Perylenequinone derivatives and uses thereof

A compound of formula IIIa or IIIb or stereoisomer or atropisomer thereof:

• wherein
• T is a C1-C4 alkylenyl, C2-C4 alkenylenyl, C1-C4 heteroalkylenyl, C2-C4 heteroalkenylenyl, or combinations thereof;
• R4 and R5 are independently hydrogen, deuterium, hydroxy, oxygen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, C1-C12 heteroaryl, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —C(O)N(R1)2, —C(O)NH(R1), —C(O)NH2 or an amino suitable protecting group,
• said C1-C4 alkylenyl, C2-C4 alkenylenyl, C1-C4 heteroalkylenyl, C2-C4 heteroalkenylenyl, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C2 heterocyclyl, and C1-C12 heteroaryl being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, C1-C8 deuterated alkyl group comprising at least one deuterated atom, —COH, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —C(O)N(R1)2, —C(O)NH(R3), —C(O)NH2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl and C1-C12 heteroaryl;
• R1 is a hydrogen atom, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aralkyl, or C1-C12 heterocyclyl;
• each R2 is independently a hydrogen atom, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aralkyl, or C1-C12 heterocyclyl;
• p is an integer having a value of 0 to 8, and when p has a value of 1 to 8, ring A is saturated, or unsaturated and having at least one double bond, said ring A being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, deuterium atom, C1-C8 deuterated alkyl group comprising at least one deuterated atom, —COH, NOH, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —CON(R6)2, —C(O)NH(R1), —C(O)NH2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, C1-C12 heteroaryl, C1-C8 azaalkyl having at least one nitrogen atom, C6-C12 azaaralkyl having at least one nitrogen atom, C1-C8 haloalkyl having at least one halogen atom, glucose, galactose, fucose, xylose, sialic acid, mannose, N-acetyl-glucosamine, N-acetyl galactoseamine, a disaccharide, a trisaccharide or derivatives thereof;
• each R6 is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, or an amino acid residue such as lysine, tryptophan, methionine, phenylalaine, threoine, valine, leucine, isolucine, arginine, tyrosine, glycine, serine, glutamic acid, aspartic acid, cystine, histidine, proline, alanine or derivatives thereof;
• and
• R7 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, or an amino acid residue such as lysine, tryptophan, methionine, phenylalaine, threoine, valine, leucine, isolucine, arginine, tyrosine, glycine, serine, glutamic acid, aspartic acid, cystine, histidine, proline, alanine or derivatives thereof;
• m is an integer having a value of 1 to 13,
• or a pharmaceutically acceptable salt thereof.

A process for preparing a compound of formula IIIa or IIIb or stereoisomer or atropisomer thereof:

• wherein
• T is a C1-C4 alkylenyl, C2-C4 alkenylenyl, C1-C4 heteroalkylenyl, C2-C4 heteroalkenylenyl, or combinations thereof;
• R4 and R5 are independently hydrogen, deuterium, hydroxy, oxygen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, C1-C12 heteroaryl, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —C(O)N(R1)2, —C(O)NH(R1), —C(O)NH2 or an amino suitable protecting group selected from the group consisting of methyl carbamate, ethyl carbamate, 9-fluorenylmethyl carbamate, 9-(2-sulfo) fluorenylmethyl carbamate, 9-(2,7-dibromo) fluorenylmethyl carbamate, 17-Tetrabenzo[a,c,g,i]fluorenylmethyl carbamate, 2-chloro-3-indenylmethyl carbamate, benz[f]-3-indenylmethyl carbamate, 1,1-dioxobenzo[b]thiophene-2-ylmethyl carbamate, 2,2,2-trichloroethyl carbamate, 2-trimethylsilylethyl carbamate, 2-phenylethyl carbamate, 1-(1-adamantyl)-1-methylethyl carbamate, 2-chloroethyl carbamate, 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate, 1,1-dimethyl-2,2,2-trichloroethyl carbamate, 1-methyl-1-(4-biphenylyl)ethyl carbamate, 1-(3,5-di-t-butylphenyl)-1-methylethyl carbamate, 2-(2′-pyridyl)ethyl carbamate, 2-(4′-pyridyl)ethyl carbamate, 2,2-bis(4′-nitrophenyl)ethyl carbamate, N-(2-pivaloylamino)-1,1-dimethylethyl carbamate, 2-[(2-nitrophenyl)dithio]-1-phenylethyl carbamate, 2-(N,N-dicyclohexylcarboxamino)ethyl carbamate, t-butyl carbamate, 1-adamantyl carbamate, 2-adamantyl carbamate,
• said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, and C1-C12 heteroaryl being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, C1-C8 deuterated alkyl group comprising at least one deuterated atom, —COH, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —C(O)N(R1)2—C(O)NH(R1), —C(O)NH2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C2 heterocyclyl, and C1-C12 heteroaryl;
• R1 is a hydrogen atom, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aralkyl, or C1-C12 heterocyclyl;
• each R2 is independently a hydrogen atom, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aralkyl, or C1-C12 heterocyclyl;
• p is an integer having a value of 0 to 8, and when p has a value of 1 to 8, ring A is saturated, or unsaturated and having at least one double bond, said ring A being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, deuterium atom, C1-C8 deuterated alkyl group comprising at least one deuterated atom, —COH, NOH, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —CON(R6)2, —C(O)NH(R1), —C(O)NH2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, C1-C12 heteroaryl, C1-C8 azaalkyl having at least one nitrogen atom, C6-C12 azaaralkyl having at least one nitrogen atom, C1-C8 haloalkyl having at least one halogen atom, a sugar and
• each R6 is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, or an amino acid residue such as lysine, tryptophan, methionine, phenylalaine, threoine, valine, leucine, isolucine, arginine, tyrosine, glycine, serine, glutamic acid, aspartic acid, cystine, histidine, proline, alanine or derivatives thereof;
• and
• R7 is hydrogen, C1-C8 alkyl, C1-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, or an amino acid residue such as lysine, tryptophan, methionine, phenylalaine, threoine, valine, leucine, isolucine, arginine, tyrosine, glycine, serine, glutamic acid, aspartic acid, cystine, histidine, proline, alanine or derivatives thereof,
• said process comprising:
• a) reacting a compound of formula (IVa) or (IVb):
• wherein
• R2 is as previously defined,
• with a compound of formula (VI):
• wherein
• T, R4, R5, and p are as previously defined,
• wherein compounds of formula (IVa) and (IVb) when reacted with compound (VI) result in compound (IIIa) and (IIIb), respectively.

A process for preparing a mixture of the compound of formula IIIa and IIIb, or a stereoisomer or atropisomer thereof:

• wherein
• T is a C1-C4 alkylenyl, C2-C4 alkenylenyl, C1-C4 heteroalkylenyl, C2-C4 heteroalkenylenyl, or combinations thereof;
• R4 and R5 are independently hydrogen, deuterium, hydroxy, oxygen, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, C1-C12 heteroaryl, —COR1, —(CH2)mOR1, CO2H, —CO2R1, —C(O)N(R1)2, —C(O)NH(R1), —C(O)NH2 or an amino suitable protecting group, said C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, and C1-C12 heteroaryl being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, C1-C8 deuterated alkyl group comprising at least one deuterated atom, —COH, —COR1, —(CH2)mR1, —CO2H, —CO2R1, —C(O)N(R1)2—C(O)NH(R1), —C(O)NH2, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, and C1-C12 heteroaryl;
• R1 is a hydrogen atom, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aralkyl, or C1-C12 heterocyclyl;
• each R2 is independently a hydrogen atom, C1-C8 alkyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aralkyl, or C1-C12 heterocyclyl;
• p is an integer having a value of 0 to 8, and when p has a value of 1 to 8, ring A is saturated, or unsaturated and having at least one double bond, said ring A being unsubstituted or substituted with at least one substituent selected from the group consisting of a halogen atom, hydroxy, carboxy, thiol, azide, nitro, deuterium atom, C1-C8 deuterated alkyl group comprising at least one deuterated atom, —COH, NOH, —COR1, —(CH2)mOR1, —CO2H, —CO2R1, —CON(R6)2, —C(O)NH(R1), —C(O)NH2, C1-C8 alkyl, C2-C8 alkenyl, C2-C6 alkynyl,
• C1-C8 alkoxy, C1-C8 thioalkoxy, C1-C8 alkylamino, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, C6-C12 aralkyl, C1-C12 heterocyclyl, C1-C12 heteroaryl, C1-C8 azaalkyl having at least one nitrogen atom, C6-C12 azaaralkyl having at least one nitrogen atom, C1-C8 haloalkyl having at least one halogen atom or a sugar,
• each R6 is independently hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, or an amino acid residue such as lysine, tryptophan, methionine, phenylalaine, threoine, valine, leucine, isolucine, arginine, tyrosine, glycine, serine, glutamic acid, aspartic acid, cystine, histidine, proline, alanine or derivatives thereof;
• and
• R7 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C4-C10 cycloalkenyl, C6-C12 aryl, or an amino acid residue such as lysine, tryptophan, methionine, phenylalaine, threoine, valine, leucine, isolucine, arginine, tyrosine, glycine, serine, glutamic acid, aspartic acid, cystine, histidine, proline, alanine or derivatives thereof,
• said process comprising:
• a) reacting a compound of formula (IVa) or (IVb):
• wherein
• R2 is as previously defined, with a compound of formula (VI):
• wherein
• T, R4, R5, and p are as previously defined.