Patent ID: 6218365
Filing Date: 2001-04-17
Classification: A61K,A61P,C07D,C07K,Y02P

Abstract:
A compound having the formula I ##STR9##whereinA 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 Damio 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 6membered ring; and R.sup.5 is a hydrophobic, basic or neutral side chain;X is an L-amino acid with a hydrophobic side chain, serine, threonine, a cyclic amino acid optionally containing an additional heteroatom selected from N, O or 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;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)alyl 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, phenyl, (1-6C)alkoxy, bennyloxy or oxo;and r is 0, 1, 2 or 3;or a prodrug thereof or a pharmaceutically acceptable salt thereof.