METHODS FOR INHIBITING ANGIOGENESIS AND TUMOR GROWTH

摘要

Angiogenesis, tumor growth, and metalloproteinase 2 (MMP2) interaction with integrin- alpha v beta 3 are inhibited by an inhibitor compound of formula (I): wherein G<1> and G<2> are each independently NH-C(O)-O-R<1>, -NH-C(O)-O-(CH2)v-(C6H4)-X<3>, -NH-C(O)-NH-(CH2)v-(C6H4)-X<3>, -O-C(O)-NH-(CH2)v-(C6H4)-X<3>,-O-C(O)-O-(CH2)v-(C6H4)-X<3>, or NH-C(O)-CH2-(C6H4)-X<3>; Y<1> and Y<2> are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or NH2; R<1> is C1-C4 alkyl; X<1> and X<2> are each independently halo or C1-C4 alkoxy; X<3> is halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -CC-, -C6H4-, cis-CH=CH-, trans CH=CH-, cis-CH2-CH=CH-CH2-, trans -CH2-CH=CH-CH2-, 1,4-naphthyl, cis-1, 3-cyclohexyl, trans-1, 3-cyclohexyl, cis-1, 4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and p, r, and v are each independently an integer having a value of 1 or 2; with provisos that when A is H, t is O; when A is a covalent bond, t is 1; when m is 0, Y<1> is C1-C4 hydroxyalkyl; and when n is 0, Y<2> is C1 C4 hydroxyalkyl.