| CPC A61K 31/505 (2013.01) [A61K 31/00 (2013.01); A61K 31/44 (2013.01); A61K 45/06 (2013.01); A61K 48/005 (2013.01); C12N 2740/16043 (2013.01)] | 9 Claims |
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1. A method of treating a retroviral infection in a subject by suppressing the reactivation potential of the retroviral reservoir, which method comprises
(a) administering to the subject during active replication and integration of the virus a LEDGIN, which is a compound that binds to the lens epithelium-derived growth factor (LEDGF/p75) binding pocket of human immune deficiency (HIV)-integrase (IN) and prevents binding of IN to LEDGF/p75 to direct retroviral integration into transcriptionally silent positions in the genome of T cells; and
(b) determining the reactivation potential of the retroviral reservoir of T cells in said subject by a viral outgrowth assay, wherein said administration of said compound is maintained until said reactivation potential is determined as non-existent in said assay, and said retroviral infection is effectively treated by providing a remission of the retroviral infection;
wherein said LEDGIN is selected from;
A) a thieno [2,3-b]pyridine derivative according to Formula (I),
 wherein,
R1 is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; or heterocycle-alkynyl;
wherein in the cycloalkyl, cycloalkenyl, cycloalkynyl, alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N; respectively;
wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl, can be unsubstituted or substituted with one or more Z11; and
wherein a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
each of R2a and R2b is independently selected from hydrogen; cyano; alkyl; alkenyl; alkynyl; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; or heterocycle-alkynyl or when R2a and R2b are taken together to form vinyl or vinylalkyl;
wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl or vinylalkyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N, respectively;
wherein said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, vinyl or vinylalkyl, can be unsubstituted or substituted with one or more Z1; and
wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, or vinylalkyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
R3 is independently selected from —COOH; —CN; —CONH2; —COOZ2; —C(O)NHCN; —C(O)NHOH; —S(O)2OH; —S(O)2NHZ4; —P(O)(OH)NH2; —P(O)(OH)O-alkyl; —P(O)(O-alkyl)2; —P(O)OH2; —NHC(O)NHS(O)2-aryl; —NHC(O)NHS(O)2-heteroaryl; —C(O)NHS(O)2-aryl; —C(O)NHS(O)2-heteroaryl, —S(O)2NHS(O)2-aryl; —S(O)2NHS(O)2-heteroaryl; or from the following structures;
 or
R2a and R3 or R2b and R3 can be taken together to form a 4, 5, 6 or 7-membered lactone;
R4 is independently selected from hydrogen; halogen; cyano; hydroxyl; alkyl; alkenyl, alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl;
wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N, respectively;
wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be unsubstituted or substituted with one or more Z1; and
wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
R5 and R6 are taken together to form a 4, 5, 6, 7, or 8-membered unsaturated cycloalkyl moiety, a 4, 5, 6, 7, or 8-membered aryl moiety, or a 4, 5, 6, 7, or 8-membered mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle together with the carbon atoms to which they are attached;
wherein said 4, 5, 6, 7, or 8-membered unsaturated cycloalkyl moiety, 4, 5, 6, 7, or 8-membered aryl moiety, or 4, 5, 6, 7, or 8-membered mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle can be unsubstituted or substituted with one or more Z1; and
wherein a carbon atom or heteroatom of the 4, 5, 6, 7, or 8-membered unsaturated cycloalkyl moiety, 4, 5, 6, 7, or 8-membered aryl moiety, or 4, 5, 6, 7, or 8-membered mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
each Z1 is independently selected from the group consisting of hydrogen; halogen; —OZ2; —SZ2; —S(O)Z3; —S(O)2Z3; —SO2NZ4Z5; trifluoromethyl; nitro; —NZ4Z5; —NZ2S(O)2Z3; cyano; —COOZ2; —C(O)NZ4Z5; —C(O)Z3 alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl;
wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N s respectively;
wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with one or more Z11; and
wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2; or
two Z1 on the same carbon atom can be taken together to form a 5, 6 or 7-membered spiro-cycloalkyl, spiro-cycloalkenyl, spiro-cycloalkynyl, or a saturated or unsaturated spiro-heterocycle together with the (4, 5, 6, 7 or 8-membered unsaturated) ring they are attached to; or
two Z1 on adjacent atoms can be taken together to form a 5, 6 or 7-membered cycloalkyl, cycloalkenyl, cycloalkynyl, aryl or heterocycle fused to the (4, 5, 6, 7, or 8-membered unsaturated) ring they are attached to;
each Z11 is independently selected from the group consisting of hydrogen; halogen; —OZ12, —SZ12—S(O)Z13; —S(O)2Z13; —SO2NZ14Z15; trifluoromethyl; nitro; —NZ14Z15; —NZ12S(O)2Z13; cyano; —COOZ12C(O)NZ14Z15; —C(O)Z1; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle; alkynyl;
each Z2 and Z12 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl; and wherein in said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N, respectively; and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
each Z3 and Z13 is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkeπyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl; and wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N, respectively; and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O Or S(O)2;
each Z4, Z5, Z14 and Z15 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl; and wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S, —N≡ and/or ≡N, respectively; and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2; and wherein Z4 and Z5, and Z14 and Z15 respectively can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or —NH2; and isomers (in particular stereo-isomers or tautomers), solvates, hydrates, salts (in particular pharmaceutically acceptable salts) or prodrugs thereof,
provided that the compounds are not selected from
[2-(2-methoxy-5-methylphenyl)-4-phenyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2,7-dimethyl-4-(2-furanyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[4-(2-thienyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2,7-dimethyl-4-phenyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2,7-dimethyl-4-(m-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2-methyl-4-(m-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[4-(4-chlorophenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[4-(4-chlorophenyl)-2-methyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetic acid;
[4-(p-anisyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
Ethyl [4-phenyl-2-(2-thienyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate;
Ethyl [2-(2-thienyl)-4-(p-tolyl)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetate;
[2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[4-phenyl-2-(2-thienyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b6]pyridin-3-yl]acetic acid;
[2-(4-ethoxyphenyl)-4-(p-tolyl)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridiπ-3-yl]acetic acid;
[2-(4-iodophenyl)-4-phenyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2-(4-propoxyphenyl)-4-p-tolyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetic acid;
[2-(3,4-dipropoxyphenyl)-4-p-tolyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetic acid;
[2-(2-thienyl)-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2-(4-pentyloxyphenyl)-4-(p-tolyl)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetic acid;
Ethyl [4-(p-tolyl)-2-(2-thienyl)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetate;
Ethyl [4-phenyl-2-(2-thienyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate;
[4-(3-fluorophenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2-methyl-4-(p-tolyl)-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]acetic acid;
[2-methyl-4-phenyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2-(2-thienyl)-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
[2-methyl-4-(p-tolyl)-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid;
B) a pyrimidine derivative according to Formula (II),
 wherein,
each dotted line represents an optional double bond, whereby if the dotted line “a” forms a double bond, the dotted line “b” does not form a double bond and whereby if the dotted line “b” forms a double bond, the dotted line “a” does not form a double bond;
R1 is independently selected from alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z1;
each of R2a and R2b is independently selected from hydrogen; cyano; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; or heterocycle-heteroalkynyl or R2a and R2b can be taken together to form vinyl, vinylalkyl or vinylheteroalkyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl or heterocycle-heteroalkynyl, vinyl, vinylalkyl or vinylheteroalkyl, can be unsubstituted or substituted with one or more Z1;
or
R2a and R7 or R2b and R7 can be taken together to form a 4, 5, 6 or 7-membered lactone;
R3 is independently selected from —CN; —CONH2; —COOR7; —C(O)NHCN; —C(O)NHOH; —S(O)2OH; —S(O)2NHZ4; —P(O)(OH)NH2; —P(O)(OH)O-alkyl; —P(O)(O-alkyl)2; —P(O)OH2; —NHC(O)NHS(O)2-aryl; —NHC(O)NHS(O)2-heteroaryl; —C(O)NHS(O)2-aryl; —C(O)NHS(O)2-heteroaryl; —S(O)2NHS(O)2-aryl; —S(O)2NHS(O)2-heteroaryl; or from the following structures:
 when the dotted line “a” forms a double bond, R4 is independently selected from hydrogen; halogen; cyano; hydroxyl; alkyl; alkenyl, alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; and heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; and heterocycle-heteroalkynyl; and when the dotted line “b” forms a double bond, R4 is independently selected from O and S;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z1;
when the dotted line “a” forms a double bond, R6 is not present and when the dotted line “b” forms a double bond, R6 is independently selected from hydrogen; alkyl; alkenyl, alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z1;
R5 is selected from halogen; cyano; —NR10R11; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more R20;
each R10 and R11 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl; or R10 and R11 can be taken together with the nitrogen to which they are attached to in order to form a 4-, 5-, 6-, 7- or 8-membered heterocycle which can be unsubstituted or substituted with one or more R20;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more R20;
each R20 is independently selected from the group consisting of halogen; —OR21; ═O; —SR21; ═S; —S(O)R22; —S(O)2R22; —S(O)2NR23R24; trifluoromethyl; nitro; —NR23R24; —NR21S(O)2R22; cyano; —NR21C(O)R22; —NR21C(O)NR23R24; —C(O)OR21; —C(O)NR23R24; —C(O)R22; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z1;
each R21 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; and heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z;
each R22 is independently selected from hydrogen; hydroxyl; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; and heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z;
each R23 and R24 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl; heterocycle-heteroalkenyl; and heterocycle-heteroalkynyl; or R23 and R24 can be taken together with the nitrogen to which they are attached to in order to form a 4-, 5-, 6-, 7- or 8-membered heterocycle which can be unsubstituted or substituted with one or more Z1;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, and heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z1;
each Z1 is independently selected from the group consisting of hydrogen; halogen; —OZ2; ═O; —SZ2; ═S; —S(O)Z3; —S(O)2Z3; —S(O)2NZ4Z5; trifluoromethyl; nitro; —NZ4Z5; —NZ2S(O)2Z3; cyano; —NZ2C(O)Z3; —NZ2C(O)NZ4Z5; —C(O)OZ2; —C(O)NZ4Z5; —C(O)Z3; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more Z11;
or two Z1 on the same carbon atom or nitrogen atom can be taken together with the 4-, 5-, 6-, 7- or 8-membered ring they are attached to form a spiro-cycloalkyl; a spiro-cycloalkenyl a spiro-cycloalkynyl; or a saturated or unsaturated spiro-heterocycle;
each Z11 is independently selected from the group consisting of hydrogen; halogen; —OZ12; ═O; —SZ12; ═S; —S(O)Z13; —S(O)2Z; —S(O)2NZ14Z15; trifluoromethyl; nitro; —NZ14Z15; —NZ12S(O)2Z13; cyano; —NZ12C(O)Z13; —NZ12C(O)NZ14Z15; —C(O)OZ12; —C(O)NZ14Z15; —C(O)Z13; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more substituents selected from the group of alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, ═O, halogen, —SH, ═S, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —C(O)OH or —NH2;
each R7, Z2 and Z12 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, ═O, halogen, —SH, ═S, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —C(O)OH or —NH2;
each Z3 and Z13 is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more selected from the group of alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, ═O, halogen, —SH, ═S, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —C(O)OH or —NH2;
each Z4, Z5, Z14 and Z15 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; heteroalkyl; heteroalkenyl; heteroalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; arylheteroalkyl; arylheteroalkenyl; arylheteroalkynyl; heterocycle-alkyl; heterocycle-alkenyl; heterocycle-alkynyl; heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl;
wherein said alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, arylheteroalkyl, arylheteroalkenyl, arylheteroalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, heterocycle-heteroalkyl, heterocycle-heteroalkenyl, or heterocycle-heteroalkynyl can be unsubstituted or substituted with one or more selected from the group of alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, ═O, halogen, —SH, ═S, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —C(O)OH or —NH2;
or wherein Z4 and Z5, and Z14 and Z15 respectively, can be taken together in order to form a (4-, 5-, 6-, 7-, or 8-membered) heterocycle which can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —C(O)OH or —NH2;
and isomers, and salts thereof;
C) an anti-viral compound according to Formula (III),
 wherein,
each dotted line represents an optional double bond, whereby if the dotted line “a” forms a double bond, the dotted line “b” does not form a double bond and whereby if the dotted line “b” forms a double bond, the dotted line “a” does not form a double bond;
R1 is independently selected from alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl;
heterocycle-alkenyl; or heterocycle-alkynyl;
wherein in the cycloalkyl, cycloalkenyl, cycloalkynyl, alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N;
and wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl, can be unsubstituted or substituted with one or more Z;
and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
each of R2a and R2b is independently selected from hydrogen; cyano; alkyl; alkenyl; alkynyl; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; or heterocycle-alkynyl; or R2a and R2b are taken together to form vinyl or vinylalkyl; provided that at least one of R2a and R2b is not hydrogen;
wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl or vinylalkyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N;
and wherein said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, vinyl or vinylalkyl, can be unsubstituted or substituted with one or more Z1;
and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, heterocycle-alkynyl, or vinylalkyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
—R20 is independently selected from —CN; —CONH2; —COOR3; —C(O)NHCN; —C(O)NHOH; —S(O)2OH; —(O)2NHZ4; —P(O)(OH)NH2; —P(O)(OH)O-alkyl; —P(O)(O-alkyl)2; —P(O)OH2; —NHC(O)NHS(O)2-aryl; —NHC(O)NHS(O)2-heteroaryl; —C(O)NHS(O)2-aryl; —C(O)NHS(O)2-heteroaryl; —S(O)2NHS(O)2-aryl; —S(O)2NHS(O)2-heteroaryl; or from the following structures:
 or
R2a and R20 or R2b and R20 can be taken together to form a 4, 5, 6 or 7-membered lactone;
R3 is selected from hydrogen; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl;
wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N; and
wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and
wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
when the dotted line “a” forms a double bond, R4 is independently selected from hydrogen; halogen; cyano; hydroxyl; alkyl; alkenyl, alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; and heterocycle-alkynyl; and when the dotted line “b” forms a double bond, R4 is independently selected from O and S;
wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N;
and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be unsubstituted or substituted with one or more Z;
and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
when the dotted line “a” forms a double bond, R5 is not present and when the dotted line “b” forms a double bond, R5 is independently selected from hydrogen; alkyl; alkenyl, alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; or heterocycle-alkynyl;
wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N;
and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be unsubstituted or substituted with one or more Z1;
and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
each of X1 and X2 is independently selected from C or N;
cycle B forms together with X1 and X2 a 5, 6, 7, or 8-membered unsaturated monocyclic cycloalkyl moiety; a 5, 6, 7, or 8-membered monocyclic aryl moiety; or a 5, 6, 7, or 8-membered monocyclic unsaturated or aromatic O, S and/or N containing heterocycle;
wherein said 5, 6, 7, or 8-membered monocyclic unsaturated cycloalkyl moiety, 5, 6, 7, or 8-membered monocyclic aryl moiety, or 5, 6, 7, or 8-membered monocyclic mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle can be unsubstituted or substituted with one or more R7;
and wherein a carbon atom or heteroatom of the 5, 6, 7, or 8-membered monocyclic unsaturated cycloalkyl moiety, 5, 6, 7, or 8-membered monocyclic aryl moiety, or 5, 6, 7, or 8-membered monocyclic mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle can be oxidized to form a C═O, C═S, N═O, N═S, S═0 or S(O)2;
cycle A is fused to cycle B and represents a 4, 5, 6, 7, or 8-membered unsaturated monocyclic cycloalkyl moiety; a 4, 5, 6, 7, or 8-membered monocyclic aryl moiety; or a 4, 5, 6, 7, or 8-membered monocyclic saturated, mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle together with the carbon or nitrogen atoms to which they are attached;
wherein said 4, 5, 6, 7, or 8-membered monocyclic unsaturated cycloalkyl moiety, 4, 5, 6, 7, or 8-membered monocyclic aryl moiety, or 4, 5, 6, 7, or 8-membered monocyclic mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle can be unsubstituted or substituted with one or more R6;
and wherein a carbon atom or heteroatom of the 4, 5, 6, 7, or 8-membered monocyclic unsaturated cycloalkyl moiety, 4, 5, 6, 7, or 8-membered monocyclic aryl moiety, or 4, 5, 6, 7, or 8-membered monocyclic mono-unsaturated, multi-unsaturated or aromatic O, S and/or N containing heterocycle can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
R6 is independently selected from R10; R11; and R12;
R7 is independently selected from R10; and R12;
each of R10, R11 and R12 are independently selected from the group consisting of halogen; —OZ2;
SZ2; —S(O)Z3; —S(O)2Z3; —SO2NZ4Z5; trifluoromethyl; nitro; —NZ4Z5; —NZ2S(O)2Z3; cyano; —COOZ2; —C(O)NZ4Z5; —C(O)Z3; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; or heterocycle-alkynyl;
and wherein said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, optionally includes one or more heteroatoms, said heteroatoms being selected from the atoms O, S and N;
and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2;
and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O; or
R10 and R11 on the same carbon atom can be taken together to form a 5, 6 or 7-membered spiro-cycloalkyl, spiro-cycloalkenyl, spiro-cycloalkynyl or a saturated or unsaturated spiro-heterocycle together with the cycle A they are attached to; or
an R10 and another R10, R11 or R12 on adjacent atoms can be taken together to form a 5, 6 or 7-membered cycloalkyl, cycloalkenyl, cycloalkynyl, aryl or heterocycle fused to the cycle A or cycle B they are attached to;
each Z1 is independently selected from the group consisting of halogen; —OZ2; —SZ2; —S(O)Z3; —S(O)2Z3; —SO2NZ4Z5; trifluoromethyl; nitro; —NZ4Z5; —NZ2S(O)2Z3; cyano; —COOZ2; —C(O)NZ4Z5; —C(O)Z3; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; and heterocycle-alkynyl;
and wherein in the alkyl, alkenyl or alkynyl moiety of said alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N;
and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with one or more Z11;
and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2; or
two Z1 on the same carbon atom can be taken together to form a 5, 6 or 7-membered spiro-cycloalkyl, spiro-cycloalkenyl, spiro-cycloalkynyl, or a saturated or unsaturated spiro-heterocycle together with the (4, 5, 6, 7 or 8-membered unsaturated) ring they are attached to; or
two Z1 on adjacent atoms can be taken together to form a 5, 6 or 7-membered cycloalkyl, cycloalkenyl, cycloalkynyl, aryl or heterocycle fused to the (4, 5, 6, 7, or 8-membered unsaturated) ring they are attached to;
each Z11 is independently selected from the group consisting of halogen; —OZ12; —SZ12, —S(O)Z13; —S(O)2Z; —SO2NZ14Z15; trifluoromethyl; nitro; —NZ14Z15; —NZ12S(O)2Z13; cyano; —COOZ12; —C(O)NZ14Z15; —C(O)Z13; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl; and heterocycle-alkynyl;
each Z2 and Z12 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl; and wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N; and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2;
each Z3 and Z13 is independently selected from hydroxyl; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl; and wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S—, —N≡ and/or ≡N; and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═0, C═S, N═O, N═S, S═O or S(O)2;
each Z4, Z5, Z14 and Z15 is independently selected from hydrogen; alkyl; alkenyl; alkynyl; aryl; heterocycle; arylalkyl; arylalkenyl; arylalkynyl; heterocycle-alkyl; heterocycle-alkenyl or heterocycle-alkynyl; and wherein in said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl, one or more —CH3, —CH2—, —CH≡ and/or ≡CH is optionally replaced by one or more —NH2, —NH—, —O—, —S, —N≡ and/or ≡N; and wherein said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or NH2; and wherein optionally a carbon atom or heteroatom of said alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl or heterocycle-alkynyl can be oxidized to form a C═O, C═S, N═O, N═S, S═O or S(O)2; and wherein Z4 and Z5, and Z14 and Z15 respectively can be taken together in order to form a (5-, 6-, or 7-membered) heterocycle which can be unsubstituted or substituted with alkyl, alkenyl, alkynyl, hydroxyl, halogen, —SH, trifluoromethyl, —O-alkyl, —OCF3, cyano, nitro, —COOH or —NH2;
or a pharmaceutically acceptable salt thereof,
provided that the compounds do not have a structure according to formula (N)
 or
D) a compound represented in Table 1
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