ChemicalBook > Product Catalog >Biochemical Engineering >Inhibitors >Proteases >HCV Protease Inhibitors >Ledipasvir

Ledipasvir

Ledipasvir Suppliers list
Company Name: Henan Fengda Chemical Co., Ltd
Tel: +8613613820652
Email: info@fdachem.com
Products Intro: Product Name: Ledipasvir
CAS:1256388-51-8
Purity:99% Package:1KG;6USD|25KG;5USD|100KG;1USD
Company Name: Beijing Cooperate Pharmaceutical Co.,Ltd
Tel: 010-60279497
Email: sales01@cooperate-pharm.com
Products Intro: Product Name:Ledipasvir
CAS:1256388-51-8
Purity:98% Package:100G;1KG;5KG;10KG;25KG;50KG;100KG
Company Name: Henan Tianfu Chemical Co.,Ltd.
Tel: +86-0371-55170693 +86-19937530512
Email: info@tianfuchem.com
Products Intro: Product Name:Ledipasvir
CAS:1256388-51-8
Purity:99% Package:25KG;5KG;1KG
Company Name: Hangzhou FandaChem Co.,Ltd.
Tel: 008657128800458; +8615858145714
Email: fandachem@gmail.com
Products Intro: Product Name:Ledipasvir Intermediate fandachem
CAS:1256388-51-8
Purity:As coa Package:As request Remarks:1256388-51-8
Company Name: ATK CHEMICAL COMPANY LIMITED
Tel: +undefined-21-51877795
Email: ivan@atkchemical.com
Products Intro: Product Name:Ledipasvir
CAS:1256388-51-8
Purity:98% HPLC Package:5G;10G;25G;50G;100G;250G;1KG

Ledipasvir manufacturers

  • Ledipasvir
  • 	Ledipasvir pictures
  • $6.00 / 1KG
  • 2024-03-28
  • CAS:1256388-51-8
  • Min. Order: 1KG
  • Purity: 99%
  • Supply Ability: g-kg-tons, free sample is available
  • Ledipasvir
  • Ledipasvir pictures
  • $0.00 / 10mg
  • 2023-11-27
  • CAS:1256388-51-8
  • Min. Order: 10mg
  • Purity: 99%
  • Supply Ability: 50kg
  • Ledipasvir
  • Ledipasvir pictures
  • $200.00 / 1kg
  • 2023-06-26
  • CAS:1256388-51-8
  • Min. Order: 1kg
  • Purity: 99%
  • Supply Ability: 1000kg/Months
Ledipasvir Basic information
Product Name:Ledipasvir
Synonyms:GS 5885;GS5885;GS-5885;Ledipasvir;GS-5885/Ledipasvir;gs-5885/gs5885;Ledipasvir / GS 5885;GS 588
CAS:1256388-51-8
MF:C49H54F2N8O6
MW:889
EINECS:1592732-453-0
Product Categories:Inhibitors;API
Mol File:1256388-51-8.mol
Ledipasvir Structure
Ledipasvir Chemical Properties
Melting point 186-190oC
density 1.42±0.1 g/cm3(Predicted)
storage temp. -20°C Freezer
solubility DMSO (Slightly, Heated), Methanol (Slightly)
pka11.20±0.10(Predicted)
form Solid
color White to Pale Beige
Safety Information
Safety Statements 24/25
RIDADR 3077
HS Code 29333990
MSDS Information
Ledipasvir Usage And Synthesis
DescriptionLedipasvir is a potent NS5A inhibitor that is approved for use in combination with sofosbuvir, a nucleotide inhibitor of viral polymerase, for the treatment of chronic hepatitis C virus genotype 1 infection. This combination was discovered and developed at Gilead Sciences and is marketed as the fixed combination with brand name of Harvoni.
UsesLedipasvir is most commonly used in combination with sofosbuvir for treatment in chronic hepatitis C genotype 1 patients. It inhibits an important viral phosphoprotein, NS5A, which is involved in viral replication, assembly, and secretion.
DefinitionChEBI: Ledipasvir is a benzimidazole derivative that is used in combination with sofosbuvir (under the trade name Harvoni) for the treatment of chronic hepatitis C genotype 1 infection. It has a role as an antiviral drug and a hepatitis C protease inhibitor. It is a carbamate ester, a L-valine derivative, a bridged compound, a carboxamide, a benzimidazole, a member of fluorenes, an organofluorine compound, a member of imidazoles, a N-acylpyrrolidine and an azaspiro compound.
PharmacokineticsOral bioavailability of sofosbuvir is at least 80% based on urinary recovery. Ledipasvir also is well absorbed orally. Approximately 65% of sofosbuvir is bound to human plasma protein, and virtually all of ledipasvir is plasma protein bound.
The sofosbuvir Tmax is 0.5 to 2 hours, with peak plasma concentration of the active metabolite occurring 2 to 4 hours after dosing. The Tmax for ledipasvir is 4 to 4.5 hours. The terminal halflife for sofosbuvir and its active metabolite are 0.4 and 27 hours, respectively, and the terminal half-life for ledipasvir is 47 hours. Sofosbuvir primarily is eliminated in the urine, whereas ledipasvir elimination occurs primarily through the biliary tract. Eighty percent of sofosbuvir is recovered in the urine, primarily as the active metabolite, and 86% of ledipasvir is recovered in the feces.
SynthesisThe synthesis of the spirocyclopropane proline intermediate 136 is described in Scheme above. Bis-iodination of cyclopropane-1,1-diyldimethanol (131) in the presence of triphenylphosphine gave diiodide 132 in 70% yield. N-Boc-glycine ethyl ester (133) was then treated with sodium hydride followed by diiodide 132 to give the protected proline analog 134 in 61% yield. Saponification of the ester followed by a classical resolution with (1S,2R)-amino-indanol gave enantomerically pure salt 135. Liberation of the free acid with 1 M HCl followed by treatment with potassium tert-butoxide provided enantiopure potassium salt 136 in high yield.
Synthesis_1256388-51-8
Iodination of 2-bromofluorene (137) produced aryl iodide 138 in 95% yield, which was then treated with lithium hexamethyldisilazide and N-fluorobenzenesulfonimide (NFSI) to give the difluoro intermediate 139 in 82% yield. Formation of the Grignard reagent of 139 through reaction with isopropylmagnesium chloride followed by condensation with Weinreb amide 140 gave chloroketone 141 in 71% yield. The potassium salt of the cyclopropyl proline intermediate 136 was coupled with 141 to give keto ester 142 in high yield. Heating 142 with ammonium acetate resulted in formation of the imidazole ring in intermediate 143 in 77% yield.
QQ??í?20210204152749.jpg
Commercially available (1R,3S,4S)-N-Boc-2-azabicyclo [2.2.1]heptane-3-carboxylic acid (144) was coupled to 4-bromo- 1,2-benzenediamine (145) using EDC/HOBt to give a mixture of amides 146a/146b in 72% yield. Heating mixture 146a/146b with acetic acid affected cyclization to benzimidazole 147 in 94% yield. Palladium mediated coupling of bromide 147 to bis(pinacolato)diboron gave intermediate 148 which was then coupled in the same reaction vessel to bromide 143. This was followed by formation of the oxalate salt to give the protected central core of ledipasvir (149) in good overall yield. Removal of the amine protecting groups gave diamine 150 which was coupled to two equivalents of Moc-valine (151) via EDC/HOBt to give ledipasvir XVII in 73% yield.
QQ??í?20210204152830.jpg
Mode of actionLedipasvir is a potent inhibitor of HCV nonstructural protein 5A (NS5A), a viral phosphoprotein that plays an important but poorly understood role in viral replication, assembly, and secretion. ;Ledipasvir is approved for the treatment of genotype 1 HCV. Its safety and efficacy have not been fully established for genotypes 2 through 6. NS5A amino acid substitutions Y93H (in genotypes 1a and 1b) and Q30E (in genotype 1a) significantly reduce susceptibility to ledipasvir in cell culture and in clinical studies. Other amino acid substitutions observed in virologic treatment failures are K24R, M28T/V, Q30H/K/L (genotype 1a), and L31V/M/I (genotype 1b). Viruses with these resistance-associated mutations remained susceptible to sofosbuvir.
Clinical claims and researchLedipasvir is an HCV NS5A inhibitor, while sofosbuvir inhibits HCV NS5B polymerase. These two agents are combined in a fixed-dose combination tablet marked under the trade name Harvoni? for the treatment of patients with chronic HCV. A phase I study in healthy subjects demonstrated that a moderate-fat (600 kcal, 25–30% fat) or high-fat, high-calorie (1000 kcal, 50% fat) meal did not significantly alter the Cmax, AUC0-∞, or tmax of ledipasvir–sofosbuvir. A post hoc analysis of the phase III clinical trial data was performed to evaluate the effect of food on the pharmacokinetics and clinical outcomes of ledipasvir–sofosbuvir and revealed no significant effects.
Ledipasvir demonstrates pH-dependent solubility in vitro and therefore was evaluated in two phase I studies examining the effects of coadministration with a histamine H2-receptor antagonist (famotidine 40 mg) and a proton-pump inhibitor (omeprazole 20 mg). Administration of a single dose of the combination product ledipasvir–sofosbuvir with famotidine or omeprazole and food did not significantly alter the AUC or Cmax of either agent. Ledipasvir–sofosbuvir may be administered without regard to meals or timing of acid-reducing agents.
references[1] 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, 57(1): 13-8.
[2] gao m et al. , chemical genetics strategy identifies an hcv ns5a inhibitor with a potent clinical effect. nature. 2010, 465: 96-100.
[3] lawitz e j et al. , a phase 1, randomized, placebo-controlled, 3-day, dose-ranging study of gs-5885, an ns5a inhibitor, in patients with genotype 1 hepatitis c. j hepatol. 2012, 57(1): 24-31.
Tag:Ledipasvir(1256388-51-8) Related Product Information
2-BROMOCARBAZOLE ILOPERIDONE ledipasvir interMediate Alogliptin benzoate Triphenylphosphine oxide Tenofovir Daptomycin Velpatasvir Donepezil Hydrochloride Y27632 (hydrochloride) Daclatasvir VX-809 Veliparib Benoxinate Hydrochloride Sofosbuvir