A-437203 is a novel, potent and selective D3 receptor antagonist with Ki of 71, 1.6, and 6220 nM for D2, D3, and D4 receptors, respectively.
Physicochemical Properties
| Molecular Formula | C20H27F3N6OS |
| Molecular Weight | 456.5282 |
| Exact Mass | 456.192 |
| Elemental Analysis | C, 52.62; H, 5.96; F, 12.48; N, 18.41; O, 3.50; S, 7.02 |
| CAS # | 220519-06-2 |
| Related CAS # | 220519-06-2 (anhydrous free base); 1160247-85-7 (fumarate dihydrate); 220519-07-3 (anhydrous); |
| PubChem CID | 9916104 |
| Appearance | Solid powder |
| LogP | 3.595 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 31 |
| Complexity | 685 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | S(C1=NC([H])=C([H])C(N1[H])=O)C([H])([H])C([H])([H])C([H])([H])N1C([H])([H])C([H])([H])N(C2C([H])=C(C(F)(F)F)N=C(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N=2)C([H])([H])C1([H])[H] |
| InChi Key | KXVAICSRMHXLJN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C20H27F3N6OS/c1-19(2,3)17-25-14(20(21,22)23)13-15(26-17)29-10-8-28(9-11-29)7-4-12-31-18-24-6-5-16(30)27-18/h5-6,13H,4,7-12H2,1-3H3,(H,24,27,30) |
| Chemical Name | 2-[3-[4-[2-tert-butyl-6-(trifluoromethyl)pyrimidin-4-yl]piperazin-1-yl]propylsulfanyl]-1H-pyrimidin-6-one |
| Synonyms | ABT-925; ABT 925; ABT925; BSF201640; BSF-201640; DAT201; A437203; A 437203; BSF 201640; LU 201640; LU201640; DAT 201; |
| 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-437203 is an antagonist that has a higher affinity for D3 receptors than other dopamine receptor subtypes, and it has a reasonably high selectivity (44 times more selective for D3 than D2) [1]. |
| ln Vivo | In the rat forced swim test (FST), A-437203, a selective D3 receptor antagonist, was first evaluated in isolation. The doses of A-437203 that were assessed were 1.75, 5.24, 17.46, and 0.52 μmol/kg ip. The choice of dosage was determined by A-437203's selectivity for D3 dopamine receptors as opposed to D2 receptors. Records show that the compound's effects at a dose of 10.46 μmol/kg (10 mg/kg) or less were presumably mediated by D3, not D2 receptors, since higher doses, like 174.6 μmol/kg (100 mg/kg), are needed to bind and prevent the irreversible inactivation of the D2 receptor caused by the alkylating agent EEDG. For all of the examined activities (immobility, F4,45 = 1.12, p = 0.359; climbing, F4,45 = 0.188, p = 0.943; swimming, F4,45 = 1.634, p = 0.182), an ANOVA revealed no significant changes between treatments. These findings led to the selection of a 17.46 μmol/kg ip dose of A-437203 for additional testing [1]. |
| References | [1]. Basso AM, et al. Antidepressant-like effect of D(2/3) receptor-, but not D(4) receptor-activation in the rat forced swim test. Neuropsychopharmacology. 2005 Jul;30(7):1257-68 |
| Additional Infomation | See also: Abt-925 (is active moiety of). |
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 | 2.1904 mL | 10.9522 mL | 21.9044 mL | |
| 5 mM | 0.4381 mL | 2.1904 mL | 4.3809 mL | |
| 10 mM | 0.2190 mL | 1.0952 mL | 2.1904 mL |