Compounds for the treatment of protozoal diseases

A method of using a compound according to formula (I)

• 183
• or a salt thereof, where
• Y is C═O, C═S, C═NH, (C═O)2 or SO2;
• (A) and (B) are each independently an aromatic hydrocarbon group which optionally contains one or more heteroatoms selected from the group consisting of S, O and N, wherein the heteroatom N is optionally substituted with R′, and/or the heteroatom S is optionally bonded to ═O or (═O)2;
• R′ is hydrogen, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, cyanoalkyl, alkyl or an unsaturated or saturated carbocyclic group selected from the group consisting of cyclopentyl, cyclohexyl, aryl, and heteroaryl;
• R1 is
• 184
• where Ra and Rc are each independently hydrogen, —O—(CO)—R′ (where R′ is as defined above), hydroxyl, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, cyanoalkyl, alkyl or an unsaturated or saturated carbocyclic group selected from the group consisting of cyclopentyl, cyclohexyl, aryl, heteroaryl;
• Rb is an optional substituent which may be independently of Ra and Rc and may be selected from the group as defined above for Ra and Rc;
• Rd is hydrogen or one of the following groups:
• —(CO)—Re where Re is independently hydrogen, alkoxy, alkylthio, halogen, haloalkyl, haloalkyloxy, hydroxyalkyl, hydroxyalkylamino, alkyl, aryl, heteroaryl, amino, aminoalkyl or alkylamino group;
• —(CH2)n—Rf where Rf is independently hydrogen, a hydroxy-alkyl, an alkyl, an allyl, an amino, an alkylamino, a morpholino, 2-tetrahydrofuran, N-pyrrolidino, a 3-pyridyl, a phenyl, a benzyl, a biphenyl or another heterocyclic group and n is 0, 1, 2 or 3;
• —NRaRb where Ra and Rb are defined above;
• or Ra forms together with Rd a 5- or 6-membered unsaturated or saturated heterocyclic ring which optionally has 0 to 3 substituents R″;
• the dotted line means a double bond unless there is a substituent Rb in the formula of R1 as defined above.
• R″ is independently hydrogen, alkoxy, alkylthio, aminoalkyl halogen, —CO2R′, —CR′O, haloalkyl, haloalkyloxy, —NO2, —CN, hydroxyalkyl, alkyl, aryl, heteroaryl, amino, alkylamino or an aminoalkyl group or a double bonded oxygen, wherein R′ is as defined above;
• R2 is a hydrogen, a halogen, alkoxy, alkylthio, —CO2R′, —CR′O, haloalkyl, haloalkyloxy, —NO2, —CN, hydroxy, hydroxyalkyl, alkyl, aryl, amino, alkylamino or an aminoalkyl group;
• R3 is a hydrogen, a halogen, haloalkyl, —NO2, —CN, alkyl or an aryl group;
• R4 is a hydrogen or a group capable of hydrogen bond formation except for a group as defined for substituent R1;
• R5 is hydrogen or, independently of R4, a group selected from the groups as defined above for R4
• R6 is hydrogen or, independently of R2, a group selected from the groups as defined above for R2;
• for the preparation of a medicament for the inhibition of the intracellular protein-degradation pathway.

A method of using a compound according to formula (I)

• 185
• or a salt thereof, where
• Y is C═O, C═S, C═NH, (C═O)2 or SO2;
• (A) and (B) are each independently an aromatic hydrocarbon group which optionally contains one or more heteroatoms selected from the group consisting of S, O and N, wherein the heteroatom N is optionally substituted with R′, and/or the heteroatom S is optionally bonded to ═O or (═O)2;
• R′ is hydrogen, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, cyanoalkyl, alkyl or an unsaturated or saturated carbocyclic group selected from the group consisting of cyclopentyl, cyclohexyl, aryl and heteroaryl;
• R1 is
• 186
• where Ra and Rc are each independently hydrogen, —O—(CO)—R′ (where R′ is as defined above), hydroxyl, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, cyanoalkyl, alkyl or an unsaturated or saturated carbocyclic group selected from the group consisting of cyclopentyl, cyclohexyl, aryl, heteroaryl;
• Rb is an optional substituent which may be independent of Ra and Rc and may be selected from the group as defined above for Ra and Rc;
• Rd is hydrogen or one of the following groups:
• —(CO)—Re where Re is independently hydrogen, alkoxy, alkylthio, halogen, haloalkyl, haloalkyloxy, hydroxyalkyl, hydroxyalkylamino, alkyl, aryl, heteroaryl, amino, aminoalkyl or alkylamino group;
• —(CH2)n—Rf where Rf is independently hydrogen, a hydroxy-alkyl, an alkyl, an allyl, an amino, an alkylamino, a morpholino, 2-tetrahydrofuran, N-pyrrolidino, a 3-pyridyl, a phenyl, a benzyl, a biphenyl or another heterocyclic group and n is 0, 1, 2 or 3;
• —NRaRb where Ra and Rb are defined above;
• or Ra forms together with Rd a 5- or 6-membered unsaturated or saturated heterocyclic ring which optionally has 0 to 3 substituents R″;
• the dotted line means a double bond unless there is a substituent Rb in the formula of R1 as defined above.
• R″ is independently hydrogen, alkoxy, alkylthio, aminoalkyl halogen, —CO2R′, —CR′O, haloalkyl, haloalkyloxy, —NO2, —CN, hydroxyalkyl, alkyl, aryl, heteroaryl, amino, alkylamino or aminoalkyl group or a double bonded oxygen, wherein R′ is as defined above;
• R2 is a hydrogen, a halogen, alkoxy, alkylthio, —CO2R′, —CR′O, haloalkyl, haloalkyloxy, —NO2, —CN, hydroxy, hydroxyalkyl, alkyl, aryl, amino, alkylamino or an aminoalkyl group;
• R3 is a hydrogen, a halogen, haloalkyl, —NO2, —CN, alkyl or an aryl group;
• R4 is a hydrogen or a group capable of hydrogen bond formation except for a group as defined for substituent R1;
• R5 is hydrogen or, independently of R4, a group selected from the groups as defined above for R4
• R6 is hydrogen or, independently of R2, a group selected from the groups as defined above for R2;
• with the proviso that the compounds of the formula (I) are not compounds in which (A) and (B) are phenyl and R4, R5 or 6 are in the ortho-position to the NH—Y—NH group of the formula (I);
• for the preparation of a medicament for the treatment of diseases caused by protozoa.