Sofosbuvir structure activity relationship of drugs

sofosbuvir structure activity relationship of drugs

Applying an intensive structure-activity relationship (SAR) study, a promising IDPP .. In order to develop novel antiviral drugs against HBV, new compounds will. Figure 1 shows the chemical structure of sofosbuvir. ST amino acid change decreases the inhibitory activity of sofosbuvir. .. Gilead Sciences (the developer of both drugs) submitted the . Disclosure: The authors report that they have no commercial or financial relationships in regard to this article. Request PDF on ResearchGate | Structure-Activity Relationship (SAR) Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug.

Bioorg Med Chem Lett ; Nucleosides with anti-hepatitis B Virus activity. Pharmacokinetics of the acyclovir prodrug valaciclovir after escalating single and multiple-dose administration to normal volunteers. Clin Pharmacol Ther ; Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture. Antimicrob Agents Chemother ; Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection.

N Engl J Med ; Synthesis and antiviral activity of 1,2,4-triazolethiocarboxamide and 1,2,4-triazolecarboxamidine ribonucleosides. Viramidine, a prodrug of ribavirin, shows better liver-targeting properties and safety profiles than ribavirin in animals.

Antiviral Chem Chemother ; Safety and efficacy of viramidine versus ribavirin in ViSER2: Arylethynyltriazole a cyclo nucleosides inhibit hepatitis C virus replication. Design and evaluation of a potential mutagen for hepatitis C virus. Synthesis and antiviral properties of novel 7-heterocyclic substituted 7-deaza-adenine nucleoside inhibitors of hepatitis C NS5B polymerase.

Bioorg Med Chem ; The versatile nature of the 6-aminoquinolone scaffold: Metabolism and pharmacokinetics of the anti-hepatitis C virus nucleotide prodrug GS Antiviral Activity and resistance emergence: Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase.

sofosbuvir structure activity relationship of drugs

Nucleic Acids Res ; Interdomain communication in hepatitis C virus polymerase abolished by small molecule inhibitors bound to a novel allosteric site. Bioorg Med Chem Elsevier ; Binding site characterization and resistance to a class of non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase.

Solution structure of substrate-based ligands when bound to hepatitis C virus NS3 protease domain. Benzimidazole inhibitors of hepatitis C virus NS5B polymerase: Non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase: Synthesis, in vitro and in silico NS5B polymerase inhibitory activity of benzimidazole derivatives.

Sofosbuvir - Wikipedia

Development and Preliminary Optimization of Indole; Development of carboxylic acid replacements in indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase. Identification of ester prodrugs with improved oral pharmacokinetics.

sofosbuvir structure activity relationship of drugs

Optimization of tetracyclic indole-based macrocycle leading to the discovery of TMC Discovery and preclinical characterization of the cyclopropyl indol benzazepine BMS, a potent allosteric inhibitor of the hepatitis C virus NS5B polymerase. Identification of thieno[3,2-b]pyrroles as allosteric inhibitors of hepatitis C virus NS5B polymerase.

Daclatasvir in combination with asunaprevir and beclabuvir for hepatitis C virus genotype 1 infection with compensated cirrhosis. Program F, Book A. Global Antiviral Journal; Interferon-free treatment of chronic hepatitis C with faldaprevir, deleobuvir and ribavirin: Faldaprevir and deleobuvir for HCV genotype 1 infection.

sofosbuvir structure activity relationship of drugs

Crystal structures and mechanism of inhibition. Molecular design and synthesis of HCV inhibitors based on thiazolone scaffold. Eur J Med Chem ; Structure-based design of novel HCV NS5B thumb pocket 2 allosteric inhibitors with submicromolar gt1 replicon potency: The discovery and structure-activity relationships of pyrano[3,4-b]indole-based inhibitors of hepatitis C virus NS5B polymerase.

The discovery and structure-activity relationships of pyrano[3,4-b]indole based inhibitors of hepatitis C virus NS5B polymerase. Synthesis, characterization and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles, and some related compounds.

New cyclohexylidenehydrazide and 4-azathiaspiro[4. Synthesis of some new triazoles as potential antifungal agents. Boll Chim Farm ; Synthesis and anticonvulsant activity of new 4-thiazolidone and 4-thiazoline derivatives. Synthesis and anticonvulsant activity of new 3-[[2-furyl]carbonyl]aminothiazolidinone and 2-[[2-furyl] carbonyl] hydrazonothiazoline derivatives.

Some reactions of 2-cyanomethylimidazo[4,5-b]pyridine with isothiocyanates. The antituberculosis activity of the obtained compounds. Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis.

Identification of anthranilic acid derivatives as a novel class of allosteric inhibitors of hepatitis C NS5B polymerase. Anthranilic acid-based thumb pocket 2 HCV NS5B polymerase inhibitors with sub-micromolar potency in the cell-based replicon assay.

Discovery of substituted N-phenylbenzene sulphonamides as a novel class of non-nucleoside hepatitis C virus polymerase inhibitors.

sofosbuvir structure activity relationship of drugs

Evaluation of VCH monotherapy in hepatitis C infection. Pregnant women with hepatitis C who take ribavirin have shown some cases of birth defects and death in their fetus. Common side effects are fatigue, headache, nausea, rash, irritability, dizziness, back pain, and anemia. Most side effects are significantly more common in interferon-containing regimens as compared to interferon-free ones.

Sofosbuvir

Therefore, inducers of intestinal P-glycoprotein, such as rifampicin and St. John's wortcould reduce the absorption of sofosbuvir. Thus, coadministration is not recommended.

SAR of acetylcholine / structural activity relationship of acetylcholine/ SAR of parasympathomimetic

Pharmacokinetics[ edit ] Sofosbuvir is only administered orally. The peak concentration after oral administration is 0. The half life of sofosbuvir is 0. This low potency arises in part because the enzymatic addition of the first of the three phosphate groups of the triphosphate is slow.

The design of sofosbuvir, based on the ProTide approach, avoids this slow step by building the first phosphate group into the structure of the drug during synthesis.

Additional groups are attached to the phosphorus to temporarily mask the two negative charges of the phosphate group, thereby facilitating entry of the drug into the infected cell. As sofosbuvir clinical development progressed, physicians began to "warehouse" people in anticipation of its availability. They specifically asked Gilead CEO John Martin to "explain how the drug was priced, what discounts are being made available to low-income patients and government health programs, and the potential impact to public health by insurers blocking or delaying access to the medicine because of its cost.