Imidazolidine derivatives, their preparation, their use, and pharmaceutical preparations comprising them

A compound of the formula I,

• 48
• in which
• W is R1-A-C(R13) or R1—CH═C;
• Z is oxygen or sulfur;
• A is a direct bond or (C1-C2)-alkylene;
• B is a divalent radical selected from the group consisting of (C1-C6)-alkylene, (C2-C6)-alkenylene, phenylene, phenylene-(C1-C3)-alkyl, (C1-C3)-alkylenephenyl, where the divalent (C1-C6)-alkylene radical can be unsubstituted or substituted by a radical selected from the group consisting of (C1-C8)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkyl-(C1-C6)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C6)-alkyl optionally substituted in the aryl radical, optionally substituted heteroaryl, and heteroaryl-(C1-C6)-alkyl optionally substituted in the heteroaryl radical;
• E is tetrazolyl, (R8O)2P(O), HOS(O)2, R9NHS(O)2 or R10CO;
• R is hydrogen, (C1-C8)-alkyl, (C3-C12)-cycloalkyl, (C3-C12)-cycloalkyl-(C1-C8)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical, optionally substituted heteroaryl, or heteroaryl-(C1-C8)-alkyl optionally substituted in the heteroaryl radical;
• R0 is hydrogen, (C1-C8)-alkyl, (C3-C12)-cycloalkyl, (C3-C12)-cycloalkyl-(C1-C8)-alkyl, (C6-C12)-bicycloalkyl, (C6-C12)-bicycloalkyl-(C1-C8)-alkyl, (C6-C12)-tricycloalkyl, (C6-C12)-tricycloalkyl-(C1-C8)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical, optionally substituted heteroaryl, heteroaryl-(C1-C8)-alkyl optionally substituted in the heteroaryl radical, H—CO, (C1-C8)-alkyl-CO, (C3-C12)-cycloalkyl-CO, (C3-C12)-cycloalkyl-(C1-C8)-alkyl-CO, (C6-C12)-bicycloalkyl-CO, (C6-C12)-bicycloalkyl-(C1-C8)-alkyl-CO, (C6-C12)-tricycloalkyl-CO, (C1-C12)-tricycloalkyl-(C1-C8)-alkyl-CO, optionally substituted (C6-C14)-aryl-CO, (C6-C14)-aryl-(C1-C8)-alkyl-CO optionally substituted in the aryl radical, optionally substituted heteroaryl-CO, heteroaryl-(C1-C8)-alkyl-CO optionally substituted in the heteroaryl radical, (C1-C8)-alkyl-S(O)n, (C3-C12)-cycloalkyl-S(O)n, (C3-C12)-cycloalkyl-(C1-C8)-alkyl-S(O)n, (C6-C12)-bicycloalkyl-S(O)n, (C6-C12)-bicycloalkyl-(C1-C8)-alkyl-S(O)n, (C6-C12)-tricycloalkyl-S(O)n, (C6-C12)-tricycloalkyl-(C1-C8)-alkyl-S(O)n, optionally substituted (C6-C14)-aryl-S(O)n, (C6-C14)-aryl-(C1-C8)-alkyl-S(O)n optionally substituted in the aryl radical, optionally substituted heteroaryl-S(O), or heteroaryl-(C1-C8)-alkyl-S(O)n optionally substituted in the heteroaryl radical, where n is 1 or 2;
• R1 is an optionally substituted radical selected from the group consisting of phenyl, furyl, thienyl, pyrrolyl, imidazolyl, and pyridyl, where each of these radicals can also be benzo-fused;
• R2 is hydrogen, (C1-C8)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical or (C3-C8)-cycloalkyl;
• R3 is hydrogen, (C1-C8)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical, optionally substituted heteroaryl, heteroaryl-(C1-C8)-alkyl optionally substituted in the heteroaryl radical, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C8)-alkyl, (C6-C12)-bicycloalkyl, (C6-C12)-bicycloalkyl-(C1-C8)-alkyl, (C6-C12)-tricycloalkyl, (C6-C12)-tricycloalkyl-(C1-C8)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, R11NH, CON(CH3)R4, CONHR4, COOR15, CON(CH3)R15 or CONHR15;
• R4 is hydrogen or (C1-C10)-alkyl which can optionally be monosubstituted or polysubstituted by identical or different radicals selected from the group consisting of hydroxyl, (C1-C8)-alkoxy, R5, optionally substituted (C3-C8)-cycloalkyl, hydroxycarbonyl, aminocarbonyl, mono- or di-((C1-C18)-alkyl)-aminocarbonyl, (C6-C14)-aryl-(C1-C8)-alkoxycarbonyl which can also be substituted in the aryl radical, (C1-C8)-alkoxycarbonyl, Het-CO, R6—CO, tetrazolyl, and trifluoromethyl;
• R5 is optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical, or an optionally substituted monocyclic or bicyclic 5-membered to 12-membered heterocyclic ring which can be aromatic, partially hydrogenated or completely hydrogenated and which can contain one, two or three identical or different heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• R6 is the radical of a natural or unnatural amino acid, imino acid, optionally N—(C1-C8)-alkylated or N—((C6-C14)-aryl-(C1-C8)-alkylated) azamino acid which can also be substituted in the aryl radical, or the radical of a dipeptide, and their esters and amides, where free functional groups can be protected by protective groups;
• R8 is hydrogen, (C1-C18)-alkyl, optionally substituted (C6-C14)-aryl or (C6-C14)-aryl-(C1-C8)-alkyl which can also be substituted in the aryl radical;
• R9 is hydrogen, aminocarbonyl, (C1-C18)-alkylaminocarbonyl, (C3-C8)-cycloalkylaminocarbonyl, optionally substituted (C6-C14)-arylaminocarbonyl, (C1-C18)-alkyl, optionally substituted (C6-C14)-aryl or (C3-C8)-cycloalkyl;
• R10 is hydroxyl, (C1-C18)-alkoxy, (C6-C14)-aryl-(C1-C8)-alkoxy which can also be substituted in the aryl radical, optionally substituted (C6-C14)-aryloxy, (C1-C8)-alkylcarbonyloxy-(C1-C6)-alkoxy, (C6-C14)-arylcarbonyloxy-(C1-C6)-alkoxy, amino or mono- or di-((C1-C18)-alkyl)-amino;
• R10 is hydrogen, R12a, R12a—CO, H—CO, R12b—O—CO, R12b—CO, R12b—CS, R12a—S(O)2 or R12b—S(O)2;
• R12a is (C1-C18)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C3-C12)-cycloalkyl, (C3-C12)-cycloalkyl-(C1-C8)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical, optionally substituted heteroaryl, heteroaryl-(C1-C8)-alkyl optionally substituted in the heteroaryl radical, or the radical R15;
• R12b is amino, di-((C1-C18)-alkyl)-amino, or R12a—NH;
• R13 is hydrogen, (C1-C6)-alkyl, optionally substituted (C6-C14)-aryl, (C6-C14)-aryl-(C1-C6)-alkyl optionally substituted in the aryl radical, (C3-C8)-cycloalkyl, or (C3-C8)-cyclo-(C1-C6)-alkyl;
• R15 is R16—(C1-C6)-alkyl or R16;
• R16 is a 6-membered to 24-membered bicyclic or tricyclic radical which is saturated or partially unsaturated and which can also contain one, two, three or four identical or different hetero atoms selected from the group consisting of nitrogen, oxygen, and sulfur and which can also be substituted by one or more identical or different substituents selected from the group consisting of (C1-C4)-alkyl and oxo;
• Het is the radical of a 5-membered to 10-membered, saturated monocyclic or polycyclic heterocycle bonded via a ring nitrogen atom, which can contain one, two, three, or four identical or different additional ring hetero atoms selected from the group consisting of oxygen, nitrogen, and sulfur and which can optionally be substituted on carbon atoms and on additional ring nitrogen atoms, where substituents on additional ring nitrogen atoms can be identical or different radicals selected from the group consisting of hydrogen, Rh, HCO, RhCO, and RhO—CO and Rh is (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C8)-alkyl, optionally substituted (C6-C14)-aryl or (C6-C14)-aryl-(C1-C8)-alkyl optionally substituted in the aryl radical;
• e and h independently of one another are 0 or 1;
• in any of its stereoisomeric forms and mixtures thereof in any ratio, or a physiologically tolerable salt of the compound.