VU6005649 is a CNS penetrant mGlu7/8 receptor agonist with EC50s of 0.65 μM and 2.6 μM for mGlu7 receptor and mGlu8 receptor, respectively.
Physicochemical Properties
| Molecular Formula | C16H12F5N3O |
| Molecular Weight | 357.278000831604 |
| Exact Mass | 357.09 |
| Elemental Analysis | C, 53.79; H, 3.39; F, 26.59; N, 11.76; O, 4.48 |
| CAS # | 2137047-43-7 |
| PubChem CID | 131954513 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 3.8 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 25 |
| Complexity | 479 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | NYBZCKAQIIPSDS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H12F5N3O/c1-7-6-11(16(19,20)21)24-15(22-7)12(8(2)23-24)9-4-5-10(25-3)14(18)13(9)17/h4-6H,1-3H3 |
| Chemical Name | 3-(2,3-difluoro-4-methoxyphenyl)-2,5-dimethyl-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine |
| Synonyms | VU6005649; VU-6005649; VU 6005649 |
| 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
| Targets | mGlu7 Receptor ( EC50 = 0.65 μM ); mGlu8 Receptor ( EC50 = 2.6 μM ) |
| ln Vitro | VU6005649 is a mGlu7/8 receptor agonist that penetrates the central nervous system. Its EC50 values for the mGlu7 and mGlu8 receptors are 0.65 μM and 2.6 μM, respectively. The terminal Kp of VU6005649 is 2.43, and its total brain levels are approximately 9× higher than the mGlu7 positive allosteric modulator (PAM) in vitro EC50[1]. |
| ln Vivo | VU6005649 (compound 9f) does not show any efficacy in this assay when dosed at 30 mg/kg IP in 10% Tween 80/H2O (0.75 mg/kg. s.c. amphetamine). In wild-type mice, VU6005649 exhibits small but noteworthy pro-cognitive effects on associative learning. It also provides the first instance of a mGlu7/8 positive allosteric modulator's (PAM) effectiveness in this model[1]. |
| Animal Protocol | VU6005649 (compound 9f) is formulated in 10% polysorbate 80 and administered intraperitoneally (3 times per time point) to 20-week-old female C57/Bl6 mice for tissue distribution studies. Animals are put to death and beheaded at 0.25, 0.5, 1, 3, and 6 hours after the dose. Blood is drawn by cardiac puncture, and the brains are extracted, thoroughly cleaned in cold phosphate-buffered saline, and then frozen on dry ice right away[1]. |
| References |
[1]. Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines. ACS Med Chem Lett. 2017 Sep 1;8(10):1110-1115. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~140.0 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.00 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 (7.00 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 | 2.7989 mL | 13.9946 mL | 27.9893 mL | |
| 5 mM | 0.5598 mL | 2.7989 mL | 5.5979 mL | |
| 10 mM | 0.2799 mL | 1.3995 mL | 2.7989 mL |