Patent ID: 6034067
Filing Date: 2000-03-07
Classification: A61K,A61P,C07K,Y02P

Abstract:
A compound having the formula I ##STR9## wherein A is H, optionally substituted D,L .alpha.-hydroxyacetyl, R.sup.1, R.sup.1 --O--C(O)--, R.sup.1 --C(O)--, R.sup.1 --SO.sub.2 --, R.sup.2 OOC--(CHR.sup.2).sub.m --SO.sub.2 --, R.sup.2 OOC-(CHR.sup.2).sub.m --, H.sub.2 NCO-(CHR.sup.2) .sub.m --, or an N-protecting group, wherein R.sup.1 is selected from (1-12C)alkyl, (2-12C)alkenyl, (2-12C)alkynyl and (3-8C)cycloalkyl, which groups may optionally be substituted with (3-8C)cycloalkyl, (1-6C)alkoxy, oxo, OH, COOH, CF.sub.3 or halogen, and from (6-14C)aryl, (7-15C)aralkyl and (8-16)aralkenyl, the aryl groups of which may optionally be substituted with (1-6C)alkyl, (3-8C)cycloalkyl, (1 -6C)alkoxy, OH, COOH, CF.sub.3 or halogen; each group R.sup.2 is independently H or has the same meaning as R.sup.1 ; m is 1, 2 or 3;B is a bond, an amino acid of the formula --NH--CH[(CH.sub.2).sub.p C(O)OH]--C(O)-- or an ester derivative thereof with p being 0, 1, 2 or 3, --N((1-12C)alkyl)--CH.sub.2 --CO--, --N((2-12C)alkenyl)--CH.sub.2 --CO--, --N((2-12C)alkynyl)--CH.sub.2 --CO--, --N(benzyl)--CH.sub.2 --CO--, D-1-Tiq, D-3-Tiq, D-Atc, Aic, D-1-Piq, D-3-Piq or a L- or D-amino acid having a hydrophobic, basic or neutral side chain, which amino acid may optionally be N-(1-6C)alkyl substituted; or A and B together are the residue R.sup.3 R.sup.4 N--CHR.sup.5 --C(O)--, wherein R.sup.3 and R.sup.4 independently are R.sup.1, R.sup.1 --O--C(O)--, R.sup.1 --C(O)--, R.sup.1 --SO.sub.2 --, R.sup.2 OOC--(CHR.sup.2).sub.m --SO.sub.2 --, R.sup.2 OOC--(CHR.sup.2).sub.m --, H.sub.2 NCO--(CHR.sup.2).sub.m --, or an N-protecting group, or one of R.sup.3 and R.sup.4 is connected with R.sup.5 to form a 5- or 6-membered ring together with ""N-C"" to which they are bound, which ring may be fused with an aliphatic or aromatic 6-membered ring; and R.sup.5 is a hydrophobic, basic or neutral side chain;X is an L-amino acid with a hydrophobic side chain, being a (1-12C)alkyl, optionally substituted with one or more (3-8C)cycloalkyl groups or (6-14C)aryl groups, which hydrophobic side chain may optionally be substituted with halogen, trifluoromethyl, lower alkyl, lower alkoxy, phenyloxy, or benzyloxy, or X is serine, threonine, a cyclic amino acid optionally containing an additional heteroatom selected from N, O and S, and optionally substituted with (1-6C)alkyl, (1-6C)alkoxy, benzyloxy or oxo, or X is --NR.sup.2 --CH.sub.2 --C(O)-- or the fragment ##STR10## wherein n is 2, 3, or 4, and W is CH or N; Q is H or --C(O)Y, wherein Y is H, --CHF.sub.2, --CF.sub.3, --CO--NH--(1-6C)alkylene-C.sub.6 H.sub.5, --COOR.sup.6 and R.sup.6 being H or (1-6C)alkyl, --CONR.sup.7 R.sup.8 and R.sup.7 and R.sup.8 being independently H or (1-6C)alkyl or R.sup.7 and R.sup.8 together being (3-6C)alkylene, or Y is a heterocycle selected from 2-thiazole, 2-thiazoline, 2-benzothiazole, 2-oxazole, 2-oxazoline and 2-benzoxazole, which heterocycles may optionally be substituted with (1-6C)alkyl, (1-6C)alkoxy or oxo;Z is H or (1-6C)alkyl;r is 0 or 1 if Q is --C(O)Y or is 0, 1, 2, 3 or 4if Q is H;or a prodrug thereof or a pharmaceutically acceptable salt thereof.