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| Neue Antithrombotika mit Pyrazol-Partialstruktur KhademBashi, Laleh |
| Main title | Neue Antithrombotika mit Pyrazol-Partialstruktur |
| Title variations | New Antithrombotica with Pyrazol partial structure |
| Author(s) | KhademBashi, Laleh
Place of birth: Teheran, Iran |
| 1. Referee | Prof. Dr. K. Rehse |
| Further Referee(s) | Prof. Dr. R. Gust |
| Keywords | antithrombotic, Pyrazol-matrix |
| Classification (DDC) | 540 Chemistry and allied sciences |
| Summary | The aim of this work, was to synthesize new inhibiting agents of the phosphodiestrase 5 (PDE 5) or direct activators of the soluble guanylatcyclase (sGC). According to the structures of sildenafil a PDE 5-inhibitor and YC-1 a direct activator of the soluble guanylatcyclase (sGC), the new substances were synthesized with a pyrazole-matrix and analyzed according to its physiological activity of clotting. The starting material compounds got in this work was the 5-amino-1-phenyl-1H-pyrazol-4- carbonic acid ethyl ester which in dependence to the substance A (sGC)-activator with 4-chlorphenylsulfonacidchloride sulfonates and subsequently implemented with different amines to the appropriate carbonic acid amides (type 3-13). As the substance 13b showed a moderate antithrombotic activity in the laser-thrombosis-model in arterioles, significant effects of inhibition of the thrombus generation and in the Born-Test after 20 minutes of incubation time, the next step was to build the compounds of type 14-29. To get an accurate analysis of the effect of the substances, some of them were analyzed with more specific aggregation induces. Then the substances which were examined in vitro in a Born-Test were examined in vivo in the laser-thrombosis-model to investigate their antithrombotic activity. The substance 7 which showed the best antiaggregation activity after adding of collagen after 20min. of incubation time and in addition shows very good PAF-antagonistic effects, surprisingly showed no effect in the laser-thrombosis-model. The best antithrombotic activities of were measured for the substance 13b, 19b and 27b. On the basis of the structural formula of the substances 13b, 21b and 27b the following structural elements can be made responsible for the antithrombotic activity: A methoxy group in the side chain, who´s distance to the amide function is three methylen groups. An electron withdrawing group at the exocyclic amino group in position 5 of the pyrazole ring, which carries a chlorine substituent in para-position of the aromaic ring of the benzoyl or sulfonyl group. To examine , whether the antithrombotic activity of the substances is caused by the inhibition of the phosphodiesterase 5 or by the activation of the soluble guanylatcyclase (sGC), three structural different substances were chosen and analyzed by the Bayer company in two enzyme assays. From the tested substances none could inhibit the phosphodiesterase 5 (PDE-5) or activate the soluble guanylatcyclase (sGC). This shows, that the antithrombotic and/or antiaggregative activity of the analysed substances is not caused by the inhibition of PDE 5 or activation of the soluble guanylatcyclase. |
| Documents |
FUDISS_derivate_000000002602
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| FU Department | Department of Biology, Chemistry and Pharmacy |
| Year of publication | 2007 |
| Document type | Doctoral thesis |
| Media type/Format | Text |
| Language | German |
| Terms of use/Rights | Nutzungsbedingungen |
| Date of defense | 2006-12-21 |
| Created at | 2007-03-11 : 12:00:00 |
| Last changed | 2010-02-19 : 02:05:17 |
| Old Darwin URL | http://www.diss.fu-berlin.de/2007/214/ |
| Static URL | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000002602 |
| NBN | urn:nbn:de:kobv:188-fudissthesis000000002602-6 |
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