FR194921 is a potent, selective, orally bioactive Adenosine A1 antagonist that penetrates the BBB (blood-brain barrier), with Kis of 6.6 and 5400 nM for A1 and A2A, respectively. FR194921 displays cognitive enhancing and anxiolytic (anti-anxiety) activity.

Physicochemical Properties

Molecular Formula	C23H23N5O
Molecular Weight	385.46
Exact Mass	385.19
CAS #	202646-80-8
PubChem CID	9821511
Appearance	Off-white to light yellow solid powder
LogP	3.429
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	29
Complexity	662
Defined Atom Stereocenter Count	0
SMILES	CN1CCC(CC1)N2C(=O)C=CC(=N2)C3=C4C=CC=CN4N=C3C5=CC=CC=C5
InChi Key	YHDRUTMZCJZJAL-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H23N5O/c1-26-15-12-18(13-16-26)28-21(29)11-10-19(24-28)22-20-9-5-6-14-27(20)25-23(22)17-7-3-2-4-8-17/h2-11,14,18H,12-13,15-16H2,1H3
Chemical Name	2-(1-methylpiperidin-4-yl)-6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)pyridazin-3-one
Synonyms	FR194921; FR 194921; FR-194921
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 Vivo	The stent exhibits good oral bioavailability for FR194921 (32 mg/kg; po), as evidenced by its AUC of 6.91 µg·h/mL, Cmax of 2.13 µg/mL, Tmax of 0.63 h, and BA of 60.6% [1]. The lowest dosages of FR194921 (0.032, 0.1, and 0.32 mg/kg) are required to restrict CPA-induced hypomotility [2]. Scopolamine-induced memory impairments are greatly improved by FR194921 (0.1–10 mg/kg; intraperitoneal administration) [2].
Animal Protocol	Animal/Disease Models: SD rats [2] Doses: 0.032, 0.1, 0.32 mg/kg Route of Administration: Po; . Oral administration of CPA (0.056 mg/kg; ip) 25 minutes before intraperitonealadministration Experimental Results: Dose-dependent attenuation of CPA-induced hypokinesia with an ED50 value of 0.08 mg/kg, statistically significant at 0.32 mg/kg Attachment. Animal/Disease Models: SD rat [2] Doses: 0.1, 0.32, 1, 3.2, 10 mg/kg Route of Administration: intraperitoneal (ip) injection; Scopolamine (1 mg/kg, intraperitoneal (ip) injection) Experimental Results: After scopolamine-induced memory deficit in rats Cognitive abilities are Dramatically enhanced.
References	[1]. Kuroda S, et al. Design, synthesis and biological evaluation of a novel series of potent, orally active adenosine A1 receptor antagonists with high blood-brain barrier permeability. Chem Pharm Bull (Tokyo). 2001 Aug;49(8):988-98. [2]. Maemoto T, et al. Pharmacological characterization of FR194921, a new potent, selective, and orally active antagonist for central adenosine A1 receptors. J Pharmacol Sci. 2004 Sep;96(1):42-52.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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	2.5943 mL	12.9715 mL	25.9430 mL
	5 mM	0.5189 mL	2.5943 mL	5.1886 mL
	10 mM	0.2594 mL	1.2972 mL	2.5943 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.