New benzoxazine derivatives useful as integrin receptor antagonists

A pharmaceutical composition comprising a therapeutically effective amount of the compound of the formula (I):

• 41
• or a pharmaceutically acceptable salt, prodrug or ester thereof, wherein:
• G is selected from the group consisting of
• 42
• wherein Q is NH or O and Q′ is selected from the group consisting of H, C1-C6 alkyl, phenyl, and phenyl-C1-C4-alkyl;
• 43
• wherein R′ and R″ are independently H or C1-C4-alkyl;
• B is C1-C4 alkyl or C2-C4 alkenyl;
• A is selected from the group consisting of CH2, O, S(O)p wherein p is zero, 1 or 2, NH, a group CON(R′″) or N(R′″)CO wherein R′″ is hydrogen or CH3;
• R1 is selected from the group consisting of H, C1-C4 alkyl, C1-C4 alkoxy, OH, halogen, and CF3;
• X is (C═O)m wherein m is 0 or 1;
• R2 is selected from the group consisting of H, C1-C4 alkyl, C3-C7 cycloalkyl, C1-C4-alkylcycloalkyl;
• aryl unsubstituted or optionally substituted by one to three substituents independently selected from halogen, CF3, C1-C4 alkyl, hydroxy and C1-C4 alkoxy;
• aralkyl;
• and C5-C7 monocyclic heteroaryl ring containing one to three heteroatoms selected from O, S, and N, unsubstituted or optionally substituted by one to three substituents independently selected from the group consisting of halogen, CF3, C1-C4 alkyl, hydroxy and C1-C4 alkoxy;
• Y is (CH2)n wherein n is 1 or 2;
• R is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl or aryl-C1-C4 alkyl.
• With the proviso that m can not be 0 when G is:
• 44
• wherein Q′ is H and Q is O and X is (C═O)m.

A method for treating a condition mediated by the αvβ3 integrin in a mammal in need of such treatment, including a human, comprising administering to said mammal an effective αvβ3 inhibiting amount of a compound of the formula (I)

• 49
• wherein:
• G is selected from the group consisting of
• 50
• wherein Q is NH or O and Q′ is selected from the group consisting of H, C1-C6 alkyl, phenyl, and phenyl-C1-C4-alkyl;
• 51
• wherein R′ and R″ are independently H or C1-C4-alkyl;
• B is C1-C4 alkyl or C2-C4 alkenyl;
• A is selected from the group consisting of CH2, O, S(O)p wherein p is zero, 1 or 2, NH, a group CON(R′″) or N(R′″)CO wherein R′″ is hydrogen or CH3;
• R1 is selected from the group consisting of H, C1-C4 alkyl, C1-C4 alkoxy, OH, halogen, and CF3;
• X is (C═O)m wherein m is 0 or 1;
• R2 is selected from the group consisting of H, C1-C4 alkyl, C3-C7 cycloalkyl, C1-C4-alkylcycloalkyl;
• aryl unsubstituted or optionally substituted by one to three substituents independently selected from halogen, CF3, C1-C4 alkyl, hydroxy and C1-C4 alkoxy;
• aralkyl;
• and C5-C7 monocyclic heteroaryl ring containing one to three heteroatoms selected from O, S, and N, unsubstituted or optionally substituted by one to three substituents independently selected from the group consisting of halogen, CF3, C1-C4 alkyl, hydroxy and C1-C4 alkoxy;
• Y is (CH2)n wherein n is 1 or 2;
• R is selected from the group consisting of hydrogen, C1-C6 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, aryl or aryl-C1-C4 alkyl.
• With the proviso that m can not be 0 when G is:
• 52
• wherein Q′ is H and Q is O and X is (C═O)m.