Cipralisant (GT-2331) is an orally bioactive, low-toxic, effective, selective, and high-affinity histamine H3 receptor blocker (antagonist) in vivo and an agonist of histamine H3 receptor in vitro. For histamine H3 receptor, its pKi The Ki of rat histamine H3 receptor is 0.47 nM. Cipralisant may be used for studying attention deficit hyperactivity disorder. Cipralisant is a reagent for click chemistry. It has Alkyne groups and could undergo CuAAc (copper-catalyzed azide-alkyne cycloaddition reaction) with compounds bearing Azide groups.

Physicochemical Properties

Molecular Formula	C14H20N2
Molecular Weight	216.322
Exact Mass	216.163
CAS #	213027-19-1
Related CAS #	Cipralisant maleate;223420-20-0;Cipralisant (enantiomer);223420-11-9
PubChem CID	6450823
Appearance	White to off-white solid powder
Density	1.03g/cm3
Boiling Point	386.7ºC at 760 mmHg
Flash Point	188.5ºC
Vapour Pressure	7.72E-06mmHg at 25°C
Index of Refraction	1.536
LogP	3.342
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	3
Heavy Atom Count	16
Complexity	302
Defined Atom Stereocenter Count	2
SMILES	CC(C)(C)CCC#C[C@@H]1C[C@H]1C2=CN=CN2
InChi Key	CVKJAXCQPFOAIN-VXGBXAGGSA-N
InChi Code	InChI=1S/C14H20N2/c1-14(2,3)7-5-4-6-11-8-12(11)13-9-15-10-16-13/h9-12H,5,7-8H2,1-3H3,(H,15,16)/t11-,12-/m1/s1
Chemical Name	5-[(1R,2R)-2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole
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	Cipralisant is a complete agonist for adenylyl cyclase inhibition. Cipralisant (HEK cells) suppresses forskolin-induced cAMP accumulation, showing that it is a strong complete histamine H3 receptor agonist. Cipralisant enhances basal [35S]GTPγS binding activity (EC50, 5.6 nM) in HEK cells expressing rat histamine H3 receptors [3].
ln Vivo	In five trials, cipraisant (0.3 to 30 mg/kg; subcutaneous injection) improved collection; at 1 mg/kg, it became significant [2]. Alcohol consumption produced by R-alpha-methylhistamine is totally blocked by Cipralisant (10 mg/kg; oral) [3]. In rats, cipralisant increases wakefulness. Cipralisant's strong affinity for rat H3 receptors and strong CNS penetration are consistent with its ability to effectively and dramatically increase performance in repeated acquisition models. Cipralisant seems to be less efficacious than 3 mg/kg ciproxifene at the maximal effective dose [2]. In a rat brain synaptosome model, cipralisant functions as a partial agonist [3].
Animal Protocol	Animal/Disease Models: Male SHR puppies (35–50 g) [2] Doses: 0.3~30 mg/kg Route of Administration: subcutaneous injection Experimental Results: At the dose of 1 mg/kg, the performance of SHR puppies was Dramatically enhanced and was consistent with Dose related. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat [3] Doses: 10 and 30 mg/kg Route of Administration: Oral Experimental Results: Greater brain exposure was achieved, monitor water intake for 60 minutes after dosing.
References	[1]. Histamine H3 antagonists for treatment of cognitive deficits in CNS diseases. Curr Top Med Chem. 2010;10(2):153-169. [2]. Effects of histamine H(3) receptor ligands GT-2331 and ciproxifan in a repeated acquisition avoidance response in the spontaneously hypertensive rat pup. Behav Brain Res. 2002;131(1-2):151-161. [3]. Detailed pharmacological characterization of GT-2331 for the rat histamine H3 receptor. Eur J Pharmacol. 2006;529(1-3):40-46. [4]. High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models. Eur J Pharmacol. 1998;351(3):307-311.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~924.56 mM)

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	4.6228 mL	23.1139 mL	46.2278 mL
	5 mM	0.9246 mL	4.6228 mL	9.2456 mL
	10 mM	0.4623 mL	2.3114 mL	4.6228 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.