Oligopeptide derivatives for the electrochemical measurement of protease activity

A compound which is an oligopeptide derivative of the formula (I) or a salt thereof

• in which
• R1 is
• (a) a hydrogen atom, a C2-8-alkanoyl group optionally having an amino group in the ω position, a phenyl-C2-4-alkanoyl group whose phenyl radical is optionally substituted in the p position by an amino group;
• or
• (b) a cyclohexylcarbonyl group which is optionally substituted in the 4 position by an aminomethyl radical, a benzoyl group which is optionally substituted in the o or p position by methyl, amino or halogen, a C1-8-alkoxycarbonyl group, a benzyloxycarbonyl group which is optionally substituted in the p position by methoxy, methyl or chlorine;
• or
• (c) a radical of the formula —SO2—R5 where R5 can be a C1-6-alkyl radical, an optionally substituted aryl or heteroaryl radical or a radical of a bicyclic terpene derivative;
• or
• (d) a group of the formula —CO—CH(R6)—NH—R7, where R6 is hydrogen, a C1-6-alkyl radical, a 1- or 2-hydroxyethyl radical, a methylmercaptoethyl radical, an aminobutyl radical, a guanidinopropyl radical, a carboxy-C1-4-alkyl radical, a carboxamido-C1-4-alkyl radical, a phenyl-C1-4-alkyl radical whose phenyl radical is optionally substituted by OH, halogen, C1-4-alkyl or methoxy, or a cyclohexyl or cyclohexylmethyl radical whose ring is option-ally substituted by OH, halogen, C1-4-alkyl or methoxy, or a nitrogen-containing heteroaryl-C1-4-alkyl radical with 3 to 8 carbon atoms in the heterocyclic system, where the group —CO—CH(R6)—NH—R7 may be racemic or have the D or L configuration, and R7 can be a group of type (a), (b) or (c);
• or
• (e) a group of the formula
• wherein m can be 1 or 2, and one of the methylene groups can be substituted by hydroxyl, carboxyl, C1-4-alkyl or aryl-C1-4-alkyl;
• R2 is hydrogen, C1-6-alkyl, C1-2-hydroxyalkyl, C1-4-alkoxy-C1-6-alkyl, benzyloxy-C1-2-alkyl, an ω-carboxy-C1-3-alkyl radical, an ω-C1-4-alkoxy-carbonyl-C1-3-alkyl radical, an ω-benzyloxycarbonyl-C1-3-alkyl radical or a cyclohexyl, cyclohexylmethyl, 4-hydroxycyclohexylmethyl, phenyl, benzyl, 4-hydroxybenzyl or imidazolyl-4-methyl radical;
• R3 is
• (a) hydrogen or C1-4-alkyl and R3 is hydrogen;
• or
• (b) together with R3 a tri- or tetramethylene group, where one of the methylene groups can be substituted by hydroxyl, carboxyl, C1-4-alkyl or aryl-C1-4-alkyl;
• and
• R4 is
• (a) an aniline residue of the formula
• where R8 can be hydroxyl and R9 can be hydrogen, halogen, amino, C1-4-alkyl, C1-4-alkoxy or C1-4-alkanoyl;
• or
• (b) a quinoline residue of the formula
• where one of R10, R11 and R12 is an —NH group via which the quinoline residue is linked to the Arg residue, another can be hydroxyl or amino, and the other can be hydrogen, hydroxyl or amino.