Novel viral replication inhibitors

Abstract

The present invention relates to a series of novel compounds having antiviral activity, more specifically HIV (Human Immunodeficiency Virus) replication inhibiting properties. The invention also relates to methods for the preparation of such compounds, as well as to novel intermediates useful in one or more steps of such syntheses. The invention also relates to pharmaceutical compositions comprising an effective amount of such compounds as active ingredients. This invention further relates to the use of such compounds as medicines or in the manufacture of a medicament useful for the treatment of animals suffering from viral infections, in particular HIV infection. This invention further relates to methods for the treatment of viral infections in animals by the administration of a therapeutical amount of such compounds, optionally combined with one or more other drugs having antiviral activity.

1 . A compound a according to the formula (A1): 
       
         
           
           
               
               
           
         
       
       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; 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 Z 1 ; 
 
 each of R 2a  and R 2b  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 R 2a  and R 2b  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 Z 1 ; 
 or 
 
 R 2a  and R 7  or R 2b  and R 7  can be taken together to form a 4, 5, 6 or 7-membered lactone; 
 R 3  is independently selected from —CN; —CONH 2 ; —COOR 7 ; —C(O)NHCN; —C(O)NHOH; —S(O) 2 OH; —S(O) 2 NHZ 4 ; —P(O)(OH)NH 2 ; —P(O)(OH)O-alkyl; —P(O)(O-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: 
 
       
         
           
           
               
               
           
         
         when the dotted line “a” forms a double bond, R 4  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, R 4  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 Z 1 ; 
 
         when the dotted line “a” forms a double bond, R 6  is not present and when the dotted line “b” forms a double bond, R 6  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 Z 1 ; 
 
         R 5  is selected from halogen; cyano; —NR 10 R 11 ; 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 R 20 ; 
 
         each R 10  and R 11  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 R 10  and R 11  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 R 20 ; 
         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 R 20 ; 
         each R 20  is independently selected from the group consisting of halogen; —OR 21 ; ═O; —SR 21 ; ═S; —S(O)R 22 ; —S(O) 2 R 22 ; —S(O) 2 NR 23 R 24 ; trifluoromethyl; nitro; —NR 23 R 24 ; —NR 21 S(O) 2 R 22 ; cyano; —NR 21 C(O)R 22 ; —NR 21 C(O)NR 23 R 24 ; —C(O)OR 21 ; —C(O)NR 23 R 24 ; —C(O)R 22 ; 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 Z 1 ; 
 
         each R 21  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 1 ; 
 
         each R 22  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 1 ; 
 
         each R 23  and R 24  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 R 23  and R 24  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 Z 1 ;
 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 1 ; 
 
         each Z 1  is independently selected from the group consisting of hydrogen; halogen; —OZ 2 ; ═O; —SZ 2 ; ═S; —S(O)Z 3 ; —S(O) 2 Z 3 ; —S(O) 2 NZ 4 Z 5 ; trifluoromethyl; nitro; —NZ 4 Z 5 ; —NZ 2 S(O) 2 Z 3 ; cyano; —NZ 2 C(O)Z 3 ; —NZ 2 C(O)NZ 4 Z 5 ; —C(O)OZ 2 ; —C(O)NZ 4 Z 5 ; —C(O)Z 3 ; 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 Z 11 ; 
 
         or two Z 1  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; or a saturated or unsaturated spiro-heterocycle; 
         each Z 11  is independently selected from the group consisting of hydrogen; halogen; —OZ 12 ; ═O; —SZ 12 ; ═S; —S(O)Z 13 ; —S(O) 2 Z 13 ; —S(O) 2 NZ 14 Z 15 ; trifluoromethyl; nitro; —NZ 14 Z 15 ; —NZ 12 S(O) 2 Z 13 ; cyano; —NZ 12 C(O)Z 13 ; —NZ 12 C(O)NZ 14 Z 15 ; —C(O)OZ 12 ; —C(O)NZ 14 Z 15 ; —C(O)Z 13 ; 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, —OCF 3 , cyano, nitro, —C(O)OH or —NH 2 ; 
 
         each R 7 , Z 2  and Z 12  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, —OCF 3 , cyano, nitro, —C(O)OH or —NH 2 ; 
 
         each Z 3  and Z 13  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, —OCF 3 , cyano, nitro, —C(O)OH or —NH 2 ; 
 
         each Z 4 , Z 5 , Z 14  and Z 15  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, —OCF 3 , cyano, nitro, —C(O)OH or —NH 2 ; 
 
       
       or wherein Z 4  and Z 5 , and Z 14  and Z 15  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, —OCF 3 , cyano, nitro, —C(O)OH or —NH 2 ; 
       and isomers, and salts thereof. 
     
     
         2 . The compound according to  claim 1 , wherein R 3  is —C(O)OH. 
     
     
         3 . The compound according to  claim 1 , wherein R 1  is selected from aryl or heteroaryl, wherein said aryl or heteroaryl can be unsubstituted or substituted with one or more Z 1 . 
     
     
         4 . The compound according to  claim 3 , wherein R 1  is selected from benzothiazolyl, quinolinyl, piperidinyl, 1-H-azepinyl, 4-methyl-piperazinyl, naphtyl, benzothiophenyl, benzofuranyl, indazolyl, N-methyl-indazolyl, chromanyl, 4H-isoquinolinyl, isochromanyl, 5-F-8-Me-isochromanyl, 5 Cl-isochromanyl, t-butyl, ethyl, phenyl, and phenyl substituted with 1, 2 or 3 substituents independently selected from the group consisting of C 1 -C 4 -alkyl, chloro, fluoro, hydroxy, methoxy, trifluoromethyl. 
     
     
         5 . The compound according to  claim 1 , wherein one of R 2a  and R 2b  is hydrogen, and the other of R 2a  and R 2b  is selected from hydrogen; cyano; 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; or R 2a  and R 2b  can be taken together to form vinyl or vinylalkyl;
 and wherein said alkyl, alkenyl, alkynyl, 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 Z 1 .   
     
     
         6 . The compound according to  claim 1 , wherein R 5  is selected from NR 10 R 11 ; aryl; arylalkyl; arylalkenyl; NH-aryl, and heterocycle; wherein said aryl, arylalkyl, and heterocycle can be unsubstituted or substituted with one or more substituents independently selected from the group consisting of halogen; —OH; —O-phenyl, —N(CH 3 ) 2 , NH(CO)(phenyl); —C(O)NH(C 1 -C 4 -alkyl); C 1 -C 4 -alkyl; phenyl; 1,2,4-oxadiazolyl; benzyl; phenylethylenyl, wherein said 1,2,4-oxadiazolyl is further substituted with one C1-C4-alkyl, preferably with isopropyl. 
     
     
         7 . The compound according to  claim 1 , wherein the compound has a structure according to formula (C2), 
       
         
           
           
               
               
           
         
       
       wherein each of R 1 , R 2a , R 2b  and R 5  are as in  claim 1 . 
     
     
         8 . The compound according to  claim 1 , wherein the compound has a structure according to formula (E), 
       
         
           
           
               
               
           
         
       
       wherein each of R 2b , R 5  and Z 1  are as in  claim 1 . 
     
     
         9 . The compound according to  claim 1 , wherein the compound has a structure according to formula (G1), 
       
         
           
           
               
               
           
         
       
       wherein each of R 1 , R 2a , R 2b , R 5  and R 6  are as in  claim 1 . 
     
     
         10 . The compounds according to  claim 1  selected from the list of:
 methyl 2-(2-(dimethylamino)-4-methyl-6-phenylpyrimidin-5-yl)pentanoate 
 2-(2-(dimethylamino)-4-methyl-6-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-benzyl-4-methyl-6-phenylpyrimidin-5-yl)pentanoate 
 2-(2-benzyl-4-methyl-6-phenylpyrimidin-5-yl)pentanoic acid 
 (E)-methyl 2-(4-methyl-6-phenyl-2-styrylpyrimidin-5-yl)pentanoate 
 (E)-2-(4-methyl-6-phenyl-2-styrylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-phenethyl-6-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-phenethyl-6-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2,6-dip-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2,6-dip-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(cyclohexyl(methyl)amino)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(cyclohexyl(methyl)amino)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-phenyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-phenyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(2-chlorophenyl)-4-methyl-6-phenylpyrimidin-5-yl)pentanoate 
 2-(2-(2-chlorophenyl)-4-methyl-6-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(2-chlorophenyl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(2-chlorophenyl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-phenyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-phenyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2,6-diphenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2,6-diphenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(3-hydroxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(3-hydroxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-morpholino-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-morpholino-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(pyrrolidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(pyrrolidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(4-methylpiperazin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(4-methylpiperazin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(3,5-dimethylpiperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(3,5-dimethylpiperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(azepan-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(azepan-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(3-(isobutylcarbamoyl)piperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(3-(isobutylcarbamoyl)piperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(3-methylpiperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(3-methylpiperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(3,4-dihydroisoquinolin-2(1H)-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(3,4-dihydroisoquinolin-2(1H)-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(4-benzyl-1,4-diazepan-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(4-benzyl-1,4-diazepan-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(3-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(3-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(3-phenoxypiperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(3-phenoxypiperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(3-phenylpiperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(3-phenylpiperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-((S)-3-(dimethylamino)pyrrolidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-((S)-3-(dimethylamino)pyrrolidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(4-benzamidopiperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(4-benzamidopiperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(4-ethyl-1,4-diazepan-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(4-ethyl-1,4-diazepan-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(2-(indolin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate 
 2-(2-(indolin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-phenyl-6-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-phenyl-6-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(azepan-1-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(azepan-1-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(4-methylpiperazin-1-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(4-methylpiperazin-1-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(3,4-dimethylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(3,4-dimethylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(naphthalen-2-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(naphthalen-2-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2,3-dihydrobenzofuran-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(2,3-dihydrobenzofuran-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(benzofuran-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(benzofuran-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(1-methyl-1H-indol-5-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(1-methyl-1H-indol-5-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(3,4-dihydroisoquinolin-2(1H)-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(3,4-dihydroisoquinolin-2(1H)-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-phenoxy-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-phenoxy-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(1H-indol-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(1H-indol-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(1H-indol-6-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(1H-indol-6-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(benzo[b]thiophen-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(benzo[b]thiophen-5-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(chroman-6-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(chroman-6-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(1-methyl-1H-indol-6-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(1-methyl-1H-indol-6-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(4-chloro-2-fluorophenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(4-chloro-2-fluorophenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(1-methylindolin-5-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(1-methylindolin-5-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2-fluoro-4-methylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(2-fluoro-4-methylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(4-chlorophenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(4-chlorophenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(2-oxoindolin-6-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(2-oxoindolin-6-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(4-isopropylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(4-isopropylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-phenyl-6-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-phenyl-6-(4-(trifluoromethyl)phenyl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(4-chloro-2-methoxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(4-chloro-2-methoxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 2-(4-(4-chloro-2-hydroxyphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-6-(3-oxo-2,3-dihydro-1H-inden-5-yl)-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-methyl-6-(3-oxo-2,3-dihydro-1H-inden-5-yl)-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(benzo[d]thiazol-6-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(benzo[d]thiazol-6-yl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-benzyl-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-benzyl-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2-hydroxy-4-methylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-(2-hydroxy-4-methylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 2-(4-(2-methoxy-4-methylphenyl)-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid 
 methyl 4-methoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)butanoate 
 4-methoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)butanoic acid 
 methyl 6,6,6-trifluoro-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)hexanoate 
 6,6,6-trifluoro-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)hexanoic acid 
 methyl 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)-3-phenylpropanoate 
 2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)-3-phenylpropanoic acid 
 methyl 3-methyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 3-methyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2,4-difluorophenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(2,4-difluorophenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2,4-dimethylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(2,4-dimethylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(4-isopropylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(4-isopropylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2-fluoro-4-methoxyphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(2-fluoro-4-methoxyphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(piperidin-1-yl)-6-(quinolin-5-yl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(piperidin-1-yl)-6-(quinolin-5-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(piperidin-1-yl)-6-(quinolin-8-yl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(piperidin-1-yl)-6-(quinolin-8-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2-(piperidin-1-yl)-6-(2,4,5-trifluorophenyl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-2-(piperidin-1-yl)-6-(2,4,5-trifluorophenyl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(2-chloro-4-methylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(2-chloro-4-methylphenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(4-chloro-2-fluorophenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate; 
 2-(4-(4-chloro-2-fluorophenyl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-methyl-2,6-di(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-methyl-2,6-di(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(1,2-dihydroacenaphthylen-5-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(1,2-dihydroacenaphthylen-5-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 4,4-dimethyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoate 
 4,4-dimethyl-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)pentanoic acid 
 methyl 2-tert-butoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetate 
 2-tert-butoxy-2-(4-methyl-2-(piperidin-1-yl)-6-p-tolylpyrimidin-5-yl)acetic acid 
 methyl 2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(2,3-dihydropyrano[4,3,2-de]quinolin-7-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2(4-(8-fluoro-5-methylchroman-6-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(8-fluoro-5-methylchroman-6-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 methyl 2-(4-(5-chlorochroman-6-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoate 
 2-(4-(5-chlorochroman-6-yl)-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)pentanoic acid 
 2-(1-methyl-6-oxo-2-(piperidin-1-yl)-4-p-tolyl-1,6-dihydropyrimidin-5-yl)pentanoic acid 
 2-(1-ethyl-6-oxo-2-(piperidin-1-yl)-4-p-tolyl-1,6-dihydropyrimidin-5-yl)pentanoic acid 
 2-(1-benzyl-6-oxo-2-(piperidin-1-yl)-4-p-tolyl-1,6-dihydropyrimidin-5-yl)pentanoic acid 
 methyl 2-tert-butoxy-2-(4-tert-butyl-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)acetate 
 2-tert-butoxy-2-(4-tert-butyl-6-methyl-2-(piperidin-1-yl)pyrimidin-5-yl)acetic acid 
 methyl 2-(4-ethyl-6-methyl-2-phenylpyrimidin-5-yl)pentanoate 
 2-(4-ethyl-6-methyl-2-phenylpyrimidin-5-yl)pentanoic acid. 
 
     
     
         11 - 18 . (canceled) 
     
     
         19 . A method for the preparation of the compounds according to  claim 1  comprising the steps of:
 preparing a substituted or non-substituted 2-(4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetic acid derivative; 
 converting a substituted or non-substituted 2-(4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetic acid derivative into a substituted or non-substituted 2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetic acid derivative which is ultimately converted in a substituted or non-substituted 2-(pyrimidin-5-yl)acetate; 
 preparing a substituted or non-substituted 2-(6-oxo-1,6-dihydropyrimidin-5-yl)acetic acid derivative; 
 converting a substituted or non-substituted 2-(6-oxo-1,6-dihydropyrimidin-5-yl)acetic acid derivative into a substituted or non-substituted 2-(pyrimidin-5-yl)acetate; 
 substituting a 2-(pyrimidin-5-yl)acetate derivative on position 2 and/or 4 of the pyrimidine moiety and/or on position 2 of the acetate side chain sequentially and in a specific manner (amination, alkylation, arylation) with suitable chemical reagents to obtain the desired compounds; and 
 hydrolyzing the obtained compounds in the previous step to obtain the desired 2-(pyrimidin-5-yl)acetic acid derivatives. 
 
     
     
         20 . A pharmaceutical composition comprising the compounds according to  claim 1  as an active ingredient in admixture with at least a pharmaceutically acceptable carrier. 
     
     
         21 . The pharmaceutical composition according to  claim 20 , having antiviral activity. 
     
     
         22 . The pharmaceutical composition according to  claim 21 , having anti-HIV activity. 
     
     
         23 . The pharmaceutical composition according to  claim 21 , further comprising a compound with antiviral activity selected from reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, entry inhibitors and compounds with other mechanisms of action. 
     
     
         24 . A method of treatment or prevention of a viral 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 any of the  claim 1 . 
     
     
         25 . (canceled)