GNE 5729 is a novel, potent, brain permeable positive allosteric modulator (PAM) and GluN2A subunit-selective of NMDAR with an EC50 of 37 nM for GluN2A, 4.7 and 9.5 μM for GluN2C and GluN2D, respectively. The N-methyl-d-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, gated by the endogenous coagonists glutamate and glycine, permeable to Ca2+ and Na+. NMDAR dysfunction is associated with numerous neurological and psychiatric disorders, including schizophrenia, depression, and Alzheimer's disease. GNE-0723 is a and brain-penetrant positive allosteric modulatorof NMDARs.
Physicochemical Properties
| Molecular Formula | C17H10CL2F3N5O |
| Molecular Weight | 428.195411205292 |
| Exact Mass | 427.021 |
| CAS # | 2026635-66-3 |
| PubChem CID | 122630795 |
| Appearance | White to yellow solid powder |
| Density | 1.7±0.1 g/cm3 |
| Boiling Point | 527.6±60.0 °C at 760 mmHg |
| Flash Point | 272.9±32.9 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.702 |
| LogP | 2.73 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 28 |
| Complexity | 900 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C1[C@H]([C@@H]1C2=C(C=CC3=NC(=CC(=O)N32)CN4C(=CC(=N4)C(F)(F)F)Cl)Cl)C#N |
| InChi Key | GPMGDUIAVSFGGH-WCBMZHEXSA-N |
| InChi Code | InChI=1S/C17H10Cl2F3N5O/c18-11-1-2-14-24-9(7-26-13(19)5-12(25-26)17(20,21)22)4-15(28)27(14)16(11)10-3-8(10)6-23/h1-2,4-5,8,10H,3,7H2/t8-,10+/m0/s1 |
| Chemical Name | (1R,2R)-2-(7-chloro-2-((5-chloro-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-6-yl)cyclopropane-1-carbonitrile |
| Synonyms | GNE-5729; GNE 5729; GNE5729. |
| 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 | The NMDAR positive allosteric modulator GNE 5729 penetrates the brain and has an EC50 of 37 nM for GluN2A, 4.7 μM for GluN2C, and 9.5 μM for GluN2D [1]. |
| References |
[1]. GluN2A-Selective Pyridopyrimidinone Series of NMDAR Positive Allosteric Modulators with an Improved in Vivo Profile. ACS Med Chem Lett. 2016 Oct 31;8(1):84-89. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~233.54 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.84 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 (5.84 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3354 mL | 11.6768 mL | 23.3536 mL | |
| 5 mM | 0.4671 mL | 2.3354 mL | 4.6707 mL | |
| 10 mM | 0.2335 mL | 1.1677 mL | 2.3354 mL |