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

A compound of the formulae Ia and Ib, 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,

• G is chosen from the series consisting of R71—O—C(O)—, R72—N(R73)—C(O)—, NC— and tetrazol-5-yl;
• R1 is chosen from the series consisting of hydrogen, halogen, (C1-C6)-alkyl, CF3, (C3-C7)-cycloalkyl-CsH2s—, Ar—CsH2s—, Ar—O, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m— and NC—;
• wherein s is an integer chosen from the series consisting of 0, 1, 2 and 3;
• R2 is chosen from the series consisting of hydrogen, halogen, (C1-C6)-alkyl, CF3, HO—, (C1-C6)-alkyl-O—, and NC—;
• R10 is chosen from the series consisting of R11, Het2-C(O)—, R14—C(O)— and (C1-C4)-alkyl-S(O)m—;
• R11 is chosen from the series consisting of hydrogen, R14, (C3-C7)-cycloalkyl, Ar and Het3;
• R14 is (C1-C10)-alkyl which is optionally substituted by one or more identical or different substituents chosen from the series 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—;
• R16 is (C1-C6)-alkyl which is optionally substituted by one or more identical or different substituents chosen from the series consisting of HO—, (C1-C4)-alkyl-O— and NC—;
• R30 is chosen from the series consisting of R31, (C3-C7)-cycloalkyl, R32—CuH2u— and Het3-CuH2u—, wherein u is an integer chosen from the series consisting of 0, 1, 2 and 3;
• R31 is (C1-C10)-alkyl which is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, (C3-C7)-cycloalkyl, HO—, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m— and NC—;
• R32 is chosen from the series consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle which comprises one, two or three identical or different ring heteroatoms chosen from the series 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 chosen from the series 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—, (C1-C6)-alkyl-NH—, di((C1-C6)-alkyl)N—, Het1, (C1-C4)-alkyl-C(O)—NH—, (C1-C4)-alkyl-S(O)2—NH— and NC—;
• R33 is chosen from the series consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle which comprises one, two or three identical or different ring heteroatoms chosen from the series 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 chosen from the series consisting of halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, HO—, (C1-C6)-alkyl-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— and NC—;
• R40 is chosen from the series 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 an integer chosen from the series consisting of 2, 3, 4 and 5;
• R50 is chosen from the series consisting of hydrogen, (C1-C6)-alkyl, HO— and (C1-C6)-alkyl-O—;
• R60 is chosen from the series 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 an integer chosen from the series consisting of 2, 3, 4 and 5;
• R71 is chosen from the series consisting of hydrogen and (C1-C8)-alkyl which is optionally substituted by one or more identical or different substituents chosen from the series consisting (C1-C6)-alkyl-O— and (C1-C6)-alkyl-C(O)—O—;
• R72 is chosen from the series 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 chosen from the series consisting of halogen, HO—, HOOC—, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-C(O)—O—, NC—, and N((C1-C4)-alkyl)2, and wherein b is 0, 1 or 2;
• R73 is chosen from the series 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 chosen from the series consisting of nitrogen, oxygen and sulfur, which is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, (C1-C4)-alkyl, HO— and (C1-C4)-alkyl-O—;
• Ar, independently of each other group Ar, is chosen from the series consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle which comprises one, two or three identical or different ring heteroatoms chosen from the series 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 chosen from the series consisting of halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-O—, —O—CH2—O—, —O—CH2—CH2, —O—CF2—O—, CF3, (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 which comprises a ring nitrogen atom via which Het1 is bonded and optionally one or two identical or different further ring heteroatoms chosen from the series consisting of nitrogen, oxygen and sulfur, which is optionally substituted by one or more identical or different substituents chosen from the series 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 which comprises a ring nitrogen atom via which Het2 is bonded and optionally one further ring heteroatom chosen from the series consisting of nitrogen, oxygen and sulfur, which is optionally substituted by one or more identical or different substituents chosen from the series 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 which comprises one or two identical or different ring heteroatoms chosen from the series 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 chosen from the series 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 which comprises one to four ring heteroatoms chosen from the series consisting of nitrogen, oxygen and sulfur which is optionally substituted by one or more identical or different substituents chosen from the series consisting of halogen, (C1-C4)-alkyl, HO—, (C1-C4)-alkyl-O—, oxo and NC—;
• and
• m, independently of each other number m, is an integer chosen from the series consisting of 0, 1 and 2;
• wherein all cycloalkyl groups, independently of each other, are optionally substituted by one or more identical or different substituents chosen from the series consisting of fluorine and (C1-C4)-alkyl;
• and
• 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.