, RfRgC═N— and RkO—, wherein R1 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(Oc), -(alkyl)(NRcRe), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Re), —C(O)Rc, —C(O)ORc and —C(O)NRcRe;
• R2 and R3 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, alkyl, aryl, arylalkyl, heteroaryl, heterocycle, heteroarylalkyl, cyano, halo, —N(Ra)(Rb), RaRbNC(O)—, —SRa, —S(O)Ra, —S(O)2Ra and RaC(O)—;
• wherein R2 and R3 are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of Ra, alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, -(alkyl)(ORk), -(alkyl)(NRaRb), —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), C(O)Ra, —C(O)ORa and —C(O)NRaRb;
• alternatively, R2 and R3, together with the carbon atoms to which they are attached form a five- or six-membered ring selected from the group consisting of aryl, cycloalkyl, heteroaryl and heterocycle, wherein said aryl, cycloalkyl, heteroaryl and heterocycle is optionally substituted with (R6)m;
• R4 is selected from the group consisting of alkoxy, arylalkoxy, aryloxy, halo, hydroxy, RaRbN—, N3—, ReS—, wherein R4 is independently substituted with 0, 1 or 2 substituents independently selected from the group consisting of halo, nitro, cyano, —OH, —NH2, and —COOH;
• R5 is independently selected at each occurrence from the group consisting of alkenyl, alkoxy, alkyl, alkynyl, aryl, arylalkyl, arylcarbonyl, aryloxy, azidoalkyl, formyl, halo, haloalkyl, halocarbonyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, hydoxyalkyl, cycloalkyl, cyano, cyanoalkyl, nitro, RaRbN—, RaC(O)—, RaS—, Ra(O)S—, Ra(O)2S—, RaRbNalkyl-, Ra(O)SN(Rf)—, RaSO2N(Rf)—, Ra(O)SN(Rf)alkyl-, RaSO2N(Rf)alkyl-, RaRbNSO2N(Rf)—, RaRbNSO2N(Rf)alkyl-, RaRbNC(O)—, RkOC(O)—, RkOC(O)alkyl-, RkOalkyl-, RaRbNSO2—, RaRbNSO2alkyl-, (RbO)(Ra)P(O)O— and —ORk, wherein each R5 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• R6 is independently selected at each occurrence from the group consisting of alkyl, alkenyl, alkynyl, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclealkyl, -(alkyl)(ORk), -(alkyl)(NRaRb), —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb;
• wherein each R6 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, haloalkyl, cyano, nitro, —ORa, —NRaRb, —SRa, SORa, SO2Ra, —C(O)ORa, C(O)NRaRb and —NC(O)Ra;
• Ra and Rb, at each occurrence, are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkylsulfanylalkyl, aryl, arylalkenyl, arylalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, formylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkenyl, heterocyclealkyl, hydroxyalkylcarbonyl, nitroalkyl, RcRdN—, Rk—. RkOalkyl-, RcRdNalkyl-, RcRdNC(O)alkyl-, RcSO2—, RcSO2alkyl-, RcC(O)—, RcC(O)alkyl-, RcOC(O)—, RcOC(O)alkyl-, RcRdNalkylC(O)—, RcRdNC(O)—, RcRdNC(O)Oalkyl-, RcRdNC(O)N(Re)alkyl-, wherein Ra and Rb are substituted with 0, 1 or 2 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORs, —N(R)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• alternatively, Ra and Rb, together with the nitrogen atom to which they are attached form a three- to six-membered ring selected from the group consisting of heteroaryl and heterocycle, wherein the heteroaryl and heterocycle are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), -(alkyl)SO2NRcRd, -alkylC(O)NRcRd, —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)OR and —C(O)NRcRd;
• Rc and Rd, at each occurrence, are independently selected from the group consisting of hydrogen, —NRfRh, —ORf, —CO(Rf), —SRf, —SORf, —SO2Rf, —C(O)NRfRh, —SO2NRfRh, —C(O)ORf, alkenyl, alkyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl;
• wherein each Rc and Rd is independently substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORf), -(alkyl)(NRfRh), —SRf, —S(O)Rf, —S(O)2Rf, —ORf, —N(Rf)(Rh), —C(O)Rf, —C(O)ORf, —C(O)NRfRh, —C(O)N(H)NRfRh, —N(R)C(O)ORf, —N(Re)SO2NRfRh, —N(Re)C(O)NRfRh, -(alkyl)N(Re)C(O)ORf, -(alkyl)N(Re)SO2NRfRh, and -alkylN(Re)C(O)NRfRh;
• alternatively, Rc and Rd, together with the nitrogen atom to which they are attached form a three- to six-membered ring selected from the group consisting of heteroaryl and heterocycle, wherein the heteroaryl and heterocycle are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORf), -(alkyl)(NRfRh), —SRf, —S(O)Rf, —S(O)2Rf, —ORf, —N(Rf)(Rh), —C(O)Rf, —C(O)ORf and —C(O)NRfRh;
• Re is selected from the group consisting of hydrogen, alkenyl, alkyl and cycloalkyl;
• Rf, Rg and Rh, at each occurrence, are independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, heteroaryl and heteroarylalkyl;
• wherein each Rf, Rg and Rh is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, oxo, nitro, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, heteroarylalkyl, —OH, —O(alkyl), —NH2, —N(H)(alkyl), —N(alkyl)2, —S(alkyl), —S(O)(alkyl), —SO2alkyl, -(alkyl)-OH, -(alkyl)-O-alkyl, -(alkyl)NH2, -(alkyl)N(H)(alkyl), -(alkyl)N(alkyl)2, -alkylS(alkyl), -(alkyl)S(O)(alkyl), -(alkyl)SO2alkyl, —N(H)C(O)NH2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)NH2, —C(O)N(H)(alkyl), and —C(O)N(alkyl)2;
• alternatively, Rf and Rg together with the carbon atom to which they are attached form a three- to seven-membered ring selected from the group consisting of cycloalkyl, cycloalkenyl and heterocycle;
• alternatively, Rf and Rh together with the nitrogen atom to which they are attached form a three- to seven-membered ring selected from the group consisting of heterocycle and heteroaryl;
• wherein each of the heterocycle and heteroaryl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, oxo, nitro, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, heteroarylalkyl, —OH, —O(alkyl), —NH2, —N(H)(alkyl), —N(alkyl)2, —S(alkyl), —S(alkyl), —S(O)(alkyl), -(alkyl)-OH, -(alkyl)-O-alkyl, -(alkyl)NH2, -(alkyl)N(H)(alkyl), -alkylS(alkyl), -(alkyl)S(O)(alkyl), -(alkyl)SO2alkyl, -(alkyl)N(alkyl)2, —N(H)C(O)NH2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)NH2, —C(O)N(H)(alkyl), and —C(O)N(alkyl)2;
• Rk is selected from the group consisting of hydrogen, alkenyl, alkyl, aryl, arylalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, formylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, nitroalkyl, RaRbNalkyl-, RaOalkyl-, RaRbNC(O)—, RaRbNC(O)alkyl, RaS—, RaS(O)—, RaSO2—, RaSalkyl-, Ra(O)Salkyl-, RaSO2alkyl-, RaOC(O)—, RaOC(O)alkyl-, RaC(O)—, RaC(O)alkyl-, wherein each Rk is substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NcRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• m is 0, 1, 2,3, or 4;
• and
• n is 0, 1, 2,3, or 4;
• with the proviso that when A is a monocyclic ring other than
• 440
• and R4 is alkoxy, aryloxy, hydroxy or ReS—, and R5 is hydrogen, alkenyl, alkoxy, alkyl, alkynyl, aryl, halo, heteroaryl, heterocyclealkyl, cycloalkyl, cyano, nitro, RaRbN—, RaC(O)—, RaS—, Ra(O)S—, Ra(O)2S—, RaSO2N(Rf)—, RaRbNC(O)—, RkOC(O), RaRbNSO2— or —ORk, and R6 is hydrogen, alkyl, alkenyl, alkynyl, halo, cyano, nitro, aryl, heteroaryl, heterocyclealkyl, —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb, then R1 is not hydrogen, alkenyl, alkyl, alkynyl, aryl, arylalkenyl, arylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocyclealkenyl or heterocyclealkyl;
• and with the further proviso that when A is
• 441
• and R4 is hydroxy or ReS—, and R5 is hydrogen, unsubstituted alkyl, halo or —ORk, and R6 is hydrogen, alkyl, alkenyl, alkynyl, halo, cyano, nitro, aryl, heteroaryl, heterocyclealkyl, —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb, then R1 is not hydrogen, alkenyl, alkyl, alkynyl, aryl, arylalkenyl, arylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocyclealkenyl or heterocyclealkyl;
• comprising:
• (a) contacting a compound of formula (26)
• 442
• with tris(methylthio)methyl methyl sulfate in the presence of a base to provide a compound of formula (27)
• 443
• and
• (b) contacting the compound of formula (27) with a compound of formula (13)
• 444

A compound having formula (IX),

• 445
• or a pharmaceutically acceptable salt form, tautomer or stereoisomer thereof, wherein
• R1 is selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonylalkyl, alkyl, alkylcarbonylalkyl, alkylsulfanylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkynyl, aryl, arylalkenyl, arylalkyl, arylsulfanylalkyl, arylsulfonylalkyl, carboxyalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, (cycloalkyl)alkenyl, (cycloalkyl)alkyl, formylalkyl, haloalkoxyalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heteroarylsulfonylalkyl, heterocycle, heterocyclealkenyl, heterocyclealkyl, hydroxyalkyl, nitroalkyl, RaRbN—, RaRbNalkyl-, RaRbNC(O)alkyl-, RaRbNC(O)Oalkyl-, RaRbNC(O)NRcalkyl-, RfRgC═N— and RkO—, wherein R1 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRe), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Re), —C(O)Rc, —C(O)ORc and —C(O)NRcRe;
• R2 and R3 are independently selected from the group consisting of hydrogen, alkenyl, alkynyl, alkoxyalkyl, alkoxycarbonyl, alkyl, aryl, arylalkyl, heteroaryl, heterocycle, heteroarylalkyl, cyano, halo, —N(Ra)(Rb), RaRbNC(O)—, —SRa, —S(O)Ra, —S(O)2Ra and RaC(O)—;
• wherein R2 and R3 are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of Ra, alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, -(alkyl)(ORk), -(alkyl)(NRaRb), —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb;
• alternatively, R2 and R3, together with the carbon atoms to which they are attached form a five- or six-membered ring selected from the group consisting of aryl, cycloalkyl, heteroaryl and heterocycle, wherein said aryl, cycloalkyl, heteroaryl and heterocycle is optionally substituted with (R6)m;
• R6 is independently selected at each occurrence from the group consisting of alkyl, alkenyl, alkynyl, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, heterocyclealkyl, -(alkyl)(ORk), -(alkyl)(NRaRb), —SRa, —S(O)Ra, —S(O)2Ra, —ORk, —N(Ra)(Rb), —C(O)Ra, —C(O)ORa and —C(O)NRaRb;
• wherein each R6 is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, haloalkyl, cyano, nitro, —ORa, —NRaRb, —SRa, —SORa, —SO2Ra, —C(O)ORa, —C(O)NRaRb and —NC(O)Ra;
• Ra and Rb, at each occurrence, are independently selected from the group consisting of hydrogen, alkenyl, alkyl, alkylsulfanylalkyl, aryl, arylalkenyl, arylalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, formylalkyl, haloalkyl, heteroaryl, heteroarylalkenyl, heteroarylalkyl, heterocycle, heterocyclealkenyl, heterocyclealkyl, hydroxyalkylcarbonyl, nitroalkyl, RcDN—, RkO—. RkOalkyl-, R-cRdNalkyl-, RcRdNC(O)alkyl-, RcSO2—, RcSO2alkyl-, RcC(O)—, RcC(O)alkyl-, RcOC(O)—, RcOC(O)alkyl-, RcRdNalkylC(O)—, RcRdNC(O)—, RcRdNC(O)Oalkyl-, RcRdNC(O)N(Re)alkyl-, wherein Ra and Rb are substituted with 0, 1 or 2 substituents selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(d), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• alternatively, Ra and Rb, together with the nitrogen atom to which they are attached form a three- to six-membered ring selected from the group consisting of heteroaryl and heterocycle, wherein the heteroaryl and heterocycle are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), -(alkyl)SO2NRcRd, -alkylC(O)NRcRd, —SRc, —S(O)Rc, —S(O)2, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• Rc and Rd, at each occurrence, are independently selected from the group consisting of hydrogen, —NRfRh, —ORf, —CO(Rf), —SRf, —SORf, —SO2Rf, —C(O)NRfRh, —SO2NRfRh, —C(O)ORf, alkenyl, alkyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, arylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle and heterocyclealkyl;
• wherein each Rc and Rd is independently substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORf), -(alkyl)(NRfRh), —SRf, —S(O)Rf, —S(O)2Rf, —ORf, —N(Rf)(Rh), —C(O)Rf, —C(O)ORf, —C(O)NRfRh, —C(O)N(H)NRfRh, —N(Re)C(O)ORf, —N(Re)SO2NRfRh, —N(Re)C(O)NRfRh, -(alkyl)N(Re)C(O)ORf, -(alkyl)N(Re)SO2NRfRh, and -alkylN(Re)C(O)NRfRh;
• alternatively, Rc and Rd, together with the nitrogen atom to which they are attached form a three- to six-membered ring selected from the group consisting of heteroaryl and heterocycle, wherein the heteroaryl and heterocycle are independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORf), -(alkyl)(NRfRh), —SRf, —S(O)Rf, —S(O)2Rf, —ORf, —N(Rf)(Rh), —C(O)Rf, —C(O)ORf and —C(O)NRfRh;
• Re is selected from the group consisting of hydrogen, alkenyl, alkyl and cycloalkyl;
• Rf, Rg and Rh, at each occurrence, are independently selected from the group consisting of hydrogen, alkyl, alkenyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heterocycle, heterocyclealkyl, heteroaryl and heteroarylalkyl;
• wherein each Rf, Rg and Rh is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, oxo, nitro, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, heteroarylalkyl, —OH, —O(alkyl), —NH2, —N(H)(alkyl), —N(alkyl)2, —S(alkyl), —S(O)(alkyl), —SO2alkyl, -(alkyl)-OH, -(alkyl)-O-alkyl, -(alkyl)NH2, -(alkyl)N(H)(alkyl), -(alkyl)N(alkyl)2, -alkylS(alkyl), -(alkyl)S(O)(alkyl), -(alkyl)SO2alkyl, —N(H)C(O)NH2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)NH2, —C(O)N(H)(alkyl), and —C(O)N(alkyl)2;
• alternatively, Rf and Rg together with the carbon atom to which they are attached form a three- to seven-membered ring selected from the group consisting of cycloalkyl, cycloalkenyl and heterocycle;
• alternatively, Rf and Rh together with the nitrogen atom to which they are attached form a three- to seven-membered ring selected from the group consisting of heterocycle and heteroaryl;
• wherein each of the heterocycle and heteroaryl is independently substituted with 0, 1, 2 or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, cyano, halo, oxo, nitro, aryl, arylalkyl, cycloalkyl, cycloalkenyl, heterocycle, heteroaryl, heteroarylalkyl, —OH, —O(alkyl), —NH2, —N(H)(alkyl), —N(alkyl)2, —S(alkyl), —S(alkyl), —S(O)(alkyl), -(alkyl)-OH, -(alkyl)-O-alkyl, -(alkyl)NH2, -(alkyl)N(H)(alkyl), -alkylS(alkyl), -(alkyl)S(O)(alkyl), -(alkyl)SO2alkyl, -(alkyl)N(alkyl)2, —N(H)C(O)NH2, —C(O)OH, —C(O)O(alkyl), —C(O)alkyl, —C(O)NH2, —C(O)NH2, —C(O)N(H)(alkyl);
• and —C(O)N(alkyl)2;
• Rk is selected from the group consisting of hydrogen, alkenyl, alkyl, aryl, arylalkyl, cyanoalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkyl, cycloalkylalkyl, formylalkyl, haloalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, nitroalkyl, RaRbNalkyl-, RaOalkyl-, RaRbNC(O)—, RaRbNC(O)alkyl, RaS—, RaS(O)—, RaSO2—, RaSalkyl-, Ra(O)Salkyl-, RaSO2alkyl-, RaOC(O)—, RaOC(O)alkyl-, RaC(O)—, RaC(O)alkyl-, wherein each Rk is substituted with 0, 1, 2, or 3 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, oxo, halo, cyano, nitro, haloalkyl, haloalkoxy, aryl, heteroaryl, heterocycle, arylalkyl, heteroarylalkyl, alkoxyalkoxyalkyl, -(alkyl)(ORc), -(alkyl)(NRcRd), —SRc, —S(O)Rc, —S(O)2Rc, —ORc, —N(Rc)(Rd), —C(O)Rc, —C(O)ORc and —C(O)NRcRd;
• m is 0, 1, 2,3, or 4;
• and
• R11 and R12 are independently selected from the group consisting of alkyl, alkenyl and alkynyl.