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Proxorphan Synthesis
Proxorphan ( INN), also known as proxorphan tartate ( USAN) (developmental code name BL-5572M), is an opioid analgesic and antitussive drug of the morphinan family that was never marketed. It acts preferentially as a κ-opioid receptor partial agonist and to a lesser extent as a μ-opioid receptor partial agonist. Synthesis Starting material for this preparation is ketoester 1, available by one of the classical benzomorphan syntheses. Condensation with the ylide from Triethyl phosphonoacetate (HWE reaction) affords diester 2. Catalytic hydrogenation proceeds from the less hindered face to afford the corresponding saturated diester (3). The esters are then reduced by means of LiAlH4 to give the glycol (4); this undergoes internal ether formation on treatment with acid to form the pyran ring of 5. Von Braun reaction with BrCN (or ethyl chloroformate) followed by saponification of the intermediate leads to the 2° amine (6). This is converted to the cyclopropylmethyl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pyran
In chemistry, pyran, or oxine, is a six-membered heterocyclic, non-aromatic ring, consisting of five carbon atoms and one oxygen atom and containing two double bonds. The molecular formula is C5H6O. There are two isomers of pyran that differ by the location of the double bonds. In 2''H''-pyran, the saturated carbon is at position 2, whereas, in 4''H''-pyran, the saturated carbon is at position 4. 4''H''-Pyran was first isolated and characterized in 1962 via pyrolysis of 2-acetoxy-3,4-dihydro-2''H''-pyran. It was found too unstable, particularly in the presence of air. 4''H''-pyran easily disproportionates to the corresponding dihydropyran and the pyrylium ion, which is easily hydrolyzed in aqueous medium. Although the pyrans themselves have little significance in chemistry, many of their derivatives are important biological molecules, such as the pyranoflavonoids. The term pyran is also often applied to the saturated ring analog, which is more properly referred to as tetrahydrop ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Moxazocine
Moxazocine (BL-4566) is an opioid analgesic of the benzomorphan family which was never marketed. It acts as a partial agonist or mixed agonist/antagonist of the opioid receptors and binds preferentially to the κ-opioid receptor. Despite its failure to reach the market, clinical studies demonstrated moxazocine to be approximately 10x as potent by weight as morphine as an analgesic. Synthesis Reduction of the carbonyl group in oxygenated benzomorphan 1 affords the corresponding alcohol (2). This intermediate is then N-demethylated by means of BrCN. Acylation with cyclopropylcarbonyl chloride gives the amide (3). The alcohol is then converted to the ether by treatment with MeI and base (4). Treatment with LiAlH4 serves to reduce the amide function. Cleavage of the phenolic ether by one of the standard schemes affords moxazocine (6). See also * Benzomorphan Benzomorphan is a chemical compound that is the base for a series of drugs which variably act on the opioid kappa and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Levorphanol
Levorphanol (brand name Levo-Dromoran) is an opioid medication used to treat moderate to severe pain. It is the levorotatory enantiomer of the compound racemorphan. Its dextrorotatory counterpart is dextrorphan. It was first described in Germany in 1946. The drug has been in medical use in the United States since 1953. Pharmacology Levorphanol acts predominantly as an agonist of the μ-opioid receptor (MOR), but is also an agonist of the δ-opioid receptor (DOR), κ-opioid receptor (KOR), and the nociceptin receptor (NOP), as well as an NMDA receptor antagonist and a serotonin-norepinephrine reuptake inhibitor (SNRI). Levorphanol, similarly to certain other opioids, also acts as a glycine receptor antagonist and GABA receptor antagonist at very high concentrations. Levorphanol is 6 to 8 times as potent as morphine at the MOR. Relative to morphine, levorphanol lacks complete cross-tolerance and possesses greater intrinsic activity at the MOR. The duration of action is general ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Levomethorphan
Levomethorphan (LVM) (INN, BAN) is an opioid analgesic of the morphinan family that has never been marketed. It is the L-stereoisomer of racemethorphan (methorphan). The effects of the two isomers of the racemethorphan are quite different, with dextromethorphan (DXM) being an antitussive at low doses and a dissociative hallucinogen at much higher doses. Levomethorphan is about five times stronger than morphine. Levomethorphan is a prodrug to levorphanol, analogously to DXM acting as a prodrug to dextrorphan or codeine behaving as a prodrug to morphine. As such, levomethorphan has similar effects to levorphanol but is less potent as it must be demethylated to the active form by liver enzymes before being able to produce its effects. As a prodrug of levorphanol, levomethorphan functions as a potent agonist of all three of the opioid receptors, μ, κ (κ1 and κ3 but notably not κ2), and δ, as an NMDA receptor antagonist, and as a serotonin-norepinephrine reuptake inhibitor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Levallorphan
Levallorphan (INN, BAN) (brand names Lorfan, Naloxifan, Naloxiphan), also known as levallorphan tartrate (USAN), is an opioid modulator of the morphinan family used as an opioid analgesic and opioid antagonist/antidote. It acts as an antagonist of the μ-opioid receptor (MOR) and as an agonist of the κ-opioid receptor (KOR), and as a result, blocks the effects of stronger agents with greater intrinsic activity such as morphine whilst simultaneously producing analgesia. Levallorphan was formerly widely used in general anesthesia, mainly to reverse the respiratory depression produced by opioid analgesics and barbiturates used for induction of surgical anaesthesia whilst maintaining a degree of analgesia (via KOR agonism). It is now less commonly employed for this purpose as the newer drug naloxone tends to be used instead. Levallorphan was also used in combination with opioid analgesics to reduce their side effects, mainly in obstetrics, and a very small dose of levallorphan used ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ketorfanol
Ketorfanol (INN, USAN) (developmental code name SBW-22), or ketorphanol, is an opioid analgesic of the morphinan family that was found to possess "potent antiwrithing activity" in animal assays but was never marketed. It is a 17-cycloalkylmethyl derivative of morphinan and as such, is closely related structurally to butorphanol, cyclorphan, oxilorphan, proxorphan, and xorphanol, which act preferentially as κ-opioid receptor agonists and to a lesser extent as μ-opioid receptor partial agonists/antagonists. See also * Butorphanol * Levallorphan * Levomethorphan * Levorphanol * Nalbuphine * Xorphanol Xorphanol (INN) (developmental code name TR-5379 or TR-5379M), also known as xorphanol mesylate (USAN), is an opioid analgesic of the morphinan family that was never marketed. Xorphanol is a mixed agonist–antagonist of opioid receptors, acti ... References Phenols Analgesics Ketones Morphinans Opioids {{analgesic-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclorphan
Cyclorphan is an opioid analgesic of the morphinan family that was never marketed. It acts as a μ-opioid receptor (MOR) weak partial agonist or antagonist, κ-opioid receptor (KOR) full agonist, and, to a much lesser extent, δ-opioid receptor (DOR) agonist (75-fold lower affinity relative to the KOR). The drug was first synthesized in 1964 by scientists at Research Corporation.Varghese V & Hudlicky T. A Short History of the Discovery and Development of Naltrexone and Other Morphine Derivatives. Chapter 6 in Natural Products in Medicinal Chemistry, Volume 60 of Methods and Principles in Medicinal Chemistry. Ed. Stephen Hanessian. John Wiley & Sons, 2013. In clinical trials, it had relatively long duration, good absorption, and provided strong pain relief but produced psychotomimetic effects via KOR activation, so its development was not continued. See also * Butorphanol * Levomethorphan * Levorphanol * Nalbuphine * Oxilorphan * Proxorphan * Xorphanol Xorphanol ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Butorphanol
Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans. It was patented in 1971 and approved for medical use in 1979. Medical uses The most common indication for butorphanol is management of migraine using the intranasal spray formulation. It may also be used parenterally for management of moderate-to-severe pain, as a supplement for balanced general anesthesia, and management of pain during labor. Butorphanol is also quite effective at reducing post-operative shivering (owing to its Kappa agonist activity). Butorphanol is more effective in reducing pain in women than in men. Pharmacology Butorphanol exhibits partial agonist and antagonist activity at the μ-opioid ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ethanethiol
Ethanethiol, commonly known as ethyl mercaptan, is an organosulfur compound with the formula CH3CH2SH. is a colorless liquid with a distinct odor. Abbreviated EtSH, it consists of an ethyl group (Et), CH3CH2, attached to a thiol group, SH. Its structure parallels that of ethanol, but with sulfur in place of oxygen. The odor of EtSH is infamous. Ethanethiol is more volatile than ethanol due to a diminished ability to engage in hydrogen bonding. Ethanethiol is toxic in high concentrations. It occurs naturally as a minor component of petroleum, and may be added to otherwise odorless gaseous products such as liquefied petroleum gas (LPG) to help warn of gas leaks. At these concentrations, ethanethiol is not harmful. Preparation Ethanethiol is prepared by the reaction of ethene with hydrogen sulfide over a catalyst. The various producers utilize different catalysts in this process. It has also been prepared commercially by the reaction of ethanol with hydrogen sulfide gas over an a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Saponification
Saponification is a process of converting esters into soaps and alcohols by the action of aqueous alkali (for example, aqueous sodium hydroxide solutions). Soaps are salts of fatty acids, which in turn are carboxylic acids with long carbon chains. Sodium stearate is a typical soap. Saponification of fats Vegetable oils and animal fats are the traditional materials that are saponified. These greasy materials, triesters called triglycerides, are mixtures derived from diverse fatty acids. Triglycerides can be converted to soap in either a one- or a two-step process. In the traditional one-step process, the triglyceride is treated with a strong base (e.g. lye), which cleaves the ester bond, releasing fatty acid salts (soaps) and glycerol. This process is also the main industrial method for producing glycerol. In some soap-making, the glycerol is left in the soap. If necessary, soaps may be precipitated by salting it out with sodium chloride. Fat in a corpse converts into adipoce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
