233600-52-7

Basic information

• Product Name: rel-(2R,3R)-2-(3-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
• Synonyms: rel-(2R,3R)-2-(3-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol;(2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethylmorpholin-2-ol
• CAS NO: 233600-52-7
• Molecular Formula: C13H18ClNO2
• Molecular Weight: 255.74
• Mol File: 233600-52-7.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: rel-(2R,3R)-2-(3-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol(CAS DataBase Reference)
• NIST Chemistry Reference: rel-(2R,3R)-2-(3-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol(233600-52-7)
• EPA Substance Registry System: rel-(2R,3R)-2-(3-Chlorophenyl)-3,5,5-trimethylmorpholin-2-ol(233600-52-7)

Safety Data

• Hazardous Substances Data: 233600-52-7(Hazardous Substances Data)

Upstream product

• 34841-39-9 bupropion 
• 34911-51-8 2-bromo-3'-chloropropiophenone 
• 124-68-5 2-Amino-2-methyl-1-propanol 
• 34841-35-5 3'-chloro-propiophenone 
• 908852-26-6 C₃₅H₃₉ClN₂O₈ 
• 913728-80-0 C₃₅H₃₇ClN₂O₈ 
• 291275-45-1 (Z)-tert-butyl-[1-(3-chlorophenyl)prop-1-enyloxy]dimethylsilane 
• 287477-53-6 (S)-1-(3-chlorophenyl)-2-hydroxypropan-1-one 
• 291275-47-3 Trifluoro-methanesulfonic acid (S)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester 
• 291275-46-2 (R)-(+)-1-(3-chlorophenyl)-2-hydroxypropan-1-one 
• 1231951-61-3 (S)-3,5,5-trimethylmorpholin-2-one 
• 36229-42-2 (3-chlorophenyl)magnesium bromide 
• 291275-48-4 Trifluoro-methanesulfonic acid (R)-2-(3-chloro-phenyl)-1-methyl-2-oxo-ethyl ester 

Relevant articles and documents

Metabolism of bupropion by baboon hepatic and placental microsomes

The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 μM, Vmax 258 ± 32 pmol mg protein-1 min-1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB.

HYDROXYBUPROPION ANALOGUES FOR TREATING DRUG DEPENDENCE

The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: Aids to smoking cessation

To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropions possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,3S)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3′,4′-dichlorophenyl [(±)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3′-fluorophenyl, 3′-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of α4β2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,3S)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of α4β2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.

Enhancing transdermal delivery of opiod antagonists and agonistis using codrugs links to bupropion or hydroxybupropion

The present invention is directed to novel codrugs comprising bupropion or hydroxybupropion and an opioid antagonist or an opioid agonist joined together by chemical bonding. The codrugs provide a significant increase in the transdermal flux across human skin, as compared to the basic opioid antagonist or opioid agonist.

Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6β-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents

A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was to design and synthesize codrugs for simultaneous treatment of alcohol abuse and tobacco dependence. Two novel tripartate codrugs of naltrexone (NTX) and naltrexol (NTXOL) covalently linked to hydroxybupropion (BUPOH) were synthesized (25 and 26, respectively), and their hydrolytic cleavage to the parent drugs was determined. These codrugs were generally less crystalline when compared to NTX, or NTXOL, as indicated by their lower melting points, and were expected to be more lipid-soluble. Also, the calculated c logP values were found to be higher for the codrugs compared to those for NTX and NTXOL. The studies on the hydrolysis of the codrugs provided good evidence that they could be efficiently converted to the parent drugs in buffer at physiological pH. Thus, these codrugs are likely to be cleaved enzymatically in vivo to generate the parent drugs, and are considered to be potential candidates for simultaneous treatment of alcohol abuse and tobacco dependence.

RESOLUTION PROCESS FOR PREPARING (+)-(2S,3S)-2-(3-CHLOROPHENYL)-3,3,3-TRIMETHYL-2-MORPHOLINOL

Disclosed is a method for preparing (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol and pharmaceutically acceptable salts such as the (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride salt via dynamic kinetic resolution.

ENZYME-CATALYZED DYNAMIC KINETIC RESOLUTION PROCESS FOR PREPARING (+)-(2S, 3S)-2-(3-CHLOROPHENYL)-3,5,5-TRIMETHYL-2-MORPHOLINOL, SALTS, AND SOLVATES THEREOF

A process for preparing (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol, pharmaceutically acceptable salts and solvates thereof such as the (+)-(2S, 3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride salt via enzyme-cataly

Pharmaceutically active morpholinol

Disclosed is the compound (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions comprising them, and processes for their preparation; also disclosed is a method of treating depression, attention deficit hyperactivity disorder (ADHD), obesity, migraine, pain, sexual dysfunction, Parkinson's disease, Alzheimer's disease, addiction to cocaine or nicotine-containing (especially tobacco) products, or addiction to alcohol using such compound, salts, solvates or compositions.

Pharmaceutically active morpholinol

Disclosed is the compound (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions comprising them, and processes for their preparation; also disclosed is a method of treating depression, attention deficit hyperactivity disorder (ADHD), obesity, migraine, pain, sexual dysfunction, Parkinson's disease, Alzheimer's disease, addiction to cocaine or tobacco products, seasonal affective disorder, chronic fatigue, narcolepsy or cognitive impairment using such compound, salts, solvates or compositions.

Pharmaceutically active morpholinol

Disclosed is the compound (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol and pharmaceutically acceptable salts and solvates thereof, pharmaceutical compositions comprising them, and processes for their preparation; also disclosed is a method of treating depression, attention deficit hyperactivity disorder (ADHD), obesity, migraine, pain, sexual dysfunction, Parkinson's disease, Alzheimer's disease, addiction to cocaine or nicotine-containing (especially tobacco) products, or addiction to alcohol using such compound, salts, solvates or compositions.