3-[1-(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-1,3-benzodiazol-5-yl)-N-(pyridin-2-yl)formamido]propanoic acid

• ChemBase ID: 72889
• Molecular Formular: C25H25N7O3
• Molecular Mass: 471.5111
• Monoisotopic Mass: 471.2018877
• SMILES: c1(ccc2c(c1)nc(n2C)CNc1ccc(cc1)C(=N)N)C(=O)N(CCC(=O)O)c1ncccc1
• Canonical SMILES: OC(=O)CCN(C(=O)c1ccc2c(c1)nc(n2C)CNc1ccc(cc1)C(=N)N)c1ccccn1
• InChI: InChI=1S/C25H25N7O3/c1-31-20-10-7-17(25(35)32(13-11-23(33)34)21-4-2-3-12-28-21)14-19(20)30-22(31)15-29-18-8-5-16(6-9-18)24(26)27/h2-10,12,14,29H,11,13,15H2,1H3,(H3,26,27)(H,33,34)
• InChIKey: YBSJFWOBGCMAKL-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-[1-(2-{[(4-carbamimidoylphenyl)amino]methyl}-1-methyl-1H-1,3-benzodiazol-5-yl)-N-(pyridin-2-yl)formamido]propanoic acid
• IUPAC Traditional name: dabigatran
• Synonyms: N-[[2-[[[4-(Aminoiminomethyl)phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-β-alanine; BIBR 953; BIBR 953ZW; Dabigatran; Dabigatran; Pradaxa; BIBR953; BIBR 953

Database IDs

• CAS Number: 211914-51-1
• PubChem SID: 162037810
• PubChem CID: 216210

CALCULATED PROPERTIES

• Acid pKa: 3.4953113
• H Acceptors: 8
• H Donor: 4
• LogD (pH = 5.5): 0.06167832
• LogD (pH = 7.4): 0.07667542
• Log P: 0.076810434
• Molar Refractivity: 143.2611 cm^3
• Polarizability: 50.423977 Å^3
• Polar Surface Area: 150.22 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Solubility: Aqueous Acid
• Apperance: Tan Solid
• Melting Point: 268-272°C

Safety Information

• Storage Condition: -20°C; Refrigerator, Under Inert Atmosphere

Pharmacology Properties

• Target: thrombin

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S2196

Research Area

• Description: Cardiovascular Disease

Biological Activity

• Description: BIBR 953 (Dabigatran, Pradaxa) is potent nonpeptide thrombin inhibitor with an IC50 of 9.3 nM.
• Targets: Thrombin
• IC50: 9.3 nM ^[1]
• In Vitro: BIBR 953 is a very potent anticoagulant. BIBR 953 shows that the terminal phenyl can be substituted by the more hydrophilic 2-pyridyl group without substantial loss of activity. BIBR 953 inhibits thrombin, plasmin, factor Xa, trypsin, tPA and activated protein C with Ki of 4.5 nM, 1.7 μM, 3.8 μM, 50 nM, 45 μM and 20 μM, respectively. ^[1] BIBR 953 specifically and reversibly inhibits thrombin. ^[2]
• In Vivo: BIBR 953 exhibits the most favorable activity profile following i.v. administration to rats. ^[1] The bioavailability of dabigatran after p.o. administration of dabigatran etexilate is 7.2%. Dabigatran is predominantly excreted in the feces after p.o. treatment and in the urine after i.v. treatment. The mean terminal half-life of dabigatran is approximately 8 hours. Dabigatran acylglucuronides accounts for 0.4% and 4% of the dose in urine after p.o. and i.v. dosing, respectively. ^[3]
• Clinical Trials: Dabigatran has entered in a phase III clinical trial in the treatment of atrial fibrillation.
• Features: Dabigatran is a reversible, competitive, direct thrombin inhibitor.

Protocol

• Protocol: Kinase Assay ^[1]
• Measurement of thrombin inhibition: The thrombin inhibitory effects (IC50) of BIBR 953 is determined with a commercially available chromogenic assay. Human thrombin (0.042 U/mL) is preincubated for 10 minutes at 37 °C with 10 different dilutions (concentration range of 0.003 μM -100 μM) of BIBR 953 dissolved in DMSO or with DMSO as control. Upon addition of the preincubation mixture to the chromogenic substrate, tosyl-glycyl-prolyl-arginine-4-nitranilide acetate, nitraniline is cleaved by thrombin and the increase in absorbance at 405 nm, related to the free nitraniline, is measured in a spectrophotometer. By plotting the absorbance at 405 nm vs the concentration of BIBR 953, the concentration that induces a 50% thrombin inhibition (IC50) is calculated. All measurements are performed in duplicate, and the mean values of both determinations are represented.
• Protocol: Animal Study ^[1]
• Animal Models: Rats
• Administration: Administered via i.v.

References

• References: [1] Hauel NH, et al. J Med Chem. 2002, 45(9), 1757-1766.
• References: [2] Stangier J, et al. Br J Clin Pharmacol. 2007, 64(3), 292-303.
• References: [3] Blech S, et al. Drug Metab Dispos. 2008, 36(2), 386-399.

Toronto Research Chemicals - D100090

Nonpeptide, direct thrombin inhibitor. Antithrombotic.

REFERENCES

• Hauel NH, et al. J Med Chem. 2002, 45(9), 1757-1766.
• Stangier J, et al. Br J Clin Pharmacol. 2007, 64(3), 292-303.
• Blech S, et al. Drug Metab Dispos. 2008, 36(2), 386-399.
• Hauel, N., et al.: J. Med. Chem., 45, 1757 (2002)
• Mungall, D., et al.: Curr. Opin. Invest. Drugs, 3, 095 (2002)
• Stangier, J., et al.: J. Clin. Pharmacol., 45, 555 (2002)