Hexa-, hepta-, and octapeptides having antiangiogenic activity

A compound of formula (I)

• Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9 (SEQ ID NO:1) (I),
• or a therapeutically acceptable salt thereof, wherein
• Xaa1 is selected from the group consisting of hydrogen and 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, (1R,4S)-1-aminocyclopen-2-ene-4-carbonyl, asparaginyl, D-asparaginyl, t-butylglycyl, citrullyl, cyclohexylglycyl, glutaminyl, D-glutaminyl, glutamyl, glycyl, histidyl, isoleucyl, leucyl, lysyl(N-epsilon-acetyl), methionyl, norvalyl, phenylalanyl, prolyl, 3-(3-pyridyl)alanyl, homoseryl, seryl, thienylalanyl, threonyl, D-valyl, and valyl;
• Xaa3 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;
• Xaa4 is selected from the group consisting of allothreonyl, aspartyl, glutaminyl, D-glutaminyl, N-methylglutaminyl, glycyl, histidyl, homoseryl, isoleucyl, lysyl(N-epsilon-acetyl), methionyl, D-norvalyl, N-methylnorvalyl, seryl, N-methylseryl, threonyl, D-threonyl, tryptyl, tyrosyl, tyrosyl(O-methyl), and N-methylvalyl;
• Xaa5 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), 3-(3-pyridyl)alanyl, sarcosyl, seryl, N-methylseryl, threonyl, tryptyl, valyl, and N-methylvalyl;
• Xaa6 is selected from the group consisting of alanyl, alloisoleucyl, aspartyl, citrullyl, isoleucyl, D-isoleucyl, N-methylisoleucyl, leucyl, D-leucyl, lysyl(N-epsilon-acetyl), D-lysyl(N-epsilon-acetyl), norvalyl, phenylalanyl, prolyl, and D-prolyl;
• Xaa7 is selected from the group consisting of arginyl, D-arginyl, citrullyl, histidyl, homoarginyl, lysyl, lysyl(N-epsilon-isopropyl), ornithyl, and 3-(3-pyridyl)alanyl;
• Xaa8 is absent or selected from the group consisting of N-methyl-D-alanyl, 2-aminobutyryl, 2-aminoisobutyryl, D-glutaminyl, homoprolyl, hydroxyprolyl, leucyl, phenylalanyl, prolyl, D-prolyl, and D-valyl;
• and
• Xaa9 is selected from the group consisting of D-alanylamide, azaglycylamide, glycylamide, lysyl(N-epsilon-acetyl)amide, D-lysyl(N-epsilon-acetyl)amide, —NHCH(CH3)2, 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.