465-65-6

Usage

Chemical Description

Naloxone is an opioid antagonist that can reverse the effects of opioids such as morphine.

Uses

Used in Antineoplastic Applications:
Naloxone is utilized as an antineoplastic agent, indicating its potential role in cancer treatment. The specific application reason and mechanism of action in this context are not provided in the materials.
Used in Medical Industry:
Naloxone is used as a specific opioid antagonist and a narcotic antagonist in the medical industry. It is primarily employed to counteract the effects of opioid overdose, helping to restore normal respiration and counteracting the central nervous system depression caused by excessive opioid consumption.

Therapeutic Function

Narcotic antagonist

Biological Functions

Because of its fast onset (minutes), naloxone (Narcan) administered IV is used most frequently for the reversal of opioid overdose. However, it fails to block some side effects of the opioids that are mediated by the δ- receptor, such as hallucinations. The rapid offset of naloxone makes it necessary to administer the drug repeatedly until the opioid agonist has cleared the system to prevent relapse into overdose. The half-life of naloxone in plasma is 1 hour. It is rapidly metabolized via glucuronidation in the liver and cleared by the kidney. Naloxone given orally has a large first-pass effect, which reduces its potency significantly. Often an overshoot will follow the administration of naloxone for overdose. The heart rate and blood pressure of the patient may rise significantly. The overshoot is thought to be due to precipitation of acute withdrawal signs by naloxone. Given alone to nonaddicts, naloxone produces no pharmacological effects. Naloxone is approved for use in neonates to reverse respiratory depression induced by maternal opioid use. In addition, naloxone has been used to improve circulation in patients in shock, an effect related to blockade of endogenous opioids. Other experimental and less well documented uses for naloxone include reversal of coma in alcohol overdose, appetite suppression, and alleviation of dementia from schizophrenia. Side effects of naloxone are minor.

Synthesis

Naloxone, (-)-17-(allyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-one (3.1.92), is synthesized by the alkylation of 14-hydroxydihydronormorphinane (3.1.82) by allylbromide [55–58].

InChI:InChI=1/C19H21NO4/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11/h2-4,14,17,21,23H,1,5-10H2/t14-,17+,18+,19-/m1/s1

Upstream product

• 357-08-4 naloxone hydrochloride 
• 50798-31-7 3,14-diacetoxy-7,8-didehydro-4,5-epoxy-17-methylmorphinan-6-one 
• 64643-76-1 4,5α-epoxy-3,14-diacetoxy-6-oxo-17-methylmorphinan 
• 52446-24-9 (-)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride 
• 57093-47-7 3-acetyloripavine 
• 1407592-43-1 (5aR,8aS,11aR,11bS)-2-acetoxy-5,5a,9,10-tetrahydro-6,11b-ethano-7Hfuro[2',3',4',5':4,5]phenanthro[9,8a-d]oxazol-11(11aH)-one 
• 1826-67-1 vinyl magnesium bromide 
• 1449113-80-7 (5aR,6R,8aS,11aR,11bS)-2-acetoxy-5,5a,9,10-tetrahydro-11(11aH)-spiro-2-(1,3-dioxolan)-6,11b-ethano-7H-furo[2',3‘,4‘,5 ‘:4,5]phenanthro[9,8a-d]oxazole 
• 1449113-77-2 17-allyl-4,5α-epoxy-3,14-dihydroxy-6,6-dimethoxymorphinan 
• 1449113-76-1 (5aR,6R,8aS,11aR,11bS)-2-acetoxy-5,5a,9,10-tetrahydro-11,11-dimethoxy-6,11b-ethano-7H-furo[2’,3’,4’,5’:4,5]phenanthro[9,8a-d]oxazole 
• 646032-89-5 4,5α-epoxy-3,14β-dihydroxy-17-(prop-2-enyl)-morphinane-6-spiro-2’-(1,3-dioxolan) 
• 1407592-41-9 3-acetyloxymorphone N-oxide 
• 75660-23-0 3-acetyloxymorphone 
• 102272-79-7 3-O,N-bis-ethoxycarbonyl noroxymorphone 

Downstream Products

• 93302-47-7 N-methylnaloxonium iodide 
• 33522-95-1 noroxymorphone 
• 73232-47-0 (4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-(prop-2-yn-1-yl)-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one 
• 646032-89-5 4,5α-epoxy-3,14β-dihydroxy-17-(prop-2-enyl)-morphinane-6-spiro-2’-(1,3-dioxolan) 
• 16617-07-5 naltrexone methyl ether 
• 57664-96-7 noroxycodone 
• 1616556-70-7 C₃₁H₃₉NO₅ 
• 1616556-69-4 C₄₀H₅₁NO₅Si 
• 1616556-68-3 C₄₂H₅₃NO₆Si 
• 1616556-60-5 C₃₂H₄₁NO₅ 
• 1616556-71-8 (4bR,7S,8aS,9R)-3-(benzyloxy)-11-(cyclopropylmethyl)-8a-hydroxy-7-(2-hydroxyethyl)-8,8a,9,10-tetrahydro-5H-9,4b-(epiminoethano)phenanthren-6(7H)-one 
• 1616556-61-6 (4bR,7S,8aS,9R)-7-(2-(benzyloxy)ethyl)-11-(cyclopropylmethyl)-8a-hydroxy-3-methoxy-8,8a9,10-tetrahydro-5H-9,4b-(epiminoethano)phenanthren-6(7H)-one 
• 1373215-01-0 17-allyl-3,14β-dihydroxy-4,5α-epoxy-6β-(cyclohexanamido)morphinan 
• 1373214-94-8 17-allyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4-phenyl)benzamido]morphinan 

Relevant academic research and scientific papers

Studies of 3-O-acyl derivatives of naloxone as its potential prodrugs

An efficient method has been proposed for the preparation of a series of 3-O-acyl derivatives of naloxone. The features of the steric structure and NMR spectra are discussed. Pharmaceutical investigation has shown the promise within the synthesized compou

COVALENT MODIFICATION AND CONTROLLED DELIVERY OF MU OPIOID RECEPTOR ANTAGONISTS

Polymer conjugates comprising a hydrophobic biodegradable polymer covalently attached to a mu opioid receptor (MOR) antagonist are described. Biodegradable covalent nanoparticles comprising the hydrophobic biodegradable polymer covalently attached to a MOR antagonist are provided as a vehicle for the sustained delivery of the MOR antagonist. The described MOR antagonist delivery system may be used to more effectively prevent or overcome the toxic effects of synthetic opioids.

PROCESS FOR THE PREPARATION OF MORPHINANE COMPOUNDS

The invention describes the process of catalytic O-demethylation of 3-methoxy-morphinane compounds using boron tribromide. Addition of catalysts reduces the reaction time, improves reacting the substrate to give the product in very good purity and yield. The said approach can be used, for example, for the preparation of oxymorphone, naltrexone, naloxone and nalbuphine from their respective O-methyl derivatives.

PROCESS FOR OBTAINING 3,14-DIACETYLOXYMORPHONE FROM ORIPAVINE

The present invention relates to a new process for obtaining 3,14-diacetyloxymorphone from oripavine, a process to transform the obtained 3,14-diacetyloxymorphone into a noroxymorphone and a process to transform said noroxymorphone into naloxone, naltrexone, nalbuphine, nalfurafine or nalmefene.

REDUCTION OF ALPHA, BETA-UNSATURATED KETONE LEVELS IN MORPHINAN DERIVATIVE COMPOSITIONS

The disclosure relates to processes for reducing the amount of a compound of formula (I) or a salt or a solvate thereof present in a composition comprising compounds of formulae (I) and (II) or a salt or a solvate thereof.

PROCESS FOR THE PREPARATION OF OPIOID COMPOUNDS

The present invention is directed to a process for the preparation of opioid compounds such as buprenorphine, naltrexone, naloxone, nalbuphone, nalbuphine, and the like.

PROCESS FOR THE PREPARATION OF OPIOID COMPOUNDS

The present invention is directed to a process for the preparation of opioid compounds such as buprenorphine, naltrexone, naloxone, nalbuphone, nalbuphine, and the like.

PROCESS FOR THE PREPARATION OF MORPHINE ANALOGS VIA THE REACTION OF ORGANOMETALLIC REAGENTS WITH AN OXAZOLIDINE DERIVED FROM MORPHINANS

The oxazolidine derived from the reaction of oxymorphone with the Burgess reagent, temporariiy protected at 0-3 and C-6, reacts with Grignard or other suitable metallic or organometallic reagents to directly provide, for example, A/-allyl, A/-methylcyclopropyl and /V-methylcyclobutyl derivatives that are further converted into naltrexone, naloxone, nalbuphone and nalbuphine in excellent yields. These morphine analogs can be prepared from the oxazolidine in a one- pot synthesis.

General method of synthesis for naloxone, naltrexone, nalbuphone, and nalbuphine by the reaction of grignard reagents with an oxazolidine derived from oxymorphone

The N-oxide of O-acyloxymorphone, when treated with the Burgess reagent, provides the corresponding oxazolidine in a one-pot sequence and in excellent yield. The oxazolidine derived from oxymorphone, temporarily protected at O-3 and C-6, reacts with Grignard reagents to provide directly N-allyl, N-cyclopropylmethyl, and N-cyclobutylmethyl derivatives that are further converted to the title compounds, namely naltrexone, naloxone, nalbuphone, and nalbuphine in excellent yields. Each of these medicinal agents is obtained from the oxazolidine in a one-pot sequence. Complete spectral and experimental data are provided for all compounds. Copyright

Processes and Intermediates in the Preparation of Morphine Analogs via N-Demethylation of N-Oxides Using Cyclodehydration Reagents

A high-yielding method for the N-demethylation of oxycodone- and oxymorphone-N-oxides by the reaction of these compounds with cyclodehydration reagents has been performed. This method has been utilized to improve the synthesis of various morphine analogs, such as naltrexone, nalbuphone and naloxone.