AZD-2066 is a potent, selective, orally bioavailable and brain penetrant antagonist mGlu5 (metabotropic glutamate receptor 5) with IC50 in the nanomolar range for rat and human receptors, respectively. It displays discriminative effects in rats. The discriminative effects of AZD9272 and AZD2066 are similar to those of previously investigated mGluR5 antagonists and dissimilar to those of cocaine, PCP, chlordiazepoxide, and (-)-Δ(9)-THC. The discriminative half-life of AZD9272 is approximately 7-fold longer than for MTEP. These data support and extend previous findings suggesting that mGluR5 antagonism causes psychoactive effects selectively mediated by mGluR5 mechanisms.
Physicochemical Properties
| Molecular Formula | C19H16CLN5O2 |
| Molecular Weight | 381.815642356873 |
| Exact Mass | 381.099 |
| CAS # | 934282-55-0 |
| Related CAS # | AZD 2066 hydrate |
| PubChem CID | 16041426 |
| Appearance | White to off-white solid powder |
| LogP | 4.325 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 27 |
| Complexity | 481 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | C[C@H](C1=NOC(=C1)C2=CC(=CC=C2)Cl)OC3=NN=C(N3C)C4=CC=NC=C4 |
| InChi Key | SXWHYTICXCLKDG-GFCCVEGCSA-N |
| InChi Code | 1S/C19H16ClN5O2/c1-12(16-11-17(27-24-16)14-4-3-5-15(20)10-14)26-19-23-22-18(25(19)2)13-6-8-21-9-7-13/h3-12H,1-2H3/t12-/m1/s1 |
| Chemical Name | 4-[5-[(1R)-1-[5-(3-Chlorophenyl)-3-isoxazolyl]ethoxy]-4-methyl-4H-1,2,4-triazol-3-yl]pyridine |
| Synonyms | AZD-2066; AZD 2066; AZD2066. |
| 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 | In mGlu5/HEK cells, striatum, hippocampal, and cortical cultures, AZD 2066 (1–10 μM) suppresses Ca2+ responses with IC50 values of 27.2±9.1, 3.56±0.52, 96.2±17.8, and 380±78.0 nM, respectively [2]. In mGlu5/HEK cells, AZD 2066 (1–10 μM) prevents the DHPG or Quis effect and suppresses the oscillatory Ca2+ response brought on by the bath solution [2]. Striatal neurons are poorly affected by AZD 2066 (1–10 μM) [2]. |
| ln Vivo | Rats treated orally with AZD 2066 (0.3–30 mg/kg) have distinct effects [1]. |
| Animal Protocol |
Animal/Disease Models: Male Wistar rat (weight 240-250 grams) [1] Doses: 0.03, 0.1, 0.3, 1, 3, 10, 30 mg/kg Route of Administration: Po (60 minutes after administration) Experimental Results:Caused Adequacy and dose-dependent response to AZD9272 is appropriate. |
| References |
[1]. AZD9272 and AZD2066: selective and highly central nervous system penetrant mGluR5 antagonists characterized by their discriminative effects. J Pharmacol Exp Ther. 2014 Aug;350(2):212-22. [2]. Location and Cell-Type-Specific Bias of Metabotropic Glutamate Receptor, mGlu 5, Negative Allosteric Modulators. ACS Chem Neurosci. 2019 Nov 20; 10(11): 4558-4570. |
| Additional Infomation | AZD2066 has been used in trials studying the treatment and basic science of Pain, Chronic Pain, Reflux Episodes, Neuropathic Pain, and Diabetic Neuropathy, among others. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6190 mL | 13.0952 mL | 26.1904 mL | |
| 5 mM | 0.5238 mL | 2.6190 mL | 5.2381 mL | |
| 10 mM | 0.2619 mL | 1.3095 mL | 2.6190 mL |