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Proxorphan
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 deriva ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proxorphan Synthesis
Proxorphan (International Nonproprietary Name, INN), also known as proxorphan tartate (United States Adopted Name, 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 kappa-opioid receptor, κ-opioid receptor partial agonist and to a lesser extent as a mu-opioid receptor, 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, 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 saponific ... [...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] |
Morphinan
Morphinan is the prototype chemical structure of a large chemical class of psychoactive drugs, consisting of opiate analgesics, cough suppressants, and dissociative hallucinogens, among others. Structure Morphinan has a phenanthrene core structure with the ''A'' ring remaining aromatic and the ''B'' and ''C'' rings being saturated, and an additional nitrogen-containing, six-membered, saturated ring, the ''D'' ring, being attached to carbons 9 and 13 of the core, and with the nitrogen being at position 17 of the composite. Of the major naturally occurring opiates of the morphinan type—morphine, codeine and thebaine—thebaine has no therapeutic properties (it causes seizures in mammals), but it provides a low-cost feedstock for the industrial production of at least four semi-synthetic opiate agonists, including hydrocodone, hydromorphone, oxycodone and oxymorphone, and the opioid antagonist naloxone. Structure-activity relationship The physiological behavior of morphinans ... [...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 Nalbuphine, sold under the brand names Nubain among others, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Von Braun Reaction
The von Braun reaction is an organic reaction in which a tertiary amine reacts with cyanogen bromide to an organocyanamide. An example is the reaction of ''N'',''N''-dimethyl-1-naphthylamine: These days, most chemist have replaced cyanogen bromide reagent with chloroethyl chloroformate reagent instead. It appears as though Olofson et al. was the first chemist to have reported this. Reaction mechanism The reaction mechanism consists of two nucleophilic substitutions: the amine is the first nucleophile displacing the bromine atom which then acts as the second nucleophile. In following the mechanism is described using trimethylamine as example: First, the trimethylamine reacts with the cyanogen bromide to form a quaternary ammonium salt, which in the next step reacts by splitting off bromomethane to give the dimethylcyanamide. This is a second-order nucleophilic substitution ( SN2). See also * von Braun amide degradation The von Braun amide degradation is the chemical re ... [...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 Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides (cuts the C-terminus of methionine), and synthesize other compounds .... 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 ... [...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 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ketorfanol
Ketorfanol (International Nonproprietary Name, INN, United States Adopted Name, USAN) (developmental code name SBW-22), or ketorphanol, is an opioid analgesic of the morphinan family that was found to possess "potent antinociception, antiwrithing activity" in animal research, 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/receptor antagonist, antagonists. See also * Butorphanol * Levallorphan * Levomethorphan * Levorphanol * Nalbuphine * Xorphanol References Phenols Analgesics Ketones Morphinans Opioids {{analgesic-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
