105618-26-6

Basic information

• Product Name: NOR-BINALTORPHIMINE DIHYDROCHLORIDE
• Synonyms: N-DESMETHYLBINALTORPHIMINE;NOR-BINALTORPHIMINE DIHYDROCHLORIDE;NORBNI;NOR-BNI DIHYDROCHLORIDE;NOR-BNL 2HCL;norbinaltorphimine;4,8:11,15-DIMETHANO-20H-BISBENZOFURO[2,3-A:3',2'-I]DIPYRIDO[4,3-B:3',4'-H]CARBAZOLE-1,8A,10A,18-TETROL, 7,12-BIS(CYCLOPROPYLMETHYL)-5,6,7,8,9,10,11,12,13,14,19A,20B-DODECAHYDRO-, (4BS,8R,8AS,10AS,11R,14AS,19AR,20BR), DIHYDROCHLORIDE;17,17'-(DICYCLOPROPYLMETHYL)-6,6',7,7'-6,6'-IMINO-7,7'-BINORPHINAN-3,4',14,14'-TETROL DIHYDROCHLORIDE
• CAS NO: 105618-26-6
• Molecular Formula: C₄₀H₄₃N₃O₆
• Molecular Weight: 734.71
• Product Categories: Opioid receptor and opioid-like receptor;Opioids
• Mol File: 105618-26-6.mol
• Article Data: 4

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: tan/
• Density: 1.63 g/cm³
• Refractive Index: 1.834
• Storage Temp.: −20°C
• Solubility: artificial CSF: soluble2mg/mL (prepare with sonication for 4 min
• PKA: 9.11±0.60(Predicted)
• CAS DataBase Reference: NOR-BINALTORPHIMINE DIHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: NOR-BINALTORPHIMINE DIHYDROCHLORIDE(105618-26-6)
• EPA Substance Registry System: NOR-BINALTORPHIMINE DIHYDROCHLORIDE(105618-26-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• RTECS: IO1320000
• Hazardous Substances Data: 105618-26-6(Hazardous Substances Data)

Usage

Chemical Properties

Tan solid

Biological Activity

A selective κ -opioid receptor antagonist.

Biochem/physiol Actions

Highly selective k-opioid receptor antagonist. nor-Binaltorphimine has antidepressant properties.

InChI:InChI=1/C40H43N3O6/c44-27-7-5-21-13-25(19-1-2-19)42-11-9-39-29(21)33(27)48-35(39)31-23(15-37(39,46)17-42)24-16-38(47)18-43-12-10-40(38)30-22(14-26(43)20-3-4-20)6-8-28(45)34(30)49-36(40)32(24)41-31/h5-8,19-20,25-26,35-36,41,44-47H,1-4,9-18H2

Synthetic route

naltrexone Hydrochloride (16676-29-2) → norbinaltorphimine (105618-26-6)

Conditions	Yield
With hydrazine dihydrochloride; methanesulfonic acid In N,N-dimethyl-formamide at 105℃; Temperature; Solvent; Reagent/catalyst; Inert atmosphere;	96%
With hydrazine dihydrochloride; methanesulfonic acid 1.) DMF, 100 deg C, 6 h, 2.) DMSO, 130 deg C, 3 h; Yield given. Multistep reaction;

naltrexone Hydrochloride (16676-29-2) → C40H46N4O6*2ClH + norbinaltorphimine (105618-26-6)

Conditions	Yield
With hydrazine dihydrochloride In N,N-dimethyl-formamide at 100℃; Reagent/catalyst; Temperature;	A 80% B 9%
With hydrazine dihydrochloride; methanesulfonic acid In N,N-dimethyl-formamide at 109℃; Reagent/catalyst; Temperature;	A 30% B 60%

naltrexone Hydrochloride (16676-29-2) + hydromorphone hydrochloride (71-68-1) → norbinaltorphimine (105618-26-6) + 17-(cyclopropylmethyl),17'-methyl-6,6',7,7'-tetradehydro-4,5:4',5'-diepoxy-6,6'-(imino)<7,7'-bimorphinan>-3,3',14-triol + C34H35N3O4*2ClH

Conditions	Yield
With 1-amino-pyrrolidine-2,5-dione; hydrochloride In N,N-dimethyl-formamide at 100℃; for 18h;	A 19% B 24.5% C 12%

Naltrexone (16590-41-3) → norbinaltorphimine (105618-26-6)

Conditions	Yield
Stage #1: Naltrexone With hydrazine In N,N-dimethyl-formamide at 100℃; Stage #2: With methanesulfonic acid In dimethyl sulfoxide at 130℃;

methyl 2-(bromomethyl)propenoate (4224-69-5) + norbinaltorphimine (105618-26-6) → 3,3'-bis<(2-carbomethoxyallyl)oxy>-17,17'-bis(cyclopropylmethyl)-6,6',7,7'-tetradehydro-4,5:4',5'-diepoxy-6,6'-imino<7,7'-bimorphinan>-14,14'-diol

Conditions	Yield
With sodium hydroxide; tetrabutylammomium bromide In dichloromethane for 2h;	97%

benzyl bromide (100-39-0) + norbinaltorphimine (105618-26-6) → 17,17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-4,5:4',5'-diepoxy-6,6'-(benzylimino)[7,7'-bimorphinan]-3,3',14,14'-tetrol dihydrochloride

Conditions	Yield
Stage #1: norbinaltorphimine With 18-crown-6 ether; sodium hydride In tetrahydrofuran at 20℃; for 0.333333h; Stage #2: benzyl bromide In tetrahydrofuran for 43h; Stage #3: With hydrogenchloride In methanol at 90℃; for 40h;	63%

diazomethane (186581-53-3, 908094-01-9) + norbinaltorphimine (105618-26-6) → 17,17'-bis(cyclopropylmethyl)-3-methoxy-6,6',7,7'-tetradehydro-4,5:4',5'-diepoxy-6,6'-(imino)<7,7'-bimorphinan>-3',14,14'-triol + 17,17'-bis(cyclopropylmethyl)-3,3'-dimethoxy-6,6',7,7'-tetradehydro-4,5:4',5'-diepoxy-6,6'-(imino)<7,7'-bimorphinan>-14,14'-diol

Conditions	Yield
In methanol; diethyl ether at 24℃; for 0.166667h;	A 56% B 28%

Upstream product

• 16676-29-2 naltrexone Hydrochloride 
• 16590-41-3 Naltrexone 
• 71-68-1 hydromorphone hydrochloride 

Relevant articles and documents

Binaltorphimine-Related Bivalent Ligands and Their κ Opioid Receptor Antagonist Selectivity

In an effort to develop selective antagonists for κ opioid receptors, bivalent ligands that contain opioid antagonist pharmacophores derived from naltrexone or other morphinans were synthesized and tested on the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations.The minimum requirements for κ selectivity are at least one free phenolic OH group and one N-cyclopropyl or N-allyl substituent.Several compounds (3, 8, 10) with κ selectivity as good as or better than norbinaltorphimine (nor-BNI, 2) were discovered.The structure-activity relationship revealed that the pyrrole ring functions strictly as a spacer and does not contribute to κ selectivity.The pharmacologic data suggest that only one antagonist pharmacophore may be required for κ selectivity and that the other morphinan portion of the molecule confers selectivity by interacting with a unique subsite proximal to the antagonist pharmacophore recognition locus.

Bimorphinans as highly selective, potent κ opioid receptor antagonists

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