Balapiravir (Ro 4588161; R1626) is an orally active proagent of a nucleoside analogue inhibitor of the RNA-dependent RNA polymerase (RdRp) of HCV (R1479; 4'-Azidocytidine).Anti-HCV activity is present in balapiravir. A click chemistry reagent, balapiravir has an azide group and can react with molecules that have alkyne groups through the copper-catalyzed azide-alkyne cycloaddition reaction (CuAAc). Alkyne-azide cycloaddition (SPAAC) that is promoted by strain can also happen to molecules that have BCN or DBCO groups in them.

Physicochemical Properties

Molecular Formula	C21H30N6O8
Molecular Weight	494.4983
Exact Mass	494.213
Elemental Analysis	C, 51.01; H, 6.12; N, 17.00; O, 25.88
CAS #	690270-29-2
Related CAS #	Balapiravir hydrochloride;690270-65-6
PubChem CID	11691726
Appearance	Off-white to light yellow solid powder
LogP	1.729
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	12
Heavy Atom Count	35
Complexity	971
Defined Atom Stereocenter Count	4
SMILES	O=C1N=C(N)C=CN1[C@@H]2O[C@](N=[N+]=[N-])(COC(C(C)C)=O)[C@@H](OC(C(C)C)=O)[C@H]2OC(C(C)C)=O
InChi Key	VKXWOLCNTHXCLF-DXEZIKHYSA-N
InChi Code	InChI=1S/C21H30N6O8/c1-10(2)17(28)32-9-21(25-26-23)15(34-19(30)12(5)6)14(33-18(29)11(3)4)16(35-21)27-8-7-13(22)24-20(27)31/h7-8,10-12,14-16H,9H2,1-6H3,(H2,22,24,31)/t14-,15+,16-,21-/m1/s1
Chemical Name	(2R,3S,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-azido-2-((isobutyryloxy)methyl)tetrahydrofuran-3,4-diyl bis(2-methylpropanoate)
Synonyms	R1626; R-1626; R 1626; RO4588161; RO-4588161; RO 4588161
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	Upon administering 28.1 mg/kg of balapiravir orally to CD-1 mice (Ro 4588161; R1626), R1479 exhibits a Cmax and a minimum concentration in plasma (Cmin) of 24.38 μM and 6.34 μM, respectively, two and twenty-four hours after dosing[3].
References	[1]. A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients. J Infect Dis. 2013 May 1;207(9):1442-1450. [2]. Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients.Ann Hepatol. 2012 Jan-Feb;11(1):15-31. [3]. Activation of Peripheral Blood Mononuclear Cells by Dengue Virus Infection Depotentiates Balapiravir. J Virol. 2014 Feb;88(3):1740-7.
Additional Infomation	R1626 is one of a new class of hepatitis C therapies called polymerase inhibitors. It achieves significant reductions in viral load in chronic hepatitis C patients infected with the difficult to treat genotype 1 virus. R1626 is very effective in inhibiting viral replication Balapiravir has been used in trials studying the treatment of Dengue and Hepatitis C, Chronic. Balapiravir is an orally administered prodrug with activity against the hepatitis C virus (HCV). Balapiravir is a tri-isobutyrate ester prodrug of R1479, a nucleoside analogue inhibitor of HCV RNA-dependent RNA polymerase. Drug Indication Investigated for use/treatment in hepatitis (viral, C).

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~202.22 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.06 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 (5.06 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 (5.06 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	2.0222 mL	10.1112 mL	20.2224 mL
	5 mM	0.4044 mL	2.0222 mL	4.0445 mL
	10 mM	0.2022 mL	1.0111 mL	2.0222 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.