CAS 1256388-51-8|Ledipasvir

Introduction：Basic information about CAS 1256388-51-8|Ledipasvir, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Ledipasvir BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Synonyms

Common Name	Ledipasvir
CAS Number	1256388-51-8	Molecular Weight	889.000
Density	1.4±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₄₉H₅₄F₂N₈O₆	Melting Point	/
MSDS	/	Flash Point	/

Names

Name	ledipasvir
Synonym	More Synonyms

Ledipasvir BiologicalActivity

Description	Ledipasvir is an inhibitor of the hepatitis C virus NS5A, with EC50s of 34 pM and 4 pM against genotype 1a and 1b replicon, respectively.
Related Catalog	Signaling Pathways >>Metabolic Enzyme/Protease >>HCV ProteaseSignaling Pathways >>Anti-infection >>HCVResearch Areas >>Infection
Target	EC50: 34 pM (GT1a), 4 pM (GT1b)[1]
In Vitro	Ledipasvir has GT1a and 1b EC50 values of 31 and 4 pM, respectively, and protein-adjusted EC50 values of 210 pM (GT1a) and 27 pM (GT1b) and the intrinsic EC50 of 39 is 310 fM for GT1a and 40 fM for GT1b. Ledipasvir is highly protein-bound both in human serum and in the cell-culture medium (containing 10% BSA) of the replicon assay[1]. Ledipasvir exhibits an EC50 value of 141 nM against the JFH/3a-NS5A replicon[2].
In Vivo	Ledipasvir is remarkable not only on the basis of its high replicon potency but also on the basis of its low clearance, good bioavailability, and long half-lives in rat, dog, and monkey and low predicted clearance in human. The pharmacokinetics of Ledipasvir is measured in rats and dogs. Ledipasvir shows good half-lives (rat 1.83 ± 0.22 hr, dog 2.63 ± 0.18 hr) in plasma, low systemic clearance (CL), and moderate volumes of distribution (Vss) that are greater than total body water volume[1].
Animal Admin	Rats, Dogs and Monkeys[1] Pharmacokinetic studies are performed in male naı̈ve Sprague-Dawley(SD) rats, non-naive beagle dogs, and cynomolgus monkeys (three animals per dosing route). Intravenous (IV) administration is dosed via infusion over 30 min in a vehicle containing 5% ethanol, 20% PEG400, and 75% water (pH adjusted to 3.0 with HCl). Oral dosing is administered by gavage in a vehicle containing 5% ethanol, 45% PEG 400, and 50% of 50 mM citrate buffer, pH 3. Blood samples are collected over a 24 h period postdose into Vacutainer tubes containing EDTA-K2. Plasma was isolated, and the concentration of the test compound in plasma was determined with LC/MS/MS after protein precipitation with acetonitrile.
References	[1]. Link JO, et al. Discovery of ledipasvir (GS-5885): a potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection. J Med Chem. 2014 Mar 13;57(5):2033-46 [2]. Hernandez D, et al. Natural prevalence of NS5A polymorphisms in subjects infected with hepatitis C virus genotype 3 and their effects on the antiviral activity of NS5A inhibitors. J Clin Virol. 2013 May;57(1):13-8.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Molecular Formula	C₄₉H₅₄F₂N₈O₆
Molecular Weight	889.000
Exact Mass	888.413452
PSA	174.64000
LogP	6.77
Index of Refraction	1.677
InChIKey	VRTWBAAJJOHBQU-KMWAZVGDSA-N
SMILES	COC(=O)NC(C(=O)N1CC2(CC2)CC1c1ncc(-c2ccc3c(c2)C(F)(F)c2cc(-c4ccc5nc(C6C7CCC(C7)N6C(=O)C(NC(=O)OC)C(C)C)[nH]c5c4)ccc2-3)[nH]1)C(C)C

Safety Information

Hazard Codes	Xi
Safety Phrases	24/25
RIDADR	3077
HS Code	29333990

Synonyms

Carbamic acid, N-[(1S)-1-[[(6S)-6-[5-[9,9-difluoro-7-[2-[(1R,3S,4S)-2-[(2S)-2-[(methoxycarbonyl)amino]-3-methyl-1-oxobutyl]-2-azabicyclo[2.2.1]hept-3-yl]-1H-benzimidazol-6-yl]-9H-fluoren-2-yl]-1H-imidazol-2-yl]-5-azaspiro[2.4]hept-5-yl]carbonyl]-2-methylpropyl]-, methyl ester

Methyl [(2S)-1-{(1R,3S,4S)-3-[5-(9,9-difluoro-7-{2-[(6S)-5-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-5-azaspiro[2.4]hept-6-yl]-1H-imidazol-4-yl}-9H-fluoren-2-yl)-1H-benzimidazol-2-yl]-2-azabicyclo[2.2.1]hept-2-yl}-3-methyl-1-oxo-2-butanyl]carbamate

UNII-013TE6E4WV

Ledipasvir

GS-5885

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