Abstract |
A suitable inhibitor of activated thrombin activatable fibrinolysis inhibitor (TAFIa) has the potential to be a novel treatment for thrombosis. The TAFIa inhibitor UK-396082 (1) was used as a starting point to seek more potent analogues. With knowledge of encouraging human pharmacokinetics and toleration for the clinical candidate (1), the programme continued to seek structure-activity relationships (SAR) that could positively impact on both potency and half-life, and therefore the projected dose of any future nominated clinical agent. A series of oxygenated analogues based on compound 1 were prepared to evaluate changes in pharmacology, selectivity and pharmacokinetics.
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Authors | Dafydd R Owen, David J Bull, Mark E Bunnage, Melanie S Glossop, Robert J Maguire, Ross S Strang |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 20
Issue 1
Pg. 92-6
(Jan 01 2010)
ISSN: 1464-3405 [Electronic] England |
PMID | 19954973
(Publication Type: Journal Article)
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Copyright | Copyright 2009 Elsevier Ltd. All rights reserved. |
Chemical References |
- 5-amino-2-((1-n-propyl-1H-imidazol-4-yl)methyl)pentanoic acid
- Amino Acids
- Fibrinolytic Agents
- Imidazoles
- Protease Inhibitors
- Carboxypeptidase B2
- Oxygen
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Topics |
- Administration, Oral
- Amino Acids
(chemical synthesis, chemistry, pharmacokinetics)
- Animals
- Carboxypeptidase B2
(antagonists & inhibitors, metabolism)
- Fibrinolytic Agents
(chemical synthesis, chemistry, pharmacokinetics)
- Half-Life
- Humans
- Imidazoles
(chemical synthesis, chemistry, pharmacokinetics)
- Oxygen
(chemistry)
- Protease Inhibitors
(chemical synthesis, chemistry, pharmacokinetics)
- Rats
- Structure-Activity Relationship
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