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|Title:||FVIIa/TF activity inhibiting compounds|
|Abstract:||The invention relates to compounds inhibiting the activation of FX to FXa by TF/FVIIa. The compounds are anticoagulants. The invention also relates to a method of identifying a drug candidate.|
|Inventor(s):||Jakobsen; Palle (Vaerl.o slashed.se, DK), Persson; Egon (.ANG.karp, SE)|
|Assignee:||Novo Nordisk A/S (Bagsvaerd, DK)|
|Filing Date:||Apr 27, 2001|
|Claims:||1. A compound having an inhibitory action on Factor VII-Tissue Factor (FVII-TF) activity, wherein said compound exhibits: (i) half-maximal inhibition at a concentration of 20 .mu.M or less in a FX activation assay, (ii) half-maximal inhibition at a concentration of 100 .mu.M or more in a FXa amidolytic assay, and (iii) half-maximal inhibition at a concentration of 20 .mu.M or more in a TF/FVIIa amidolytic assay. |
2. A compound as defined in claim 1, wherein said compound further exhibits clotting activity corresponding to a clot ratio of more than 1 in a FVIIa/TF-initiated clotting assay.
3. A pharmaceutical composition comprising a compound as defined in claim 1 and a pharmaceutically acceptable carrier or excipient.
4. A method for treatment of a FVIIa/TF-related disease or disorder in a subject, which method comprises administering an effective amount of at least one compound according to claim 1 to a subject in need of such treatment.
5. A method according to claim 4, wherein the FVIIa/TF-related disease or disorder is selected from the group consisting of: deep venous thrombosis, arterial thrombosis, post surgical thrombosis, coronary artery bypass graft (CABG), percutaneous transdermal coronary angioplastry (PTCA), stroke, tumour metastasis, angiogenesis, thrombolysis, arteriosclerosis and restenosis following angioplastry, inflammation, septic chock, septicemia, hypotension, adult respiratory distress syndrome (ARDS), disseminated intravascular coagulopathy (DIC), pulmonary embolism, platelet deposition, myocardial infarction, and a disease or disorder requiring one or more of dialysis procedures, blood filtration, or blood bypass during surgery.
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