Abstract:
The present invention relates to compounds of formula (1), wherein R1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substitutents selected from (1-8C)alkyl or (1-8C)alkoxy; R2 and R3 are independently H or (1-8C)alkyl; R4 is (1-8C)alkyl or (3-8C)cycloalkyl; or R3 and R4 together with the nitrogen atom to which they are bonded are a nonaromatic (4-8)membered ring optionally containing another heteroatom, the ring optionally being substituted with (1-8C)alkyl or SO2-(1-8C)alkyl; Q is a spacer having a chain length of 10 to 70 atoms; and Z is a negatively charged oligosaccharide residue comprising two to six monosaccharide units, the charge being compensated by positively charged counterions; or a pharmaceutically acceptable salt thereof or a prodrug thereof.
Type:
Grant
Filed:
December 18, 2000
Date of Patent:
November 26, 2002
Assignees:
Akzo Nobel N.V., University Leiden
Inventors:
Cornelia Maria Tromp, Johannes Egbertus Maria Basten, Constant Adriaan Anton van Boeckel, Rogier Christian Buijsman
Abstract: A method for determining whether an individual is at increased risk for thrombosis, comprising detecting the presence or absence of a genetic mutation located in the 3' untanslated region of the prothrombin gene (G to A mutation at position 20210) that is correlated with elevated prothrombin levels in individuals with the mutation, wherein the elevated prothrombin levels are associated with increased risk for thrombosis. Also provided are kits and primers that specifically hybridize adjacent to the region of the prothrombin gene that contains the G to A mutation at position 20210.
Type:
Grant
Filed:
November 3, 1997
Date of Patent:
March 28, 2000
Assignee:
Rijks University Leiden
Inventors:
Rogier Maria Bertina, Pieter Hendrick Reitsma, Swibertus Rudolfus Poort, Frits Richard Rosendaal