Akzo Nobel N.v.

Other

N.v. Organon

Merck Sharp + Dohme B.v.

Msd Oss B.v.

Msd Oss B.v. Netherlands

Constant Adriaan Anton Van Boeckel

Johannes Bernardus Maria Rewinkel

Martin De Kort

Philippus Johannes Marie Van Galen

Johannes Egbertus Maria Basten

Maurice Petitou

Philippe Duchaussoy

Rogier Christian Buijsman

Ebo S Bos

Tamara Theodora Maria Geertsen

Cornelia Maria Dreef-Tromp

Cornelia Maria Tromp

Cornelis Maria Tromp

Meertinus Jan Smit

Charles David Nicholson

The present invention relates compounds of the formula (I)oligosaccharide-spacer-A&#x2003;&#x2003;(I),

Antithrombotic dual inhibitors comprising a biotin residue

The present invention relates compounds of the formula: oligosaccharide-spacer-(GpIIb/IIIa antagonist), wherein the oligosaccharide is a negatively charged oligosaccharide residue comprising four to twenty five monosaccharide units, the charge being compensated by positively charged counterions, and wherein the oligosaccharide residue is derived from an oligosaccharide which has (AT-III mediated) anti-Xa activity per se; the spacer is a bond or an essentially pharmacologically inactive linking residue; the GpIIb/IIIa antagonist is a residue mimicking the RGD and/or K(QA)GD fragment of fibrinogen, comprising a carboxylate moiety and a basic moiety located within the residue at a distance of 10-20 &#x212b; from each other; or a pharmaceutically acceptable salt thereof or a prodrug or a solvate thereof; wherein the compound of formula I further comprises at least one covalent bond with a biotin label or an analogue thereof. The compounds of the invention have antithrombotic activity and can be used in treating or preventing thrombotic diseases. The antithrombotic activity of the compound of this invention can be neutralized in case of emergency upon administration of avidin, streptavidin and analogues thereof having high biotin affinity.

Anticoagulant antithrombotic dual inhibitors comprising a biotin label

The present invention relates to compounds of the formula (I) oligosaccharide-spacer-A (1), wherein the oligosaccharide is a negatively charged oligosaccharide residue comprising two to twenty five monosaccharide units, the charge being compensated by positively charged counterions, and wherein the oligosaccharide residue is derived from an oligosaccharide which has (AT-III mediated) anti-Xa activity per se; the spacer is an essentially pharmacologically inactive flexible linking residue having a chain length of 10 to 70 atoms; A is the residue &#x2014;CH[NH&#x2014;SO&#x2014;R[CO&#x2014;NR&#x2014;CH(4-benzamidine)-CO&#x2014;NRR], 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 substituents selected from (1-8C)alkyl or (1-8C)alkoxy; and wherein Rand Rare independently H or (1-8C)alkyl; Ris (-8C)alkyl or (3-8C)cycloalkyl; or Rand Rtogether 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 SO-(1-8C)alkyl; or a pharmaceutically acceptable salt thereof a prodrug or solvate thereof; wherein the compound of formula I further comprises at least one covalent bond with a biotin residue or an analogue thereof. The compounds of the invention have antithrombotic activity and can be used in treating or preventing thrombosis or other thrombin-related diseases. The antithrombotic activity of the compound of this invention can be neutralized in case of emergency upon administration of avidin, streptavidin and analogues thereof having high biotin affinity.

The present invention relates to conjugates of a polypeptide and an oligosaccharide, wherein the polypeptide is conjugated to at least one oligosaccharide-spacer residue, the oligosaccharide being a synthetic sulfated oligosaccharide comprising 4-18 monosaccharide units and per se having affinity to antithrombin III and the spacer being a bond or an essentially pharmacologically inactive flexible linking residue, or a pharmaceutically acceptable salt thereof. The conjugates of the invention have improved pharmacokinetic properties when compared to the original polypeptides (i.e. the corresponding non-conjugated polypeptides per se).

Conjugates of a polypeptide and a pentasaccharide

The present invention relates to compounds of the formula (I), wherein R is independently SOor CH; the spacer is a flexible spacer of a length of 13-25 atoms; the charge of the pentasaccharide residue is compensated by positively charged counterions; and the total number of sulfate groups in the pentasaccharide residue is 4, 5 or 6; or a pharmaceutically acceptable salt, a prodrug or a solvate thereof. The compounds of the invention have antithrombotic activity and can be used in treating or preventing thrombin-related diseases.

Antithrombotic compound

The present invention relates to antithrombotic compounds comprising the group Q, Q having formula (I), wherein the substructure (i) is a structure selected from (a, b and c), wherein X is O or S; X&prime; being independently CH or N; and m is 0, 1, 2 or 3; wherein the group Q is bound through an oxygen atom or an optionally substituted nitrogen or carbon atom, or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention are therapeutically active and in particular are antithrombotic agents.

Heterocyclic derivatives and their use as antithrombotic agents

Antithrombotic compounds

The present invention relates to heterocyclic antithrombotic compounds comprising a compound of the Formula I, wherein X&prime; is independently CH or N, and m is 0, 1, 2 or 3, or a pharmaceutically acceptable salt or prodrug thereof.

The present invention relates to therapeutically active antithrombotic compounds.

The invention relates to a carbohydrate derivative having formula I

Growing community of inventors

Oss, Netherlands

Constant Adriaan Anton Van Boeckel