Physicochemical Properties
| Molecular Formula | C16H20N2O3 |
| Molecular Weight | 288.34 |
| Exact Mass | 404.158 |
| CAS # | 527680-56-4 |
| Related CAS # | PHA 568487;527680-57-5 |
| PubChem CID | 9932000 |
| Appearance | White to off-white solid powder |
| LogP | 1.322 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 21 |
| Complexity | 395 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C1CN2CCC1[C@H](C2)NC(=O)C3=CC4=C(C=C3)OCCO4 |
| InChi Key | LUVXHMJTVXZFPD-ZDUSSCGKSA-N |
| InChi Code | InChI=1S/C16H20N2O3/c19-16(17-13-10-18-5-3-11(13)4-6-18)12-1-2-14-15(9-12)21-8-7-20-14/h1-2,9,11,13H,3-8,10H2,(H,17,19)/t13-/m0/s1 |
| Chemical Name | N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide |
| 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 | A α-7 nAchR-specific agonist, PHA 568487, inhibits NF-κb activation in cells[2]. Following in vitro ischemia, PHA 568487 treatment dramatically lowers the expression of leukocyte infiltration molecules in MCAO rats and endothelial cells[3]. |
| ln Vivo | Through the promotion of inflammation resolution, PHA 568487 therapy mitigates the cognitive deterioration in mice resulting from aseptic bone fractures. Intraperitoneally administered PHA 568487 (PHA; 0.8 mg/kg) decreases TUNEL positive neurons and infarct volume in the peri-infarct areas of permanent middle cerebral artery occlusion (pMCAO) and pMCAO+tibia fracture mice[2]. The decrease of [18F]DPA-714 binding in ischemic rats treated with the a7 agonist PHA 568487 at day 7 after MCAO[3] provides evidence for the role a7 receptors play in neuroinflammation. When compared to non-treated MCAO rats, ischemic rats treated with PHA 568487 exhibit a significant reduction in cerebral infarct volumes and an improvement in the neurologic outcome[3]. |
| Animal Protocol |
Animal/Disease Models: C57BL/6J male mice (10-12 weeks old) with pMCAO[2] Doses: 0.4 and 0.8 mg/kg Route of Administration: Injected intraperitoneally (ip) once on day 1, or twice on days 1 and 2, after pMCAO Experimental Results: 0.8 mg/kg on days 1 and 2 after pMCAO yielded the best effect on infarct volume and behavior tests. Animal/Disease Models: Adult male SD (Sprague-Dawley) rats[3] Doses: 1.25 mg/kg Route of Administration: Treated ip daily with 0.1 mL Experimental Results: demonstrated a significant decrease of [18F]DPA-714 binding in the ischemic cerebral hemisphere in comparison to non-treated ischemic rats. |
| References |
[1]. Multiple species metabolism of PHA-568487, a selective alpha 7 nicotinic acetylcholine receptor agonist. Drug Metab Lett. 2010 Aug;4(3):162-72. [2]. Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture. J Neurochem. 2014 Nov;131(4):498-508. [3]. In vivo imaging of Α7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia. Glia. 2018 Aug;66(8):1611-1624. |
Solubility Data
| Solubility (In Vitro) | DMSO: 25 mg/mL (86.70 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.21 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 (7.21 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (7.21 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 | 3.4681 mL | 17.3406 mL | 34.6813 mL | |
| 5 mM | 0.6936 mL | 3.4681 mL | 6.9363 mL | |
| 10 mM | 0.3468 mL | 1.7341 mL | 3.4681 mL |