 Chemical Structure.png)
Ciproxifan (formerly known as FUB-359) is a highly potent and selective histamine H3-receptor antagonist with IC50 of 9.2 nM, with low apparent affinity at other receptor subtypes. In addition, Ciproxifan has been reported to competitively antagonize the (R) α-MeHA induced relaxation of electrically stimulated guinea pig ileum longitudinal muscle. Besides, Ciproxifan has been revealed to have the effect on [125I]iodoproxyfan binding with a Ki value of 0.7±0.2 nM.
Physicochemical Properties
| Molecular Formula | C20H22N2O6 |
| Molecular Weight | 386.404 |
| Exact Mass | 386.147 |
| Elemental Analysis | C, 62.17; H, 5.74; N, 7.25; O, 24.84 |
| CAS # | 184025-19-2 |
| Related CAS # | Ciproxifan;184025-18-1 |
| PubChem CID | 16219152 |
| Appearance | White to off-white solid powder |
| Boiling Point | 743.6ºC at 760 mmHg |
| Flash Point | 403.5ºC |
| Vapour Pressure | 3.22E-23mmHg at 25°C |
| LogP | 2.725 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 28 |
| Complexity | 441 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])C([H])([H])C([H])([H])C1=C([H])N=C([H])N1[H])C1([H])C([H])([H])C1([H])[H].O([H])C([H])=O.O([H])C(C([H])=C([H])[H])=O |
| InChi Key | RLQFKEYRALXXEJ-BTJKTKAUSA-N |
| InChi Code | InChI=1S/C16H18N2O2.C4H4O4/c19-16(12-3-4-12)13-5-7-15(8-6-13)20-9-1-2-14-10-17-11-18-145-3(6)1-2-4(7)8/h5-8,10-12H,1-4,9H2,(H,17,18)1-2H,(H,5,6)(H,7,8)/b2-1- |
| Chemical Name | Cyclopropyl-(4-(3-1H-imidazol-4-yl)propyloxyphenyl)ketone maleate |
| Synonyms | FUB-359 FUB 359 FUB359 Ciproxifan. Ciproxifan maleate |
| 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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 | Using a Ki of 0.5 nM, ciprofan suppresses the release of [3H]HA from rat cerebral cortex synaptosomes[1]. [125I]iodoproxyfan's binding to rat striatal membranes is inhibited by ciprofan (0.01 nM-1 μM; 60 minutes) with a Ki of 0.7 nM [1]. |
| ln Vivo | In the mouse brain, ciprofloxan (1 mg/kg; single oral dose) raises t-MeHA levels with an ED50 of 0.14 mg/kg[1]. In rats, ciprofen (3 mg/kg, i.p.) increased response accuracy in a five-choice task only when the stimulus duration was 0.25 seconds rather than 0.50 seconds [1]. Cats given ciprofen (0.15-2 mg/kg; oral) exhibit definite evidence of neocortical EEG activation, as evidenced by an increase in the density of fast rhythms and near-complete wakefulness [1]. The half-lives (t1/2) of the distribution and elimination phases in mice are 13 and 87 minutes, respectively, and ciprofen (1 mg/kg; single intravenous injection) can lower the concentration of H3 receptor ligands in the serum [1]. Mice show oral bioavailability (F=62%) and maximum concentration (Cmax=420 nM) for ciprofen (1 mg/kg; single oral dose) [1]. |
| References |
[1]. Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist. J Pharmacol Exp Ther. 1998 Nov;287(2):658-66. [2]. Motawaj M, Arrang JM. Ciproxifan, a histamine H3-receptorantagonist / inverse agonist, modulates methamphetamine-induced sensitization in mice. Eur J Neurosci. 2011 Apr;33(7):1197-204. doi: 10.1111/j.1460-9568.2011.07618.x. [3]. Bardgett ME, Davis NN, Schultheis PJ, Griffith MS. Ciproxifan, an H3 receptor antagonist, alleviates hyperactivity and cognitive deficits in the APP Tg2576 mouse model of Alzheimer's disease. Neurobiol Learn Mem. 2011 Jan;95(1):64-72. [4]. Bardgett ME, Points M, Kleier J, Blankenship M, Griffith MS. The H3 antagonist, ciproxifan, alleviates the memory impairment but enhances the motor effects of MK-801 (dizocilpine) in rats. Neuropharmacology. 2010 Nov;59(6):492-502. [5]. Day M, et al . Differential effects of ciproxifan and nicotine on impulsivity and attention measures in the 5-choice serial reaction time test. Biochem Pharmacol. 2007 Apr 15;73(8):1123-34. [6]. Pillot C, Héron A, Schwartz JC, Arrang JM. Ciproxifan, a histamine H3-receptor antagonist/inverse agonist, modulates the effects of methamphetamine on neuropeptide mRNA expression in rat striatum. Eur J Neurosci. 2003 Jan;17(2):307-14. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~258.80 mM) H2O : ~3.57 mg/mL (~9.24 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.47 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 (6.47 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 (6.47 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 | 2.5880 mL | 12.9400 mL | 25.8799 mL | |
| 5 mM | 0.5176 mL | 2.5880 mL | 5.1760 mL | |
| 10 mM | 0.2588 mL | 1.2940 mL | 2.5880 mL |