Antithrombotic dual inhibitors comprising a biotin residue

US8168595B2 · kind B2 · utility

Assignee

• MSD OSS B.V. · NL

Inventors

• Martin De Kort · Oss, NL
• Constant Adriaan Anton Van Boeckel · Oss, NL

Key dates

• Filing date: Dec 21, 2005
• Grant date: May 1, 2012
• Expiry date: Feb 29, 2028

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07H15/26
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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 —CH[NH—SO2—R1[CO—NR2—CH(4-benzamidine)-CO—NR3R4], 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 R2 and R3 are independently H or (1-8C)alkyl; R4 is (-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)alk…