US 7,008,925 B1Granted

Melanocortin 1 receptor selective compounds

AssigneeAction Pharma A/S

InventorsMichael Szardenings, Ruta Muceniece, Ilze Mutule, Felikss Mutulis, Jarl Wikberg

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Abstract

A compound of general formula (1) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are H or methyl, R13, R14, R15 and R16 are H or alkyl, wherein L1 and L2 are linkers selected from single bond, methyl, ethyl, wherein R19, R20 and R21 are H or —CH2X, NT is selected from H, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide and functional group, CT is selected from hydrogen, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide and functional group shows high selectivity and high affinity for MC1-receptors in combination with effective stimulation or inhibiton of cAMP formation in MC1-receptor expressing cells but low affinity for other subtypes of MC-receptors and may be used to treat a wide range of inflammatory conditions. Also disclosed is a DNA molecule and a corresponding vector encoding the compound, a fusion protein comprising a copy of it, a vector comprising DNA encoding the fusion protein, and a pharmaceutical composition comprising the compound.

Claims43

Dependent claims

A compound of general formula (1):

wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are selected independently from H and methyl, and wherein R13, R14, R15 and R16 are selected independently from H and alkyl and wherein optionally one hydrogen in R13 and one hydrogen in R14 is exchanged for a bond between R13 and R14, and wherein optionally one hydrogen in R15 and one hydrogen in R16 is exchanged for a bond between R15 and R16, and wherein L1 and L2 are linkers which are independently selected from the group consisting of single bond, methyl, and ethyl,
and wherein R19, R20 and R21 are selected independently from H and —CH2X, where X is H, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, heteroalkenyl, substituted heteroalkenyl, alkynyl, substituted alkynyl, heteroalkynyl, substituted heteroalkynyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substitute cycloheteroalkyl, cycloalkenyl, substitute cycloalkenyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and functional group Q, where Q is selected from the group consisting of amino, alkylamino, dialkylamino, arylamino, arylazido, heteroarylamino, heteroarylazido, hydroxy, alkylhydroxy, fluorinated alkylhydroxy, cyano, carboxy, alkylcarboxy, arylcarboxy, halogen, nitro, hydroxylamino, acyl, fluorinated acyl, nitroso, sulfonyl, sulfinyl, thio, alkylthio, and arylthio,
and wherein NT is selected from H, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide and functional group Q, and CT is selected from hydrogen, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide and functional group Q, and wherein each asymmetric center (*) is in R or S configuration.

A compound, of the general formula (4):

wherein moiety A is optionally exchanged for hydrogen, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide, or functional group,
wherein moiety B is optionally exchanged for hydrogen, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide, or functional group,
wherein optionally moiety D is exchanged for aminoacid or aminoacid analogue,
wherein optionally moiety E is exchanged for aminoacid or aminoacid analogue, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 are selected independently from H and methyl, and wherein R13, R14, R15 and R16 are selected independently from H and alkyl and wherein optionally one hydrogen in R13 and one hydrogen in R14 is exchanged for a bond between R13 and R14, and wherein optionally one hydrogen in R15 and one hydrogen in R16 is exchanged for a bond between R15 and R16, and wherein L1 and L2 are linkers which are independently selected from the group consisting of single bond, methyl, and ethyl,
and wherein R19, R20 and R21 are selected independently from H and —CH2X, where X is H, alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl, heteroalkenyl, substituted heteroalkenyl, alkynyl, substituted alkynyl, heteroalkynyl, substituted heteroalkynyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substitute cycloheteroalkyl, cycloalkenyl, substitute cycloalkenyl, cycloheteroalkenyl, substituted cycloheteroalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and functional group Q, where Q is selected from the group consisting of amino, alkylamino, dialkylamino, arylamino, arylazido, heteroarylamino, heteroarylazido, hydroxy, alkylhydrxy, fluorinated alkylhydroxy, cyano, carboxy, alkylcarboxy, arylcarboxy, halogen, nitro, hydroxylamino, acyl, fluorinated acyl, nitroso, sulfonyl, sulfinyl, thio, alkylthio, and arylthio, and wherein NT is selected from H, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide and functional group Q, and CT is selected from hydrogen, hydroxyl, alkyl, aminoacid, aminoacid analogue, polypeptide and functional group Q, and wherein each asymmetric center (*) is in R or S configuration.

2 more elements

Dependencies are inferred from the claim text.