Physicochemical Properties
| Molecular Formula | C20H18FN3O5 |
| Molecular Weight | 399.372428417206 |
| Exact Mass | 399.123 |
| CAS # | 1850385-64-6 |
| PubChem CID | 118599727 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 731.4±60.0 °C at 760 mmHg |
| Flash Point | 396.1±32.9 °C |
| Vapour Pressure | 0.0±2.4 mmHg at 25°C |
| Index of Refraction | 1.597 |
| LogP | 1.1 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 29 |
| Complexity | 662 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CNC(=O)C[C@H]1COC2=C(N1C(=O)C3=CC4=C(C=C3)OCC(=O)N4)C=CC(=C2)F |
| InChi Key | MBKYLPOPYYLTNW-ZDUSSCGKSA-N |
| InChi Code | InChI=1S/C20H18FN3O5/c1-22-18(25)8-13-9-28-17-7-12(21)3-4-15(17)24(13)20(27)11-2-5-16-14(6-11)23-19(26)10-29-16/h2-7,13H,8-10H2,1H3,(H,22,25)(H,23,26)/t13-/m0/s1 |
| Chemical Name | 2-[(3S)-7-Fluoro-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]-N-methylacetamide |
| Synonyms | AZD9977 AZD-9977 AZD 9977 |
| 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 effects of eplerenone and balcinrenone (AZD9977) on MR, GR, PR, and AR in binding tests. For MR, GR, and PR, the observed pKi were 7.5, 5.4, and 4.6, respectively. Using a reporter test in which full-length MR drives a luciferase reporter gene in U2-OS cells, the functional relationship between balcinrenone and MR was investigated. MR triggered by aldosterone is inhibited by balcinrenone, with an IC50 of 0.28 μM. Balcinrenone in this experiment reduced only 69% of MR activity, despite eplerenone being a complete antagonist. MR LBDs from humans, mice, or rats were used in reporter gene assays to assess the species-selective efficacy of balcinrenone. The IC50 values that correspond to these are 0.37μM, 0.08μM, and 0.08μM, in that order. |
| ln Vivo | In uninephrectomized male Sprague Dawley rats given aldosterone and fed a high-salt diet, balcinrenone (AZD9977) (oral; 10-100 mg/kg; 4 weeks) dose-dependently lowers UACR compared to vehicle. Balcinrenone is just as effective in protecting the kidneys as a complete MR antagonist, despite the observation of partial antagonism in in vitro tests [1]. In comparison to vehicle treatment, oral balcinrenone (100 mg/kg) coadministered with enalapril avoided further progression of the disease and decreased urine albumin excretion (UAE). Even though the reduction in UAE was not statistically significant, coadministration of enalapril had a definite additive effect [1]. |
| Animal Protocol |
Animal/Disease Models: Uninephrectomized male Sprague Dawley rats were given aldosterone and fed a high-salt diet AZD9977 [1] Doses: 10, 30 and 100 mg/kg Route of Administration: po (po (oral gavage)) 10-100 mg/kg; 4 weeks Experimental Results: Improved renal function and histology in animal models of CKD. Animal/Disease Models: 8weeks old uninephrectomized Db/db mice, treated from 18 weeks to 22 weeks of age [1] Doses: 100 mg/kg Route of Administration: oral; Route of Administration: oral. 100 mg/kg; co-administration with enalapril results in: reduction of proteinuria in patients with diabetic nephropathy. Coadministration of enalapril and AZD9977 has an additive effect on renal pathology scores. |
| References |
[1]. Clinical safety, tolerability, pharmacokinetics and effects on urinary electrolyte excretion of AZD9977, a novel, selective mineralocorticoid receptor modulator. Br J Clin Pharmacol. 2018 Jul;84(7):1486-1493. |
| Additional Infomation | AZD-9977 is under investigation in clinical trial NCT03843060 (A Phase 1 Study to Assess the Pharmacokinetics of AZD9977 Administered Alone and in Combination With Itraconazole in Healthy Volunteers). |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~625.99 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.21 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 20.8 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: ≥ 2.08 mg/mL (5.21 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 20.8 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: ≥ 2.08 mg/mL (5.21 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 20.8 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 | 2.5039 mL | 12.5197 mL | 25.0394 mL | |
| 5 mM | 0.5008 mL | 2.5039 mL | 5.0079 mL | |
| 10 mM | 0.2504 mL | 1.2520 mL | 2.5039 mL |