83777-64-4

Usage

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

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

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 academic research and scientific papers

A Method for the Catalytic Enantioselective Synthesis of Chiral α-Azido and α-Amino Ketones from Racemic α-Bromo Ketones, and Its Generalization to the Formation of Bonds to C, O, and S

A new and practical method has been developed for the transformation of racemic α-bromo ketones to chiral α-azido and α-amino ketones with high enantioselectivity using phase transfer, ion-pair mediated reactions with a recoverable chiral quaternary salt (10 mol %) as catalyst in fluorobenzene-water. The process has been generalized to a variety of other attachments including of C, O, S, and NHR.

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.

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.

CRYSTAL FORMS AND METHODS OF SYNTHESIS OF (2R, 6R)-HYDROXYNORKETAMINE AND (2S, 6S)-HYDROXYNORKETAMINE

The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

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.

Synthesis and N-Methyl- d -aspartate (NMDA) Receptor Activity of Ketamine Metabolites

Ketamine is rapidly metabolized in the human body to a variety of metabolites, including the hydroxynorketamines. At least two hydroxynorketamines have significant antidepressant action in rodent models, with limited action against the N-methyl-d-aspartate (NMDA) receptor. The synthesis of 12 hydroxynorketamines and their binding affinity to the NMDA receptor is presented here.

KETAMINE DERIVATIVES

The present invention relates to ketamine derivatives of the formula (I), pharmaceutical compositions comprising them, and methods for treating pain comprising administering them, and their use in the manufacture of medicaments for treating pain. The present invention also relates to methods for anaesthetizing and methods for sedating a subject comprising administering ketamine derivatives of the formula (II).