Substituted 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals

A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate of any of them,

• wherein
• A is selected from the group consisting of C(R1) and N;
• D is selected from the group consisting of C(R2) and N;
• E is selected from the group consisting of C(R3) and N;
• L is selected from the group consisting of C(R4) and N;
• wherein one of A, D, E, and L is N;
• G is selected from the group consisting of R71—O—C(O)—, R72—N(R73)—C(O)— and tetrazol-5-yl;
• R1 is selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, HO—, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m— and NC—;
• R2 is selected from the group consisting of hydrogen, halogen, (C1-C7)-alkyl, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-CO—, (C1-C6)-alkyl-CO—HN—, —NR12R13, Het2, (C3-C7)-cycloalkyl-CsH2s— and Ar—CsH2s—, wherein s is 0, 1, 2 or 3;
• R3 is selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-S(O)m—, Het4-(O)t—, —NR12R13, Het2, R12—N(R13)—C(O)—O— and Het2-C(O)—O— and NC—, wherein s is 0, 1, 2, or 3, and t is 0 or 1;
• R4 is selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-O—, HO—, NR12R13, Het2;
• R10 is selected from the group consisting hydrogen, halogen, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m—, HO—, —NR12R13, Het2, phenyl-CsH2s—(O)t—, wherein s is 0, 1, 2 or 3, and t is 0 or 1;
• or R1 and R2 or R2 and R3 form pyridyl;
• or R1 and R2 are —C((C1-C3)-alkyl)═N—N((C1-C3)-alkyl)-;
• or R2 and R3 are —NH—CH═N—;
• with the proviso that one of R′, R2, R4 or R10 is a cyclic substituent;
• R11 is selected from the group consisting of hydrogen, R14, (C3-C7)-cycloalkyl, Ar and Het3;
• R12 and R13 are independently selected from the group consisting of hydrogen and R15;
• R14 is (C1-C10)-alkyl, which is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, HO—, R16—O—, oxo, (C3-C7)-cycloalkyl, Ar, Het1, Het3, NC—, H2N—C(O)—, (C1-C4)-alkyl-NH—C(O)—, di((C1-C4)-alkyl)N—C(O)—, Het1-C(O)—, (C1-C4)-alkyl-C(O)—NH— and (C1-C4)-alkyl-S(O)m—;
• R15 is (C1-C6)-alkyl which is optionally substituted by one or more identical or different substituents selected from the group consisting halogen, HO— and (C1-C6)-alkyl-O—;
• R16 is (C1-C6)-alkyl which is optionally substituted by one or more identical or different substituents selected from the group consisting of HO—, (C1-C4)-alkyl-O— and NC—;
• R30 is selected from the group consisting of R31, (C3-C7)-cycloalkyl, R32—CuH2u— and Het3-CuH2u—, wherein u is an integer selected from the group consisting of 0, 1, 2 and 3;
• R31 is (C1-C10)-alkyl, which is optionally substituted by one or two identical or different substituents selected from the group consisting of halogen, (C3-C7)-cycloalkyl, HO—, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m— and NC—;
• R32 is selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle which comprises one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and is bonded via a ring carbon atom, wherein the phenyl and the heterocycle all are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, R33, HO—, (C1-C6)-alkyl-O—, R33—O—, R33—(C1-C4)-alkyl-O—, —O—CH2—O—, —O—CF2—O—, (C1-C6)-alkyl-S(O)m—, H2N—S(O)2—, (C1-C4)-alkyl-NH—S(O)2—, di((C1-C4)-alkyl)N—S(O)2—, H2N—, NH—, di((C1-C6)-alkyl)N—, Het1, (C1-C4)-alkyl-C(O)—NH—, Ar—C(O)—NH—, (C1-C4)-alkyl-S(O)2—NH— and NC—;
• R33 is selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle which comprises one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and is bonded via a ring carbon atom, wherein the phenyl and the heterocycle all are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, HO—, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)n—, H2N—S(O)2—, (C1-C4)-alkyl-NH—S(O)2—, di((C1-C4)-alkyl)N—S(O)2— and NC—;
• R40 is selected from the group consisting of hydrogen and (C1-C4)-alkyl;
• or R30 and R40 together are (CH2)x which is optionally substituted by one or more identical or different (C1-C4)-alkyl substituents, wherein x is 2, 3, 4, or 5;
• R50 is selected from the group consisting of hydrogen, (C1-C6)-alkyl, HO— and (C1-C6)-alkyl-O—;
• R60 is selected from the group consisting of hydrogen and (C1-C6)-alkyl;
• or R50 and R60 together are (CH2)y which is optionally substituted by one or more identical or different (C1-C4)-alkyl substituents, wherein y is 2, 3, 4 or 5;
• R71 is selected from the group consisting of hydrogen and (C1-C8)-alkyl, which is optionally substituted by one or more identical or different substituents selected from the group consisting (C1-C6)-alkyl-O— and (C1-C6)-alkyl-C(O)—O—;
• R72 is selected from the group consisting of hydrogen, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, —CH2—(CH2)b—(C3-C6)-cycloalkyl, Het4 and —(CH2)b-Het4, where alkyl or cycloalkyl is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, HO—, HOOC—, (C1-C6)-alkyl-O— and (C1-C6)-alkyl-C(O)—O—, NC—, N((C1-C4)-alkyl)2, and b is 0, 1 or 2;
• R73 is selected from the group consisting of hydrogen and (C1-C6)-alkyl;
• or
• R72 and R73, together with the nitrogen atom to which they are bonded, form a saturated 4-membered to 7-membered monocyclic heterocycle, which contain optionally one further ring heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, HO— and (C1-C4)-alkyl-O—;
• Ar, independently of each other group Ar, is selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and is bonded via a ring carbon atom, wherein the phenyl and the heterocycle all are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, HO—(C1-C6)-alkyl, Het4, —(CH2)x-Phenyl, (C1-C6)-alkyl-O—, (C3-C7)-cycloalkyl-(CH2)x—O—, —CF3, —CO—(C1-C6)-alkyl, —NR12R13, Het2, —CO—NR12R13, CO-Het2, (C1-C6)-alkyl-S(O)m—, H2N—S(O)2— and NC—;
• and wherein phenyl may be substituted by —CH═CH—CH═CH—, —O—CH2—O—, —O—CH2—CH2—O—, —O—CF2—O— or —N((C1-C3)-alkyl)-CH═CH—;
• Het1, independently of each other group Het1, is a saturated or unsaturated 4-membered to 8-membered monocyclic heterocycle containing a ring nitrogen atom via which Het1 is bonded, and optionally, one or two identical or different further ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, HO—, (C1-C4)-alkyl-O—, oxo and NC—;
• Het2 is a saturated 4-membered to 7-membered monocyclic heterocycle containing a ring nitrogen atom via which Het2 is bonded and optionally one further ring heteroatom selected from the group consisting of nitrogen, oxygen and sulfur, which is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, HO— and (C1-C4)-alkyl-O—;
• Het3, independently of each other group Het3, is a saturated 4-membered to 7-membered monocyclic heterocycle containing one or two identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and is bonded via a ring carbon atom, which is optionally substituted by one or more identical or different substituents selected from the group consisting of fluorine, (C1-C4)-alkyl and oxo;
• Het4, independently of each other group Het4, is a saturated or unsaturated 4-membered to 8-membered monocyclic heterocycle containing one to four ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur which is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, HO—, (C1-C4)-alkyl-O—, oxo and NC—;
• m, independently of each other number m, is 0, 1 or 2;
• wherein all cycloalkyl groups, independently of each other, are optionally substituted by one or more identical or different substituents selected from the group consisting of fluorine and (C1-C4)-alkyl;
• wherein all alkyl, CsH2s, CuH2u, (CH2)x and (CH2)y groups, independently of each other, and independently of any other substituents, are optionally substituted by one or more fluorine substituents.