Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa

A compound of the formula (I)

• or a stereoisomer thereof or a physiologically tolerated salt of any of the foregoing, wherein
• X is —C(O)— or —SO2—;
• U is an oxygen atom;
• A is an oxygen atom, or —(C0-C4)-alkylene-;
• V is
• 1) —(C5-C9)-alkylene-, wherein said alkylene is unsubstituted or substituted independently of one another once, twice or three times by —OH, NH2 or halogen, or
• 2) —(C3-C9)-alkenylene-;
• D is —(C1-C2)-alkylene-;
• Y is
• —(C6-C14)-aryl, wherein said aryl is unsubstituted or substituted independently of one another once, twice or three times by R15;
• R1 is
• 1) a hydrogen atom,
• 2) —(C1-C6)-alkyl,
• 3) —(C1-C6)-alkyl-OH,
• 4) —(C0-C4)-alkyl-(C3-C6)-cycloalkyl,
• 5) —(C1-C10)-alkyl-O—C(O)—O—R2,
• 6) —(CH2)r—(C6-C14)-aryl, wherein said aryl is unsubstituted or substituted independently of one another once, twice or three times by R15, and r is the integer zero, 1, 2 or 3, or
• 7) —(CH2)s-Het, wherein Het is a 4- to 15-membered heterocyclic ring system having 4 to 15 ring atoms which are present in one, two or three ring systems which are connected together, and which comprise, depending on the ring size, one, two, three or four identical or different heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and in which Het is unsubstituted or substituted independently of one another once, twice or three times by R15, and s is the integer zero, 1, 2 or 3;
• R2 is
• 1) —(C1-C6)-alkyl,
• 2) —(CH2)r—(C6-C14)-aryl, wherein said aryl is unsubstituted or substituted independently of one another once, twice or three times by R15, and r is the integer zero, 1, 2 or 3, or
• 3) —(C0-C4)-alkyl-(C3-C6)-cycloalkyl;
• R3 is
• 1) —(C2-C6)-alkylene-NH2, wherein said alkylene is unsubstituted or substituted once, twice, three or four times by halogen,
• 2) —(C1-C4)-alkylene-O—(C1-C4)-alkylene-NH2,
• 3) —(C1-C4)-alkylene-SO2—(C1-C4)-alkylene-NH2,
• 4) —(C0-C4)-alkylene-Het, wherein said Het is as defined above and is substituted by —NH2 and once, twice or three times by R15,
• 5) —(C0-C4)-alkylene-(C3-C8)-cycloalkyl-NH2, or
• 6) —(C0-C6)-alkylene-cyclic amine, wherein the cyclic amine is selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, azepinyl, morpholinyl, and thiomorpholinyl;
• R6 is
• 1) a hydrogen atom,
• 2) —(C1-C6)-alkyl, wherein said alkyl is unsubstituted or substituted independently of one another once, twice or three times by R16,
• 3) —O—(C1-C6)-alkyl, wherein said alkyl is unsubstituted or substituted independently of one another once, twice or three times by R16,
• 4) —(C0-C4)-alkylene-Het, wherein said Het is as defined above, wherein said alkylene and Het are unsubstituted or substituted independently of one another once, twice or three times by R16,
• 5) —(C0-C4)-alkylene-aryl, wherein said alkylene and aryl are unsubstituted or substituted independently of one another once, twice or three times by R16, or
• 6) —(C0-C4)-alkylene-(C3-C8)-cycloalkyl, wherein said alkylene and cycloalkyl are unsubstituted or substituted independently of one another once, twice or three times by R16;
• R7 is a hydrogen atom, halogen or —(C1-C6)-alkyl;
• R8 is a hydrogen atom, halogen or —(C1-C6)-alkyl;
• R9 is a hydrogen atom, halogen or —(C1-C6)-alkyl;
• R15 is a hydrogen atom, —(C1-C4)-alkyl, —O—CF3, —NH2, —OH, —CF3 or halogen;
• and
• R16 is —O—CF3, —NH2, —OH, —CF3 or halogen.