Malonamide derivatives with antithrombotic activity

A compound of formula I,

• T1 and T2 independent from one another are selected from the group consisting of a carbon atom, which is substituted by R12, and a nitrogen atom, D1 and D2 independently from one another are
• 1) a hydrogen atom,
• 2) —C(O)—(C1-C6)-alkyl,
• 3) —C(O)—(C0-C6)-alkylene-aryl,
• 4) —C(O)—O—(C1-C6)-alkyl or
• 5) —C(O)—O—(C0-C6)-alkylene-aryl,
• 6) —C(O)—O—(C1-C6)-alkylene-O—C(O)—(C1-C6)-alkyl
• D1 is a hydrogen atom, when D2 is
• 1) —OH,
• 2) —O—C(O)—(C1-C6)-alkyl or
• 3) —O—C(O)—(C0-C6)-alkylene-aryl,
• 4) —C(O)—O—(C1-C6)-alkylene-O—C(O)—(C1-C6)-alkyl
• R1 and R2 independently of one another are
• 1) a hydrogen atom,
• 2) —OH or
• 3) —(C0-C6)-alkylene-T-(C0-C6)-alkylene-W, wherein T is an oxygen atom, a sulfur atom, —SO2— or —N(R17)-,
• R17 is a hydrogen atom or —(C1-C6)-alkyl, wherein the alkyl is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R13,
• W is a hydrogen atom or aryl, wherein the aryl is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R13,
• R7, R8, R12, R14, R15 and R16 independently of one another are
• 1) a hydrogen atom,
• 2) —(C1-C6)-alkyl,
• 3) —OH,
• 4) —O—(C1-C6)-alkyl,
• 5) halogen or
• 6) —NH2,
• X is 1) halogen,
• 2) —(C1-C3)-perfluoroalkyl,
• 3) —O—(C1-C3)-perfluoroalkyl,
• 4) —S(O)n—(C1-C3)-perfluoroalkyl, wherein n is the integer 1 or 2,
• 5) —(C0-C4)-alkylene-aryl, wherein aryl is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R13, wherein R13 is halogen, —(C1-C3)-perfluoroalkyl, —(C1-C4)-alkyl, —(C0-C6)-alkylene-O—R6, —(C0-C6)-alkylene-C(O)—R6, —(C0-C6)-alkylene-C(O)—O—R6, —O—(C1-C3)-perfluoroalkyl, —S(O)r—(C1-C4)-alkyl, wherein r is the integer 1 or 2 or —(C0-C4)-alkylene-(C3-C7)-cycloalkyl, wherein R6 is a hydrogen atom or —(C1-C6)-alkyl,
• 6) —(C0-C4)-alkylene-Het, wherein Het is a heterocycle consisting of 1, 2 or 3 rings, in which one or more of the 4 to 15 ring carbon atoms are replaced by at least 1 heteroatom selected from nitrogen, oxygen or sulfur and wherein Het is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R5, wherein R5 is —(C1-C4)-alkyl, halogen, ═O, —(C0-C6)-alkylene-O—R6, —(C0-C6)-alkylene-C(O)—R6, —(C0-C6)-alkylene-C(O)—O—R6, —(C0-C4)-alkylene—(C3-C7)-cycloalkyl, or —(C0-C4)-alkylene-aryl, wherein aryl is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R13, or
• 7) a hydrogen atom,
• Y is 1) —N(R4)-, wherein R4 is a hydrogen atom or —(C1-C6)-alkyl,
• 2) —C(O)—,
• 3) —C(O)—N(R4)-,
• 4) —N(R4)-C(O)—,
• 5) —O—,
• 6) —S(O)n—, wherein n is the integer zero, 1 or 2, or
• 7) —S(O)m—N(R4)-, wherein m is the integer zero, 1 or 2,
• Z is 1) —(C0-C4)-alkylene-Het, wherein Het is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R5,
• 2) —(C1-C6)-alkylene-C(O)—O—R6,
• 3) —(C1-C6)-alkylene-O—R9, wherein R9 is a hydrogen atom or —(C1-C6)-alkyl,
• 4) —(C1-C6)-alkylene-N(R10)-R11, wherein R10 and R11 independently from one another are hydrogen atom, —(C0-C4)-alkylene-C(O)—R6, —(C0-C4)-alkylene-O—R6 or —(C1-C6)-alkyl,
• 5) —(C0-C4)-alkylene-C(O)—R6,
• 6) —(C2-C6)-alkynyl,
• 7) —(C1-C3)-perfluoroalkyl ,
• 8) —(C0-C4)-alkylene-(C3-C7)-cycloalkyl-R5,
• 9) —(C1-C4)-alkylene-aryl, wherein aryl is unsubstituted or mono-, di-, tri- or tetra-substituted independently of one another by R13,
• 10) phenyl, wherein phenyl is mono-, di-, tri- or tetra-substituted independently of one another by —(C0-C4)-alkylene-(C3-C7)-cycloalkyl, ═O, —(C0-C6)-alkylene-C(O)—O—R6, —(C1-C6)-alkylene-O—R6 or —S(O)s—(C1-C3)-alkyl, wherein s is the integer zero, 1 or 2,
• 11) —S(O)r—(C1-C3)-alkyl, wherein r is the integer zero, 1 or 2, provided Y is —N(R4)-, or
• 12) —(C1-C3)-perfluoroalkyl, or
• Y and Z together are a hydrogen atom and X is
• 1) —(C1-C3)-alkyl-CN,
• 2) —(C1-C3)-perfluoroalkyl,
• 3) —O—(C1-C3)—,
• 4) —S(O)m—(C1-C3)-perfluoroalkyl, wherein m is the integer 1 or 2,
• 5) —(C0-C4)-alkylene-Het, wherein Het is mono-, di-, tri- or tetra-substituted independently of one another by aryl, or
• 6) phenyl substituted by —N(R3)-S(O)p, wherein R3 is a hydrogen atom or —(C1-C6)-alkyl and p is the integer 1 or 2,
• in all its stereoisomeric forms and mixtures thereof in any ratio, and its physiologically tolerable salts.