Octa- and nonapeptides having antiangiogenic activity

A compound of formula (I)

• Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10 (I), (SEQ ID NO:1)
• or a therapeutically acceptable salt thereof, wherein
• Xaa1 is absent or R—(CH2)n—C(O)—, wherein n is an integer from 0 to 8 and R is selected from the group consisting of alkoxy, alkyl, amino, aryl, carboxyl, cycloalkenyl, cycloalkyl, and heterocycle;
• Xaa2 is selected from the group consisting of alanyl, (1S,3R)-1-aminocyclopentane-3-carbonyl, (1S,4R)-1-aminocyclopent-2-ene-4-carbonyl, (1R,4S)-1-aminocyclopent-2-ene-4-carbonyl, 3-cyanophenylalanyl, 4-cyanophenylalanyl, 3,4-dimethoxyphenylalanyl, 4-fluorophenylalanyl, 3-(2-furyl)alanyl, glutaminyl, glycyl, lysyl(N-epsilon acetyl), and 4-methylphenylalanyl;
• Xaa3 is selected from the group consisting of alanyl, (1R,4S)-1-aminocyclopent-2-ene-4-carbonyl, asparaginyl, D-asparaginyl, t-butylglycyl, citrullyl, cyclohexylglycyl, glutaminyl, D-glutaminyl, glutamyl, glycyl, isoleucyl, leucyl, lysyl(N-epsilon-acetyl), methionyl, norvalyl, phenylalanyl, prolyl, seryl, 3-(2-thienylalanyl), threonyl, and valyl;
• Xaa4 is selected from the group consisting of D-alanyl, D-alloisoleucyl, D-allylglycyl, D-4-chlorophenylalanyl, D-citrullyl, D-3-cyanophenylalanyl, D-homophenylalanyl, D-homoseryl, isoleucyl, D-isoleucyl, D-leucyl, N-methyl-D-leucyl, D-norleucyl, D-norvalyl, D-penicillaminyl, D-phenylalanyl, D-prolyl, D-seryl, D-thienylalanyl, and D-threonyl;
• Xaa5 is selected from the group consisting of allothreonyl, aspartyl, glutaminyl, D-glutaminyl, N-methylglutaminyl, glycyl, histidyl, homoseryl, isoleucyl, lysyl(N-epsilon-acetyl), methionyl, seryl, N-methylseryl, threonyl, D-threonyl, tryptyl, tyrosyl, and tyrosyl(O-methyl);
• Xaa6 is selected from the group consisting of alanyl, N-methylalanyl, allothreonyl, arginyl, glutaminyl, glycyl, homoseryl, leucyl, lysyl(N-epsilon-acetyl), norleucyl, norvalyl, D-norvalyl, N-methylnorvalyl, octylglycyl, ornithyl(N-delta-acetyl), sarcosyl, seryl, N-methylseryl, 3-(3-pyridyl)alanyl, threonyl, tryptyl, valyl, and N-methylvalyl;
• Xaa7 is selected from the group consisting of alanyl, alloisoleucyl, aspartyl, citrullyl, isoleucyl, D-isoleucyl, leucyl, D-leucyl, lysyl(N-epsilon-acetyl), D-lysyl(N-epsilon-acetyl), N-methylisoleucyl, norvalyl, phenylalanyl, prolyl, and D-prolyl;
• Xaa8 is selected from the group consisting of arginyl, D-arginyl, citrullyl, histidyl, homoarginyl, lysyl, lysyl(N-epsilon-isopropyl), omithyl, and 3-(3-pyridyl)alanyl;
• Xaa9 is selected from the group consisting of N-methyl-D-alanyl, 2-aminobutyryl, D-glutaminyl, homoprolyl, hydroxyprolyl, leucyl, prolyl, D-prolyl, and D-valyl;
• and
• Xaa10 is selected from the group consisting of D-alanylamide, azaglycylamide, glycylamide, D-lysyl(N-epsilon-acetyl)amide, a group represented by the formula —NH—(CH2)n—CHR1R2;
• and a group represented by the formula —NHR3, wherein n is an integer from 0 to 8;
• R1 is selected from the group consisting of hydrogen, alkyl, cycloalkenyl, and cycloalkyl;
• R2 is selected from the group consisting of hydrogen, alkoxy, alkyl, aryl, cycloalkenyl, cycloalkyl, heterocycle, and hydroxyl, with the proviso that when n is 0, R2 is other than alkoxy or hydroxyl;
• and R3 is selected from the group consisting of hydrogen, cycloalkenyl, cycloalkyl, and hydroxyl.