AZD5423 is the first clinical candidate that displayed a potent inhibition of lung edema in a rat model of allergic airway inflammation following dry powder inhalation combined with a moderate systemic GR-effect, assessed as thymic involution. Further optimization of inhaled drug properties provided a second, equally potent, candidate, AZD7594 (also known as AZ13189620), which is a novel, potent selective nonsteroidal indazole ether-based glucocorticoid receptor modulators (SGRMs) with an IC50 of 0.9 nM. AZD-7594 is an inhaled selective glucocorticoid receptor (GCCR) modulator for the inhaled treatment of respiratory diseases. AZD7594 demonstrated an improved therapeutic ratio over the benchmark inhaled corticosteroid 3 (fluticasone propionate) and prolonged the inhibition of lung edema, indicating potential for once-daily treatment. AZD-7594 is currently in phase II clinical trials by AstraZeneca for the treatment of mild to moderate asthma. It is also in phase I clinical trials for the treatment of chronic obstructive pulmonary disorder (COPD).
Physicochemical Properties
| Exact Mass | 487.151 |
| CAS # | 1034148-04-3 |
| PubChem CID | 24825740 |
| Appearance | White to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 573.8±50.0 °C at 760 mmHg |
| Flash Point | 300.8±30.1 °C |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.574 |
| LogP | 5.89 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 35 |
| Complexity | 704 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C[C@@H]([C@@H](C1=CC(=CC=C1)OC)OC2=CC3=C(C=C2)N(N=C3)C4=CC=C(C=C4)F)NC(=O)C(F)(F)F |
| InChi Key | FCNQMDSJHADDFT-WNSKOXEYSA-N |
| InChi Code | InChI=1S/C25H21F4N3O3/c1-15(31-24(33)25(27,28)29)23(16-4-3-5-20(12-16)34-2)35-21-10-11-22-17(13-21)14-30-32(22)19-8-6-18(26)7-9-19/h3-15,23H,1-2H3,(H,31,33)/t15-,23-/m0/s1 |
| Chemical Name | 2,2,2-Trifluoro-N-((1R,2S)-1-((1-(4-fluorophenyl)-1H-indazol-5-yl)oxy)-1-(3-methoxyphenyl)-2-propanyl)acetamide |
| Synonyms | AZD-5423; AZD 5423; AZD5423; UNII-641H0Q518W; |
| 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
| ln Vitro | AZD5423 is >900-fold selective for other steroid hormone receptors and has significant affinity for the glucocorticoid receptor, with an IC50 of 0.9 nM in the radioligand human glucocorticoid receptor assay [1]. |
| References |
[1]. Safety, Pharmacokinetics and Pharmacodynamics of the Selective Glucocorticoid Receptor Modulator AZD5423 after Inhalation in Healthy Volunteers. Basic Clin Pharmacol Toxicol. 2016 Dec;119(6):574-581. [2]. A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses. Am J Respir Crit Care Med. 2015 Jan 15;191(2):161-7. |
| Additional Infomation | AZD5423 has been used in trials studying the basic science and treatment of Asthma, Bioavailability and AUC, and Chronic Obstructive Pulmonary Disease (COPD). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~205.15 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.27 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 20.8 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: ≥ 2.08 mg/mL (4.27 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 20.8 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.) |