Physicochemical Properties
| Molecular Formula | C16H15N7O2 |
| Molecular Weight | 337.34 |
| Exact Mass | 337.128 |
| Elemental Analysis | C, 56.97; H, 4.48; N, 29.07; O, 9.49 |
| CAS # | 139180-30-6 |
| Related CAS # | 139180-30-6 |
| PubChem CID | 176407 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Index of Refraction | 1.791 |
| LogP | 0.89 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 25 |
| Complexity | 435 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O1C([H])=C([H])C([H])=C1C1N=C2N=C(N=C(N([H])[H])N2N=1)N([H])C([H])([H])C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H] |
| InChi Key | PWTBZOIUWZOPFT-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C16H15N7O2/c17-14-20-15(18-8-7-10-3-5-11(24)6-4-10)21-16-19-13(22-23(14)16)12-2-1-9-25-12/h1-6,9,24H,7-8H2,(H3,17,18,19,20,21,22) |
| Chemical Name | 4-[2-[[7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl]amino]ethyl]phenol |
| Synonyms | ZM-241385; ZM241385; 139180-30-6; ZM241385; ZM 241385; ZM-241385; 4-(2-((7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino)ethyl)phenol; 4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol; 4-[2-[[7-amino-2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl]amino]ethyl]phenol; 5NIC36BO71; ZM 241385 |
| 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 | A2AR ( Ki = 1.4 nM ) |
| ln Vitro | ZM241385 (1 μM; 24-48 hours; PC12 cells) treatment counteracts the significant upregulation of A2AR mRNA and protein levels caused by A2AR agonist CGS21680[1]. |
| ln Vivo | ZM241385 (0.2 μg/mouse, 0.4 μg/mouse; intraperitoneal injection; every day; for 11 weeks; female C57BL/6 WT mice) treatment decreases tumor volume, increases CD8+ T cell activation, and splenic MDSC frequency[4]. |
| Enzyme Assay | 1. This paper describes the in vitro pharmacology of ZM 241385 (4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin- 5-yl amino]ethyl) phenol), a novel non-xanthine adenosine receptor antagonist with selectivity for the A2a receptor subtype. 2. ZM 241385 had high affinity for A2a receptors. In rat phaeochromocytoma cell membranes, ZM 241385 displaced binding of tritiated 5'-N-ethylcarboxamidoadenosine (NECA) with a pIC50 of 9.52, (95% confidence limits, c.l., 9.02-10.02). In guinea-pig isolated Langendorff hearts, ZM 241385 antagonized vasodilatation of the coronary bed produced by 2-chloroadenosine (2-CADO) and 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) with pA2 values of 8.57 (c.l., 8.45-8.68) and 9.02 (c.l., 8.79-9.24) respectively. 3. ZM 241385 had low potency at A2b receptors and antagonized the relaxant effects of adenosine in the guinea-pig aorta with a pA2 of 7.06, (c.l., 6.92-7.19). 4. ZM 241385 had a low affinity at A1 receptors. In rat cerebral cortex membranes it displaced tritiated R-phenylisopropyladenosine (R-PIA) with a pIC50 of 5.69 (c.l., 5.57-5.81). ZM 241385 antagonized the bradycardic action of 2-CADO in guinea-pig atria with a pA2 of 5.95 (c.l., 5.72-6.18). 5. ZM 241385 had low affinity for A3 receptors. At cloned rat A3 receptors expressed in chinese hamster ovary cells, it displaced iodinated aminobenzyl-5'-N-methylcarboxamido adenosine (AB-MECA) with a pIC50 of 3.82 (c.l., 3.67-4.06). 6. ZM 241385 had no significant additional pharmacological effects on the isolated tissues used in these studies at concentrations three orders of magnitude greater than those which block A2a receptors[3]. |
| Cell Assay |
Cell Line: PC12 cells Concentration: 1 μM Incubation Time: 24 hours Result: Suppressed the increased A2AR mRNA levels engendered by CGS21680. |
| Animal Protocol |
Female C57BL/6 WT mice received 4-nitroquinoline-N-oxide 0.2 μg/mouse, 0.4 μg/mouse Intraperitoneal injection; every day; for 11 weeks |
| References |
[1]. Static magnetic field exposure reproduces cellular effects of the Parkinson's disease drugcandidate ZM241385. PLoS One. 2010 Nov 8;5(11):e13883. doi: 10.1371/journal.pone.0013883. [2]. Characterization of human A(2B) adenosine receptors: radioligandbinding, western blotting, and coupling to G(q) in human embryonickidney 293 cells and HMC-1 mast cells. Mol Pharmacol. 1999 Oct;56(4):705-13. [3]. The in vitro pharmacology of ZM 241385, a potent, non-xanthine A2a selective adenosinereceptor antagonist. Br J Pharmacol. 1995 Jul;115(6):1096-102. [4]. Impact of combination immunochemotherapies on progression of 4NQO-induced murine oral squamous cell carcinoma. Cancer Immunol Immunother. 2019 Jul;68(7):1133-1141. |
| Additional Infomation | 4-[2-[[7-amino-2-(2-furanyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl]amino]ethyl]phenol is a diamino-1,3,5-triazine. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 30 mg/mL (~88.9 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.17 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 (6.17 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.17 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 | 2.9644 mL | 14.8218 mL | 29.6437 mL | |
| 5 mM | 0.5929 mL | 2.9644 mL | 5.9287 mL | |
| 10 mM | 0.2964 mL | 1.4822 mL | 2.9644 mL |