Ether analogues of galiellalactone

A compound according to formula (I) or formula (II),

• wherein
• R1 and R1′ are independently selected from the group consisting of H, C1-5 alkyl, C1-5 fluoroalkyl, halo, cyano, nitro, —OH, OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, C3-8 non-aromatic carbocycle, OC1-5 fluoroalkyl, C1-3 alkyleneOC1-5 fluoroalkyl, OC(O)C1-5 alkyl, C1-3 alkyleneOC(O)C1-5 alkyl, OC2-3 alkyleneNH2, OC2-3 alkyleneNH(C1-5 alkyl), OC2-3 alkyleneN(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, —NH2, —NH(C1-5 alkyl), C1-3 alkyleneNH2, C1-3 alkyleneNH(C1-5 alkyl), —N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C1-3 alkyleneN(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, NHC(O)C1-5 alkyl, N(C1-5 alkyl)C(O)C1-5 alkyl, C1-3 alkyleneNHC(O)C1-5 alkyl, C1-3 alkyleneN(C1-5 alkyl)C(O)C1-5 alkyl,
• NHaryl, C1-3 alkyleneNHaryl, wherein the aryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, NH2, NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• NHheteroaryl, C1-3 alkyleneNHheteroaryl, wherein said heteroaryl is a 5- or 6-membered heteroaryl, said heteroaryl being unsubstituted or substituted with a one or several substituents independently selected from C1-5 alkyl, C(O)NH2, C(O)NHC1-5 alkyl, C1-3 alkyleneC(O)NH2, C1-3 alkyleneC(O)NHC1-5 alkyl, C(O)N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C1-3 alkyleneC(O)N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C(O)N(C4-5 alkylene), C1-3 alkyleneC(O)N(C4-5 alkylene), C(O)OH, C(O)OC1-5 alkyl, C1-3 alkyleneC(O)OH, C1-3 alkyleneC(O)OC1-5 alkyl, and a 3- to 8-membered non-aromatic heterocycle,
• aryl, C1-3 alkylene-aryl, wherein the aryl is unsubstituted or substituted with one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, —NH2, —NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• heteroaryl, C1-3 alkylene-heteroaryl, wherein said heteroaryl is a 5- or 6-membered heteroaryl, said heteroaryl being unsubstituted or substituted with one or several substituents independently selected from C1-5 alkyl groups, halo, cyano, —CH2-cyano, —SH, SC1-5 alkyl, SO2H, SO2C1-5 alkyl, C1-3 alkyleneSO2H, C1-3 alkyleneSO2C1-5 alkyl, nitro, C(O)H, C(O)C1-C5 alkyl, C(O)C1-C5 fluoroalkyl, NHSO2C1-C5 alkyl, N(C1-C3 alkyl)SO2C1-C5 alkyl, NHSO2C1-5 fluoroalkyl, and N(C1-C5 alkyl)SO2C1-5 fluoroalkyl,
• —SH, —SC1-5 alkyl, C1-5 alkylene-SH, C1-5 alkylene-SC1-5 alkyl, SC1-5 fluoroalkyl, C1-5 alkyleneSC1-5 fluoroalkyl, SO2C1-5 alkyl, C1-5 alkylene-SO2C1-5 alkyl, SO2C1-5 fluoroalkyl, C1-5 alkylene-SO2C1-5 fluoroalkyl, SO2NH2, SO2NH(C1-5 alkyl), SO2N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C1-5 alkyleneSO2NH2, C1-5 alkyleneSO2NH(C1-5 alkyl), C1-5 alkyleneSO2N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• SO2NHaryl, C1-5 alkyleneSO2NHaryl, wherein the aryl is unsubstituted or substituted with a one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, —NH2, —NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• SO2N(C1-5 alkyl)aryl, and C1-5 alkyleneSO2N(C1-5 alkyl)aryl, wherein the aryl is unsubstituted or substituted with a one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, —NH2, —NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different;
• R2, R2′, R3, and R3′ are each independently selected from the group consisting of H, halo, —OH, C1-5 alkyl, and C1-5 fluoroalkyl;
• R4 and R4′ are independently selected from the group consisting of H, C1-5 alkyl, aryl, and CH2aryl;
• A is selected from the group consisting of a bond, C1-C5 alkylene or NR10;
• R10 is H or C1-C3 alkyl;
• Cy1 is a ring selected from the group consisting of aryl, heteroaryl, a non-aromatic carbocycle, and a non-aromatic heterocycle;
• R5 is independently selected from the group consisting of C1-8 alkyl, C1-5 haloalkyl, halo, cyano, —CH2-cyano, —OH, OC1-5 alkyl, C1-8 alkyleneOC1-5 alkyl, O-aryl, C1-8 alkylene-O-aryl, —SH, SC1-5 alkyl, SO2H, SO2C1-5 alkyl, C1-3 alkyleneSO2H, C1-3 alkyleneSO2C1-5 alkyl, OC1-3 fluroroalkyl, C1-3 alkyleneOC1-3 fluroroalkyl, NH2, NH(C1-3 alkyl), C1-3 alkylene-NH2, C1-3 alkyleneNH(C1-3 alkyl), N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C1-3 alkyleneN(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C(O)OH, C(O)OC1-5 alkyl, C1-3 alkyleneC(O)OH, C1-3 alkyleneC(O)OC1-5 alkyl, OC(O)H, OC(O)C1-5 alkyl, C1-3 alkyleneOC(O)H, C1-3 alkyleneOC(O)C1-5 alkyl, NHC(O)H, NHC(O)C1-5 alkyl, N(C1-3 alkyl)C(O)H, N(C1-3 alkyl)C(O)C1-5 alkyl, C1-3 alkyleneNHC(O)H, C1-3 alkyleneNHC(O)C1-5 alkyl, C1-3 alkyleneN(C1-3 alkyl)C(O)H, C1-3 alkyleneN(C1-3 alkyl)C(O)C1-5 alkyl, C(O)NH2, C(O)NH(C1-3 alkyl), C1-3 alkyleneC(O)NH2, C1-3 alkyleneC(O)NH(C1-3 alkyl), C(O)N(C1-5 alkyl)2, in which the C1-5 alkyl are the same or different, C1-3 alkyleneC(O)N(C1-5 alkyl)2, in which the C1-5 alkyl are the same or different, nitro, C(O)H, C(O)C1-C5 alkyl, NHSO2C1-C3 alkyl, N(C1-C3 alkyl)SO2C1-C3 alkyl, NHSO2C1-C3 fluoroalkyl, N(C1-C3 alkyl)SO2C1-C3 fluoroalkyl, OC2-C3 alkyleneNH2, OC2-C3 alkyleneNH(C1-C3 alkyl), OC2-C3 alkyleneN(C1-C3 alkyl)2 in which the C1-3 alkyl are the same or different, and
• wherein
• D is selected from the group consisting of a bond, C1-3 alkylene, O—C1-3 alkylene, C1-3 alkylene-O—C1-3 alkylene, OC(O)C1-3 alkylene, C1-3 alkylene-OC(O)—C1-3 alkylene, C(O)OC1-3 alkylene, C1-3 alkylene-C(O)O—C1-3 alkylene, C(O)N(H)(C1-3 alkylene), C(O)N(C1-3 alkyl)(C1-3 alkylene), C1-3 alkylene-C(O)N(H)(C1-3 alkylene), C1-3 alkylene-C(O)N(C1-3 alkyl)(C1-3 alkylene), N(H)C(O)C1-3 alkylene, N(C1-3 alkyl)C(O)C1-3 alkylene, C1-3 alkylene-N(H)C(O)C1-3 alkylene, C1-3 alkylene-N(C1-3 alkyl)C(O)C1-3 alkylene, —NHSO2-, —SO2NH—, SO2, SO, C(O), C1-3 alkylene-C(O), C(O)C1-3 alkylene, C1-3 alkylene C(O)C1-3 alkylene, NH, N(C1-3 alkyl), NH—C1-3 alkylene, N(C1-3 alkyl)-C1-3 alkylene, C1-3 alkylene-NH, C1-3 alkylene-N(C1-3 alkyl), C1-3 alkylene-NH—C1-3 alkylene, C1-3 alkylene-N(C1-3 alkyl)-C1-3 alkylene, and S;
• Cy2 is a 5-membered heteroaryl, a 6-membered heteroaryl, phenyl, a 3- to 8-membered non-aromatic heterocycle or a C3-8 non-aromatic carbocycle;
• m is an integer selected from the group consisting of 0, 1, 2, 3, 4, and 5;
• R6 is independently selected from oxo, C1-5 alkyl, C1-5 fluoroalkyl, halo, cyano, —CH2-cyano, —OH, OC1-5 alkyl, C1-5 alkylene-OH, C1-5 alkyleneOC1-5 alkyl, —SH, SC1-5 alkyl, SO2H, SO2C1-5 alkyl, C1-3 alkyleneSO2H, C1-3 alkyleneSO2C1-5 alkyl, OC1-3 fluoroalkyl, C1-3 alkyleneOC1-3 fluoroalkyl, NH2, NH(C1-3 alkyl), C1-3 alkylene-NH2, C1-3 alkylene-NH(C1-3 alkyl), N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C1-3 alkyleneN(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C(O)OH, C(O)OC1-5 alkyl, C1-3 alkylene-C(O)OH, C1-3 alkylene-C(O)OC1-5 alkyl, OC(O)H, OC(O)C1-5 alkyl, C1-3 alkylene-OC(O)H, C1-3 alkylene-OC(O)C1-5 alkyl, NHC(O)H, NHC(O)C1-3 alkyl, N(C1-3 alkyl)C(O)H, N(C1-3 alkyl)C(O)C1-3 alkyl, C1-3 alkylene-NHC(O)H, C1-3 alkylene-NHC(O)C1-3 alkyl, C1-3 alkylene-N(C1-3 alkyl)C(O)H, C1-3 alkylene-N(C1-3 alkyl)C(O)C1-3 alkyl, C(O)NH2, C(O)NH(C1-3 alkyl), C1-3 alkylene-C(O)NH2, C1-3 alkylene-C(O)NH(C1-3 alkyl), C(O)N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C1-3 alkyleneC(O)N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, C(O)N(C4-5 alkylene), C1-3 alkyleneC(O)N(C4-5 alkylene), nitro, C(O)H, C(O)C1-C5 alkyl, C(O)C1-C3 fluoroalkyl, NHSO2C1-C3 alkyl, N(C1-C3 alkyl)SO2C1-C3 alkyl, NHSO2C1-C3 fluoroalkyl, N(C1-C3 alkyl)SO2C1-C3 fluoroalkyl, OC2-C3alkyleneNH2, OC2-C3alkyleneNH(C1-C3 alkyl), and OC2-C3alkyleneN(C1-C3 alkyl)2 in which the C1-3 alkyl are the same or different;
• or
• when two R6 are present, each R6 is combined to form a fused ring or spiro ring with Cy2;
• n is an integer selected from the group consisting of 0, 1, and 2;
• R9 is a moiety according to formula (III),
• wherein the waved line indicates the point of attachment to the sulfur atom in formula (II);
• Z is a C1-5 alkylene;
• Q is a bond, a phenylene, or a heteroarylene, wherein said heteroarylene is a 5- or 6-membered heteroarylene;
• E is a bond or a C1-5 alkylene;
• X is selected from the group consisting of NH, NC1-C5 alkyl or “O” (oxygen);
• R7 is selected from the group consisting of H, C1-C10 alkyl, C1-5 alkyleneN(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• aryl, C1-3 alkylene-aryl wherein the aryl is unsubstituted or substituted with a one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, —OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, NH2, NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• C1-3 alkylene heteroaryl, wherein said heteroaryl is a 5- or 6-membered heteroaryl, said heteroaryl being unsubstituted or substituted with a one or several substituents independently selected from C1-5 alkyl groups, an amino acid residue selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine and valine, which amino acid residue is connected to the moiety according to formula (III) at the N-terminal of the amino acid residue and optionally esterified at the C-terminal with a C1-5 monohydric alkanol, and a di-, a tri-, or a tetrapeptide residue, wherein the amino acid residues in said peptide residue are independently selected from the group consisting alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine and valine, the peptide residue being connected to the moiety according to formula (III) at the N-terminal of the peptide and optionally esterified at the C-terminal with a C1-5 monohydric alkanol;
• provided that R7 cannot be H if X is “O” (oxygen);
• and
• R8 is selected from the group consisting of:
• C(O)C1-C6 alkyl, C(O)OC1-C6 alkyl,
• C(O)-aryl, C(O)C1-3 alkylene-aryl wherein the aryl is unsubstituted or substituted with a one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, —OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, NH2, NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• C(O)-heteroaryl, C(O)C1-3 alkylene-heteroaryl wherein said heteroaryl is a 5- or 6-membered heteroaryl, said heteroaryl being unsubstituted or substituted with one or several substituents independently selected from C1-5 alkyl groups, an amino acid residue selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine and valine, which amino acid residue is connected to the moiety according to formula (III) at the C-terminal of the amino acid residue, and which amino acid residue is optionally N-acylated, wherein said acyl group is selected from the group consisting C(O)C1-C6 alkyl, C(O)-aryl, and C(O)C1-3 alkylene-aryl, wherein the aryl is unsubstituted or substituted with a one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, —OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, NH2, NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different, and
• a di-, a tri-, or a tetrapeptide residue, wherein the amino acid residues in said peptide residue are independently selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threonine, tryptophan, tyrosine and valine, the peptide residue being connected to the moiety according to formula (III) at the C-terminal of the peptide, and the N-terminal of the peptide optionally being N-acylated, wherein said acyl group is selected from the group consisting C(O)C1-C6 alkyl, C(O)-aryl, and C(O)C1-3 alkylene-aryl, wherein the aryl is unsubstituted or substituted with a one or several substituents independently selected from the group consisting of C1-5 alkyl, C1-5 fluoroalkyl, halo, —OH, —OC1-5 alkyl, C1-5 alkyleneOH, C1-5 alkyleneOC1-5 alkyl, nitro, cyano, NH2, NH(C1-5 alkyl), and N(C1-5 alkyl)2 in which the C1-5 alkyl are the same or different,
• as a free base, an acid in its non-charged protonated form, a pharmaceutically acceptable addition salt, solvate, solvate of a salt thereof, a pure diastereomer, a pure enantiomer, a diastereomeric mixture, a racemic mixture, a scalemic mixture, a corresponding tautomeric form resulting from a hydrogen shift between two hetero-atoms and/or the corresponding tautomeric form resulting from a keto-enol tautomerization.