Integrin receptor ligands

A compound of the formula I

• B—G—L I
• where B, G and L have the following meanings:
• L is a structural element of the formula IL
• —U—T IL
• where
• T is a COOH group or COR1
• where R1 is a branched or unbranched C1–C8 alkoxy group, and
• —U— is —(CRL1RL2)a(CRL3RL4)c(CRL5RL6)e(CRL7RL8)g—
• where
• a, c, e, and g are, independently of one another, 0, 1, 2 or 3, and
• RL1, RL2, RL3, RL4, RL5, RL6, RL7, and RL8 are, independently of one another, hydrogen, halogen, a hydroxyl group, a branched or unbranched, optionally substituted C1–C6-alkyl, C2–C5-alkenyl, C2–C6-alkynyl or C1–C6-alkylene-C3–C7-cycloalkyl radical, a radical —(CH2)w-(YL)y-RL9, an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical or, in each case independently of one another, two radicals are RL1 and RL2 or RL3 and RL4 or RL5 and RL6 or RL7 and RL8 together are a 3- to 7-membered, optionally substituted, saturated or unsaturated carbocyclic or heterocyclic system which may contain up to three heteroatoms from the group of O, N or S,
• w is 0, 1, 2, 3 or 4,
• y is 0 or 1
• YL is —CO—, —CO—N(Ry1)—, —N(Ry1)—CO—, —N(Ry1)—CO—N(Ry1*)—, —N(Ry1)—CO—O—, —O—, —S—, —SO2—, —SO2—N(Ry1)—, —SO2—O—, —CO—O—, —O—CO—, —O—CO—N(Ry1)—, —N(Ry1)— or —N(Ry1)—SO2—,
• Ry1 and Ry1* are, independently of one another, hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C1–C6-alkoxyalkyl, C2–C6-alkenyl, C3–C12-alkynyl, CO—C1–C6-alkyl, CO—O—C1–C6-alkyl or SO2—C1–C6-alkyl radical or an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, CO—O-alkylene-aryl, CO-alkylene-aryl, CO-aryl, SO2-aryl, hetaryl, CO-hetaryl or SO2-alkylene-aryl radical,
• RL9 is hydrogen, or a hydroxyl group, CN, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl radical, an optionally substituted C3–C7-cycloalkyl, aryl, heteroaryl or arylalkyl radical, an optionally C1–C4-alkyl- or aryl-substituted C2–C6-alkynyl or C2–C6-alkenyl radical, an optionally substituted C6–C12-bicycloalkyl, C1–C6-alkylene-C6–C12-bicyclo-alkyl, C7–C20-tricycloalkyl or C1–C6-alkylene-C7–C20-tricycloalkyl radical, or a 3- to 8-membered, saturated or unsaturated heterocyclic system which is substituted by up to three identical or different radicals and which may contain up to three different or identical heteroatoms O, N or S, it being possible for two radicals together to be a fused, saturated, unsaturated or aromatic carbocyclic or heteocyclic system which may contain up to three different or identical heteroatoms O, N or S, and it being possible for the cyclic system to be optionally substituted, or for another, optionally substituted, saturated, unsaturated or aromatic cyclic system to be fused to this cyclic system, or the radical RL9 forms together with Ry1 or Ry1* a saturated or unsaturated C3–C7-heterocycle which may optionally contain up to two further heteroatoms selected from the group of O, S or N,
• G is a structural element of the formula IG
• where the structural element L is attached to the nitrogen atom G, and
• RG2 is hydrogen, CN, NO2, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C2–C6-alkenyl or C2–C6-alkynyl radical, a branched or unbranched, optionally substituted C1–C4-alkylene-ORG4, C1–C4-alkylene-CO—ORG4, C1–C4-alklene-NRG5RG6 or C1–C4-alkylene-SRG4 radical, an optionally substituted C3–C7-cycloalkyl, C1–C4-alkylene-C3–C7-cycloalkyl, C1–C4-alkylene-C3–C7-heterocycloalkyl or C1–C4-alkylene-C3–C7-heterocycloalkenyl radical, optionally substituted aryl, arylalkyl, hetaryl or hetarylalkyl radical, or an —S—RG4, —O—RG4, or —SO—RG4 radical,
• RG4 is hydrogen, a branched or unbranched, optionally substituted C1–C8-alkyl, C2–C6-alkenyl, C2–C6-alkynyl, bisalkylaminoalkylene or acylaminoalkylene radical or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C3–C7-cycloalkyl, C1–C4-alkylene-C3–C7-cycloalkyl, arylalkyl, C1–C4-alkylene-C3–C7-cycloalkyl, arylalkyl, C1–C4-alkylene-heterocycloalkyl, C1–C4-alkylene-heterocycloalkenyl or hetarylalkyl radical,
• RG5 and RG6 are, independently of one another, hydrogen, a branched or unbranched optionally substituted C1–C8-alkyl, C2–C5-alkenyl, C2–C6-alkynyl, C1–C5-alkylene-C1–C4-alkoxy, mono- and bisalkylaminoalkylene or acylaminoalkylene radical or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C3–C7-cycloalkyl, C1–C4-alkylene-C3–C7-cycloalkyl, arylalkyl, C1–C4-alkylene-heterocycloalkyl, C1–C4-alkylene-heterocycloalkenyl or hetarylalkyl radical, or an —SO2—RG4, —CO—ORG4, —CO—NRG4RG4* or —CO—RG4 radical, and
• RG4* is an RG4 radical independent of RG4,
• B is a structural element of the formula IB
• A—E— IB
• where A and E have the following meanings:
• A is a structural element selected from the group of structural elements of the formula IA1 to IA19,
• where
• m, p, q are, independently, of one another, 1, 2 or 3,
• RA1 and RA2 are, independently of one another, hydrogen, CN, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl or CO—C1–C6-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, hetarylalkyl or C3–C7-cycloalkyl radical or a CO—O—RA14, O—RA14, S—RA14, NRA15RA16, CO—NRA15RA16 or SO2NRA15RA16 radical or the two radicals RA1 and RA2 together are a fused, optionally substituted, 5- or 6-membered, unsaturated or aromatic carbocyclic or heterocyclic system which may contain up to three heteroatoms selected from the group of O, N or S,
• RA13 and RA13* are, independently of one another, hydrogen, CN, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C3–C7-cycloalkyl radical or a CO—O—RA14, O—RA14, S—RA14, NRA15RA16, SO2—NRA15RA16 or CO—NRA15RA16 radical,
• where
• RA14 is hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, alkylene-C1–C4-alkoxy, C2–C6-alkenyl, C2–C6-alkynyl or C1–C6-alkylene-C3–C7-cycloalkyl radical or an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical,
• RA15 and RA16 are, independently of one another, hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, CO—C1–C6-alkyl, SO2—C1–C6-alkyl, COO—C1–C6-alkyl, CO—NH—C1–C6-alkyl, arylalkyl, COO-alkylene-aryl, SO2-alkylene-aryl, CO—NH-alkylene-aryl, CO—NH-alkylene-hetaryl or hetarylalkyl radical or an optionally substituted C3–C7-cycloalkyl, aryl, CO-aryl, CO—NH-aryl, SO2-aryl, hetaryl, CO—NH-hetaryl, or CO-hetaryl radical,
• RA3, RA4 are, indpendently of one another, hydrogen, —(CH2)n—(XA)j—RA12, or the two radicals together are a 3- to 8-membered, saturated, unsaturated or aroamtic N heterocyclic system which may additionally contain two other, identical or different heteroatoms O, N or S, it being possible for the cyclic system optionally to be substituted, or for another, optionally substituted, saturated, unsaturated or aromatic cyclic system to be fused to this cyclic system,
• where
• n is 0, 1, 2 or 3,
• j is 0 or 1,
• XA is —CO—, —CO—N(Rx1)—, —N(Rx1)—CO—, —N(Rx1)—CO—N(Rx1*)—, —N(Rx1)—CO—, —O—, —S—, —SO2—, —SO2—N(Rx1)—, —SO2—O—, —CO—O—, —O—CO—, —O—CO—N(Rx1)—, —N(Rx1)— or —N(Rx1)—SO2—,
• RA12 is hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl radical, an optionally substituted C1–C4-alkyl- or aryl-substituted C2–C6-alkynyl or C2–C6-alkenyl radical or a 3- to 6-membered, saturated or unsaturated heterocyclic system which is substituted by up to three identical or different radicals and which may contain up to three different or identical heteroatoms O, N or S, or C3–C7-cycloalkyl, aryl or heteroaryl radical, it being possible for two radicals together to be a fused, saturated, unsaturated or aromatic carbocyclic or heterocyclic system which may contain up to three different or identical heteroatoms O, N, or S, and it being possible for the cyclic system optionally to be substituted or for another, optionally substituted, saturated, unsaturated or aromatic cyclic system to be fused to this cyclic system, or the RA12 radical forms together with Rx1 or Rx1* a saturated or unsaturated C3–C7-heterocycle which may optionally contain up to two other heteroatoms selected from the group of O, S or N,
• Rx1, Rx1* are, independently of one another, hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C1–C6-alkoxyalkyl, C2–C6-alkenyl, C2–C12-alkynyl, CO—C1–C6-alkyl, CO—O—C1–C6-alkyl or SO2—C1–C6-alkyl radical or an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, CO—O-alkylene-aryl, CO-alkylene-aryl, CO-aryl, SO2-aryl, hetaryl, CO-hetaryl or SO2-alkylene-aryl radical,
• RA5 is a branched or unbranched, optionally substituted C1–C6-alkyl, arylalkyl, C3–C7-cycloalkyl or C1–C4-alkylene-C3–C7-cycloalkyl radical or an optionally substituted aryl, hetaryl, heterocycloalkyl or heterocycloalkenyl radical,
• RA6 and RA6* are hydrogen, a branched or unbranched, optionally substituted C1–C4-alkyl, —CO—O—C1–C4-alkyl, arylalkyl, —CO—O-alkylene-aryl, —CO—O-allyl, —CO—C1–C4-alkyl, —CO-alkylene-aryl, C3–C7-cycloalkyl or —CO-allyl radical or the two radicals RA6 and RA6* in the structural element IA7 together are an optionally substituted, saturated, unsaturated or aromatic heterocyclic system which, in addition to the ring nitrogen, may contain up to two other different or identical heteroatoms O, N or S,
• RA7 is hydrogen, —OH, —CN, —CONH2, a branched or unbranched, optionally substituted C1–C4-alkyl, C1–C4-akoxy, C3–C7-cycloalkyl or —O—CO—C1–C4-alkyl radical or an optionally substituted arylalkyl, —O-alkylene-aryl, —O—CO-aryl, —O—CO-alkylene-aryl or —O—CO-allyl radical, or the two radicals RA6 and RA7 together are an optionally substituted, unsaturated or aromatic heterocyclic system which, in addition to the ring nitrogen, may contain up to two other different or identical heteroatoms O, N or S,
• RA8 is hydrogen, a branched or unbranched, optionally substituted C1–C4-alkyl, CO—C1–C4-alkyl, SO2—C1–C4-alkyl or CO—O—C1–C4-alkyl radical or an optionally substituted aryl, CO-aryl, SO2-aryl, CO—O-aryl, CO-alkylene-aryl, SO2-alkylene-aryl, CO—O-alkylene-aryl or alkylene-aryl radical,
• RA9 and RA10 are, independently of one another, hydrogen, —CN, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C3–C7-cycloalkyl radical or a CO—O—RA14, O—RA14, S—RA14, NRA15RA16, SO2—NRA15RA16 or CO—NRA15RA16 radical, or the two radicals RA9 and RA10 in the structural element IA14 together are a 5- to 7-membered saturated, unsaturated or aromatic carbocyclic or heterocyclic system which may contain up to three different or identical heteroatoms O, N, S and is optionally substituted by up to three identical or different radicals,
• RA11 is hydrogen, —CN, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl radical or an optionally substituted aryl, arylalkyl, hetaryl, C3–C7-cycloalkyl radical or a CO—O—RA14, O—RA14, S—RA14, NRA15RA16, SO2—NRA15RA16 or CO—NRA15RA16 radical,
• RA17 is hydrogen or the two radicals RA9 and RA17 in the structural element IA16 together are a 5- to 7-membered saturated, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, may contain up to three different or identical heteroatoms O, N, S and is optionally substituted by up to three identical or different radicals,
• RA18 and RA19 are, independently of one another, hydrogen, a branched or unbranched, optionally substituted C1–C8-alkyl, C2–C6-alkenyl, C2–C6-alkynyl-, C1–C6-alkylene-C1–C4-alkoxy, mono- and bisalkylaminoalkylene or acylaminoalkylene radical or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C3–C7-cycloalkyl, C1–C4-alkylene-C3–C7-cycloalkyl, arylalkyl, C1–C4-alkylene-heterocycloalkyl, C1–C4-alkylene-heterocycloalkenyl or hetarylalkyl radical, or an —SO2—RG4, —CO—ORG4, —CO—NRG4RG4* or —CO—RG4 radical,
• Z1, Z2, Z3 and Z4 are, independently of one another, nitrogen, C—H, C-halogen or a branched or unbranched, optionally substituted C—C1–C4-alkyl or C—C1—C4-alkoxy radical,
• Z5 is NRA8, oxygen or sulfur, and
• E is a structural element of the formula IE
• —(NRE1)i—E1—(UE)h— IE
• where
• UE is oxygen, sulfur or NRE2
• h is 0 or 1,
• i is 0 or 1,
• RE1, RE2 are, independently of one another, hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C1–C6-alkoxyalkyl, C2–C6-alkenyl, C2–C12-alkynyl, CO—C1–C6-alkyl, CO—O—C1–C6-alkyl, CO—NH—C1–C6-alkoxyalkyl, CO—NH—C1–C6-alkyl or SO2—C1–C6-alkyl radical or an optionally substituted hetaryl, arylalkyl, C3–C7-cycloalkyl, CO—O-alkylene-aryl, CO—NH-alkylene-aryl, CO-alkylene-aryl, CO-aryl, CO—NH-aryl, SO2-aryl, CO-hetaryl, SO2-alkylene-aryl, SO2-hetaryl or SO2-alkylene-hetaryl radical,
• E1 is a structural element of the formula IE1
• —(CRE3RE4)K1-(LE)K2-(CRE5RE6)K3-(QE)K4-(CRE7RE8)K5-(TE)K6-(CRE9RE10)K7— IE1
• where
• k2, k4, k6 are 0 or 1
• k1, k3, k5, k7 are 0, 1 or 2,
• RE3, RE4, RE5, RE6, RE7, RE8, RE9, RE10 are, independently of one another, hydrogen, halogen, a hydroxyl group, a branched or unbranched, optionally substituted C1–C8-alkyl, C2–C6-alkenyl, C2–C6-alkynyl or alkylene-cycloalkyl radical, a —(CH2)x-(YE)RE11 radical, an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical or independently of one another, in each case two radicals RE3 and RE4 or RE5 and RE6 or RE7 and RE8 or RE9, and RE10 together are a 3- to 7-membered, optionally substituted, saturated or unsaturated carbo- or heterocyclic system which may contain up to three heteroatoms from the group of O, N or S,
• x is 0, 1, 3, 3 or 4, 5
• z is 0 or 1
• y is —CO—, —CO—H(RY2)—, N(RY2)—CO—, —H(RY2)—CO—N(RY2*)—, —NCRY2—CO—O—, —O—, —S—, —SO—, —SO2—N(RY2)—, —SO2—O—, —CO—O—, —O—CO—, —O—CO—N(RY2)—, —N(RY2)— or —N(RY2)—SO2—,
• RY2, RY2* are, independently of one another, hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C2–C6-alkenyl, C2–C6-alkynyl, CO—C1–C6-alkyl, CO—O—C1–C6-alkyl or SO2—C1–C6-alkyl radical or an optionally substituted hetaryl, hetarylalkyl, arylalkyl, C3–C7-cycloalkyl, CO—O-alkylene-aryl, CO-alkylene-aryl, CO-aryl, SO2-aryl, CO-hetaryl or SO2-alkylene-aryl radical
• RE11 is hydrogen, a hydroxyl group, CN, halogen, a branched or unbranched, optionally substituted C1–C6-alkyl radical, an optionally substituted C3–C7-cycloalkyl, aryl, hetaryl or arylalkyl radical, an optionally C1–C4-alkyl-or aryl-substituted C2–C6-alkynyl or C2–C6-alkenyl radical, an optionally substituted C6–C12-bicycloalkyl, C1–C6-alkylene-C6–C12-bicycloalkyl, C7–C20-tricycloalkyl or C1–C6-alkylene-C7–C20-tricycloalkyl radical, or a 3- to 8-membered, saturated or unsaturated heterocyclic system which is substituted by up to three identical or different radicals and which may contain up to three different or identical or different radicals and which may contain up to three different or identical heteroatoms O, N, S, it being possible for two radicals together to be a fused, or N saturated, unsaturated or aromatic carbocyclic or heterocyclic system which may contain up to three different or identical heteroatoms O, N, S, and it being possible for the cyclic system optionally to be substituted or for another, optionally substituted, saturated, unsaturated or aromatic cyclic system to be fused to this cyclic system, or the RE11 radical forms together with RY2 and RY2* a saturated or unsaturated C3–C7-heterocyclic system which may optionally contain up to two other heteroatoms selected from the group of O, S or N
• LE, TE Are, independently of one another, CO, CO—NRE12, HRE12—CO, sulfur, SO, SO2, SO2—NRE12, NRE12—SO2, CS, CS—NRE12, NRE12CS, CS—O, O—CS, CO—O, O—CO, oxygen, ethynylene, CRE13—O—CRE14, C(═CRE13RE14)—CRE13CRE14, —CRE13(ORE15)—CHRE14—, —CHRE13—RE14—(ORE15)—,
• RE12 is hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C2–C6-alkenyl, C2–C6-alkynyl, an optionally substituted C3–C7-cycloalkyl, hetaryl, arylalkyl or hetarylalkyl radical or a CO—RE16, COORE16 or SO2—RE16 radical,
• RE13, RE14 are, independently of one another, hydrogen, a hydroxyl group, a branched or unbranched, optionally substituted C1–C6-alkyl, C1–C4-alkoxy, C2–C6-alkenyl, C2–C6-alkynyl or alkylene-cycloalkyl radical or an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical,
• RE15 is hydrogen, a branched or unbranched, optionally substituted C1–C6-alkyl, C2–C6-alkenyl, C2–C6-alkynyl or alkylene-cycloalkyl radical or an optionally substituted C3–C7-cycloalkyl, aryl, arylalkyl, hetaryl or hetarylalkyl radical,
• RE16 is hydrogen, a hydroxyl group, a branched or unbranched, optionally substituted C1–C6-alkyl, C2–C6-alkenyl, C2–C6-alkynyl or C1–C5-alkylene-C1–C4-alkoxy radical, or an optionally substituted aryl, heterocycloalkyl, heterocycloalkenyl, hetaryl, C3–C7-cycloalkyl-, C1–C4-alkylene-C3–C7-cycloalkyl, arylalkyl, C1–C4-alkylene-C3–C7-heterocycloalkenyl, C1–C4-alkylene-C3–C7-heterocycloalkenyl or hetarylalkyl radical and
• QE is an optionally substituted 4- to 11-membered mono- or polycyclic aliphatic or aromatic hydrocarbon which may contain up to 6 double bonds and up to 6 identical or different heteroatoms selected from the group N, O or S, it being possible for the ring carbons or ring nitrogens optionally to be substituted, and
• wherein the optional substituents are selected from the group consisting of NO2, NH2, OH, CN, COOH, —OCH2—COOH, halogen, a branched or unbranched C1–C4 alkyl radical, a branched or unbranched —CO—O—C1–C4-alkyl, C3–C7-cyccloalkyl, C1–C4-alkoxy, C1–C4-thioalkyl, —NH—CO—O—C1–C4-alkyl, —O—CH2—COOO—C1–C4-alkyl, —NH—CO—C1–C4-alkyl, —CO—NH—C1–C4-alkyl, —NH—SO2—C1–C4-alkyl, —SO2—NH—C1–C4-alkyl, —N(C1–C4-alkyl)2, —NH—C1–C4-alkyl, or —SO2—C1–C4-alkyl, —NH—CO—O-aryl, —NH—CO—O-alkylene-aryl, —NH—SO2-aryl, —SO2—NH-aryl, —CO—NH-benzyl, —NH—SO2-bezyl or —SO2—NH-benzyl, —SO2—NR4R5, or —CO—NR4R5, it being possible for R4 and R5 radicals independently of one another to have the meaning as RL14, or the two of R4 and R5 radicals together being a 3- to 6-membered, saturated, unsaturated or aromatic heterocycle which, in addition to the ring nitrogen, may contain up to three other different or identical heteroatoms, O, N, S and optionally two radicals substituted or this heterocycle together are a fused, saturated, unsaturated or aromatic carbocyclic or heterocyclic system which may contain up to three different or identical heteroatoms, O, N, S, and it being possible for another cyclic system to be fused to this cyclic system;
• or a physiologically tolerated salt, enantiomerically pure, diastereomerically pure or tautomeric form thereof.