Dabigatran Etexilate (BIBR-1048) is the prodrug of dabigatran used as an thrombin inhibitor to treat blood clot. It is a potent and nonpeptidic small molecule that specifically and reversibly inhibits both free and clot-bound thrombin by binding to the active site of the thrombin molecule. Dabigatran (also known as IBR 953) is a potent nonpeptide thrombin inhibitor with an IC50 of 9.3 nM in a cell-free assay. Dabigatran is designed to be converted into an orally active prodrug BIBR 1048 due to its highly polar, zwitterionic nature and poor oral absorption. Dabigatran inhibits thrombin in a competitive fashion.
理化性质和储存条件
| Molecular Weight (MW) | 627.73 |
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| Formula | C34H41N7O5 |
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| CAS No. | 211915-06-9 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 126 mg/mL (200.7 mM) |
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| Water: <1 mg/mL |
| Ethanol: 12 mg/mL (19.1 mM) |
Other info
| Chemical Name: (E)-ethyl 3-(2-(((4-(N'-((hexyloxy)carbonyl)carbamimidoyl)phenyl)amino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate
InChi Key: KSGXQBZTULBEEQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C34H41N7O5/c1-4-6-7-10-21-46-34(44)39-32(35)24-12-15-26(16-13-24)37-23-30-38-27-22-25(14-17-28(27)40(30)3)33(43)41(20-18-31(42)45-5-2)29-11-8-9-19-36-29/h8-9,11-17,19,22,37H,4-7,10,18,20-21,23H2,1-3H3,(H2,35,39,44)
SMILES Code: O=C(OCC)CCN(C1=NC=CC=C1)C(C2=CC=C3N(C)C(CNC4=CC=C(/C(N)=N\C(OCCCCCC)=O)C=C4)=NC3=C2)=O |
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| Synonyms | BIBR 1048; BIBR953; Pradaxa; BIBR1048; BIBR-1048; BIBR 953; BIBR-953; Prazaxa |
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实验参考方法
| In Vitro | In vitro activity: Dabigatran selectively and reversibly inhibits human thrombin (Ki: 4.5 nM) as well as thrombin-induced platelet aggregation (IC50: 10 nM), while showing no inhibitory effect on other platelet-stimulating agents. Dabigatran selectively and reversibly inhibits human thrombin (Ki: 4.5 nM) as well as thrombin-induced platelet aggregation (IC50: 10 nM), while showing no inhibitory effect on other platelet-stimulating agents. Dabigatran inhibits thrombin generation in platelet-poor plasma (PPP) with IC50 of 0.56 μM, measured as the endogenous thrombin potential (ETP). Dabigatran demonstrates concentrationdependent anticoagulant effects in various species in vitro, doubling the activated partial thromboplastin time (aPTT), prothrombin time (PT) and ecarin clotting time (ECT) in human PPP at concentrations of 0.23, 0.83 and 0.18 μM, respectively. |
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| In Vivo | Dabigatran prolongs the aPTT dose-dependently after intravenous administration in rats (0.3, 1 and 3 mg/kg) and rhesus monkeys (0.15, 0.3 and 0.6 mg/kg). Dabigatran etexilate (20 mg/kg, orally) produces less prolongation of K value and less decreases in angle and maximum amplitude than enoxaparin in swine. Dabigatran (0.01-0.1 mg/kg) reduces thrombus formation dose-dependently, with an ED50 (50% of the effective dose) of 0.033 mg/kg and complete inhibition at 0.1 mg/kg. Dabigatran etexilate (5-30 mg/kg) inhibits thrombus formation in a dose- and time-dependent manner, with maximum inhibition within 30 min of pretreatment, suggesting a rapid onset of action. |
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| Animal model | Rats and monkeys |
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| Formulation & Dosage | Intravenous administration in rats (0.3, 1 and 3 mg/kg) and rhesus monkeys (0.15, 0.3 and 0.6 mg/kg). |
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| References | J Med Chem. 2002 Apr 25;45(9):1757-66; Thromb Haemost. 2007 Jul;98(1):155-62; J Thorac Cardiovasc Surg. 2011 Jun;141(6):1410-6. |
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