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Ledipasvir Sofosbuvir
Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences. After completing Phase III clinical trials, on February 10, 2014, Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C. The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin. Ledipasvir is an inhibitor of NS5A, a hepatitis C virus protein. Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of the nucleotide analog inhibitor sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1. The sofosbuvir/ledipasvir coformulation is being tested with and without ri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sofosbuvir
Sofosbuvir, sold under the brand name Sovaldi among others, is a medication used to treat hepatitis C. It is taken Oral administration, by mouth. Common side effects include fatigue, headache, nausea, and trouble sleeping. Side effects are generally more common in interferon-containing regimens. Sofosbuvir may reactivate hepatitis B in those who have been previously infected. In combination with ledipasvir, daclatasvir or simeprevir, it is not recommended with amiodarone due to the risk of an bradycardia, abnormally slow heartbeat. Sofosbuvir is in the nucleotide analog family of medications and works by blocking the hepatitis C NS5B protein. Sofosbuvir was discovered in 2007 and approved for medical use in the United States in 2013. It is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. Medical uses Initial HCV treatment In 2016, the American Association for the Study of Liver Diseases and the Infectious Diseases ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), but the agency also enforces other laws, notably Section 361 of the Public Health Service Act, as well as associated regulations. Much of this regulatory-enforcement work is not d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Breakthrough Therapy
Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's "breakthrough therapy" designation is not intended to imply that a drug is actually a "breakthrough" or that there is high-quality evidence of treatment efficacy for a particular condition; rather, it allows the FDA to grant priority review to drug candidates if preliminary clinical trials indicate that the therapy may offer substantial treatment advantages over existing options for patients with serious or life-threatening diseases. The FDA has other mechanisms for expediting the review and approval process for promising drugs, including fast track designation, accelerated approval, and priority review. Requirements A breakthrough therapy designation can be assigned to a drug if "it is a drug which is intended alone or in combination with ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Imidazoles
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non-adjacent nitrogen atoms in meta-substitution. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. This ring system is present in important biological building blocks, such as histidine and the related hormone histamine. Many drugs contain an imidazole ring, such as certain antifungal drugs, the nitroimidazole series of antibiotics, and the sedative midazolam. When fused to a pyrimidine ring, it forms a purine, which is the most widely occurring nitrogen-containing heterocycle in nature. The name "imidazole" was coined in 1887 by the German chemist Arthur Rudolf Hantzsch (1857–1935). Structure and properties Imidazole is a planar 5-membered ri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclopropanes
Cyclopropane is the cycloalkane with the molecular formula (CH2)3, consisting of three methylene groups (CH2) linked to each other to form a ring. The small size of the ring creates substantial ring strain in the structure. Cyclopropane itself is mainly of theoretical interest but many of its derivatives are of commercial or biological significance. History Cyclopropane was discovered in 1881 by August Freund, who also proposed the correct structure for the substance in his first paper. Freund treated 1,3-dibromopropane with sodium, causing an intramolecular Wurtz reaction leading directly to cyclopropane. The yield of the reaction was improved by Gustavson in 1887 with the use of zinc instead of sodium. Cyclopropane had no commercial application until Henderson and Lucas discovered its anaesthetic properties in 1929; industrial production had begun by 1936. In modern anaesthetic practice, it has been superseded by other agents. Anaesthesia Cyclopropane was introduced into clin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Benzimidazoles
Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a colorless solid. Preparation Benzimidazole is produced by condensation of o-phenylenediamine with formic acid,. or the equivalent trimethyl orthoformate: :C6H4(NH2)2 + HC(OCH3)3 → C6H4N(NH)CH + 3 CH3OH 2-substituted derivatives are obtained when the condensation is conducted with aldehydes in place of formic acid, followed by oxidation.Robert A. Smiley "Phenylene- and Toluenediamines" in Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. Reactions Benzimidazole is a base: :C6H4N(NH)CH + H+ → 6H4(NH)2CHsup>+ It can also be deprotonated with stronger bases: :C6H4N(NH)CH + LiH → Li 6H4N2CH + H2 The imine can be alkylated and also serves as a ligand in coordination chemistry. The most prominent benzimidazole complex features ''N''-ribosyl-dimethylbenzimidazole as foun ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carbamates
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally obtained by replacing one or more of the hydrogen atoms by other organic functional groups; as well as salts with the carbamate anion (e.g. ammonium carbamate). Polymers whose units are joined by carbamate groups are an important family of plastics, the polyurethanes. Properties While carbamic acids are unstable, many carbamate esters or ionic) are stable and well known. Equilibrium with carbonate and bicarbonate In water solutions, the carbamate anion slowly equilibrates with the ammonium cation and the carbonate or bicarbonate anions: : : Calcium carbamate is soluble in water, whereas calcium carbonate is not. Adding a calcium salt to an ammonium carbamate/carbonate solution will precipitate some calcium carbonate immediately, a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Fluorenes
Fluorene , or 9''H''-fluorene is an organic compound with the formula (C6H4)2CH2. It forms white crystals that exhibit a characteristic, aromatic odor similar to that of naphthalene. It has a violet fluorescence, hence its name. For commercial purposes it is obtained from coal tar. It is insoluble in water and soluble in many organic solvents. Although sometimes classified as a polycyclic aromatic hydrocarbon, the five-membered ring has no aromatic properties. Fluorene is mildly acidic. Synthesis, structure, and reactivity Although fluorene is obtained from coal tar, it can also be prepared by dehydrogenation of diphenylmethane. Alternatively, it can be prepared by the reduction of fluorenone with zinc or hypophosphorous acid–iodine. The fluorene molecule is nearly planar,D. M. Burns, John Iball (1954), ''Molecular Structure of Fluorene'' Nature volume 173, p. 635. although each of the two benzene rings is coplanar with the central carbon 9. Fluorene can be found after the i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NS5A Inhibitors
Nonstructural protein 5A (NS5A) is a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key role in Hepatitis C virus RNA replication. It appears to be a dimeric form without ''trans''-membrane helices. Structure NS5A is derived from a large polyprotein that is translated from the HCV genome, and undergoes post-translation processing by nonstructural protein 3 (NS3) viral protease. Despite no inherent enzymatic activity being attributed to NS5A, its function is mediated through interaction with other nonstructural (NS) viral and cellular proteins. NS5A has two phosphorylated forms: p56 and p58, which differ in the electrophoretic mobility. p56 is basally phosphorylated by host cellular protein kinase at the center and near the C terminus, whereas p58 is a form of hyper-phosphorylated NS5A at the center of the serine-rich region. Protein mass spectrometry identified several phosphorylated serine residues in this region including serine 225, 229, 232, and 235 res ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Discovery And Development Of NS5A Inhibitors
Nonstructural protein 5A (NS5A) inhibitors are direct acting antiviral agents (DAAs) that target viral proteins, and their development was a culmination of increased understanding of the viral life cycle combined with advances in drug discovery technology. However, their mechanism of action is complex and not fully understood. NS5A inhibitors were the focus of much attention when they emerged as a part of the first curative treatment for hepatitis C virus (HCV) infections in 2014. Favorable characteristics have been introduced through varied structural changes, and structural similarities between NS5A inhibitors that are clinically approved are readily apparent. Despite the recent introduction of numerous new antiviral drugs, resistance is still a concern and these inhibitors are therefore always used in combination with other drugs. Hepatitis C virus HCV is a positive-sense single-stranded RNA virus that has been demonstrated to replicate in the hepatocytes of both humans and chi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NS5B
Nonstructural protein 5B (NS5B) is a viral protein found in the hepatitis C virus (HCV). It is an RNA-dependent RNA polymerase, having the key function of replicating HCV's viral RNA by using the viral positive RNA strand as a template to catalyze the polymerization of ribonucleoside triphosphates (rNTP) during RNA replication. Several crystal structures of NS5B polymerase in several crystalline forms have been determined based on the same consensus sequence BK (HCV-BK, genotype 1). The structure can be represented by a right hand shape with fingers, palm, and thumb. The encircled active site, unique to NS5B, is contained within the palm structure of the protein. Recent studies on NS5B protein genotype 1b strain J4's (HC-J4) structure indicate a presence of an active site where possible control of nucleotide binding occurs and initiation of de-novo RNA synthesis. De-novo adds necessary primers for initiation of RNA replication. Drugs targeting NS5B Several drugs are either on the ma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Uridine
Uridine (symbol U or Urd) is a glycosylated pyrimidine analog containing uracil attached to a ribose ring (or more specifically, a ribofuranose) via a β-N1-glycosidic bond. The analog is one of the five standard nucleosides which make up nucleic acids, the others being adenosine, thymidine, cytidine and guanosine. The five nucleosides are commonly abbreviated to their symbols, U, A, dT, C, and G, respectively. However, thymidine is more commonly written as 'dT' ('d' represents 'deoxy') as it contains a 2'-deoxyribofuranose moiety rather than the ribofuranose ring found in uridine. This is because thymidine is found in deoxyribonucleic acid (DNA) and usually not in ribonucleic acid (RNA). Conversely, uridine is found in RNA and not DNA. The remaining three nucleosides may be found in both RNA and DNA. In RNA, they would be represented as A, C and G whereas in DNA they would be represented as dA, dC and dG. Biosynthesis Uridine is widely produced in nature as uridine monophosp ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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