Invention Grant
- Patent Title: Antithrombotic dual inhibitors comprising a biotin residue
- Patent Title (中): 包含生物素残基的抗血栓双重抑制剂
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Application No.: US11722444Application Date: 2005-12-21
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Publication No.: US08168595B2Publication Date: 2012-05-01
- Inventor: Martin De Kort , Constant Adriaan Anton Van Boeckel
- Applicant: Martin De Kort , Constant Adriaan Anton Van Boeckel
- Applicant Address: NL AB Oss
- Assignee: Msd Oss B.V
- Current Assignee: Msd Oss B.V
- Current Assignee Address: NL AB Oss
- Agent Richard S. Parr; Catherine D. Fitch
- Priority: EP04106964 20041223
- International Application: PCT/EP2005/057011 WO 20051221
- International Announcement: WO2006/067173 WO 20060629
- Main IPC: A61K31/7052
- IPC: A61K31/7052 ; C07H15/20

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)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.
Public/Granted literature
- US20100004186A1 Antithrombotic Dual Inhibitors Comprising A Biotin Residue Public/Granted day:2010-01-07
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