Ispronicline (AZD-3480; TC-1734) is a novel and potent alpha4beta2 nicotinic acetylcholine receptor agonist. As an orally bioactive and brain-selective α4β2 nicotine acetylcholine receptor (nAChR) partial agonist, it exhibits memory-enhancing properties in rodents and a good tolerability profile.
Physicochemical Properties
| Molecular Formula | C14H22N2O |
| Molecular Weight | 234.343 |
| Exact Mass | 234.173 |
| Elemental Analysis | C, 71.76; H, 9.46; N, 11.95; O, 6.83 |
| CAS # | 252870-53-4 |
| Related CAS # | 252870-53-4;252870-54-5 (hemigalactarate);957106-98-8 (phosphate);957107-01-6 (citrate); |
| PubChem CID | 9824145 |
| Appearance | Colorless to light yellow oily liquid |
| LogP | 3.27 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 17 |
| Complexity | 228 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O(C1=C([H])N=C([H])C(=C1[H])/C(/[H])=C(\[H])/C([H])([H])[C@]([H])(C([H])([H])[H])N([H])C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H] |
| InChi Key | RPCVIAXDAUMJJP-PZBABLGHSA-N |
| InChi Code | InChI=1S/C14H22N2O/c1-11(2)17-14-8-13(9-16-10-14)7-5-6-12(3)15-4/h5,7-12,15H,6H2,1-4H3/b7-5+/t12-/m0/s1 |
| Chemical Name | (E,2S)-N-methyl-5-(5-propan-2-yloxypyridin-3-yl)pent-4-en-2-amine |
| Synonyms | AZD-3480 TC1734AZD 3480 TC-1734 AZD3480 Ispronicline |
| 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 Vivo | Ispronicline (10-20 mg/kg; subcutaneous injection) stimulates c-Fos expression in specific regions of the rat forebrain [1]. The pharmacokinetics of isopronicline (half-life in rats is 2 hours) stand in stark contrast to the long-lasting effects in working memory (18 hours to 2 days) [2]. |
| Animal Protocol |
Animal/Disease Models: Male Wistar rat, body weight 180-200 g[1] Doses: 10 and 30 mg/kg Route of Administration: subcutaneous injection Experimental Results: c-Fos was induced in the medial paraventricular nucleus of the hypothalamus. Treatment with 30 mg/kg isopronicline (but not 10 mg/kg) Dramatically increased the number of c-Fos immunoreactive cells in the medial parvocellular part of the paraventricular nucleus (PVN) compared with controls. |
| References |
[1]. The α4β2 nicotine acetylcholine receptor agonist ispronicline induces c-Fos expression in selective regions of the rat forebrain. Neurosci Lett. 2012 Apr 25;515(1):7-11. |
| Additional Infomation | Ispronicline is under investigation in clinical trial NCT00109564 (A Safety and Efficacy Study of Ispronicline (TC-1734-112) in Subjects With Age Associated Memory Impairment (AAMI)). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~426.73 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.67 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 (10.67 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 25.0 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: ≥ 2.5 mg/mL (10.67 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 | 4.2673 mL | 21.3365 mL | 42.6730 mL | |
| 5 mM | 0.8535 mL | 4.2673 mL | 8.5346 mL | |
| 10 mM | 0.4267 mL | 2.1337 mL | 4.2673 mL |