| abstract |
Disclosed is the use of compounds of the formula (Ia) or (Ib) in the manufacture of a medicament for treating a disease mediated by VLA-4 in a patient, wherein, in formula (Ia), R1 and R2 together with the carbon atom and W to which they are bound respectively, are joined to form an aryl, cycloalkenyl, heteroaryl or heterocyclic group having at least five atoms in the aryl, cycloalkenyl, heteroaryl or heterocyclic group and optionally containing or additionally containing in the case of heteroaryl and heterocyclic groups 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and wherein the heteroaryl or heterocyclic group is mono-cyclic; in formula (Ib), R1 and R2 together with the carbon atom and W' to which they are bound respectively, are joined to form a cycloalkyl, cycloalkenyl or heterocyclic group having at least five atoms in the cycloalkyl, cycloalkenyl or heterocyclic group and optionally containing or additionally containing in the case of the heterocyclic group 1 to 3 heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur, and wherein the heterocyclic group is mono-cyclic; and further wherein said aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocyclic group of formula (Ia) or (lb) is optionally substituted, on any ring atom capable of substitution, with 1-3 substituents R3 and R3' are independently selected from the group consisting of hydrogen, isopropyl, -CH2Z; and where R3 and R3' a joined to form a substituent selected from the group consisting of =CHZ; Q is selected from the group consisting of -O-. -S-, -S(O)-, -S(O)2 and -NR4; W is selected from the group consisting of nitrogen and carbon; and W' is selected from the group consisting of nitrogen, carbon, oxygen, sulfur, S(O), and S(O)2; X is selected from the group consisting of hydroxyl, alkoxy, substituted alkoxy, alkenoxy, substituted alkenoxy, cycloalkoxy, substituted cycloalkoxy, cycloalkenoxy, substituted cycloalkenoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclyloxy, substituted heterocyclyloxy and -NR"R"; and enantiomers, diastereomers and pharmaceutically acceptable salts thereof; and further wherein the compound of formula (Ia) and/or (lb) has a binding affinity to VLA4 as expressed by an IC50 of about l5 uM or less. (62) Divided out of 512563 |