Synthesis and Identification of Chiral Aminomethylpiperidine Carboxamides as Inhibitor of Collagen Induced Platelet Activation
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Kumar K S, Anil
Misra, Ankita Siddiqi, T I Srivastava, Stuti Jain, Manish Bhatta, R S Barthwal, M K Dikshit, Madhu Dikshit, D K |
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| Date |
2014-09-02T06:00:36Z
2014-09-02T06:00:36Z 2014 |
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| Identifier |
European Journal of Medicinal Chemistry. 2014, 81, 456-72
http://hdl.handle.net/123456789/1387 |
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| Description |
A series of chiral lactamcarboxamides of aminomethylpiperidine were synthesized and investigated for the collagen induced in vitro anti-platelet efficacy and collagen plus epinephrine induced in vivo pulmonary thromboembolism. The compound 31a (30 μM/Kg) displayed a remarkable antithrombotic efficacy (60% protection) which was sustained for more than 24 hours and points to its excellent bioavailability. The compounds 31a (IC50= 6.6µM) and 32a (IC50=37µM), as well as their racemic mixture 28i (IC50=16µM) significantly inhibited collagen-induced human platelet aggregation in vitro. Compound 34c displayed dual mechanism of action against both collagen (IC50=3.3µM) and U46619 (IC50=2.7M) induced platelet aggregation. The pharmacokinetic study of 31a indicated very faster absorption, prolonged and constant systemic exposure and thereby exhibiting better therapeutic response.
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442877 bytes
application/pdf |
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| Language |
en
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| Relation |
CSIR-CDRI Communication No. 8694
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| Subject |
Thrombosis
Antiplatelet Pyroglutamic Acid Aminomethylpiperidine Collagen Epinephrine |
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| Title |
Synthesis and Identification of Chiral Aminomethylpiperidine Carboxamides as Inhibitor of Collagen Induced Platelet Activation
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| Type |
Article
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