Alkynylpyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same

A compound of general formula (I):

• in which
• R1 is selected from the group consisting of hydrogen, halogen, nitro, cyano, —C1-C6-alkyl, —C1-C6-alkylthio, —C1-C6-haloalkyl, C3-C10-cycloalkyl, —(CH2)mORc, —(CH2)mNRd1Rd2, and —(CH2)mC(O)Rb;
• R2 represents hydrogen, —C(O)Rb, —S(O)2Rb, —P(O)(ORf)2, or —S(O)2—(CH2)2—Si(RhRkRl), or is selected from the group consisting of —C1-C6-alkyl, —C2-C6-alkenyl, —C2-C6-alkynyl, —C3-C10-cycloalkyl, aryl, heteroaryl and —C3-C10-heterocycloalkyl, wherein said residues are unsubstituted or substituted one or more times independently from each other with halogen, nitro, cyano, —C1-C6-alkyl, aryl, heteroaryl, —ORc, —NRd1Rd2—C1-C6-haloalkyl, —C(O)Rb, or —S(O)2Rb;
• R3 is selected from the group consisting of —C1-C6-alkyl, —C2-C6-alkenyl, —C2-C6-alkynyl, aryl, heteraryl and —C3-C10-cycloalkyl, wherein said residues are unsubstituted or substituted one or more times independently from each other with halogen, nitro, cyano, —C1-C6-alkyl, aryl, heteraryl, —ORc, —NRd1Rd2, —C1-C6-haloalkyl, —C(O)Rb, or —S(O)2Rb;
• R4 is selected from the group consisting of hydrogen, —OR7, —SR7and —NR7R8;
• R5 is selected from the group consisting of hydrogen, halogen, nitro, cyano, —C1-C6-alkyl, —C3-C10-cycloalkyl, -C1-C6-haloalkyl, —C1-C6-alkylthio, —(CH2)nORf, —(CH2)nNRsC(O)Rm, —(CH2)nNRsS(O)2Rm, —(CH2)nNRg1Rg2, —(CH2)nC(O)Rn, and —(CH2)nS(O)2Rn;
• R6 is selected from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, -C1-C6-alkyl, C3-C10-cycloalkyl, —C1-C6-haloalkyl, —C1-C6-haloalkoxy, —C1-C6-alkoxy, and —C1-C6-alkylthio;
• R7, R8 independently from each other are selected from the group consisting of hydrogen, —C1-C6-alkyl, —C2-C6-alkenyl, —C2-C6-alkynyl, —C3-C10-cycloalkyl, —(CH2)p-aryl, —(CH2)p-heteroaryl and —C3-C10-heterocycloalkyl, wherein said residues are unsubstituted or substituted one or more times independently from each other with halogen, nitro, cyano, —C1-C6-alkyl, —C3-C10-cycloalkyl, —C3-C10-heterocycloalkyl, aryl, heteroaryl, —ORc, —NRd1Rd2, —C1-C6-haloalkyl, —C(O)Rb, or —S(O)2Rb;
• or
• R7, R8 in the context of a NR7R8 group together with the nitrogen atom to which they are attached, form a 3 to 10 membered heterocycloalkyl ring, which is optionally substituted one or more times, the same way or differently, with C1-C6-alkyl, —NRg1Rg2—ORf, —C(O)Re, —S(O)2Re, or —OP(O)(ORf)2;
• whereby the carbon backbone of this heterocycloalkyl ring can optionally be interrupted one or more times, the same way or differently, by NH, NRa, oxygen or sulphur, and can optionally be interrupted one or more times, the same way or differently, with a —C(O)—, —S(O)—, and/or —S(O)2-group, and can optionally contain one or more double bonds;
• Ra is selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl, wherein C1-C6-alkyl, and C3-C10-cycloalkyl are optionally substituted one or more times with hydroxyl, halogen, or C1-C6-alkoxy;
• Rb is selected from the group consisting of —ORc, —SRc, —NRd1Rd2, aryl, heteroaryl, C1-C6-alkyl, and C3-C10-cycloalkyl, wherein C1-C6-alkyl, and C3-C10-cycloalkyl are optionally substituted one or more times with hydroxyl, halogen, —NRg1Rg2or C1-C6-alkoxy;
• Rc is selected from the group consisting of hydrogen, —C(O)Re, —S(O)2Re, —P(O)(ORf)2, C1-C6-alkyl, C1-C6-haloalkyl C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl, wherein C1-C6-alkyl, C1-C6-haloalkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl are optionally substituted one or more times with halogen, aryl, —ORf, —NRd1 Rd2, or —OP(O)(ORf)2;
• Rd1, Rd2 independently from each other are selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl, or a group —C(O)Re or —S(O)2Re wherein C1-C6-alkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl are optionally substituted one or more times, the same way or differently with halogen, hydroxyl, aryl, —C1-C6-alkyl, —NRg1Rg2, —ORf, —C(O)Re, —S(O)2Re, or —OP(O)(ORf)2;
• or
• Rd1 and Rd2 together with the nitrogen atom to which they are attached, form a 3 to 10 membered heterocycloalkyl ring, which is optionally substituted one or more times, the same way or differently, with C1-C6-alkyl, —NRg1Rg2, —ORf, —C(O)Re, —S(O)2Re, or —OP(O)(ORf)2;
• whereby the carbon backbone of this heterocycloalkyl ring can optionally be interrupted one or more times, the same way or differently, by NH, NRa, oxygen or sulphur, and can optionally be interrupted one or more times, the same way or differently, with a —C(O)—, —S(O)—, and/or —S(O)2-group, and can optionally contain one or more double bonds;
• Re is selected from the group consisting of, —NRg1Rg2, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C6-alkoxy, aryl and heteroaryl;
• Rf is selected from the group consisting of hydrogen, —C(O)Re, C1-C6-alkyl, C1-C6-haloalkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl, wherein C1-C6-alkyl, C1-C6-haloalkyl, C3-C10-cycloalkyl, C3-C10-heterocycloalkyl, aryl, and heteroaryl are optionally substituted one or more times with hydroxyl, halogen, C1-C6-alkoxy, aryl, or —NRg1Rg2;
• Rg1, Rg2 independently from each other are selected from the group consisting of hydrogen, C1-C6-alkyl, C3-C10-cycloalkyl, and C3-C10-heterocycloalkyl;
• or
• Rg1 and Rg2 together with the nitrogen atom to which they are attached, form a 3 to 10 membered heterocycloalkyl ring, which is optionally substituted one or more times, the same way or differently, with C1-C6-alkyl, —C1-C6-alkoxy, or hydroxy;
• whereby the carbon backbone of this heterocycloalkyl ring can optionally be interrupted one or more times, the same way or differently, by NH, NRa, oxygen or sulphur, and can optionally be interrupted one or more times, the same way or differently, with a —C(O)—, —S(O)—, and/or —S(O)2-group, and can optionally contain one or more double bonds;
• Rh, Rk,and Rl independently from each other represent —C1-C6-alkyl or phenyl;
• Rm is selected from the group consisting of C1-C6-alkyl, C3-C10-cycloalkyl and C3-C10-heterocycloalkyl;
• Rn is selected from the group consisting of —NRg1Rg2, C1-C6-alkyl, C3-C6-cycloalkyl, hydroxyl and C1-C6-alkoxy;
• Rs represents hydrogen or C1-C6-alkyl
• A represents aryl or heteroaryl;
• m represent an integer of 0, 1 or 2;
• n represent an integer of 0, 1 or 2;
• p represent an integer of 0, 1 or 2;
• wherein each occurrence of Ra, Rb, Rc, Rd1, Rd2, Re, Rf, Rg1 or Rg2 may be the same or different;
• or a salt or tautomer thereof.