Methods for inhibiting angiogenesis and tumor growth

Details Methods for inhibiting angiogenesis and tumor growth Methods for inhibiting angiogenesis and tumor growth

A - Human Necessities

61

K

A61K 31/27 (2006.01) A61K 31/216 (2006.01) A61P 9/00 (2006.01) A61P 35/00 (2006.01) C07C 271/22 (2006.01)

Patent

CA 2403630

Angiogenesis, tumor growth, and metalloproteinase 2(MMP2) interaction with integrin-.alpha.v.beta.3 are inhibited by an inhibitor compound of formula (I): wherein G1 and G2 are each independently NH- C(O)-O-R1, -NH-C(O)-O-(CH2)v-(C6H4)-X3, -NH-C(O)-NH-(CH2)v-(C6H4)-X3, -O-C(O)-NH-(CH2)v-(C6H4)-X3,-O-C(O)-O-(CH2)v- (C6H4)-X3, or NH-C(O)-CH2-(C6H4)-X3; Y1 and Y2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or NH2; R1 is C1-C4 alkyl; X1 and X2 are each independently halo or C1-C4 alkoxy; X3 is halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C.ident.C-, -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, Y1 is C1-C4 hydroxyalkyl; and when n is 0, Y2 is C1 C4 hydroxyalkyl.

l'angiogenèse, la croissance des tumeurs et l'interaction de la métalloprotéinase 2 (MMP2) avec l'intégrine- alpha v beta 3 sont inhibées par le composé inhibiteur représenté par la formule (I). Dans cette formule, G<1> et G<2> sont chacun indépendamment 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>, ou NH-C(O)-CH2-(C6H4)-X<3>; Y<1> et Y<2> sont chacun indépendamment OH, C1-C4 alkyle, C1-C4 hydroxyalkyle, C1-C4 alkoxy, phényle, benzyle, ou NH2; R<1> est C1-C4 alkyle; X<1> et X<2> sont chacun indépendamment halo ou C1-C4 alkoxy; X<3> est halo, nitro, C1-C4 alkyle, C1-C4 alkoxy, ou C1-C4 perfluoroalkyle; Z est -CC-, -C6H4-, cis-CH=CH-, trans CH=CH-, cis-CH2-CH=CH-CH2-, trans -CH2-CH=CH-CH2-, 1,4-naphthyle, cis-1, 3-cyclohexyle, trans-1, 3-cyclohexyle, cis-1, 4-cyclohexyle, ou trans-1,4-cyclohexyle; A est H ou une liaison covalente; m et n sont chacun indépendamment un entier de valeur 0 ou 1; t est un entier de valeur 0 ou 1; et p, r, et v sont chacun indépendamment un entier de valeur 1 ou 2; à condition que lorsque A est H, t est O; lorsque A est une liaison covalente, t est 1; lorsque m est 0, Y<1> est C1-C4 hydroxyalkyle; et lorsque n est 0, Y<2> est C1 C4 hydroxyalkyle.

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