Method for eliciting an αvβ5 or dual αvβ3/αvβ5 antagonizing effect

A method for inhibiting a condition selected from the group consisting of restenosis, angiogenesis, diabetic retinopathy, inflammation, and tumor growth in a mammal which comprises administering to the mammal a therapeutically effective amount of a compound of the formula:

• and pharmaceutically acceptable salts thereof, wherein
• X is
• a 5- or 6-membered monocyclic aromatic ring system containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O or S and either unsubstituted or substituted with R1 or R2, or
• a 9- to 10-membered polycyclic ring system, wherein one or more of the rings is aromatic, containing 0, 1, 2, 3 or 4 heteroatoms selected from N, O or S and either unsubstituted or substituted with R1 or R2,
• wherein R1 and R2 are independently selected from the group consisting of
• hydrogen, F, Cl, Br, I,
• C1-10 alkyl,
• C3-8 cycloalkyl,
• aryl,
• aryl C1-8 alkyl,
• amino,
• amino C1-8 alkyl,
• C1-3 acylamino,
• C1-3 acylamino C1-8 alkyl,
• C1-6 alkylamino,
• C1-6 alkylamino C1-8 alkyl,
• C1-6 dialkylamino,
• C1-6 dialkylamino C1-8 alkyl,
• C1-4 alkoxy,
• C1-4 alkoxy C1-6 alkyl,
• carboxy,
• carboxy C1-6 alkyl,
• C1-3 alkoxycarbonyl,
• C1-3 alkoxycarbonyl C1-6 alkyl,
• carboxy C1-6 alkyloxy,
• hydroxy, and
• hydroxy C1-6 alkyl;
• Y is
• where Z is O, NR8, or S;
• and R8 is defined as R1 above;
• R3 and R4 are independently
• hydrogen,
• a five or six membered mono or nine or ten membered polycyclic unsaturated, partially or fully saturated ring system containing 0, 1, 2, 3, or 4 heteroatoms selected from nitrogen, oxygen or sulfur, either unsubstituted or substituted, with one or more groups selected from hydroxyl, halogen, cyano, trifluoromethyl, C1-3 alkoxy, C1-5 alkylcarbonyloxy, C1-5 alkoxycarbonyl, C1-5 alkyl, aminoC1-5 alkyl, hydroxycarbonyl, hydroxycarbonylC1-5 alkyl, or hydroxycarbonylC1-5 alkoxy,
• —(CH2)n-aryl, wherein n=1-4 and aryl is defined as a five or six membered unsaturated or partially saturated monocyclic ring system, or nine or ten membered polycyclic ring system wherein at least one of the rings is unsaturated or partially saturated and each of the other rings is optionally unsaturated, partially saturated or fully saturated, said aryl group containing 0, 1, 2, 3, or 4 heteroatoms selected from nitrogen, oxygen and sulfur, either unsubstituted or substituted, with one or more groups selected from hydroxyl, halogen, cyano, trifluoromethyl, C1-3 alkoxy, C1-5 alkylcarbonyloxy, C1-5 alkoxycarbonyl, C1-5 alkyl, aminoC1-5 alkyl, hydroxycarbonyl, hydroxycarbonylC1-5 alkyl, or hydroxycarbonylC1-5 alkoxy,
• halogen,
• hydroxyl,
• C1-5alkylcarbonylamino,
• arylC1-5 alkoxy,
• C1-5 alkoxycarbonyl,
• aminocarbonyl,
• C1-5 alkylaminocarbonyl,
• C1-5 alkylcarbonyloxy,
• C3-8 cycloalkyl,
• oxo,
• amino,
• C1-3 alkylamino,
• aminoC1-3 alkyl,
• arylaminocarbonyl,
• arylC1-5alkylaminocarbonyl,
• aminocarbonyl,
• aminocarbonyl-C1-4 alkyl,
• hydroxycarbonyl,
• hydroxycarbonyl C1-5 alkyl,
• C1-6alkyl, either unsubstituted or substituted, with one or more groups selected from halogen, hydroxyl, C1-5alkylcarbonylamino, arylC1-5 alkoxy, C1-5 alkoxycarbonyl, aminocarbonyl, C1-5 alkylaminocarbonyl, C1-5 alkylcarbonyloxy, C3-8 cycloalkyl, oxo, amino, C1-3 alkylamino, aminoC1-3 alkyl, arylaminocarbonyl, arylC1-5alkylaminocarbonyl, aminocarbonyl, aminocarbonyl-C1-4 alkyl, hydroxycarbonyl, or hydroxycarbonyl C1-5 alkyl, provided that the carbon atom to which R3 and R4 are attached bears only one heteroatom,
• —(CH2)mC≡CH,
• —(CH2)mC≡C—C1-6 alkyl,
• —(CH2)mC≡C—C3-7cycloalkyl,
• —(CH2)mC≡C— aryl,
• —(CH2)mC≡C—C1-6 alkyl aryl,
• —(CH2)mCH═CH2,
• —(CH2)mCH═CH C1-6 alkyl,
• —(CH2)mCH═CH—C3-7cycloalkyl,
• —(CH2)mCH═CH aryl,
• —(CH2)mCH═CH C1-6 alkyl aryl,
• —(CH2)mSO2C1-6 alkyl, or
• —(CH2)mSO2C1-6 alkylaryl;
• R5 is
• hydrogen,
• fluorine,
• C1-8 alkyl,
• hydroxyl,
• hydroxy C1-6 alkyl,
• carboxy,
• carboxy C1-6 alkyl,
• C1-6 alkyloxy;
• C3-8 cycloalkyl,
• aryl C1-6 alkyloxy,
• aryl,
• aryl C1-6 alkyl,
• C1-6 alkylcarbonyloxy,
• amino,
• C1-6 alkylamino,
• amino C1-6 alkyl,
• C1-6 alkylamino C1-6 alkyl,
• aryl amino,
• aryl amino C1-6 alkyl,
• aryl C1-6 alkylamino,
• aryl C1-6 alkylamino C1-6 alkyl,
• aryl carbonyloxy,
• aryl C1-6 alkylcarbonyloxy,
• C1-6 dialkylamino,
• C1-6 dialkylamino C1-6 alkyl,
• C1-6 alkylaminocarbonyloxy,
• C1-8 alkylsulfonylamino,
• C1-8 alkylsulfonylamino C1-6 alkyl,
• aryl sulfonylamino C1-6 alkyl,
• aryl sulfonylamino,
• aryl C1-6 alkylsulfonylamino,
• aryl C1-6 alkylsulfonylamino C1-6 alkyl,
• C1-8 alkyloxycarbonylamino,
• C1-8 alkyloxycarbonylamino C1-8 alkyl,
• aryl C1-8 alkyloxycarbonylamino,
• aryl oxycarbonylamino,
• aryl oxycarbonylamino C1-8 alkyl,
• aryl C1-8 alkyloxycarbonylamino C1-8 alkyl,
• C1-8 alkylcarbonylamino,
• C1-8 alkylcarbonylamino C1-6 alkyl,
• aryl carbonylamino C1-6 alkyl,
• aryl carbonylamino,
• aryl C1-6 alkylcarbonylamino,
• aryl C1-6 alkylcarbonylamino C1-6 alkyl,
• C1-8 alkylaminocarbonylamino,
• aminocarbonylamino,
• aminocarbonylamino C1-6 alkyl,
• C1-8 alkylaminocarbonylamino C1-6 alkyl,
• aryl aminocarbonylamino C1-6 alkyl,
• aryl aminocarbonylamino,
• aryl C1-8 alkylaminocarbonylamino,
• aryl C1-8 alkylaminocarbonylamino C1-6 alkyl,
• aminosulfonylamino C1-6 alkyl,
• aminosulfonylamino,
• C1-8 alkylaminosulfonylamino,
• C1-8 alkylaminosulfonylamino C1-6 alkyl,
• aryl aminosulfonylamino C1-6 alkyl,
• aryl aminosulfonylamino,
• aryl C1-8 alkylaminosulfonylamino,
• aryl C1-8 alkylaminosulfonylamino C1-6 alkyl,
• C1-6 alkylsulfonyl,
• C1-6 alkylsulfonyl C1-6alkyl,
• aryl sulfonyl,
• aryl sulfonyl C1-6alkyl,
• aryl alkylsulfonyl,
• aryl C1-6 alkylsulfonyl,
• aryl C1-6 alkylsulfonyl C1-6alkyl,
• C1-6 alkylcarbonyl,
• C1-6 alkylcarbonyl C1-6 alkyl,
• aryl carbonyl C1-6alkyl,
• aryl carbonyl,
• aryl C1-6 alkylcarbonyl,
• aryl C1-6 alkylcarbonyl C1-6alkyl,
• C1-6 alkylthiocarbonylamino,
• C1-6 alkylthiocarbonylamino C1-6 alkyl,
• aryl thiocarbonylanmino C1-6 alkyl,
• aryl thiocarbonylamino,
• aryl C1-6 alkylthiocarbonylamino,
• aryl C1-6 alkylthiocarbonylamino C1-6 alkyl,
• aminocarbonyl C1-6 alkyl,
• aminocarbonyl,
• C1-8 alkylaminocarbonyl,
• C1-8 alkylaminocarbonyl C1-6 alkyl,
• aryl aminocarbonyl C1-6 alkyl,
• aryl aminocarbonyl,
• aryl C1-8 alkylaminocarbonyl,
• aryl C1-8 alkylaminocarbonyl C1-6 alkyl,
• wherein alkyl groups and aryl groups are optionally unsubstituted or substituted with one or more substituents selected from R1 and R2;
• and
• R6, R7, and R9 are independently
• hydrogen,
• C1-8 alkyl,
• aryl,
• aryl C1-8 alkyl,
• hydroxy,
• C1-8 alkyloxy,
• aryloxy,
• aryl C1-6 alkyloxy,
• C1-8 alkylcarbonyloxy C1-4 alkyloxy,
• aryl C1-8 alkylcarbonyloxy C1-4 alkyloxy,
• C1-8 alkylaminocarbonylmethyleneoxy, or
• C1-8 dialkylaminocarbonylmethyleneoxy,
• and wherein m and n are integers 0-6.