AR-H067637

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 531466

CAS#: 433937-74-7

Description: AR-H067637 is a rapid-binding, reversible and potent (inhibition constant K(i) = 2-4 nM), competitive inhibitor of thrombin, as well as of thrombin bound to fibrin (clot-bound thrombin) or to thrombomodulin. The total amount of free thrombin generated in platelet-poor clotting plasma was inhibited concentration-dependently by AR-H067637, with a concentration giving half maximal inhibition (IC(50)) of 0.6 microM. AR-H067637 also inhibited thrombin-induced platelet activation (by glycoprotein IIb/IIIa exposure, IC(50) 8.4 nM) and aggregation (IC(50) 0.9 nM).

Chemical Structure

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AR-H067637
CAS# 433937-74-7
Instruction

Theoretical Analysis

MedKoo Cat#: 531466
Name: AR-H067637
CAS#: 433937-74-7
Chemical Formula: C21H21ClF2N4O4
Exact Mass: 466.12
Molecular Weight: 466.870
Elemental Analysis: C, 54.03; H, 4.53; Cl, 7.59; F, 8.14; N, 12.00; O, 13.71

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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Synonym: AR-H067637; ARH067637; AR H067637.

IUPAC/Chemical Name: (2S)-N-[(4-carbamimidoylphenyl)methyl]-1-[(2R)-2-[3-chloro-5-(difluoromethoxy)phenyl]-2-hydroxyacetyl]azetidine-2-carboxamide

InChi Key: QTUUCFVBSVJGOH-DLBZAZTESA-N

InChi Code: InChI=1S/C21H21ClF2N4O4/c22-14-7-13(8-15(9-14)32-21(23)24)17(29)20(31)28-6-5-16(28)19(30)27-10-11-1-3-12(4-2-11)18(25)26/h1-4,7-9,16-17,21,29H,5-6,10H2,(H3,25,26)(H,27,30)/t16-,17+/m0/s1

SMILES Code: O=C([C@H]1N(C([C@@H](C2=CC(OC(F)F)=CC(Cl)=C2)O)=O)CC1)NCC3=CC=C(C(N)=N)C=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 466.87 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Pehrsson S, Johansson K, Kjaer M, Elg M. Evaluation of AR-H067637, the active metabolite of the new direct thrombin inhibitor AZD0837, in models of venous and arterial thrombosis and bleeding in anaesthetised rats. Thromb Haemost. 2010 Dec;104(6):1242-9. doi: 10.1160/TH09-10-0744. PubMed PMID: 20806126.

2: Deinum J, Mattsson C, Inghardt T, Elg M. Biochemical and pharmacological effects of the direct thrombin inhibitor AR-H067637. Thromb Haemost. 2009 Jun;101(6):1051-9. PubMed PMID: 19492147.

3: Lip GY, Rasmussen LH, Olsson SB, Jensen E, Hamrén B, Eriksson UG, Wåhlander K. Exposure-response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation. Br J Clin Pharmacol. 2015 Dec;80(6):1362-73. doi: 10.1111/bcp.12719. PubMed PMID: 26174611; PubMed Central PMCID: PMC4693476.

4: Dunér K, Hulthe J, Tranberg M. Determination of the thrombin inhibitor AZD0837 and its metabolites in human bile using mixed mode solid phase extraction and LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Sep 1;904:29-34. doi: 10.1016/j.jchromb.2012.06.026. PubMed PMID: 22871267.

5: Blombäck M, He S, Bark N, Wallen HN, Elg M. Effects on fibrin network porosity of anticoagulants with different modes of action and reversal by activated coagulation factor concentrate. Br J Haematol. 2011 Mar;152(6):758-65. doi: 10.1111/j.1365-2141.2010.08546.x. PubMed PMID: 21250974.

6: Johansson S, Cullberg M, Eriksson UG, Elg M, Dunér K, Jensen E, Wollbratt M, Wåhlander K. Single-dose pharmacokinetics, pharmacodynamics and safety of AZD0837, a novel oral direct thrombin inhibitor, in young healthy male subjects. Int J Clin Pharmacol Ther. 2011 Apr;49(4):258-67. doi: 10.5414/CP201465. PubMed PMID: 21429440.

7: Matsson EM, Palm JE, Eriksson UG, Bottner P, Lundahl A, Knutson L, Lennernäs H. Effects of ketoconazole on the in vivo biotransformation and hepatobiliary transport of the thrombin inhibitor AZD0837 in pigs. Drug Metab Dispos. 2011 Feb;39(2):239-46. doi: 10.1124/dmd.110.035022. PubMed PMID: 20978106.

8: Wolzt M, Eriksson UG, Gouya G, Leuchten N, Kapiotis S, Elg M, Schützer KM, Zetterstrand S, Holmberg M, Wåhlander K. Effect on perfusion chamber thrombus size in patients with atrial fibrillation during anticoagulant treatment with oral direct thrombin inhibitors, AZD0837 or ximelagatran, or with vitamin K antagonists. Thromb Res. 2012 Apr;129(4):e83-91. doi: 10.1016/j.thromres.2011.08.018. PubMed PMID: 21925716.

9: Walfridsson H, Johansson B, Englund A, Kennebäck G, Schwieler J, Kongstad O, Wåhlander K, Malm AR, Edvardsson N. Effects of AZD0837, a novel direct thrombin inhibitor, on the electrophysiological properties of the human heart: a randomized, double-blind, parallel-group, placebo-controlled study. Clin Drug Investig. 2010;30(7):461-71. doi: 10.2165/11536300-000000000-00000. PubMed PMID: 20528001.

10: Matsson EM, Eriksson UG, Palm JE, Artursson P, Karlgren M, Lazorova L, Brännström M, Ekdahl A, Dunér K, Knutson L, Johansson S, Schützer KM, Lennernäs H. Combined in vitro-in vivo approach to assess the hepatobiliary disposition of a novel oral thrombin inhibitor. Mol Pharm. 2013 Nov 4;10(11):4252-62. doi: 10.1021/mp400341t. PubMed PMID: 24079718.

11: He S, Johnsson H, Zabczyk M, Hultenby K, Cao H, Blombäck M. A fibrinogen concentrate Haemocomplettan (Riastap) or a Factor XIII concentrate Fibrogammin combined with a mini dose of tranexamic acid can reverse the fibrin instability to fibrinolysis induced by thrombin- or FXa-inhibitor. Br J Haematol. 2013 Mar;160(6):806-16. doi: 10.1111/bjh.12189. PubMed PMID: 23360261.

12: Olsson SB, Rasmussen LH, Tveit A, Jensen E, Wessman P, Panfilov S, Wåhlander K. Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Thromb Haemost. 2010 Mar;103(3):604-12. doi: 10.1160/TH09-07-0509. PubMed PMID: 20076850.

13: Wagenvoord RJ, Deinum J, Elg M, Hemker HC. The paradoxical stimulation by a reversible thrombin inhibitor of thrombin generation in plasma measured with thrombinography is caused by alpha-macroglobulin-thrombin. J Thromb Haemost. 2010 Jun;8(6):1281-9. doi: 10.1111/j.1538-7836.2010.03822.x. PubMed PMID: 20180821.

14: Lip GY, Rasmussen LH, Olsson SB, Jensen EC, Persson AL, Eriksson U, Wåhlander KF; Steering Committee.. Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists. Eur Heart J. 2009 Dec;30(23):2897-907. doi: 10.1093/eurheartj/ehp318. PubMed PMID: 19690349; PubMed Central PMCID: PMC2785945.