Patent ID: 6313095
Filing Date: 2001-11-06
Classification: A61K,C07K

Abstract:
A peptide of formula 1X--NH--CHR.sup.1 --C(W.sup.1)--NR.sup.2 --CH[CH.sub.2 C(O)--Y]--C(W.sup.2)--NH--CH[CR.sup.3 (R.sup.4)--COOH]--C(W.sup.3)--NH--CHR.sup.5 --Z 1whereinX is (1-10C)alkanoyl; (1-10C)alkanoyl monosubstituted with halo, hydroxy or lower alkoxy; (1-10C)alkoxycarbonyl; benzoyl; benzoyl monosubstituted or disubstituted with a substituent selected from halo, hydroxy, lower alkyl, lower alkoxy, phenyl, 2-carboxyphenyl or benzyl; 2,2-diphenylacetyl; phenyl(2-10C)alkanoyl; phenyl(2-10C)alkanoyl monosubstituted or disubstituted on the aromatic portion thereof with a substituent selected from halo, hydroxy, lower alkyl, lower alkoxy or phenyl; phenyl(3-10C) alkenoyl; (lower cycloalkyl)carbonyl; (lower cycloalkyl)carbonyl substituted with one to four substituents selected from halo or lower alkyl; cyclohexylcarbonyl substituted at position 2 with lower alkanoyl, phenyl(lower)alkanoyl or phenyl(lower)alkoxycarbonyl; 3,6-dimethyl-2-(phenylethoxycarbonyl)cyclohexylcarbonyl; or a straight or branched chain 1,4-dioxoalkyl containing from five to eleven carbon atoms;R.sup.1 is lower alkyl, hydroxy(lower)alkyl, mercapto(lower)alkyl, methoxy(lower)alkyl, methylthio(lower)alkyl, benzyloxy(lower)alkyl, benzylthio(lower)alkyl, carboxy(lower)alkyl, lower cycloalkyl, (lower cycloalkyl)methyl, phenyl, phenylmethyl, 2-thienyl or 2-thienylmethyl;R.sup.2 is hydrogen, lower alkyl or phenyl(lower)alkyl;R.sup.3 and R.sup.4 each independently is hydrogen or lower alkyl, or R.sup.3 and R.sup.4 together with the carbon atom to which they are attached form a lower cycloalkyl;R.sup.5 is lower alkyl, lower cycloalkyl, or (lower cycloalkyl)methyl;W.sup.1, W.sup.2, and W.sup.3 each independently is oxo or thioxo;Y isa. (1-14C)alkoxy, (3-14)alkenyloxy, CH.sub.3 (OCH.sub.2 CH.sub.2).sub.n --O wherein n is the integer 1, 2 or 3, lower cycloalkyloxy, lower alkoxy monosubstituted with a lower cycloalkyl, phenoxy, phenoxy monosubstituted with hydroxy, halo, lower alkcyl or lower alkoxy, phenyl(lower)alkoxy or phenyl(lower)alkoxy in which the aromatic portion thereof is substituted with hydroxy, halo, lower alkyl or lower alkoxy, orb. NR.sup.6 R.sup.7 wherein R.sup.6 is lower alkyl and R.sup.7 is lower alkoxy, orc. NR.sup.6 R.sup.7 wherein R.sup.6 is hydrogen or lower alkyl and R.sup.7 is (1-14C)alkyl, lower cycloalkyl, lower alkyl monosubstituted with a lower cycloalkyl; phenyl, phenyl monosubstituted with halo, lower alkyl or lower alkoxy; phenyl(lower)alkyl, phenyl(lower)alkyl in which the aromatic portion thereof is substituted with halo, lower alkyl or lower alkoxy; or (Het)-lower alkyl wherein Het represents a five or six membered heterocyclic radical containing one or two heteroatoms selected from nitrogen, oxygen or sulfur, ord. NR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 together with the nitrogen to which they are attached form a pyrrolidino, piperidino, morpholino, thiomorpholino, piperazino or 4-(lower alkyl)piperazino; andZ is hydrogen; COOH; CH.sub.2 COOH; CH.sub.2 CH.sub.2 COOH; CH.sub.2 OH; 5-1H-tetrazolyl; COOR.sup.8 wherein R.sup.8 is lower alkyl; CONR.sup.9 R.sup.10 wherein R.sup.9 and R.sup.10 each independently is hydrogen or lower alkyl; or CON(R.sup.11)OH wherein R.sup.11 is hydrogen or lower alkyl; with the provisos that (1) when X is a (1-10C)alkanoyl containing one or two carbon atoms (i.e. formyl or acetyl) then R.sup.2 is lower alkyl or phenyl lower alkyl, and that (2) when Z is hydrogen then R.sup.3 is hydrogen or lower alkyl and R.sup.4 is lower alkyl or R.sup.3 or R.sup.4 together with the carbon atom to which they are attached form a lower cycloalkyl; or a therapeutically acceptable salt thereof.