Patent ID: 6716963
Filing Date: 2004-04-06
Classification: C07K

Abstract:
A compound of the formula:A0-A1-A2-A3-A4-A5-A6-A7-A8-A9-A10 or a pharmaceutically acceptable salt, ester, solvate or prodrug thereof, wherein:A0 is an acyl group selected from: (1) Râ€”(CH2)nâ€”C(O)â€”; wherein n is an integer from 0 to 8 and R is selected from hydroxyl; methyl; N-acetylamino; methoxyl; carboxyl; cyclohexyl optionally containing one or two double bonds and optionally substituted with one to three hydroxyl groups; and a 5- or 6-membered aromatic or nonaromatic ring optionally containing one or two heteroatoms selected from nitrogen, oxygen, and sulfur, wherein the ring is optionally substituted with a moiety selected from alkyl, alkoxy, and halogen; and (2) R1â€”CH2CH2â€”OCH2CH2O)pâ€”CH2â€”C(O)â€”; wherein R1 is selected from hydrogen, alkyl, and N-acetylamino, and p is an integer from 1 to 8; A1 is an amino acyl residue selected from: (1) alanyl, (2) asparaginyl, (3) citrullyl, (4) glutaminyl, (5) glutamyl, (6) N-ethylglycyl, (7) methionyl, (8) N-methylalanyl, (9) prolyl, (10) pyro-glutamyl, (11) sarcosyl, (12) seryl, (13) threonyl, (14) â€”HNâ€”(CH2)qâ€”C(O)â€”, wherein q is 1 to 8, and (15) â€”HNâ€”CH2CH2â€”(OCH2CH2O)râ€”CH2â€”C(O)â€”, wherein r is 1 to 8; A2 is an amino acyl residue selected from: (1) alanyl, (2) asparaginyl, (3) aspartyl, (4) glutaminyl, (5) glutamyl, (6) leucyl, (7) methionyl, (8) phenylalanyl, (9) prolyl, (10) seryl, (11) â€”HNâ€”(CH2)qâ€”C(O)â€”, wherein q is 1 to 8, (12) â€”HNâ€”CH2CH2â€”(OCH2CH2O)râ€”CH2â€”C(O)â€”, wherein r is 1 to 8 and (13) glycyl; A3 is an amino acyl residue selected from: (1) alanyl, (2) asparaginyl, (3) citrullyl, (4) cyclohexylalanyl, (5) cyclohexylglycyl, (6) glutaminyl, (7) glutamyl, (8) glycyl, (9) isoleucyl, (10) leucyl, (11) methionyl, (12) norvalyl, (13) phenylalanyl, (14) seryl, (15) t-butylglycyl, (16) threonyl, (17) valyl, (18) penicillaminyl, and (19) cystyl; A4 is an amino acyl residue selected from: (1) L- or D-allo-isoleucyl, (2) glycyl, (3) L- or D-isoleucyl, (4) L- or D-prolyl, (5) L- or D-dehydroleucyl, (6) D-alanyl, (7) D-3-(naphth-1-yl)alanyl, (8) D-3-(naphth-2-yl)alanyl, (9) D-(3-pyridyl)-alanyl, (10) D-2-aminobutyryl, (11) D-allo-threonyl, (12) D-allylglycyl, (13) D-asparaginyl, (14) D-aspartyl, (15) D-3-(3-benzothienyl)alanyl (16) D-3-(4,4â€²-biphenyl)alanyl, (17) D-3-(3-chlorophenyl)alanyl, (18) D-3-(4-chlorophenyl)alanyl, (19) D-3-(3-trifluoromethylphenyl)alanyl, (20) D-3-(3-cyanophenyl)alanyl, (21) D-3-(3,4-difluorophenyl)alanyl, (22) D-citrullyl, (23) D-cyclohexylalanyl, (24) D-cyclohexylglycyl, (25) D-cystyl, (26) D-cystyl(S-t-butyl), (27) D-glutaminyl, (28) D-glutamyl, (29) D-histidyl, (30) D-homoisoleucyl, (31) D-homophenylalanyl, (32) D-homoseryl, (33) D-leucyl, (34) D-lysyl(N-epsilon-nicotinyl), (35) D-lysyl, (36) D-methionyl, (37) D-neopentylglycyl, (38) D-norleucyl, (39) D-norvalyl, (40) D-ornithyl, (41) D-penicillaminyl, (42) D-penicillaminyl(acetamidomethyl), (43) D-penicillaminyl(S-benzyl), (44) D-phenylalanyl, (45) D-3-(4-aminophenyl)alanyl, (46) D-3-(4-methylphenyl)alanyl, (47) D-3-(4-nitrophenyl)alanyl, (48) D-3-(3,4dimethoxyphenyl)alanyl, (49) D-3-(3,4,5-trifluorophenyl)alanyl, (50) D-seryl, (51) D-seryl(O-benzyl), (52) D-t-butylglycyl, (53) D-thienylalanyl, (54) D-threonyl, (55) D-threonyl(O-benzyl), (56) D-tryptyl, (57) D-tyrosyl(O-benzyl), (58) D-tyrosyl(O-ethyl), (59) D-tyrosyl, and (60) D-valyl; A5 is a glycyl residue or an amino acyl residue of L or D configuration selected from: (1) alanyl, (2) (3-pyridyl)alanyl, (3) 3-(naphth-1-yl)alanyl, (4) 3-(naphth-2-yl)alanyl, (5) allo-threonyl, (6) allylglycyl, (7) glutaminyl, (8) histidyl, (9) homoseryl, (10) isoleucyl, (11) lysyl(N-epsilon-acetyl), (12) methionyl, (13) norvalyl, (14) octylglycyl, (15) ornmithyl, (16) 3-(4-hydroxymethylphenyl)alanyl, (17) prolyl, (18) seryl, (19) threonyl (20) tryptyl, (21) tyrosyl, (22) D-allo-threonyl, (23) D-homoseryl, (24) D-seryl, (25) D-threonyl (26) penicillaminyl, and (27) cystyl; A6 is a glycyl residue or an amino acyl residue of L or D configuration selected from: (1) alanyl, (2) 3-(naphth-1-yl)alanyl, (3) 3-(naphth-2-yl)alanyl, (4) 3-pyridyl)alanyl, (5) 2-aminobutyryl, (6) allylglycyl, (7) arginyl, (8) asparaginyl, (9) aspartyl, (10) citrullyl, (11) 3-(cyclohexyl)alanyl, (12) glutaminyl (13) glutamyl, (14) histidyl, (15) homoalanyl, (16) homoleucyl, (17) homoseryl, (18) isoleucyl, (19) leucyl, (20) lysyl(N-epsilon-acetyl), (21) lysyl(N-epsilon-isopropyl), (22) methionyl(sulfone), (23) methionyl(sulfoxide), (24) methionyl, (25) norleucyl, (26) norvalyl, (27) octylglycyl, (28) phenylalanyl, (29) 3-(4-carboxyamidephenyl)alanyl, (30) propargylglycyl, (31) seryl, (32) threonyl, (33) tryptyl, (34) tyrosyl, (35) valyl, (36) D-3-(naphth-1-yl)alanyl, (37) D-3-(naphth-2-yl)alanyl, (38) D-glutaminyl, (39) D-homoseryl, (40) D-leucyl, (41) D-norvalyl, (42) D-seryl), (43) penicillaminyl, and (44) cystyl; A7 is a glycyl residue or an amino acyl residue of L or D configuration selected from: (1) alanyl, (2) allylglycyl, (3) aspartyl, (4) citrullyl, (5) cyclohexylglycyl, (6) glutamyl, (9) homoseryl, (10) isoleucyl, (11) allo-isoleucyl, (12) leucyl, (13) lysyl(N-epsilon-acetyl), (14) methionyl, (15) 3-(naphth-1-yl)alanyl, (16) 3-(naphth-2-yl)alanyl, (17) norvalyl, (18) phenylalanyl, (19) prolyl, (20) seryl (21) t-butylglycyl, (22) tryptyl, (23) tyrosyl, (24) valyl, (25) D-allo-isoleucyl, (26) D-isoleucyl, (27) penicillaminyl, and (28) cystyl; A8 is an amino acyl residue selected from: (1) 2-amino-4-[(2-amino)pyrimidinyl]butanoyl, (2) alanyl(3-guanidino), (3) alanyl(3-pyrrolidinylamidino), (4) alanyl[4-piperidinyl(N-amidino)], (5) arginyl, (6) arginyl(NGNGâ€²diethyl), (7) citrully, (8) 3-(cyclohexyl)alanyl(4-Nâ€²-isopropyl), (8) glycyl[4-piperidinyl(N-amidino)], (10) histidyl, (11) homoarginyl, (12) lysyl, (13) lysyl(N-epsilon-isopropyl), (14) lysyl(N-epsilon-nicotinyl), (15) norarginyl, (16) ornithyl(N-delta-isopropyl), (17) ornithyl(N-delta-nicotinyl), (18) ornithyl[N-delta-(2-imidazolinyl)], (19) [(4-amino(N-isopropyl)methyl)phenyl]alanyl, (20) 3-(4-guanidinophenyl)alanyl, and (21) 3-(4-amino-N-isopropylphenyl)alanyl; A9 is an amino acyl residue of L or D configuration selected from: (1) 2-amino-butyryl, (2) 2-amino-isobutyryl, (3) homoprolyl, (4) 4-hydroxyprolyl, (5) isoleucyl, (6) leucyl, (7) phenylalanyl, (8) prolyl, (9) seryl, (10) t-butylglycyl, (11) 1,2,3,4-tetrahydroisoquinoline-3-carbonyl, (12) threonyl, (13) valyl, (14) D-alanyl, and (15) D-prolyl; and A10 is selected from: (1) hydroxyl, (2) azaglycylamide, (3) D-alanylamide, (4) D-alanylethylamide, (5) glycylamide, (6) glycylethylamide, (7) sarcosylamide, (8) serylamide, (9) D-serylamide, (10) a group represented by the formula â€ƒand (11) a group represented by the formula â€”NHâ€”R4; â€ƒwherein: s is an integer selected from 0 to 8, R2 is selected from hydrogen, alkyl, and a 5- to 6-membered cycloalkyl ring; R3 is selected from hydrogen, hydroxy, alkyl, phenyl, alkoxy, and a 5- to 6-membered ring optionally containing from one to two heteroatoms selected from oxygen, nitrogen, and sulfur, provided that s is not zero when R3 is hydroxy or alkoxy; and R4 is selected from hydrogen, hydroxy, and a 5- to 6-membered cycloalkyl ring.