616202-92-7

Basic information

• Product Name: LORCASERIN
• Synonyms: LORCASERIN;(R)-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine;Apd 356;Apd356;Apd-356;Ar-10a;Unii-637E494o0z;(1R)-8-Chloro-2,3,4,5-tetrahydro-1-Methyl-1H-3-benzazepine
• CAS NO: 616202-92-7
• Molecular Formula: C11H14ClN
• Molecular Weight: 195.692
• EINECS: 1308068-626-2
• Product Categories: Amines;Aromatics;Chiral Reagents;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 616202-92-7.mol

Chemical Properties

• Boiling Point: 288 ºC
• Flash Point: 128 ºC
• Appearance: yellow oil
• Density: 1.075
• Vapor Pressure: 0.002mmHg at 25°C
• Refractive Index: 1.527
• Storage Temp.: -20?C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 9.99±0.40(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: LORCASERIN(CAS DataBase Reference)
• NIST Chemistry Reference: LORCASERIN(616202-92-7)
• EPA Substance Registry System: LORCASERIN(616202-92-7)

Safety Data

• Hazardous Substances Data: 616202-92-7(Hazardous Substances Data)

Usage

Uses

Used in Obesity Treatment:
Lorcaserin is used as an anti-obesity agent for promoting weight loss. It works by selectively targeting the 5-HT2C receptor, which is involved in regulating appetite and energy balance. By activating this receptor, Lorcaserin helps to reduce food intake and increase satiety, leading to a decrease in body weight.
Used in Opioid Use Disorder (OUD) Treatment:
Lorcaserin is also used as a treatment for Opioid Use Disorder (OUD). It has been found to help manage cravings and withdrawal symptoms associated with opioid dependence, making it a valuable tool in the fight against opioid addiction.
Used in Diet Pills:
Lorcaserin is used as an ingredient in diet pills for its appetite-suppressing properties. By reducing hunger and promoting a feeling of fullness, it can assist individuals in adhering to a calorie-restricted diet and achieving their weight loss goals.

Weight loss drugs

Lorcaserin is a new drug for the treatment of obesity , belonging to oral potent selective serotonin 2C receptor agonists, lorcaserin hydrochloride is successfully developed by the US company Arena, on June 27, 2012 by the US FDA it is approved for marketing, as adjuvant therapy for obesity or merge with at least one weight-related complications in overweight adults in low-calorie diet and exercise basis . Clinical studies show that the drug can reduce weight of obesity and overweight patients ,it can improve obesity-related metabolic parameters, and it is well tolerated. Lorcaserin affinity for the 5-HT2c 100 times higher than the 5-HT2B (valvular heart disease risk) ,it has good safety,it is the first FDA-approved weight-loss drug after 1999 . In a year of Lorcaserin treatment, the average weight loss ranges from 3 to 3.7 percent.

Drug Interactions

Due to the theoretical possibility of the mechanism of lorcaserin and serotonin syndrome, when lorcaserin is used in combination with the serotonergic neurotransmitter system drugs, extreme caution should be paid, including triptans monoamine oxidase inhibitor agent selective serotonin reuptake inhibitor selective serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants bupropion dextromethorphan, lithium tramadol and St. John's wort , etc. In addition, when the present product with CYP2D6 substrates when combined with the need to be cautious, because the product can increase the exposure of these drugs. The above information is edited by the lookchem of Tian Ye.

safety

Lorcaserin has good tolerability and safety, lorcaserin is used in non-diabetic patients, the most common adverse reactions are headache, dizziness, fatigue, nausea, dry mouth and constipation. This product is used in patients with diabetes, common adverse reactions are headache, back pain, cough, low blood sugar and fatigue.studies have found that lorcaserin and placebo are Similar in the proportion of serious adverse reactions, lorcaserin does not increase the incidence of valvular heart disease. After lorcaserin treatment , the incidence of depression is lower , the research shows that the proportion of depression led by lorcaserin 10mgbid, 10mgqd and placebo are 1.9%, 1.1% and 1.8%, emotional low incidence rates are 0.6%, 0.9% and 0.9%, the proportion of suicidal thoughts are 0.9%, 0.6% and 0.7% .the product is pregnancy X-class , pregnant women are disabled; whether this product is secreted by milk is unknown, breast-feeding women need to weigh on the use of the drug; this product is not recommended for children.

Mechanism of action

Lorcaserin acts at 5-HT2C receptors in the central nervous system (CNS), particularly the hypothalamus, to reduce appetite.

Side effects

constipationdry mouthexcessive tirednesspain in the back or musclesheadachedizzinessdifficulty falling asleep or staying asleepanxiety

Synthesis

The synthesis of?LORCASERIN is as follows:Liquid precursor 53 11-HCl (0.5mmol) was placed into a test tube equipped with a magnetic stir bar. Anhydrous 44 AlCl3?(1.75 equiv according to starting material) was added and efficiently mixed to obtain a paste. The mixture was slowly heated (10°C/min) to 150°C and stirred overnight. A saturated solution of 54 NaCl was added and the mixture was cooled. The pH was adjusted to 9.5-10 using 1M NaOH and then extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4?and the solvent was evaporated under reduced pressure. The obtained crude mixture was analyzed using?1H NMR spectroscopy (estimated yield by?1H NMR was 62%).

InChI:InChI=1/C11H14ClN/c1-8-7-13-5-4-9-2-3-10(12)6-11(8)9/h2-3,6,8,13H,4-5,7H2,1H3/t8-/m0/s1

Upstream product

• 824430-77-5 8-chloro-1-methyl-4,5-dihydro-1H-benzo[d]azepin-2(3H)-one 
• 34164-14-2 N-(4-chlorophenylethyl)-2-chloropropanamide 
• 616202-51-8 1-(8-chloro-1-methyl-1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)-2,2,2-trifluoroethan-1-one 
• 953789-37-2 1-[[2-(4-chlorophenyl)ethyl]amino]-2-chloropropane hydrochloride 
• 1247548-14-6 N-(4-chlorophenylethyl)propyl-2-ene-1-amine 
• 6529-53-9 1-(2-bromoethyl)-4-chlorobenzene 
• 1875-88-3 2-(4-Chlorophenyl)ethanol 
• 1082555-06-3 2-(3-chlorophenyl) propan-1-amine 
• 1616729-45-3 2-(3-chlorophenyl)-N-(2,2-dimethoxyethyl)propan-1-amine 
• 1006037-59-7 (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride 
• 2937-50-0 Allyl chloroformate 
• 616202-81-4 (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine 
• 1878-66-6 4-chlorophenylacetic Acid 
• 1030624-36-2 2-(4-chlorophenyl)-N-(2-hydroxypropyl)acetamide 

Downstream Products

• 824430-78-6 (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine L-(+)-tartrate 
• 824430-78-6 bis((R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine) L-(+)-tartarate 
• 824430-78-6 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine L-hemitartrate 
• 824430-78-6 (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemitartrate 
• 824430-78-6 (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hemitartrate 
• 1431697-94-7 (±)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride 
• 824430-78-6 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine L-(+)-tartrate 
• 824430-78-6 2C₁₁H₁₄ClN*C₄H₆O₆ 
• 1006037-59-7 (S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride 
• 616201-80-0 (+/-)-Lorcaserin 
• 846589-98-8 Lorcaserin hydrochloride 

Relevant articles and documents

Design of oxa-spirocyclic PHOX ligands for the asymmetric synthesis of lorcaserin: Via iridium-catalyzed asymmetric hydrogenation

Phosphine-oxazoline (PHOX) ligands are a very important class of privileged ligands in asymmetric catalysis. A series of highly rigid oxa-spiro phosphine-oxazoline (O-SIPHOX) ligands based on O-SPINOL was synthesized efficiently, and their iridium complexes were synthesized by coordination of the O-SIPHOX ligands to [Ir(cod)Cl]2 in the presence of sodium tetrakis-3,5-bis(trifluoromethyl)phenylborate (NaBArF). The cationic iridium complexes showed high reactivity and excellent enantioselectivity in the asymmetric hydrogenation of 1-methylene-tetrahydro-benzo[d]azepin-2-ones (up to 99% yield and up to 99% ee). A key intermediate of the anti-obesity drug lorcaserin could be efficiently synthesized using this protocol.

Niclosin hydrochloride pellet, and preparation method and preparation thereof

A lorcaserin hydrochloride mini-pill is provided. The mini-pill comprises a blank pill core, a medicine loading layer, a slow-release layer and a quick-release layer in order from inside to outside. The medicine loading layer comprises lorcaserin hydrochloride, lactose monohydrate, highly substituted hydroxypropylcellulose and talcum powder. The slow-release layer comprises ethyl cellulose, highly substituted hydroxypropylcellulose, talcum powder and triethyl citrate. The quick-release layer comprises lorcaserin hydrochloride, lactose monohydrate, highly substituted hydroxypropylcellulose and talcum powder. The mass ratio of the sum of the weight of the blank pill core and the weight of the medicine loading layer to the mass of the slow-release layer is 1:(0.25-0.35). The mini-pill comprises the slow-release layer and the quick-release layer, and therefore a medicine can rapidly work and functions of the medicine in a body are prolonged. A preparing method of the lorcaserin hydrochloride mini-pill and a preparation of the lorcaserin hydrochloride mini-pill are also provided.

Method for preparing lorcaserin

The invention discloses a method for preparing lorcaserin. Specifically, the method comprises the steps: taking p-chlorophenylacetonitrile as an initial raw material, preparing p-chlorophenylethylamine through reduction; carrying out a reaction with p-toluenesulfonyl chloride to form an amino occupying intermediate; enabling the intermediate to carry out a reaction with monochloroacetone under analkaline condition to form N-(2-(4-chlorphenyl)ethyl)-4-methyl-N-(2-propionyl)benzenesulfonamide, and then carrying out reduction, chlorination, p-toluenesulfonyl removal and intramolecular Friedel-Crafts alkylation to synthesize 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzoazepine, carrying out L-(+)-tartaric acid resolution and alkalization on azepine to remove tartaric acid, and acting with hydrogen chloride diethyl ether to salify to prepare lorcaserin. The method has the characteristics of simple synthesis method, good reaction selectivity, high product purity, environmental protectionand low preparation cost.

A new enantioselective synthesis of antiobesity drug lorcaserin

A simple and efficient enantioselective synthesis of anti-obesity drug lorcaerin starting from easily accessible 3-chlorostyrene oxide has been described for the first time employing hydrolytic kinetic resolution as a source of chirality. The protocol might also be useful in the synthesis of structural variants of lorcaserin.

MODIFIED-RELEASE DOSAGE FORMS OF 5-HT2C AGONISTS USEFUL FOR WEIGHT MANAGEMENT

The present invention relates to methods for weight management that utilize modified-release dosage forms comprising (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine salts and crystalline forms thereof. The present invention further relates to (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine salts, crystalline forms thereof and modified-release dosage forms comprising them.

A novel route to (R)-2-(3-chlorophenyl)propan-l-amine, a key intermediate for the synthesis of lorcaserin

A new and efficient three-step synthesis of (R)-2-(3-chlorophenyl)propan-l-amine is reported, which serves as an intermediate in the synthesis of the antiobesity drug lorcaserin. The key step is a chiral resolution due to the formation of a salt with l-(-

Synthesis of enantiopure antiobesity drug lorcaserin

Acylation of enantiomerically pure (R)-2-(3-chlorophenyl)propan-1-amine using chloroacetyl chloride, followed by borane reduction and aluminum chloride catalyzed cyclization yielded enantiopure lorcaserin.

Preparation method of key intermediate I of lorcaserin

The invention discloses a preparation method of a key intermediate I of lorcaserin. The preparation method comprises the steps as follows: (1) in an organic solvent A, 2,4'-dichloroacetophenone is subjected to a condensation reaction with isopropanolamine under catalysis of alkali, and 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one is obtained; (2) the 1-(4-chlorophenyl)-2-((2-hydroxypropyl)amino)ethane-1-one obtained in the step (1) is subjected to catalytic reduction with sodium borohydride and acid in a solvent B, and the key intermediate I of lorcaserin is obtained. The preparation method can synthesize the key intermediate I of lorcaserin from cheap and easily available raw materials under mild reaction conditions, has the advantages of being simple to operate, low in costand high in yield, and is energy-saving, environmentally friendly and suitable for mass production.

Preparation method for hemihydrate lorcaserin hydrochloride

The invention discloses a preparation method for hemihydrate lorcaserin hydrochloride. The preparation method comprises the following steps: (1) making a compound shown as a formula III react with ammonia to obtain a compound shown as a formula II; (2) under the protection of nitrogen gas, dissolving the compound shown as the formula II in an organic solvent, adding a hydrogen chloride solution of which the solvent is the organic solvent to salify, and adding water and cyclohexane to form a hemihydrate in order to obtain the compound shown as a formula I, wherein the organic solvent is isopropanol or 1,4-dioxane. In the preparation method disclosed by the invention, ammonium hydroxide substitutes for potassium carbonate in the prior art, so that unqualified ignition residues of a finial product caused by potassium chloride generated after salt removal can be avoided; an isopropoxide hydrochloride solution substitutes for the conventional hydrogen chloride gas, so that other impurities can be prevented from being introduced in a preparation process under the improper control of dosage and rate of the gas.

Preparation method of lorcaserin intermediate

The invention discloses a preparation method of a lorcaserin intermediate (I). According to the preparation method, p-chlorobenzyl cyanide is taken as the primary raw material, and the lorcaserin intermediate (I) is obtained after reduction reactions and condensation reactions. The primary raw materials (p-chlorobenzyl cyanide and 1-chloro-2-propanol) are cheap and easily available; raw materials, which can easily get polluted and are explosive, such as sulfoxide chloride, hydrobromic acid, borane, and the like are not used; the preparation method will not produce a large amount of wastewater and is beneficial for the environment protection; moreover, the requirements on the protection of workers are lowered, and safe production is guaranteed. The route design is novel, the raw materials are easily available, the operation is simple and feasible, and the preparation method is environment-friendly and can be applied to massive industrial production.