43 results about "Lorcaserin" patented technology

The present invention is drawn to combinations of pharmaceutical agents having similar chemical and/or pharmacological properties, wherein the combinations maximize the therapeutic effect of the drug while minimizing their adverse effects. The methods and compositions of the invention are particularly useful in the treatment of obesity and related conditions which involves treating a subject with a sympathomimetic agent (e.g., phentermine or a phentermine-like drug) or bupropion in combination with an anti-epileptic agent (e.g., topiramate, zonisamide), CB1 antagonists (e.g., rimonabant), or a 5HT_2C-selective serotonin receptor agonist, (e.g., lorcaserin) for the treatment of obesity and related conditions. The invention also features kits for use in the practice of these novel therapies.

The invention discloses a synthesis method of a lorcaserin derivative. The synthesis method comprises the following steps: resolving a compound shown as a formula (II) under the action of an optical resolving agent; performing post-treatment to obtain the lorcaserin derivative. In the formula (II), R is H, alkyl with 1-4 carbon atoms, halogen, methoxyl or nitryl; R2 is H, alkyl with 1-4 carbon atoms, methoxyl, carboxybenzyl, t-butyloxycarboryl, methylsulfonyl, tosyl and substituted or unsubstituted benzyl; the optical resolving agent is acyl-substituted tartaric acid. The revolving efficiency is increased by selecting the optical resolving agent having a specific structure, and an optical pure product of which the ee value is over 99 percent can be obtained by means of simple recrystallization; meanwhile, resolving operation is easy, a single solvent is used for resolving, materials are fed into one pot, and the method is suitable for industrial production. The invention further discloses a synthesis method of a salt of the lorcaserin derivative. The obtained salt of the lorcaserin derivative can be applied to preparation of novel weight-reducing medicaments.

A preparing method of (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine that is a lorcaserin intermediate is disclosed. The method includes (1) dehydrating a compound 1 and a compound 2 under catalysis by boric acid to generate an amide 3, (2) reducing the intermediate 3 with a borane dimethylsulfide complex to obtain a compound 4, and (3) subjecting the compound 4 to direct ring closing with the existence of aluminum chloride to generate the lorcaserin intermediate that is the (R,S)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine that is the compound 6. The method avoids use of 3,4,5-trimethoxyphenylboronic acid that is an expensive reagent, thus reducing the cost. The method avoids use of thionyl chloride so that the method is environmental friendly. A step of hydroxy chlorination is reduced so that the method is simple in process. The conversion ratio of raw materials and the total yield of reactions are increased. The yield of the compound 6 is increased from 60% in a patent to 82%. The method is suitable for industrial production. A reaction equation is shown in the description.

The invention relates to an application of Lorcaserin hydrochloride in preparation of a medicine for inhibiting opioid addiction and withdrawal syndrome. The Lorcaserin hydrochloride is approved to be a weight-reducing aid by the America Food and Drug Administration (FDA) in 2012. The Lorcaserin hydrochloride is a 5-hydroxytryptamine 5-HT2C receptor stimulant with high selectivity. The latest research of the invention finds that the Lorcaserin hydrochloride (0.5-1.0mg.kg<-1>) greatly reduces the naloxone-urged horizontal motion distance and speed of a morphine dependent mice and the withdrawal syndrome of the mice. It is found in the invention for the first time that the Lorcaserin hydrochloride can be applied clinically for rescuing and treating addiction and withdrawal syndrome generated by morphine and other opiates.

The invention belongs to the technical field of medicines and particularly relates to hydrochloric lorcaserin tablets and a preparing method thereof. The hydrochloric lorcaserin tablets are prepared from hydrochloric lorcaserin, a thinning agent, a dry binding agent, a disintegrating agent and a lubricating agent. The preparing process of the hydrochloric lorcaserin tablets comprises the step that powder is directly compressed into tablets or the powder is granulated and then compressed into tablets in a dry method, and the production process is simple, controllable, high in operability, short in production cycle, low in production cost and low in industrialization difficulty. The prepared hydrochloric lorcaserin tablets are good in appearance, fast in effect taking and stable in curative effect, the content and the dissolution rate of the hydrochloric lorcaserin tablets are both qualified, and taking compliance of a patient is not affected.

The present invention relates to the field of pharmaceutical chemistry, specifically to a preparation method of a weigh reducing drug lorcaserin hydrochloride and an intermediate thereof. The preparation method comprises: adopting p-chlorophenethylamine as a raw material, and sequentially carrying out acylation amino protection, allyl substitution, deprotection, Friedel-Crafts alkylation, splitting and salt forming to obtain the lorcaserin hydrochloride. According to the present invention, the preparation method has characteristics of low cost, simple operation and easy post-treatment, and is the economical and industrialized synthesis method.

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.

The invention discloses an oxa-spiro phosphine-oxazoline ligand as well as a preparation method and application thereof. The oxa-spiro phosphine-oxazoline ligand is a compound as shown in a formula (3) or a stereoisomer of the compound as shown in the formula (3), can form a catalyst complex with good catalytic performance after being complexed with a metal iridium catalyst, and can be used for asymmetric reduction reaction, particularly reduction reaction of a lorcaserin intermediate and an analogue thereof.

The present invention relates to the pharmaceutical synthesis field, particularly to a preparation method of an lorcaserin intermediate 8-chloro-1-methyl-4,5-dihydro-1H-benzo[d]azepine-2(3H)-one. The preparation method is characterized in that in an intramolecular Friedel-Crafts alkylation reaction, aluminum trichloride is adopted as a catalyst and anhydrous dichlorobenzene is adopted as a solvent so as to increase the reaction at the step to 73%, such that the method has advantages of low catalyst consumption, low reaction temperature, convenient post-treatment, easy scale-up, and the like.

The invention relates to a preparation method of a lorcaserin intermediate 1-[2-(4-chlorphenyl)-ethylamino]-2-propanol, which specifically comprises the following steps: carrying out bromination reaction on p-chlorophenethyl alcohol serving as a starting material to obtain 4-chlorphenyl ethyl bromide, and condensing with isopropanolamine to obtain a target product. Hydrobromic acid is used as a bromination reagent, potassium carbonate is used as a condensation reaction acid-binding agent, potassium iodide is used as a condensation reaction catalyst, the yield of the technological process is high, three wastes are few, the cost is low, the operation is simple, the safety is good, and industrial production requirements are met.

The present invention provides a method for preparing lorcaserin. The method is as below: A) synthesizing a lorcaserin racemate by using 1-[[2-(4-chlorphenyl) ethyl] amino]-2-chloropropane hydrochloride as a raw material by a solvent-free method; B) cooling the reaction system to 70-80 DEG C, adding an organic solvent, stirring well and cooling to 0 to 5 DEG C, wherein the organic solvent is tetrachloroethylene, chlorobenzene, toluene or cyclohexane; C) adding hydrochloric acid solution in the reaction system, dispensing the liquid, and removing an organic phase to obtain a water phase; and D) adding NaOH solution to the water phase, then adding cyclohexane or heptanes, and extracting and concentrating the organic phase to obtain a lorcaserin racemic pure product. After the solvent-free alkylation reaction, the organic solvent of tetrachloroethylene, chlorobenzene, toluene or cyclohexane is added, so as to solve the safety problem caused by rapid heat release due to direct addition of water; and the posttreatment process is simple and safe. The invention realizes industrial application of solvent-free synthesis of lorcaserin, at the same time ensures the quality of prepared lorcaserin.

The invention discloses a synthesis process of a weight-reducing drug lorcaserin hydrochloride intermediate (compound V), which is characterized in that p-chlorophenylethylamine is used as a raw material, acetic anhydride is subjected to acylation to protect amino, and allyl substitution, Friedel-Crafts alkylation and hydrochloric acid deprotection are performed to obtain a lorcaserin hydrochloride racemate. The synthesis method is simple in synthesis and preparation and high in yield, and is a lorcaserin hydrochloride intermediate synthesis process suitable for industrial large-scale production.