Physicochemical Properties
| Molecular Formula | C18H21CLN2O4 |
| Molecular Weight | 364.82 |
| Exact Mass | 364.118 |
| CAS # | 2135785-20-3 |
| PubChem CID | 130475870 |
| Appearance | White to off-white solid powder |
| LogP | 1.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 25 |
| Complexity | 545 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | C1[C@]2(COC(=O)N2)C[C@H]1C(N1CC(OCC2=CC=C(C)C(Cl)=C2)C1)=O |
| InChi Key | AKBHYCHPWZPGAH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H21ClN2O4/c1-11-2-3-12(4-15(11)19)9-24-14-7-21(8-14)16(22)13-5-18(6-13)10-25-17(23)20-18/h2-4,13-14H,5-10H2,1H3,(H,20,23) |
| Chemical Name | 2-[3-[(3-chloro-4-methylphenyl)methoxy]azetidine-1-carbonyl]-7-oxa-5-azaspiro[3.4]octan-6-one |
| 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 | Compound 4f, MAGL-IN-4, exhibits a high LLE of 5.9 and a logD of 2.3 for MAGL[1]. Regarding the similarly related serine hydrolases (FAAH and ABHD6; all IC50>10000 nM), MAGL-IN-4 shows no inhibition. Regarding cannabinoid receptors, MAGL-IN-4 exhibits negligible binding potentials (19% for CB1 and 5% for CB2 at 10 μM) and a low hERG liability (14.4 percent inh. at 10 μM, manual patch clamp, without BSA)[1]. |
| ln Vivo | In C57BL/6J mice, MAGL-IN-4 (compound 4f; 0.1-10 mg/kg; oral; single dose) causes a considerable decrease in arachidonic acid (AA) from 0.3 mg/kg and a large increase in 2-AG[1]. |
| References |
[1]. Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2 H-benzo[ b][1,4]oxazin-6-yl Moiety. J Med Chem. 2021 Aug 12;64(15. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (274.11 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.85 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 (6.85 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 (6.85 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 | 2.7411 mL | 13.7054 mL | 27.4108 mL | |
| 5 mM | 0.5482 mL | 2.7411 mL | 5.4822 mL | |
| 10 mM | 0.2741 mL | 1.3705 mL | 2.7411 mL |