AZD1283 is a novel, potent and selective antagonist of the P2Y12 receptor with EC50 of 3.0 ug/kg/min, TI >10 and with binding IC50 of 11 nM. AZD1283 demonstrated dose-dependent increases in blood flow and inhibition of ADP-induced platelet aggregation in a modified Folts model in dogs, with antithrombotic ED50 values of 3.0 μg/kg/min. The doses of 33 μg/kg/min caused a bleeding time increase greater than threefold. As a result, TI (therapeutic index) was less than 10. Based on these findings, AZD1283 was advanced into human clinical trials as a potential medication.
Physicochemical Properties
| Molecular Formula | C23H26N4O5S |
| Molecular Weight | 470.541344165802 |
| Exact Mass | 470.162 |
| Elemental Analysis | C, 58.71; H, 5.57; N, 11.91; O, 17.00; S, 6.81 |
| CAS # | 919351-41-0 |
| PubChem CID | 23649325 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.618 |
| LogP | 2.66 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 33 |
| Complexity | 835 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N#CC1C(N2CCC(C(NS(CC3C=CC=CC=3)(=O)=O)=O)CC2)=NC(C)=C(C(OCC)=O)C=1 |
| InChi Key | NEMHKCNXXRQYRF-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C23H26N4O5S/c1-3-32-23(29)20-13-19(14-24)21(25-16(20)2)27-11-9-18(10-12-27)22(28)26-33(30,31)15-17-7-5-4-6-8-17/h4-8,13,18H,3,9-12,15H2,1-2H3,(H,26,28) |
| Chemical Name | ethyl 6-[4-(benzylsulfonylcarbamoyl)piperidin-1-yl]-5-cyano-2-methylpyridine-3-carboxylate |
| Synonyms | AZD-1283; AZD1283; AZD 1283 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| 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
| Targets | P2Y12 Receptor ( IC50 = 11 nM ) |
| ln Vitro |
AZD1283 has an IC50 value of 3.6 μM, demonstrating good antiplatelet aggregation potency[1]. AZD1283 exhibits strong inhibitory effects on CYP450, as evidenced by its IC50 values of 6.62 μM, 0.399 μM, 4.28 μM, and 3.64 μM for CYP2C9, CYP2C19, CYP3A4 (requiring midazolam as substrate), and CYP3A4 (requiring testosterone as substrate), respectively[1]. AZD1283 has an antithrombotic EC50 value of 3 μg/(kg×min) and increases blood flow while inhibiting ADP-induced platelet aggregation[2]. |
| ln Vivo | AZD1283 shows inadequate liver microsomal stability in rats (T1/2 = 6.08 min), but better in dog and human microsomes (T1/2 = 201 and 65.0 min)[1]. |
| Animal Protocol |
Sprague-Dawley rats 5 mg/kg p.o.; single dosage |
| References |
[1]. Optimization of P2Y12 Antagonist Ethyl 6-(4-((Benzylsulfonyl)carbamoyl)piperidin-1-yl)-5-cyano-2-methylnicotinate (AZD1283) Led to the Discovery of an Oral Antiplatelet Agent with Improved Druglike Properties. J Med Chem . 2019 Mar 28;62(6):3088-3106. [2]. Lead optimization of ethyl 6-aminonicotinate acyl sulfonamides as antagonists of the P2Y12 receptor. separation of the antithrombotic effect and bleeding for candidate drug AZD1283. J Med Chem. 2013 Sep 12;56(17):7015-24. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~100 mg/mL (~212.5 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.31 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 (5.31 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 | 2.1252 mL | 10.6261 mL | 21.2522 mL | |
| 5 mM | 0.4250 mL | 2.1252 mL | 4.2504 mL | |
| 10 mM | 0.2125 mL | 1.0626 mL | 2.1252 mL |