Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia; the role of therapeutic goods regulation is designed to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm
A prescription drug is a pharmaceutical drug that requires a medical prescription to be dispensed. In contrast, over-the-counter drugs can be obtained without a prescription; the reason for this difference in substance control is the potential scope of misuse, from drug abuse to practicing medicine without a license and without sufficient education. Different jurisdictions have different definitions of. "Rx" is used as a short form for prescription drug in North America - a contraction of the Latin word "recipe" meaning "take". Prescription drugs are dispensed together with a monograph that gives detailed information about the drug; the use of prescription drugs has been increasing since the 1960s. In the U. S. 88% of older adults use at least 1 prescription drug, while 36% take at least 5 prescription medicines concurrently. In Australia, the Standard for the Uniform Scheduling of Medicines and Poisons governs the manufacture and supply of drugs with several categories: Schedule 1 – Defunct Schedule 2 – Pharmacy Medicine Schedule 3 – Pharmacist-Only Medicine Schedule 4 – Prescription-Only Medicine/Prescription Animal Remedy Schedule 5 – Caution Schedule 6 – Poison Schedule 7 – Dangerous Poison Schedule 8 – Controlled Drug Schedule 9 – Prohibited Substance Unscheduled SubstancesLike in the UK, the patient visits a health practitioner, who may prescribe the drug.
Many prescriptions issued by health practitioners in Australia are covered by the Pharmaceutical Benefits Scheme, a scheme that provides subsidised prescription drugs to residents of Australia to ensure that all Australians have affordable and reliable access to a wide range of necessary medicines. When purchasing a drug under the PBS, the consumer pays no more than the patient co-payment contribution, which, as of January 1, 2018, is A$39.50 for general patients. Those covered by government entitlements and or under the Repatriation Pharmaceutical Benefits Scheme have a reduced co-payment, $6.40 in 2018. The co-payments are compulsory and can be discounted by pharmacies up to a maximum of A$1.00 at cost to the pharmacy. In the United Kingdom, the Medicines Act 1968 and the Prescription Only Medicines Order 1997 contain regulations that cover the supply of sale, use and production of medicines. There are three categories of medicine: Prescription-only medicines, which may be dispensed by a pharmacist if they are prescribed by a prescriber Pharmacy medicines, which may be sold by a pharmacist without a prescription General sales list medicines, which may be sold without a prescription in any shopThe possession of a prescription-only medicine without a prescription is legal unless it is covered by the Misuse of Drugs Act 1971.
A patient visits a medical practitioner or dentist, who may prescribe drugs and certain other medical items, such as blood glucose-testing equipment for diabetics. Qualified and experienced nurses and pharmacists may be independent prescribers. Both may prescribe all POMs, but may not prescribe Schedule 1 controlled drugs, 3 listed controlled drugs for the treatment of addiction. Schedule 1 drugs have little or no medical benefit, hence their limitations on prescribing. District nurses and health visitors have had limited prescribing rights since the mid-1990s. Once issued, a prescription is taken by the patient to a pharmacy. Most prescriptions are NHS prescriptions, subject to a standard charge, unrelated to what is dispensed; the NHS prescription fee was increased to £8.80 per item in England on 1 April 2018. The pharmacy charges the NHS the actual cost of the medicine, which may vary from a few pence to hundreds of pounds. A patient can consolidate prescription charges by using a prescription payment certificate capping costs at £29.10 per quarter or £104.00 per year.
Outside the NHS, private prescriptions are issued by private medical practitioner and sometimes under the NHS for medicines that are not covered by the NHS. A patient pays the pharmacy the normal price for medicine prescribed outside the NHS. Survey results published by Ipsos MORI in 2008 found that around 800,000 people in England were not collecting prescriptions or getting them dispensed because of the cost, the same as in 2001. In the United States, the Federal Food and Cosmetic Act defines what substances require a prescription for them to be dispensed by a pharmacy; the federal government authorizes physicians, physician assistants, nurse practitioners and other advanced practice nurses, veterinarians and optometrists to prescribe any controlled substance. They are issued unique Drug Enforcement Act numbers.
In chemistry, the sulfonamide functional group is -S2-NH2, a sulfonyl group connected to an amine group. Speaking this group is unreactive; the amine center is no longer basic. The S-N bond is cleaved only with difficulty; because of the rigidity of the functional group, sulfonamides are crystalline. For this reason, the formation of a sulfonamide is a classic method to convert an amine into a crystalline derivative which can be identified by its melting point. Many important drugs contain the sulfonamide group. A sulfonamide is a compound; the general formula is RSO2NH2. For example, "methanesulfonamide" is CH3SO2NH2. Any sulfonamide can be considered as derived from a sulfonic acid by replacing a hydroxyl group with an amine group. In medicine, the term "sulfonamide" is sometimes used as a synonym for sulfa drug, a derivative or variation of sulfanilamide; the first sulfonamide was discovered in Germany in 1932. Sulfonamides can be prepared in the laboratory in many ways; the classic approach entails the reaction of sulfonyl chlorides with an amine.
RSO2Cl + R2NH → RSO2NR2 + HClA base such as pyridine is added to absorb the HCl, generated. Illustrative is the synthesis of sulfonylmethylamide. A available sulfonyl chloride source is tosyl chloride; the reaction of primary and secondary amines with benzenesulfonyl chloride is the basis of the Hinsberg reaction, a method for detecting primary and secondary amines. Sultams are cyclic sulfonamides. Bioactive sultams include the anticonvulsant sultiame. Sultams are prepared analogously to other sulfonamides, allowing for the fact that sulfonic acids are deprotonated by amines, they are prepared by one-pot oxidation of disulfides or thiols linked to amines. An alternative synthesis of sultams involves initial preparation of a linear sulfonamide, followed by intramolecular C-C bond formation, a strategy, used in the synthesis of a sultam-based deep-blue emitter for organic electronics. Sulfonamide-based compounds The related sulfinamides are amides of sulfinic acids. Chiral sulfinamides such as tert-butanesulfinamide, p-toluenesulfinamide and 2,4,6-trimethylbenzenesulfinamide are relevant to asymmetric synthesis.
The related disulfonimides are of the type R-S2-N-S2-R' with two sulfonyl groups flanking an amine. As with sulfinamides this class of compounds is used as catalysts in enantioselective synthesis. Sulfonamide Sulfamic acid Sulfamide
The drug combination atovaquone/proguanil is an antimalarial medication used in both the treatment and prevention of malaria. Atovaquone alone is not indicated for prevention of malaria as monotherapy. Atovaquone/proguanil has been commercially available from GlaxoSmithKline since 2000, its patent expired in 2013. Malarone has applications for treating chloroquine-resistant malaria. A standard tablet of Malarone contains 250 mg of atovaquone. A pediatric tablet contains 62.5 mg of atovaquone. The adult treatment dose is four standard tablets once a day for three days. In children, the drug is prescribed by body weight: 11 to 20 kg: 1 standard tablet once daily for 3 days. Atovaquone/proguanil is not licensed for use in children weighing 10 kg or less; the pediatric tablets are used for prophylaxis. Atovaquone/proguanil is not used to treat severe malaria, when an injectable drug such as quinine is used instead. A patient should always seek medical advice before choosing a medication for malaria prevention.
Since some malaria strains are resistant to atovaquone/proguanil, it is not effective in all parts of the world. It must be taken with a fatty meal, or at least some milk, for the body to absorb it adequately—and to avoid painful stomach irritation, which proguanil causes if taken without food. Stomach irritation may occur if one lies down within a half hour after taking this medicine; the adult dose is one standard tablet daily starting one or two days before traveling into a malaria-endemic area, continuing throughout the stay and for another seven days after returning from the area. The child dose is prescribed according to body weight: 11–20 kg: 1 pediatric tablet once daily; the duration of treatment is the same as for adults. Proguanil acts as synergizes with atovaquone; when atovaquone is used as a sole agent, a high natural frequency of cytochrome b mutants leads to a high failure rate. This is due to the high lipophilicity and slow uptake of atovaquone, which results in a prolonged period of parasite exposure at ineffective concentrations.
Specific mutations have been shown to confer resistance in vivo, but the other mechanisms of resistance remain unknown. Malarone is notable for having far fewer side effects than older malaria drugs. While some people experience side effects, such as coughing, dizziness, loss of appetite, mouth sores, stomach pain, vomiting, or weakness, the majority have none or few of these. Atovaquone selectively inhibits the malarial cytochrome bc1 complex in the parasitic electron transport chain, collapsing the mitochondrial membrane potential; the malarial electron transport chain does not contribute to ATP synthesis. Proguanil, via its metabolite cycloguanil, functions as a dihydrofolate reductase inhibitor, halting parasitic deoxythymidilate synthesis. Glaxo Wellcome patented the combination of atovaquone and proguanil to treat malaria in 1999. Patent protection expired in 2013; the U. S. Food and Drug Administration approved a generic formulation from Glenmark Generics in 2011. In February 2013, the United Kingdom High Court revoked Glaxo's patent on grounds of obviousness, which clears the way for firms to sell generic versions there
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1