Such cystine derivatives as to which the present invention has found a new pharmacological use are known from WO 91/185 94 and EP 463 514 to have immunomodulating activity. Nothing is reported or generally known concerning the pharmacological and/or therapeutic properties of these compounds with respect to effects or restenosis.
In connection with the present invention compounds of the general formula I are employed: ##STR1## wherein R is hydrogen, methyl, ethyl, n-propyl or a moiety -COR.sup.1, wherein R.sup.1 is a straight or branched akyl group having 1-12 carbon atoms, R.sup.2 is a straight or branched alkyl group having 1-12 carbon atoms and R.sup.3 is a moiety which provides an ester hydrolysable in body fluids to release the active compound in free acid form, or a physiologically acceptable salt and/or a stereochemical isomer thereof.
In particular compounds of the formula I wherein R is hydrogen or a moiety -CO-R.sup.1 wherein R.sup.1 is methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, isopropyl, 1-methylpropyl, 2-methylpropyl, tert. butyl, 3-methylbutyl or 2-metylbutyl, R.sup.2 is methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, isopropyl, 1-methylpropyl, 2-methylpropyl, tert. butyl, 3-methylbutyl or 2-methylbutyl and R.sup.3 is hydrogen, methyl, ethyl, propyl, isopropyl, butyl or isobutyl, or a physiologically acceptable salt and/or a stereochemical isomer thereof, are preferred.
The compounds of formula I are used in racemic form as well as stereoisomers (enantiomers, diastereomers). Of particular interest are the compounds having the L configuration, particularly interesting is N,N'-diacetyl-L-cystine.
The invention also involves the compound of formula I in the form of its physiologically acceptable salts, such as the salts of sodium, potassium, ammonium, calcium or magnesium. Also included are salts of the unesterified compounds with pharmaceutically acceptable organic bases, such as lysine, ethylenediamine, N,N'-dibenzylethylenediamine, adamantanamine, N-benzyl-2-phenylethylamine and piperazine.
Lysine and arginine can be used in its D- or L- forms. Most preferred is the L-form.
The most preferred compound is di-L-lysinium-N,N'-diacetyl-L-cystinate (compound A).
The compounds of the general formula I may be prepared by any of the processes disclosed in EP 463 514. Salts of such compounds with organic bases are prepared according to any conventional method or any method disclosed in WO 93/11104.
USPTO Backgrounds
USPTO Backgrounds