Novel antiviral compounds

Abstract

The present invention relates to compounds of formula (A), as further defined herein, having antiviral activity, more specifically HIV (Human Immunodeficiency Virus) replication inhibiting properties. The invention also relates to pharmaceutical compositions comprising an effective amount of such compounds as active ingredients. The invention further relates to the use of such compounds, optionally combined with one or more other drugs having antiviral activity, for the treatment of animals suffering from viral infections, in particular HIV infection.

1 . A compound according to the formula (A): 
       
         
           
           
               
               
           
         
       
       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; 
 R 1  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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 1 ; 
 
 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 R 2a  and R 2b  is independently selected from hydrogen, cyano, alkyl, alkenyl, alkynyl, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, or heterocycle-alkynyl, or R 2a  and R 2b  are taken together to form vinyl or vinylalkyl; provided that at least one of R 2a  and R 2b  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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 Z 1 ; 
 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 ; 
 
 R 2  is independently selected from —CN, —CONH 2 , —COOR 3 , —C(O)NHCN, —C(O)NHOH, —S(O) 2 OH, —S(O) 2 NHZ 4 , —P(OXOH)NH 2 , —P(OXOH)O-alkyl, —P(OXO-alkyl) 2 , —P(O)OH 2 , —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) 2 NHS(O) 2 -aryl, —S(O) 2 NHS(O) 2 -heteroaryl, or from the following structures: 
 
       
         
           
           
               
               
           
         
       
       or
 R 2a  and R 2c  or R 2b  and R 2c  can be taken together to form a 4, 5, 6 or 7-membered lactone; 
 R 3  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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, —OCF 3 , cyano, nitro, —COOH, or NH 2 ; 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, R 4  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, R 4  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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 1 ; 
 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, R 5  is not present and when the dotted line “b” forms a double bond, R 5  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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 ; 
 
 each of X 1  and X 2  is independently selected from C or N; 
 cycle B forms together with X 1  and X 2  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 R 7 ; 
 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═O, 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 R 6 ; 
 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 ; 
 
 R 6  is independently selected from R 10 , R 11 , and R 12 ; 
 R 7  is independently selected from R 10 , and R 12 ; 
 each of R 10 , R 11  and R 12  are independently selected from the group consisting of halogen, —OZ 2 , —SZ 2 , —S(O)Z 3 , —S(O) 2 Z 3 , —SO 2 NZ 4 Z 5 , trifluoromethyl, nitro, —NZ 4 Z 5 , —NZ 2 S(O) 2 Z 3 , cyano, —COOZ 2 , —C(O)NZ 4 Z 5 , —C(O)Z 3 , 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, —OCF 3 , cyano, nitro, —COOH or NH 2 ; 
 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 ; 
 
 R 10  and R 11  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 R 10  and another R 10 , R 11  or R 12  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 Z 1  is independently selected from the group consisting of halogen; —OZ 2 , —SZ 2 , —S(O)Z 3 , —S(O) 2 Z 3 , —SO 2 NZ 4 Z 5 , trifluoromethyl, nitro, —NZ 4 Z 5 , —NZ 2 S(O) 2 Z 3 , cyano, —COOZ 2 , —C(O)NZ 4 Z 5 , —C(O)Z 3 , 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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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 11 ; 
 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 Z 1  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 Z 1  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 Z 11  is independently selected from the group consisting of halogen, —OZ 2 , —SZ 2 , —S(O)Z 3 , —S(O) 2 Z 3 , —SO 2 NZ 4 Z 5 , trifluoromethyl, nitro, —NZ 4 Z 5 , —NZ 12 S(O) 2 Z 3 , cyano, —COOZ 2 , —C(O)NZ 4 Z 5 , —C(O)Z 3 , alkyl, alkenyl, alkynyl, aryl, heterocycle, arylalkyl, arylalkenyl, arylalkynyl, heterocycle-alkyl, heterocycle-alkenyl, and heterocycle-alkynyl; 
 each Z 2  and Z 12  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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, —OCF 3 , cyano, nitro, —COOH, or NH 2 ; 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 Z 3  and Z 13  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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, —OCF 3 , cyano, nitro, —COOH or NH 2 ; 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 Z 4 , Z 5 , Z 14  and Z 15  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 —CH 3 , —CH 2 —, —CH═ and/or ≡CH is optionally replaced by one or more —NH 2 , —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, —OCF 3 , cyano, nitro, —COOH or NH 2 ; 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 Z 4  and Z 5 , and Z 14  and Z 15  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, —OCF 3 , cyano, nitro, —COOH or —NH 2 ; or a pharmaceutically acceptable salt thereof, 
 
       provided that the compounds do not have a structure according to formula (N) 
       
         
           
           
               
               
           
         
       
     
     
         2 . A compound according to  claim 1 , wherein the compound has a structure according to formula (A1), 
       
         
           
           
               
               
           
         
       
       wherein
 each of R 1 , R 2a , R 2b , R 2c , R 4 , R 5 , X 1 , X 2 , and cycle A, are as defined in  claim 1 ; 
 each dotted line represents an optional double bond whereby maximally five non-adjacent dotted lines can form a double bond; 
 each of X 3  and X 6  are independently selected from CH, CR 10 , N, NR 2 , O, and S, wherein R 10  and R 12  are as defined in  claim 1 ; 
 each of X 4  and X 5  are independently selected from C, and N; 
 n is selected from 0, 1, 2, 3, and 4; 
 m is selected from 0, 1, 2, 3, and 4; and 
 m+n is at least 1 and maximally 4. 
 
     
     
         3 . A compound according to  claim 2 , wherein the compound has a structure according to formula (A2), 
       
         
           
           
               
               
           
         
       
       wherein,
 each of R 1 , R 2 , R 2b , R 2c , R 4 , R 5 , X 1 , X 2 , X 3 , X 6 , X 4 , X 5 , m and n are as in  claim 2 ; 
 each dotted line represents an optional double bond whereby maximally nine non-adjacent dotted lines can form a double bond; 
 W, X, Y, and Z are independently selected from CR 10 , CR 10 R 11 , N, NR 12 , O, and S depending on whether they are adjacent to a double or a single bond, wherein R 10 , R 11  and R 12  are as defined in  claim 1 ; 
 p is selected from 0, 1, 2, and 3; and 
 q is selected from 0 and 1. 
 
     
     
         4 . A compound according to  claim 1 , wherein the compound has a structure according to formula (B), (B1) or (B2), 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein R 3  is as defined in  claim 1 . 
     
     
         5 . A compound according to  claim 1 , wherein the compound has a structure according to formula (C1), (C2), (C3), (C4), (C5), (C6), (C7), (C8), (C9) or (C10) 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein,
 cycle B is aromatic; 
 m is selected from 0, 1, and 2; 
 n is selected from 0, 1, and 2; and 
 m+n is 2. 
 
     
     
         6 . A compound according to  claim 1 , wherein the compound has a structure according to formula (D1) or (D2), 
       
         
           
           
               
               
           
         
       
       wherein,
 m is selected from 0 and 1; 
 n is selected from 0 and 1; and 
 m+n is 1. 
 
     
     
         7 . A compound according to  claim 1 , wherein the compound has a structure according to formula (E1) or (E2), 
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound according to  claim 1 , wherein the compound has a structure according to formula (F1), (F2), (F3) or (F4), 
       
         
           
           
               
               
           
         
       
     
     
         9 . A compound according to  claim 1 , wherein the compound has a structure according to formula (G1) or (G2), 
       
         
           
           
               
               
           
         
       
     
     
         10 . A compound according to  claim 1 , wherein the compound has a structure according to formula (H1) or (H2), 
       
         
           
           
               
               
           
         
       
     
     
         11 . A compound according to  claim 1 , wherein the compound has a structure according to formula (I1) or (I2), 
       
         
           
           
               
               
           
         
       
     
     
         12 . A compound according to  claim 1 , wherein the compound has a structure according to formula (J1), (J2), (J3) or (J4) 
       
         
           
           
               
               
           
         
       
     
     
         13 . A compound according to  claim 1 , wherein R 2c  is COOR 3 , wherein R 3  is selected from hydrogen and alkyl. 
     
     
         14 . A compound according to  claim 1 , wherein R 2 c is COOH. 
     
     
         15 . A compound according to  claim 1 , wherein R 1  is selected from alkyl, aryl, heterocycle or arylalkyl; wherein in the alkyl moiety of said arylalkyl one —CH 2 — is optionally replaced by —NH—, —O—, or —S—; and wherein said aryl, heterocycle, or arylalkyl can be unsubstituted or substituted with one or more halogen, OH or alkyl. 
     
     
         16 . A compound according to  claim 1 , wherein R 1  is selected from C 1 -C 6  alkyl, phenyl, phenylalkyl, heteroaryl, O-phenyl, S-phenyl or NH-phenyl and wherein said phenyl, phenylalkyl, heteroaryl, O-phenyl, S-phenyl or NH-phenyl can be unsubstituted or substituted with one or more halogen, OH or C 1 -C 4 alkyl. 
     
     
         17 . A compound according to  claim 1 , wherein one of R 2a  and R 2b  is hydrogen and the other one of R 2a  and R 2b  is selected from the group consisting of C 1 -C 6  alkyl and C 1 -C 6 -alkoxy, said C 1 -C 6  alkyl and C 1 -C 6  alkoxy being optionally substituted with up to three F atoms. 
     
     
         18 . A compound according to  claim 1 , wherein the dotted line “a” forms a double bond, the dotted line “b” does not form a double bond, R 5  is not present and R 4  is selected from hydrogen, hydroxyl, alkyl or aryl, wherein said alkyl and aryl can be unsubstituted or substituted with one or more halogens. 
     
     
         19 . A compound according to  claim 1 , wherein the dotted line “b” forms a double bond, the dotted line “a” does not form a double bond, R 4  is O and R 5  is selected from C 1 -C 6 alkyl or benzyl. 
     
     
         20 . A compound according to  claim 1 , wherein cycle A is selected from a 5, 6, or 7-membered unsaturated monocyclic cycloalkyl moiety; a 6-membered monocyclic aryl moiety; or a 5 or 6-membered monocyclic saturated or mono-unsaturated O or N-containing heterocycle together with the carbon or nitrogen atoms to which they are attached; wherein said 6-membered monocyclic aryl moiety is optionally substituted with one or two groups independently selected from halogen, C 1 -C 6  alkoxy, trifluoromethyl and C 1 -C 6  alkyl. 
     
     
         21 . A compound according to  claim 1 , wherein cycle A is selected from cyclopentenyl, cyclohexenyl, and phenyl. 
     
     
         22 . (canceled) 
     
     
         23 . A compound according to  claim 1 , for the prevention or treatment of HIV infection in an animal. 
     
     
         24 . (canceled) 
     
     
         25 . A pharmaceutical composition comprising a compound according to  claim 1  as an active ingredient in admixture with at least one pharmaceutically acceptable carrier. 
     
     
         26 . A pharmaceutical composition according to  claim 25 , further comprising one or more additional compounds with antiviral, in particular anti-HIV, activity. 
     
     
         27 . A method of treatment or prevention of an HIV infection in an animal or mammal, comprising administering to the animal or mammal in need of such treatment a therapeutically effective amount of a compound according to  claim 1 .