83777-64-4

Basic information

• Product Name: R-(+)-Norketamine
• Synonyms: R-(+)-Norketamine;(R)-2-amino-2-(2-chlorophenyl)cyclohexanone;(R)-2-amino-2-(2-chlorophenyl)cyclohexanone(WXC03945)
• CAS NO: 83777-64-4
• Molecular Formula: C₁₂H₁₄ClNO
• Molecular Weight: 223.69866
• Mol File: 83777-64-4.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 368.6±42.0 °C(Predicted)
• Appearance: /
• Density: 1.208±0.06 g/cm3(Predicted)
• PKA: 6.25±0.20(Predicted)
• CAS DataBase Reference: R-(+)-Norketamine(CAS DataBase Reference)
• NIST Chemistry Reference: R-(+)-Norketamine(83777-64-4)
• EPA Substance Registry System: R-(+)-Norketamine(83777-64-4)

Safety Data

• Hazardous Substances Data: 83777-64-4(Hazardous Substances Data)

Usage

Description

R-(+)-Norketamine, a chiral compound, is the main metabolite of ketamine (K165300) and functions as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It has been identified in rat cortex and spinal cord models, indicating its potential role in the central nervous system.

Uses

Used in Pharmaceutical Industry:
R-(+)-Norketamine is used as a pharmaceutical agent for its NMDA receptor antagonist properties, which may contribute to its potential therapeutic applications in various neurological and psychiatric conditions. Its presence in the rat cortex and spinal cord models suggests that it could be involved in modulating pain perception, memory, and other cognitive functions.
Used in Research Applications:
In the field of neuroscience research, R-(+)-Norketamine serves as an important tool for studying the role of NMDA receptors in the brain. Its antagonistic effects on these receptors can help researchers understand the mechanisms underlying various neurological disorders and develop new therapeutic strategies.
Used in Drug Development:
R-(+)-Norketamine's unique interaction with NMDA receptors positions it as a candidate for drug development. Its potential use in the treatment of conditions such as chronic pain, neurodegenerative diseases, and mood disorders is currently being explored, with the aim of discovering new medications that can effectively target these receptors.

Upstream product

• 6740-85-8 (2-chlorophenyl)(cyclopentyl)methanone 
• 6740-86-9 (1-Bromocyclopentyl)(2-chlorophenyl)methanone 
• 79499-57-3 (±)-1-((2-chlorophenyl)(imino)methyl)cyclopentan-1-ol 
• 35211-10-0 norketamine 
• 17465-36-0 2'-chloro-2,3,4,5-tetrahydro-1,1'-biphenyl 
• 100477-72-3 (+)-Ketamine 
• 91393-49-6 2-amino-2-(2-chlorophenyl)cyclohexan-1-one 

Downstream Products

• 120199-64-6 (2R,6S)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexan-1-one 
• 1430202-69-9 (2R,6R)-(+)-2-amino-2-(2-chlorophenyl)-6-hydroxycyclohexanone hydrochloride 

Relevant articles and documents

Halogen Substitution Influences Ketamine Metabolism by Cytochrome P450 2B6: In Vitro and Computational Approaches

Ketamine is analgesic at anesthetic and subanesthetic doses, and it has been used recently to treat depression. Biotransformation mediates ketamine effects, influencing both systemic elimination and bioactivation. CYP2B6 is the major catalyst of hepatic ketamine N-demethylation and metabolism at clinically relevant concentrations. Numerous CYP2B6 substrates contain halogens. CYP2B6 readily forms halogen-protein (particularly Cl-π) bonds, which influence substrate selectivity and active site orientation. Ketamine is chlorinated, but little is known about the metabolism of halogenated analogs. This investigation evaluated halogen substitution effects on CYP2B6-catalyzed ketamine analogs N-demethylation in vitro and modeled interactions with CYP2B6 using various computational approaches. Ortho phenyl ring halogen substituent changes caused substantial (18-fold) differences in Km, on the order of Br (bromoketamine, 10 μM) max varied minimally (83-103 pmol/min/pmol CYP). Thus, apparent substrate binding affinity was the major consequence of halogen substitution and the major determinant of N-demethylation. Docking poses of ketamine and analogs were similar, sharing a π-stack with F297. Libdock scores were deschloroketamine m model generated with Assay Central had a ROC of 0.86. The probability of activity at 15 μM for ketamine and analogs was predicted with this model. Deschloroketamine scores corresponded to the experimental Km, but the model was unable to predict activity with fluoroketamine. The binding pocket of CYP2B6 also suggested a hydrophobic component to substrate docking, on the basis of a strong linear correlation (R2 = 0.92) between lipophilicity (AlogP) and metabolism (log Km) of ketamine and analogs. This property may be the simplest design criteria to use when considering similar compounds and CYP2B6 affinity.

PROCESS FOR SYNTHESIS AND PURIFICATION OF (2R,6R)-HYDROXYNORKETAMINE

A process for the preparation of (2R,6R)-hydroxynorketamine is provided. The process requires no chromatography purification and affords the (2R,6R)-hydroxynorketamine in eight steps with a 26% overall yield and greater than 97% purity.

Simple enantioselective syntheses of (2R,6R)-hydroxynorketamine and related potential rapid-onset antidepressants

A novel strategy for accessing cyclic α-amino ketones enantioselectively has opened a simple synthetic route to the antidepressant (2R,6R)-hydroxynorketamine and numerous analogues. Mechanistically guided catalyst selection was essential in an initial olefin epoxidation step. In a second crucial step, the epoxide was subjected to a novel O → N displacement that occurred with retention of configuration through the use of Al- or Ti-based azides, which promote epoxide activation and internal cis delivery of N3 to carbon.