Integrin antagonists

A method of eliciting a vitronectin receptor antagonizing effect in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of the formula

• wherein X is selected from a 9- to 10-membered polycyclic ring system, wherein one or more of the rings is aromatic, and wherein the polycyclic ring system contains 0, 1, 2, 3 or 4 heteroatoms selected from N, O or S, and wherein the polycyclic ring system is either unsubstituted or substituted with R1 and R2;
• Y is selected from —(CH2)r— or —(CH2)m—NR3—(CH2)t—;
• Z is
• R1, R2 and R4 are each independently selected from hydrogen, halogen, C1-10 alkyl, C3-8 cycloalkyl, C3-8 cycloheteroalkyl, C3-8 cycloalkyl C1-6 alkyl, C3-8 cycloheteroalkyl C1-6 alkyl, aryl, aryl C1-8 alkyl, amino, amino C1-8 alkyl, C1-3 acylamino, C1-3 acylamino C1-8 alkyl, (C1-6 alkyl)qamino, (C1-6 alkyl)qamino C1-8 alkyl, C1-4 alkoxy, C1-4 alkoxy C1-6 alkyl, hydroxycarbonyl, hydroxycarbonyl C1-6 alkyl, C1-3 alkoxycarbonyl, C1-3 alkoxycarbonyl C1-6 alkyl, hydroxycarbonyl-C1-6 alkyloxy, hydroxy, hydroxy C1-6 alkyl, C1-6 alkyloxy-C1-6 alkyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, trifluoroethoxy, C1-8 alkyl-S(O)q, (C1-8 alkyl)qaminocarbonyl, C1-8 alkyloxycarbonylamino, (C1-8 alkyl)qaminocarbonyloxy, oxo, (aryl C1-8 alkyl)qamino, (aryl)qamino, aryl C1-8 alkylsulfonylamino, or C1-8 alkylsulfonylamino;
• R3 is selected from
• hydrogen,
• aryl-(CH2)p—
• C1-5 alkoxycarbonyl,
• C3-8 cycloalkyl,
• (aryl)qaminocarbonyl,
• (aryl C1-5 alkyl)qaminocarbonyl,
• C1-8 alkyl,
• aryl C1-6 alkyl,
• C1-8 alkylsulfonyl,
• arylsulfonyl,
• aryl C1-6 alkylsulfonyl,
• C1-8 alkoxycarbonyl,
• aryloxycarbonyl,
• aryl C1-8 alkoxycarbonyl,
• C1-8 alkylcarbonyl,
• arylcarbonyl,
• aryl C1-6 alkylcarbonyl, or
• (C1-8 alkyl)qaminocarbonyl,
• wherein any of the alkyl groups may be unsubstituted or substituted with R1 and R2;
• R8 is selected from
• hydrogen,
• aryl,
• aryl-(CH2)p—,
• HC≡C—(CH2)s—,
• C1-6 alkyl-C≡C—(CH2)s—,
• C3-7 cycloalkyl-C≡C—(CH2)s—,
• aryl-C≡C—(CH2)s—,
• C1-6 alkylaryl-C≡C—(CH2)s—,
• CH2═CH—(CH2)s—,
• C1-6 alkyl-CH═CH—(CH2)s—,
• C3-7 cycloalkyl-CH═CH—(CH2)s—,
• aryl-CH═CH—(CH2)s—,
• C1-6 alkylaryl-CH═CH—(CH2)s—,
• C1-6 alkyl-SO2-(CH2)s—, or
• C1-6 alkylaryl-SO2-(CH2)s—;
• and
• R12 is selected from
• hydrogen,
• C1-8 alkyl,
• aryl,
• aryl C1-8 alkyl,
• C1-8 alkylcarbonyloxy C1-4 alkyl,
• aryl C1-8 alkylcarbonyloxy C1-4 alkyl,
• C1-8 alkylaminocarbonylmethylene, or
• C1-8 dialkylaminocarbonylmethylene;
• m, s and t are each independently an integer from 0 to 3;
• p is an integer from 0 to 4;
• q is an integer from 0 to 2;
• r is an integer from 0 to 6;
• and the pharmaceutically acceptable salts thereof.