Heteroarylakanoic acids as intergrin receptor antagonists

A compound or pharmaceutically acceptable salt of the compound, wherein:

• the compound corresponds in structure to Formula I:
• the structure:
• is oxadiazolyl;
• as to A1:
• A1 is selected from the group consisting of pyridinyl, dihydropyridinyl, tetrahydropyridinyl, naphthyridinyl, dihydronaphthyridinyl, tetrahydronaphthyridinyl, hexahydronaphthyridinyl, octahydronaphthyridinyl, and decahydronaphthyridinyl, wherein:
• any such substituent is optionally substituted by one or more substituents selected from the group consisting of hydroxy, alkyl, alkoxy, alkoxyalkyl, alkylthio, haloalkyl, cyano, amino, alkylamino, halogen, acylamino, sulfonamide and —COR wherein R is hydroxy, alkoxy, alkyl, or amino;
• or
• A1 is selected from the group consisting of
• A1 is selected from the group consisting of:
• Za is H, alkyl, alkoxy, hydroxy, amino, alkylamine, dialkylamine, carboxyl, alkoxycarbonyl, hydroxyalkyl, halogen, or haloalkyl;
• R1 is H, alkyl, alkoxyalkyl, acyl, haloalkyl, or alkoxycarbonyl;
• X4 and X5 are selected from the group consisting of H, alkyl, alkylamino, alkoxyalkylamino, haloalkyl, alkylthio, halogen, amino, alkoxy, aryloxy, alkoxyalkyl, hydroxy, cyano, and acylamino;
• X6 is selected from the group consisting of H, alkyl, hydroxy, halogen, alkoxy, and haloalkyl;
• Z1 is selected from the group consisting of CH2, O, CH2O, NH, CO, S, SO, CH(OH), and SO2;
• Z2 is a 1–5 carbon linker optionally containing one or more heteroatoms selected from the group consisting of O, S, and N;
• the Z1-Z2 moiety optionally further contains:
• a carboxamide, sulfone, sulfonamide, alkenyl, alkynyl, or acyl, and a phenyl or 5- or 6-membered heteroaryl, wherein:
• the phenyl or heteroaryl is optionally substituted with Rc, and
• the heteroaryl contains 1–3 heteroatoms selected from the group consisting of O, N, and S;
• any carbon and nitrogen atoms of the Z1-Z2 moiety are optionally substituted by alkyl, alkoxy, alkylthio, alkylsulfone, aryl, alkoxyalkyl, hydroxy, alkylamino, heteroaryl, alkenyl, alkynyl, carboxyalkyl, halogen, haloalky, or acylamino;
• as to X and Y:
• X is selected from the group consisting —CHRe—, —NRf—, —O—, —S—, —SO2—, and
• —CO—;
• Y is selected from the group consisting of —(CH2)p—, —CHRg—, —NRg—, —CO—, and
• —SO—;
• or
• Y5 is carbon;
• and Y3, X, Y, and Y5 together form a 3–7 membered monocyclic ring, wherein the ring:
• optionally contains one or more moieties selected from the group consisting of O, NRg, S, CO, and SO2, and
• optionally is substituted with one or more substituents selected from the group consisting of alkyl, halogen, alkoxy, haloalkyl, hydroxyalkyl, and alkoxyalkyl;
• Re is H, lower alkyl, alkoxy, cycloalkyl, alkoxyalkyl, hydroxy, alkynyl, alkenyl, haloalkyl, alkylthio, or aryl;
• Rf is selected from the group consisting of H, alkyl, aryl, benzyl, and haloalkyl;
• Rg is selected from the group consisting of H, alkyl, haloalkyl, alkoxyalkyl, alkynyl, aryl, heteroaryl, aralkyl, hydroxy, alkoxy, and carboxyalkyl;
• p is zero or 1;
• as to Y3, Y4, and Y5:
• Y5 is carbon, and Y3 and Y4 are independently selected from the group consisting of H, alkyl, haloalkyl, halogen, aryl, arakyl, heteroaralkyl, heteroaryl, alkenyl, hydroxyalkyl, and alkynyl, wherein:
• any alkyl optionally contains:
• one or more heteroatoms selected from the group consisting of N, O, and S, and a sulfone, sulfoamide, nitrile, carboxamide, carboalkoxy, or carboxyl, and any aryl and heteroaryl rings:
• are monocyclic or bicylic,
• optionally contain 1–5 heteroatoms, and are optionally substituted by one or more Rc substituents;
• Y5 is nitrogen, Y3 is absent, and Y4 is H;
• Y5 is carbon;
• and Y3, Y4, and Y5 together form a 3–8 membered monocyclic or a 7–11 membered bicyclic ring, wherein the ring:
• optionally contains one or more moieties selected from the group consisting of O, NRg, S, CO, and SO2, and
• is optionally substituted with one or more substituents selected from the group consisting of alkyl, haloalkyl, halogen, haloalkyl, alkoxy, alkynyl, cyano, alkylsulfone, sulfonamide, carboalkoxy, and carboxyalkyl;
• or
• Y5 is carbon, and:
• Y3, X, Y, and Y5 together form a 3–7 membered monocyclic ring, wherein the ring:
• optionally contains one or more moieties selected from the group consisting of O, NRg, S, CO, and SO2, and
• optionally is substituted with one or more substituents selected from the group consisting of alkyl, halogen, alkoxy, haloalkyl, hydroxyalkyl, and alkoxyalkyl;
• and
• Y4 is selected from the group consisting of H, alkyl, haloalkyl, halogen, aryl, arakyl, heteroaralkyl, heteroaryl, alkenyl, hydroxyalkyl, and alkynyl, wherein:
• the alkyl optionally contains:
• one or more heteroatoms selected from the group consisting of N, O, and S, and
• a sulfone, sulfoamide, nitrile, carboxamide, carboalkoxy, or carboxyl, and
• the aryl and heteroaryl rings:
• are monocyclic or bicylic,
• optionally contain 1–5 heteroatoms, and
• are optionally substituted by one or more Rc substituents;
• Rb is X2—Rh;
• X2 is selected from the group consisting of O, S, and NRj;
• Rh and Rj are independently selected from the group consisting of H, alkyl, aryl, aralkyl, acyl, and alkoxyalkyl;
• and
• Rc is selected from the group consisting of alkyl, haloalkyl, aryl, heteroaryl, halogen, alkoxyalkyl, aminoalkyl, hydroxy, alkoxy, carboxamide, and cyano.