153567-11-4

Usage

InChI:InChI=1/C27H29NO4/c29-20-10-11-27(30)22-14-19-8-9-21(31-16-18-4-2-1-3-5-18)24-23(19)26(27,25(20)32-24)12-13-28(22)15-17-6-7-17/h1-5,8-9,17,22,25,30H,6-7,10-16H2/t22-,25+,26+,27-/m1/s1

Upstream product

• 16676-29-2 naltrexone Hydrochloride 
• 100-39-0 benzyl bromide 
• 16590-41-3 Naltrexone 
• 100-44-7 benzyl chloride 
• 1252784-89-6 (R)-N-(cyclopropylmethyl)oripavine ammonium bromide 
• 467-04-9 oripavine 
• 14728-69-9 (4R,7aR,12bS)-3-(cyclopropylmethyl)-7-methoxy-2,3,4,7a-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-ol 

Downstream Products

• 153567-12-5 3-O-benzyl-17-(cyclopropylmethyl)-4,5α-epoxy-14-hydroxymorphinan-6-one-7-spiro-2'-indan 
• 165673-78-9 3-benzyloxy-17-(cyclopropylmethyl)-4,14β-dihydroxymorphinan-6-one 
• 194468-65-0 7α-spirobenzocyclohexyl-3-O-benzylnaltrexone 
• 194468-64-9 7β-spirobenzocyclohexyl-3-O-benzylnaltrexone 
• 156568-76-2 3-O-benzyl-7-(5',6'-benzo-2'-spiroindanyl)naltrexone 
• 156568-78-4 3-O-benzyl-7-(2',3'-dihydro-2'-spiroperinaphthenyl)naltrexone 
• 735332-77-1 3-O-benzyl-7-ethoxycarbonylnaltrexone 
• 1032282-28-2 (S)-17-cyclopropylmethyl-4,5α-epoxy-3-benzyloxy-14-hydroxy-7-methyl-morphinan-6-one 
• 1032281-27-8 17-cyclopropylmethyl-4,5α-epoxy-3-benzyloxy-14-hydroxy-7-(N,N-dimethylaminomethylene)-6-oxomorphinan 

Relevant academic research and scientific papers

Delta opioid binding selectivity of 3-ether analogs of naltrindole

Masking of the 3-phenol of naltrindole as a range of ethers caused a decrease in binding affinity at all three opiate receptors (μ, κ, δ), however for the methyl ether, the reduction in affinity at both μ and κ was greater than at δ, thereby increasing δ

Syntheses of 4,6′-epoxymorphinan derivatives and their pharmacologies

A modification of the message site in the skeleton of naltrexone was carried out to improve the potency and selectivity of the compound for an opioid receptor subtype. In the course of conversion, we synthesized 7-membered ring ether derivatives, which ha

Discovery of novel delta opioid receptor (Dor) inverse agonist and irreversible (non-competitive) antagonists

The delta opioid receptor (DOR) is a crucial receptor system that regulates pain, mood, anxiety, and similar mental states. DOR agonists, such as SNC80, and DOR-neutral antagonists, such as naltrindole, have been developed to investigate the DOR in vivo and as potential therapeutics for pain and depression. However, few inverse agonists and non-competitive/irreversible antagonists have been developed, and none are widely available. This leaves a gap in our pharmacological toolbox and limits our ability to investigate the biology of this receptor. Thus, we designed and synthesized the novel compounds SRI-9342 as an irreversible antagonist and SRI-45127/SRI-45128 as inverse agonists. Then, these compounds were evaluated in vitro for their binding affinity by radioligand binding and functional activity by35 S-GTPγS coupling and cAMP accumulation in cells expressing the human DOR. All three compounds demonstrated high binding affinity and selectivity at the DOR, and all three displayed their hypothesized molecular pharmacology of irreversible antagonism (SRI-9342) or inverse agonism (SRI-45127/SRI-45128). Together, these results demonstrate that we have designed new inverse agonists and irreversible antagonists of the DOR based on a novel chemical scaffold. These new compounds will provide new tools to investigate the biology of the DOR or even new potential therapeutics.

Design, synthesis, and preliminary evaluation of a potential synthetic opioid rescue agent

Background: One of the most prominent opioid analgesics in the United States is the high potency agonist fentanyl. It is used in the treatment of acute and chronic pain and as an anesthetic adjuvant. When used inappropriately, however, ingestion of just a

Preparation method for bromomethyl naltrexone

The invention specifically relates to a preparation method for bromomethyl naltrexone, belonging to the field of pharmaceutical chemicals. According to the invention, bromomethyl naltrexone is prepared from an intermediate, i.e., O-benzyl-N-bromomethyl na

Synthesis of Naltrexone and (R)-Methylnaltrexone from Oripavine via Direct Oxidation of Its Quaternary Salts

(R)-Methylnaltrexone and naltrexone were each prepared in four steps from oripavine in practical yields. The procedure involved quaternization of oripavine with cyclopropylmethyl halides, singlet oxygen oxidation of the quaternary salts, and the reduction of endo peraoxides to 14-hydroxyketone functionalities. (R)-Methylnaltrexone was prepared from the corresponding R-diastereomer of the oripavine salt. All diastereomeric mixtures of the quaternary salts were subjected to N-demethylation with sodium thiolate to yield cyclopropyl methylnororipavine, which was converted into naltrexone by peracid oxidation and hydrogenation according to established procedures.

An efficient synthesis of 3-OBn-6β,14-epoxy-bridged opiates from naltrexone and identification of a related dual MOR inverse agonist/KOR agonist

In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6β,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through the OBn-6α-triflate intermediate 8. Key steps to the synthesis include benzylation (96% yield), reduction (90% yield, α:β:3:2), followed by a one-pot triflation/displacement sequence (96% yield) to yield the desired bridged epoxy derivative 4. X-ray crystallographic analysis of intermediate 3-OBn-6α-naltrexol 7a supports population of the key boat conformation required for the epoxy ring closure. We also report that the 6β-mesylate 10-a high affinity opioid receptor ligand, the epimeric derivative of 11, and an analog of 12-functions as an inverse agonist at the mu opioid receptor using herkinorin pre-conditioned cells and an agonist at the kappa opioid receptor when evaluated in independent in vitro [ 35S]-GTP-γ-S assays.

N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS

Novel N-oxides of 4,5-epoxy-morphinanIum analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS

Novel N-oxides of 4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

PROCESS FOR PREPARING N-ALKYLNALTREXONE HALIDES

The invention relates to a novel process for preparing N-methylnaltrexone bromide, comprising at least the steps consisting in: (i) reacting N-methylnaltrexone methyl sulfate in aqueous solution with an alkaline agent chosen from the group constituted by sodium carbonate, potassium carbonate, calcium carbonate, magnesium carbonate, cesium carbonate, strontium carbonate and mixtures thereof, for a pH of the aqueous reaction medium of between 7 and 10, and then in(ii) reacting the product thus obtained with hydrobromic acid, which is added for a pH of the aqueous reaction medium of between 0.5 and 5, in order thus to obtain the N-methylnaltrexone bromide.