2-amino-benzimidazole derivatives and their use as 5-lipoxygenase and/or prostaglandin E synthase inhibitors

A compound having general formula II:

• wherein
• n is 0 or 1;
• X1 is CR5 or N;
• Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups;
• R5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy;
• R23 is selected from the group consisting of C1-C6 alkyl, C1-C3 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R24 is selected from the group consisting of C3-C10 cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R25 is selected from the group consisting of —(V)pR26 and —(V)p—OR14;
• wherein,
• p is 0,
• V is C1-C6 alkylene, wherein alkylene is optionally substituted with one to three C1-C3 alkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C3-C6 cycloalkyl group;
• R14 is selected from the group consisting of hydrogen, C1-C6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C1-C3 haloalkoxy groups;
• R26 is selected from the group consisting of C1-C6 alkyl, —CN and C1-C3 haloalkyl, and groups of formula IIa shown below,
• wherein,
• A2 is —O— or NH—;
• A3 is —O—, —CH2O—, —OCH2−, or —NH—;
• B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R19 is selected from the group consisting of hydrogen, —OR22 and —CH2OR22;
• R20 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
• R21 is selected from the group consisting of hydrogen, halogen and C1-C6 alkyl;
• R22 is selected from the group consisting of aryl, and heteroaryl, wherein each of said aryl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C3-C10 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C3 alkylhydroxyl, —CH2ORc, —OCH2Rc, —ORc, —CN, NO2, —NRbRc, —C(O)NRbRc, —C(NH)NH2, —C(O)Rc, —C(O)ORc, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C3 haloalkyl, —CN, —C(O)NH2, —COOH, —CO2Et and heteroaryl;
• Rb and Rc are independently, at each occurence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10 cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, —NH2;
• or
• Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salts thereof.

A compound having general formula III:

• wherein
• n is 0 or 1;
• X1 is CR5 or N;
• Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups;
• R5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy;
• R23 is selected from the group consisting of C1-C6 alkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R27 is selected from the group consisting of hydrogen, —R6, and —R9—R10;
• wherein,
• R6 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C1-C6 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R9 is C1-C4 alkylene, wherein said alkylene is optionally substituted with one to three C1-C3 alkyl groups;
• R10 is selected from the group consisting of hydroxyl, —OR11, —C(O)OR18, —C(O)NH2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R11 is independently, at each occurrence selected from the group consisting of aryl, heteroaryl and heterocyclyl group wherein said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R18 is hydrogen or C1-C6 alkyl;
• R28 is selected from the group consisting of —(V)pR29 and —(V)p—OR14;
• wherein,
• p is 0,
• V is C1-C6 alkylene, wherein alkylene is optionally substituted with one to three C1-C6 alkyl or phenyl groups;
• R14 is selected from the group consisting of hydrogen, C1-C6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C1-C3 haloalkoxy groups;
• R29 is selected from the group consisting of C2, C5-C6 alkyl and C1-C3 haloalkyl, and groups of formula IIIa shown below,
• wherein,
• A2 is —O— or NH—;
• A3 is —O—, —CH2O—, —OCH2—, or —NH—;
• B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R19 is selected from the group consisting of hydrogen, —OR22 and —CH2OR22;
• R20 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
• R21 is selected from the group consisting of hydrogen, halogen and C1-C6 alkyl;
• R22 is selected from the group consisting of aryl, and heteroaryl, wherein said aryl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C3-C10 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C3 alkylhydroxyl, —CH2OH, —OCH3, —NRbH, —C(O)NRbH, C(O)H, —CH2ORc, —OCH2Rc, —ORc, —CN, NO2, —NRbRb, —C(O)NRbRc, —C(NH)NH2, —C(O)Rc, —C(O)ORc, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C3 haloalkyl, —CN, —C(O)NH2, —CO2Et and heteroaryl;
• Rb is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, —NH2;
• Rc is independently, at each occurrence, selected from the group consisting of C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10 cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, —NH2;
• or
• Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salts thereof.

A compound having general formula I:

• wherein
• n is 0 or 1;
• X1 and X2 are independently, at each occurrence, CR5 or N;
• Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups;
• R1 is selected from the group consisting of hydrogen, halogen, C1-C6 alkoxy, —NHR6, —NR7 R8 and —NH—(R9)n—R10, n being 0 or 1;
• R2 is selected from the group consisting of C1-C6 alkyl, —NH2, —NHR6, —NR7R8 and —NH—(R9)n—R10, n being 0 or 1;
• R3 is selected from the group consisting of hydroxyl, OR11, —NR7R8, C1-C6 alkoxy, C1-C6 alkyl, C3-C10cycloalkyl, C1-C3 haloalkyl, —C(O)NHR11, aryl, heteroaryl, wherein each of said cycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one to four Ra groups;
• R4 is —N(R12)(V)pR13, R12 is H, V is C1-alkylene, p is 1, R13 is
• wherein A1 is —O—, —CH2O—, —OCH2−, —S—, —SO2−, —SO2NH—, —C(O)—, —C(O)NH—, —C(O)N(R7)—, —CH(OH)—, —CH(OR7)—, —NH—, —N(CH3)— or —N(CH2COOR7)—;
• and B is heteroaryl which is optionally substituted with one to four Ra groups;
• R5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy;
• R6 is selected from the group consisting of C1-C6 alkyl, C3-C10cycloalkyl, C1-C6 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R7 and R8 are independently, at each occurrence, heterocyclyl;
• or
• R7 and R8 are connected to each other to make a four, five or six membered heterocyclyl or heteroaryl group, wherein each of said heterocyclyl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• R9 is C1-C4 alkylene, wherein said alkylene is optionally substituted with one to three C1-C3 alkyl groups;
• R10 is selected from the group consisting of hydroxyl, —OR11, —CN, —C(O)OR18, —C(O)NH2, —C(NH)NH2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R11 is independently, at each occurrence, selected from the group consisting of aryl heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R18 is hydrogen or C1-C6 alkyl;
• R20 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, —C(O)Ra and C1-C6 haloalkoxy;
• R21 is selected from the group consisting of hydrogen, halogen and C1-C6 alkyl;
• Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C3-C10 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C3 alkylhydroxyl, —CH2OH, —OCH3, —NRbH, —C(O)NRbH, —C(O)H, —CH2ORc, —OCH2Rc, —ORc, —CN, NO2, —NRbRc, —C(O)NRbRc, —C(NH)NH2, —C(O)Rc, —C(O)ORc, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C3 haloalkyl, —CN, —C(O)NH2, —CO2Et or heteroaryl;
• Rb is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10 cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, or —NH2;
• Rc is independently, at each occurrence, selected from the group consisting of C1-C10alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10cycloalkenyl, C2-C10alkynyl, C1-C6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —N2, or —NH2;
• or
• Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salts thereof.

A compound having general formula II:

• wherein
• n is 0 or 1;
• X1 is CR5 or N;
• Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups;
• R5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6alkoxy;
• R23 is selected from the group consisting of C1-C6 alkyl, C1-C3 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R24 is selected from the group consisting of C3-C10 cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R25 is selected from the group consisting of —(V)pR26 and —(V)p—OR 14;
• wherein,
• p is 1,
• V is C1-C6 alkylene, wherein alkylene is optionally substituted with one to three C1-C3 alkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C3-C6 cycloalkyl group;
• R14 is selected from the group consisting of hydrogen, C1-C6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C1-C3 haloalkoxy groups;
• R26 is selected from the group consisting of hydrogen, C1-C6 alkyl, —CN and C1-C3 haloalkyl, and groups of formula IIa shown below,
• wherein,
• A2 is —O— or NH—;
• A3 is —O—, —CH2O—, —OCH2−, or —NH—;
• B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R19 is selected from the group consisting of hydrogen, —OR22 and —CH2OR22;
• R20 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
• R21 is selected from the group consisting of hydrogen, halogen and C1-C6 alkyl;
• R22 is selected from the group consisting of aryl, and heteroaryl, wherein each of said aryl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C3-C10 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C3 alkylhydroxyl, —CH2ORc, —OCH2Rc, —ORc, —CN, NO2, —NRbRc, —C(O)NRbRc, —C(NH)NH2, —C(O)Rc, —C(O)ORc, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C3 haloalkyl, —CN, —C(O)NH2, —COOH, —CO2Et and heteroaryl;
• Rb and Rc are independently, at each occurence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10 cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, —NH2;
• or
• Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salts thereof.

A compound having general formula III:

• wherein
• n is 0 or 1;
• X1 is CR5 or N;
• Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups;
• R5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy;
• R23 is selected from the group consisting of C1-C6 alkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R27 is selected from the group consisting of hydrogen, —R6, and —R9—R10;
• wherein,
• R6 is selected from the group consisting of C1-C6 alkyl, C3-C10 cycloalkyl, C1-C6 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R9 is C1-C4 alkylene, wherein said alkylene is optionally substituted with one to three C1-C3 alkyl groups;
• R10 is selected from the group consisting of hydroxyl, —OR11, —C(O)OR18, —C(O)NH2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R11 is independently, at each occurrence selected from the group consisting of aryl, heteroaryl and heterocyclyl group wherein said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R18 is hydrogen or C1-C6 alkyl;
• R28 is selected from the group consisting of —(V)pR29 and —(V)p—OR14;
• wherein,
• p is 1,
• V is C1-C6 alkylene, wherein alkylene is optionally substituted with one to three C1-C6 alkyl or phenyl groups;
• R14 is selected from the group consisting of hydrogen, C1-C6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C1-C3 haloalkoxy groups;
• R29 is selected from the group consisting of C4-C6 alkyl and C1-C3 haloalkyl, and groups of formula IIIa shown below,
• wherein,
• A2 is —O— or NH—;
• A3 is —O—, —CH2O—, —OCH2—, or —NH—;
• B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R19 is selected from the group consisting of hydrogen, —OR22 and —CH2OR22;
• R20 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy and C1-C6 haloalkoxy;
• R21 is selected from the group consisting of hydrogen, halogen and C1-C6 alkyl;
• R22 is selected from the group consisting of aryl, and heteroaryl, wherein said aryl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C3-C10 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C3 alkylhydroxyl, —CH2OH, —OCH3, —NRbH, —C(O)NRbH, —C(O)H, —CH2ORc, —OCH2Rc, —ORc, —CN, NO2, —NRbRc, —C(O)NRbRc, —C(NH)NH2, —C(O)Rc, —C(O)ORc, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C3 haloalkyl, —CN, —C(O)NH2, —CO2Et and heteroaryl;
• Rb is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10cycloalkenyl, C2-C10 alkynyl, C1-C6haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —N2, —NH2;
• Rc is independently, at each occurrence, selected from the group consisting of C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10cycloalkenyl, C2-C10 alkynyl, C1-C6haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, —NH2, or
• Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salts thereof.

A compound having one of the following formulae:

• No.
• Structure
• 35
• 47
• 50
• 53
• 55
• 57
• 59
• 61
• 70
• 72
• 82
• 84
• 85
• 170
• 171
• 182
• 184
• 192
• 193
• 204
• 208
• 211
• 226
• 227
• 251
• 256
• 257
• 262
• 268
• 269
• 270
• 271
• 273
• 275
• 279
• 281
• 283
• 284
• 289
• 291
• 293
• 294
• 296
• 298
• 300
• 302
• 303
• 305
• 306
• 307
• 309
• 312
• 313
• 315
• 316
• 318
• 320
• 322
• 324
• 325
• 326
• 328
• 329
• 331
• 333
• 335
• 337
• 339
• 341
• 343
• 345
• 347
• 349
• 351
• 353
• 355
• 357
• 358
• 359
• 362
• 364
• 365
• 366
• 368
• 369
• 371
• 372
• 374
• 378
• 379
• 381
• 383
• 384
• 386
• 388
• 390
• 392
• 394
• 396
• 398
• 400
• 401
• 403
• 404
• 406
• 407
• 408
• 409
• 412
• 413
• 414
• 415
• 417
• 418
• 420
• 422
• 423
• 425
• 427
• 429
• 431
• 433
• 435
• 437
• 439
• 441
• 443
• 444
• 447
• 448
• 449
• 450
• 453
• 455
• 457
• 459
• 461
• 464
• 465
• 466
• 467
• 468
• 469
• 471
• 473
• 474
• 475
• 476
• 477
• 478
• 479
• 481
• 482
• 483
• 486
• 487
• 488
• 489
• 490
• 491
• 492
• 493
• 494
• 495
• 496
• 497
• 498
• 499
• 500
• 501
• 502
• 503
• 504
• 505
• 506
• 507
• 508
• 509
• 510
• 511
• 512
• 513
• 514
• 515
• 516
• 517
• 518
• 519
• 520
• 521
• 522
• 523
• 524
• 525
• 526
• 527
• 528
• 529
• 530
• 531
• 532
• 533
• 534
• 535
• 536
• 537
• 538
• 539
• 540
• 541
• 542
• 543
• 544
• 545
• 546
• 547
• 548
• 549
• 550
• 551
• 552
• 553
• 554
• 555
• 556
• or a pharmaceutically acceptable salt thereof.

A compound having general formula I:

• wherein
• n is 0 or 1;
• X1 and X2 are independently, at each occurrence, CR5 or N;
• Y is C1-C6 alkylene, wherein alkylene is optionally substituted with one to two C1-C3 alkyl groups;
• R1 is selected from the group consisting of C1-C6 alkoxy, —NHR6, —NR7R8 and —NH—(R9)n—R10, n being 0 or 1;
• R2 is selected from the group consisting of hydrogen, C1-C6 alkyl, —NH2, —NHR6, —NR7R8 and —NH—(R9), —R10, n being 0 or 1;
• R3 is selected from the group consisting of hydroxyl, OR11, —NR7R8, C1-C6 alkoxy, C1-C6 alkyl, C3-C5, C7-C10cycloalkyl, C1-C3 haloalkyl, —C(O)NHR11, aryl, heteroaryl, wherein each of said cycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one to four Ra groups;
• R4 is selected from the group consisting of —N(R12)(V)pR13, —NH(V)p—OR14, —NHC(O)R15, and groups of formula Ia shown below,
• wherein,
• p is 0,
• V is C1-C6 alkylene, wherein alkylene is optionally substituted with one to three C1-C3 alkyl, C3-C6 cycloalkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C3-C6 cycloalkyl group;
• R5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl and C1-C6 alkoxy;
• R6 is selected from the group consisting of C1-C6 alkyl, C3-C10cycloalkyl, C1-C6haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R7 and R8 are independently, at each occurrence, heterocyclyl;
• or
• R7 and R8 are connected to each other to make a four, five or six membered heterocyclyl or heteroaryl group, wherein each of said heterocyclyl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• R9 is C1-C4 alkylene, wherein said alkylene is optionally substituted with one to three C1-C3 alkyl groups;
• R10 is selected from the group consisting of hydroxyl, —OR11, —CN, —C(O)OR18, —C(O)NH2, —C(NH)NH2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R11 is independently, at each occurrence, selected from the group consisting of aryl heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R12 is selected from the group consisting of hydrogen, C2-C6 alkyl, C1-C4 alkyl-hydroxyl and C1-C4 alkyl-alkoxy;
• R13 is selected from the group consisting of C2, C5 C6 alkyl, C3-C10 cycloalkyl, C1-C4 alkyl-hydroxyl, —OH, —C(O)NH2, —C(O)OR18, —CN, C1-C3 haloalkyl, and groups of formula 1b shown below,
• wherein,
• n is 0 or 1;
• A1 is —O—, —CH2O—, —OCH2−, —S—, —SO2−, —SO2NH—, —C(O)—, —C(O)NH—, —C(O)N(R7)—, —CH(OH)—, —CH(OR7)—, —NH—, —N(CH3)— or —N(CH2COOR7)—;
• A2 is —O— or NH—;
• B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four Ra groups;
• R14 is selected from the group consisting of hydrogen, C1-C6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C1-C3 haloalkoxy groups;
• R15 is aryl, wherein aryl is substituted with one to four halogen groups;
• R16 selected from the group consisting of hydrogen, halogen, C1-C6 alkyl and hydroxyl;
• R17 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, —C(O)R11, —C(O)NHR11, —OR11 and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four Ra groups;
• R18 is hydrogen or C1-C6 alkyl;
• R19 is selected from the group consisting of hydrogen, —OR22 and —CH2OR22;
• R20 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, —C(O)Ra and C1-C6 haloalkoxy;
• R21 is selected from the group consisting of hydrogen, halogen and C1-C6 alkyl;
• R22 is selected from the group consisting of C1-C6 haloalkyl, aryl, and heteroaryl, wherein each of said haloalkyl, aryl and heteroaryl is optionally and independently substituted with one to four Ra groups;
• Ra is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C1-C3 alkyl, C3-C10 cycloalkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C3 alkylhydroxyl, —CH2OH, —OCH3, —NRbH, —C(O)NRbH, —C(O)H, —CH2ORc, —OCH2Rc, —ORc, —CN, NO2, —NRbRc, —C(O)NRbRc, —C(NH)NH2, —C(O)Rc, —C(O)ORc, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C3 haloalkyl, —CN, —C(O)NH2, —CO2Et or heteroaryl;
• Rb is independently, at each occurrence, selected from the group consisting of hydrogen, C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C1 cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, or —NH2;
• Rc is independently, at each occurrence, selected from the group consisting of C1-C10 alkyl, C3-C10 cycloalkyl, C1-C6 alkyl-O-alkyl, C2-C10 alkenyl, C1-C4 alkoxy, C1-C3 alkylhydroxyl, C3-C10cycloalkenyl, C2-C10 alkynyl, C1-C6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C1-C3 alkyl, C1-C4 alkoxy, halogen, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, —C(O)NH2, —COOH, —COOMe, —COOEt, —CN, —NO2, or —NH2;
• or
• Rb and Rc are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring;
• or a pharmaceutically acceptable salts thereof.