AZD7624 is a novel, potent and selective inhaled p38 inhibitor with anti-inflammatory activity. In order to treat lung disease effectively without producing undesirable systemic effects, inhaled medications typically aim to have a local pharmacological effect in the lung while minimizing systemic exposure. Superior pharmacodynamic lung effects and pharmacokinetic exposure are both possible with AZD7624. When compared to intravenous dosing, the lung exposure to the drug AZD7624 in rats after inhalation was five times higher. It has been demonstrated that inhaled AZD7624 significantly reduces (85%) the amount of tumor necrosis factor α (TNFα) (induced by lipopolysaccharide, or LPS), in sputum in healthy volunteers.
Physicochemical Properties
| Molecular Formula | C27H30FN5O3 |
| Molecular Weight | 491.55720949173 |
| Exact Mass | 491.233 |
| Elemental Analysis | C, 65.97; H, 6.15; F, 3.86; N, 14.25; O, 9.76 |
| CAS # | 1095004-78-6 |
| Related CAS # | 1095004-78-6 |
| PubChem CID | 25143624 |
| Appearance | Off-white to light yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.661 |
| LogP | 1.59 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 10 |
| Heavy Atom Count | 36 |
| Complexity | 887 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | FC1C=C(C=C(C=1C)N1C=CN=C(C1=O)NC1(C2C=CC=CC=2OCCNC)CC1)C(NC1CC1)=O |
| InChi Key | NNKPHNTWNILINE-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C27H30FN5O3/c1-17-21(28)15-18(25(34)31-19-7-8-19)16-22(17)33-13-11-30-24(26(33)35)32-27(9-10-27)20-5-3-4-6-23(20)36-14-12-29-2/h3-6,11,13,15-16,19,29H,7-10,12,14H2,1-2H3,(H,30,32)(H,31,34) |
| Chemical Name | N-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide |
| Synonyms | AZD-7624; AZD7624; AZD 7624 |
| 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 |
| 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 | p38 |
| ln Vitro | AZD7624 is an inhaled p38 inhibitor that can be inhaled. With pIC50 values of 8.4, 8.1, and 9.0[1], AZD7624 inhibits LPS-induced TNFα in human mononuclear cells, whole blood, as well as in alveolar macrophages in vitro. |
| References |
[1]. AZD7624, an Inhaled p38 Inhibitor, Demonstrates Local Lung Inhibition of LPS-Induced TNFα with Minimal Systemic Exposure. J Pharmacol Exp Ther. 2018 Jun;365(3):567-572. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~10 mg/mL (~18.71 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.23 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 (4.23 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0343 mL | 10.1717 mL | 20.3434 mL | |
| 5 mM | 0.4069 mL | 2.0343 mL | 4.0687 mL | |
| 10 mM | 0.2034 mL | 1.0172 mL | 2.0343 mL |