| abstract |
Disclosed are compounds of formula I, wherein T is morpholin-4-yl which is monosubstituted or disubstituted by carbonyl oxygen, E and W together represent pyrrolidine-1,2-diyl, piperidine-1,2-diyl, oxazolidine-3,4- or -3,5-diyl, thiazolidine-3,4-diyl, 2,5-dihydro-1H-pyrrole-1,5-diyl, 1,3-dioxolane-4,5-diyl, 1,3-oxazinane-3,4-diyl, piperazine-1,4-diyl, tetrahydrofuran-3,4-diyl or azetidine-1,2-diyl, and the remaining substituents are as defined in the specification; and pharmaceutically usable derivatives, solvates, salts, stereoisomers and mixtures thereof. The compounds inhibit coagulation factor Xa and can be used in the prophylaxis and/or therapy of thrombo-embolic diseases and for treating tumors. Also disclosed are intermediates useful for preparing the compounds of formula I including (2R,4S)-BOC-4-ethynyl-4-hydroxy-pyrrolidine-2-carboxylic acid, (2R,4R)-BOC-4-ethynyl-4-hydroxy-pyrrolidine-2-carboxylic acid, alkyl (2R,4S)-BOC-4-ethynyl-4-hydroxypyrrolidine-2-carboxylate, alkyl (2R,4R)-BOC-4-ethynyI-4-hydroxypyrrolidine-2-carboxylate, N-[4-(3-oxomorpholin-4-yl)phenyl]-(S)-pyrrolidine-2-carboxamide, N-[4-(3-oxomorpholin-4-yl)phenyl]-(R)-pyrrolidine-2-carboxamide, N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-4-hydroxypyrrolidine-2-carboxamide, N-[4-(3-oxomorpholin-4-yl)phenyl]-4-hydroxypyrrolidine-2-carboxamide, N-[4-(3-oxomorpholin-4-yl)phenyl]-(R)-4,4-dimethoxypyrrolidine-2-carboxamide and N-[4-(3-oxomorpholin-4-yl)phenyl]-(2R,4R)-4-methoxypyrrolidine-2-carboxamide, (where alkyl has 1, 2, 3, 4, 5 or 6 carbon atoms); and isomers and salts thereof. |