Integrin antagonists

A compound of Formula (I):

• G-T (I)
• including stereoisomeric forms thereof, tautomeric forms thereof, pharmaceutically acceptable salt forms thereof or prodrug forms thereof, wherein:
• T is an integrin antagonist template;
• and
• G is a guanidine mimic selected from:
• 58
• D1 is selected from:
• H, NR2R4, OR3, SR3, F, Cl, Br, CF3, and C1-C4 alkyl;
• R2 at each occurrence is independently selected from:
• H, OR3, C1-C6 alkyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C0-C6 alkyl)aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl(C0-C4 alkyl), C3-C7 cycloalkyl(C0-C4 alkyl)carbonyl, C3-C7 cycloalkyl(C0-C4 alkoxy)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), aryl(C0-C6alkyl)carbonyl, heteroaryl(C0-C6 alkyl)carbonyl, C1-C6 alkylsulfonyl, aryl(C0-C6 alkyl)sulfonyl, heteroaryl(C0-C6 alkyl)sulfonyl, aryl(C1-C6 alkoxy)carbonyl, and heteroaryl(C1-C6 alkoxy)carbonyl, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• R3 at each occurrence is independently selected from:
• H, C1-C6 alkyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C0-C6 alkyl)aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl(C0-C4 alkyl), C3-C7 cycloalkyl (C0-C4 alkyl) carbonyl, cycloalkyl (C0-C4 alkoxy)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), aryl (C0-C6 alkyl) carbonyl, heteroaryl (C0-C6 alkyl)carbonyl, aryl(C1-C6 alkoxy)carbonyl, and heteroaryl(C1-C6 alkoxy)carbonyl, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• R4 is selected from:
• H, C1-C6 alkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C4 alkyl), C3-C7 cycloalkyl(C0-C4 alkyl)carbonyl, cycloalkyl(C0-C4 alkoxy)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), aryl(C0-C6 alkyl)carbonyl, heteroaryl(C0-C6 alkyl)carbonyl, aryl(C1-C6 alkoxy)carbonyl, and heteroaryl(C1-C6 alkoxy)carbonyl, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• alternatively, R2 and R4 when both substituents on the same nitrogen atom as in (—NR2R4) can be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from 1-aziridinyl, 1-azetidinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl;
• said heterocycle being optionally substituted with 0-3 groups selected from oxo, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl), C1-C6 alkylcarbonyl, C3-C7 cycloalkyl(C0-C5 alkyl)carbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, aryl(C0-C5 alkyl), heteroaryl(C0-C5 alkyl), aryl(C1-C5 alkoxy)carbonyl, heteroaryl(C1-C5 alkoxy)carbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, and heteroarylsulfonyl;
• R5 is selected from:
• H, NR2R4, OR3, NO2, NO, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl), aryl(C0-C6 alkyl), or heteroaryl(C0-C6 alkyl), wherein said aryl and heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• alternatively, —NHR2 and R5, when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form a 5-7 membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms, said heterocyclic ring being aromatic or nonaromatic, said heterocyclic ring being substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, NO2, and aryl, wherein said aryl group is substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• R6 is selected from:
• H, NR2R4, OR3, C1-C6 alkyl, aryl(C0-C5 alkyl), heteroaryl(C0-C5 alkyl), CF3, F, Cl, and Br, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• alternatively, R5 and R6, when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form a 5-7 membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms or a 5-7 membered carbocyclic ring, said carbocyclic or heterocyclic ring being aromatic or nonaromatic, said carbocyclic or heterocyclic ring being substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, NO2 and aryl, wherein said aryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• R7 is selected from:
• H, C1-C4 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, aryl(C0-C4 alkyl), and heteroaryl(C0-C4 alkyl), wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• alternatively, —NHR2 and R7, when substituents on adjacent atoms, are taken together with the atoms to which they are attached to form a 5-7 membered heterocyclic ring containing 2 or 3 nitrogen atoms, said heterocyclic ring being aromatic or nonaromatic, said heterocyclic ring being substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, NO2, and aryl, wherein said aryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2;
• U1 is selected from:
• —(CH2)n-,
• —Q1-(CH2)m-,
• —(CH2)m-Q2—,
• —(CH2)t-Q2-CH2—,
• —CH2-Q2-(CH2)t-,
• —(CH2)t-N(R3)—C(═O)—,
• —(CH2)t-N(R3)—S(═O)2—,
• —(CH2)t-C(═O)—N(R3)—,
• —(CH2)t-S(═O)2—N(R3)—,
• —C(═O)—N(R4)—(CH2)t-,
• —N(R4)—,
• —N(R4)—(CH2)q-Q2-,
• —N(R4)—C(═O)—(CH2)r-, and
• —N(R4)—(CH2)t-C(═O)—;
• U2 is selected from:
• —(CH2)h-,
• —Q1-(CH2)r-,
• —(CH2)r-Q2-,
• —(CH2)i-N(R3)—C(═O)—,
• —(CH2)i-N(R3)—S(═O)2—,
• —(CH2)i-C(═O)—N(R3)—,
• —(CH2)i-S(═O)2—N(R3)—,
• —(CH2)i-Q2—CH2—,
• —CH2-Q2-(CH2)i-,
• —C(═O)—N(R4)—(CH2)i-,
• —N(R4)—,
• —N(R4)—(CH2)2-Q2-,
• —N(R4)—C(═O)—(CH2)i-, and
• —N(R4)—(CH2)t-C(═O)—;
• U3 is selected from:
• —(CH2)h-,
• —(CH2)q-Q2-,
• —(CH2)q-N(R3)—C(═O)—,
• —(CH2)t-C(═O)—(R3)—,
• —(CH2)q-S(O)2—N(R3),
• —(CH2)q-N(R3)-S(O)2—,
• —(CH2)q-N(R3)—CH2—,
• —(CH2)q-O-CH2—,
• —(CH2)h-C(═O)—,
• —C(═O)—(CH2)r-, and
• —C(═O)—N(R4)-(CH2)p;
• U4 is selected from:
• —(CH2)h-,
• —(CH2)2-Q2,
• —(CH2) 2—O—CH2—,
• —(CH2)r-C(═O)—,
• —C(═O)—(CH2)r-, and
• —C(═O)—N(R4)—(CH2)r;
• Q1 is —O—, —S—, or N(R4);
• Q2 is —O—, —S—, —S(═O)—, —S(═O)2—, or N(R3);
• h is 0-4;
• i is 0-2;
• m is 1-4;
• n is 0-5;
• q is 2-3;
• r is 0-3;
• t is 1-3;
• and
• p is 0-2.
• provided that when R6 is hydrogen then D1 is not hydrogen.