Merck Sharp + Dohme B.v.

Merck Sharp + Dohme Corp.

Sanofi-aventis

N.v. Organon

Msd Oss B.v.

Msd Oss B.v. Netherlands

Martin De Kort

Constant Adriaan Anton Van Boeckel

Wesley Peter Blackaby

Cornelis Marius Timmers

Mark Enthoven

Paul Stuart Hinchliffe

Saskia Verkaik

Christian Bernard Matthijs Poulie

Rogier Christian Buijsman

Ebo S Bos

Constant Van Boeckel

Dirk Gerrit Meuleman

Charles David Nicholson

Constant Adriaan Van Boeckel

Meertinus Jan Smit

Cristian Bernard Matthijs Poulie

Jeffry Abraham Jacobus Wisse

Miranda Maria Cornelia Van Der Lee

Marion Blomenrohr

Christian Bernard Poulie

Marion BLOMENRÖHR

The invention relates to FSH receptor antagonist according to general formula I or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders.

FSH receptor antagonists

The invention relates to FSH receptor antagonist according to general formula (I) or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders. 

The invention relates to kisspeptide-pentasaccharide conjugates having the general formula (I) wherein Zis Tyr or D-Tyr; Zis Trp, Hyp, Phe or Lys(R); Zis Thr, Aib or Ala; Zis Gly or azaGly; Zis Leu; or Zand Ztogether represent; Zis Phe or Trp; n is 0 or 1; or R, when present, represents a pentasaccharide derivative having the formula (II) wherein R is methyl or SOX; X is a positively charged counterion; with the proviso that when Ris present, Ris H or (C) alkylcarbonyl; Ris H or (C)alkyl; and L represents a pharmacologically inactive linker moiety having 10-50 atoms; or a pharmaceutically acceptable salt thereof; to pharmaceutical compositions comprising the same as well as to the use of said kisspeptide-pentasaccharide conjugates in the treatment of female infertility. 

Kisspeptide-pentasaccharide conjugates

The invention relates to FSH receptor antagonist according to general formula I or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders. 

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 compounds of the formula Aoligosaccharide-spacer-GpIIb/IIIa antagonist &#x2003;&#x2003;(A). The compounds of the invention have antithrombotic activity and can be used in treating or preventing thrombotic diseases.

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Oss, Netherlands

Martin De Kort