Terutroban (S18886; S-18886) is a selective TP (thromboxane-prostaglandin receptor) receptor antagonist with antiplatelet activity and the potential to be used for the secondary prevention of acute thrombotic complications. It can enhance endothelial function in patients with coronary artery disease after just one administration because it is a selective antagonist of the prostaglandin endoperoxide and thromboxane A(2) receptors. Terutroban may help high-risk patients avoid cardiovascular events by enhancing endothelium-dependent vasodilatation over time and preventing platelet aggregation.
Physicochemical Properties
| Molecular Formula | C20H22CLNO4S | |
| Molecular Weight | 407.9 | |
| Exact Mass | 407.096 | |
| Elemental Analysis | C, 58.89; H, 5.44; Cl, 8.69; N, 3.43; O, 15.69; S, 7.86 | |
| CAS # | 165538-40-9 | |
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| PubChem CID | 9938840 | |
| Appearance | White to off-white solid powder | |
| Density | 1.389g/cm3 | |
| Boiling Point | 591.818ºC at 760 mmHg | |
| Flash Point | 311.721ºC | |
| Vapour Pressure | 0mmHg at 25°C | |
| Index of Refraction | 1.637 | |
| LogP | 4.973 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 5 | |
| Rotatable Bond Count | 6 | |
| Heavy Atom Count | 27 | |
| Complexity | 612 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | O=C(O)CCC1=C2CC[C@@H](NS(=O)(C3=CC=C(Cl)C=C3)=O)CC2=CC=C1C |
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| InChi Key | HWEOXFSBSQIWSY-MRXNPFEDSA-N | |
| InChi Code | InChI=1S/C20H22ClNO4S/c1-13-2-3-14-12-16(6-9-19(14)18(13)10-11-20(23)24)22-27(25,26)17-7-4-15(21)5-8-17/h2-5,7-8,16,22H,6,9-12H2,1H3,(H,23,24)/t16-/m1/s1 | |
| Chemical Name | 3-[(6R)-6-[(4-chlorophenyl)sulfonylamino]-2-methyl-5,6,7,8-tetrahydronaphthalen-1-yl]propanoic acid | |
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| HS Tariff Code | 2934.99.03.00 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vivo |
Background: The aim of the present study is to investigate the effectiveness of terutroban, a selective antagonist of the thromboxane/prostaglandin endoperoxide receptor, in preventing retinal ischaemia in a model of diabetes in rats.[1] Methods: Experimental diabetes was induced with streptozotocin. Rats were distributed into five groups (n = 20): (1) non-diabetic rats, (2) rats with diabetes (DR) treated with vehicle, (3) DR treated with aspirin (2 mg/kg/day p.o.), (4) DR treated with terutroban (5 mg/kg/day p.o.), (5) DR treated with terutroban (30 mg/kg/day p.o.). The follow-up period was 3 months. The main assessment was the percentage of retinal surface covered with vessels permeable to peroxidase. Platelet aggregation, aortic prostacyclin and nitric oxide production, plasma levels of lipid peroxides (thiobarbituric-acid-reactive substances) and 3-nitrotyrosine and serum levels of IL-6 were evaluated.[1] Results: Diabetes induced a reduction in retinal vascularity (76.9%), aortic prostacyclin (37.8%) and nitric oxide production (35.0%), and increased platelet aggregation, lipid peroxides, 3-nitrotyrosine. When compared with vehicle-treated DR, terutroban increased the percentage of retinal surface covered by PVPP (38% for terutroban-5 and 61% for terutroban-30), aortic prostacyclin (188% for terutroban-5 and 146% for terutroban-30) and nitric oxide production (320% for terutroban-5 and 390% for terutroban-30). Moreover, terutroban reduced platelet reactivity (27.8–95.1%, according to the inducer), lipid peroxides (60.7% for terutroban-5 and 50.0% for terutroban-30), 3-nitrotyrosine (43.8% for terutroban-5 and 36.8% for terutroban-30) and IL-6 concentration (18.0% for terutroban-30). The effect of terutroban in retinal, nitrosative and aortic parameters was significantly higher than that of aspirin.[1] Conclusions: Terutroban significantly protected retinal vascularity from ischaemia in experimental diabetes, and this result could be attributed not only to its antiplatelet/antithrombotic activities but also to its vascular properties. |
| References |
[1]. Effects of terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, on retinal vascularity in diabetic rats. Diabetes Metab Res Rev. 2012 Feb;28(2):132-138. [2]. Thromboxane prostaglandin receptor antagonist and carotid atherosclerosis progression in patients with cerebrovascular disease of ischemic origin: a randomized controlled trial. Stroke. 2014 Aug;45(8):2348-2353. [3]. Daily administration of the TP receptor antagonist terutroban improved endothelial function in high-cardiovascular-risk patients with atherosclerosis. Br J Clin Pharmacol.2011 Jun;71(6):844-851. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4516 mL | 12.2579 mL | 24.5158 mL | |
| 5 mM | 0.4903 mL | 2.4516 mL | 4.9032 mL | |
| 10 mM | 0.2452 mL | 1.2258 mL | 2.4516 mL |