Peptide derivatives with therapeutic activity

摘要

Dipeptide compounds containing a histidine residue proved to have interesting blocking activity on secondary products from lipid oxidative stress, in particular on unsaturated aldehydes such as malondialdehyde and hydroxynonenal, which are known to contribute to the inset of quite a number of chronic pathologies such as neurodegenerative, inflammatory chronic, cardiovascular diseases, diabetes complications and cataract.

主权项

1. Compounds of general formula I in which:one of R and R1 is hydrogen:
and the other is selected from an aryl-C1-C5-alkyl, heteroaryl-C1-C5-alkyl group; or an aryl or heteroaryl group optionally substituted with a group selected from hydroxy, methoxy, amino, C1-C5-mono- or di-alkylamino, C1-C5-acylamino groups, straight or branched or cyclic alkyl groups, and halogen atom; R2, R3 and R4 are hydrogen, or an amino group optionally substituted with an alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, arylalkylcarbonyl, heteroarylalkylcarbonyl, alkyloxycarbonyl, or arylalkyloxycarbonyl group; or:R and R1, taken together, form compounds of formula II in which X and Y, which can be the same or different, are a sulfur, nitrogen, or oxygen atom or a CH2 group, n and m, which can be the same or different, have a value ranging from 0 to 5;or
R and R1, taken together, form a double bond to give compounds of formula III; R2 and R3, which can be the same or different, are: hydrogen, a straight or branched C1-C20 or cyclic C3-C7 alkylcarbonyl group optionally containing one or more double bonds, an arylcarbonyl or arylalkylcarbonyl group, a straight or branched C1-C10 or cyclic C3-C7 alkyloxycarbonyl group optionally containing one or more double bonds, an aryloxycarbonyl or arylalkyloxycarbonyl group, an amino group, a hydroxy group, a group of general formula IV in which M is nitrogen, oxygen or sulfur and A is hydrogen or an amino group; R4 is:
a hydroxy group,an amino group optionally mono or disubstituted by groups, which can be the same or different, selected from:
a straight or branched C1-C20 or cyclic C3-C7 alkyl group, optionally containing one or more double bonds,an aryl or arylalkyl group, anda straight or branched C1-C20 or cyclic C3-C7 alkyloxycarbonyl group, optionally containing one or more double bonds,an aryl, heteroaryl, heteroarylalkyl or arylalkyl group,a straight or branched C1-C10 or cyclic C3-C7 alkoxy group, optionally containing one or more double bonds,an alkoxycarbonyloxyalkoxy or alkylcarbonyloxyalkoxy group bearing a straight, branched or cyclic alkyl,an aryloxy, heteroaryloxy, heteroarylalkyloxy or arylalkoxy group.