58175-86-3

Usage

Chirality

Chiral compound

Active enantiomer

(+)-enantiomer

Medical use

Cough suppressant

Availability

Over-the-counter cough medications

Mechanism of action

Acts on the cough center in the brain, suppressing the urge to cough

Additional effect

Local anesthetic effect on respiratory passages

Potential issues

Restricted use in some countries due to potential for abuse and dependence

Upstream product

• 50-63-5 chloroquine phosphate 
• 54-05-7 Chloroquine 
• 105-14-6 5-diethylamino-2-pentanone 
• 140-80-7 5-diethylamino-2-pentylamine 
• 86-98-6 4,7-dichloroquinoline 
• 67459-50-1 (R)-(-)-4-amino-1-(diethylamino)pentane 
• 1198-40-9 4-amino-7-chloroquinoline 
• 67459-52-3 (S)-N¹,N¹-diethylpentane-1,4-diamine 
• 108-95-2 phenol 
• 77529-81-8 N,N-diethyl-(S)-glutamine hydrochloride 
• 77529-85-2 (S)-2-amino-5-(diethylamino)pentan-1-ol 

Downstream Products

• 69698-56-2 (R)-chloroquine phosphate 
• 69698-56-2 (R)-chloroquine phosphate 

Relevant academic research and scientific papers

Enantioselective analyses of chloroquine and hydroxychloroquine in rat liver microsomes through chiral liquid chromatography–tandem mass spectrometry

An efficient, sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS) chiral analysis method was established for determination of chloroquine and hydroxychloroquine enantiomers in rat liver microsomes. Effects of polysaccharide c

Optically active chloroquine and hydroxychloroquine and analogues thereof, and preparation method, composition and application of optically active chloroquine and hydroxychloroquine

The invention provides a rapid and simple method for preparing optically active chloroquine, hydroxychloroquine and analogues thereof, which comprises the following steps: reacting racemates of chloroquine, hydroxychloroquine and analogues thereof with an acidic chiral resolution reagent to generate corresponding salts, and separating and purifying to obtain optically pure salts of chloroquine, hydroxychloroquine and analogues thereof, and reacting with alkali to obtain (R)- or (S)- chloroquine with high optical purity and (R)- or (S)- hydroxychloroquine and analogues thereof. The method is simple and convenient to operate and low in cost, the enantiomer purity can reach 99.9% ee, and industrial production of chloroquine, hydroxychloroquine and analogues thereof with single chiral configuration is easy to realize. The invention also provides (R)- or (S)- chloroquine and (R)- or (S)- hydroxychloroquine and analogues thereof, pharmaceutical compositions and uses thereof, optically activechloroquine and hydroxychloroquine and analogues thereof reduce toxic and side effects, and have better treatment effects on coronavirus, influenza virus and autoimmune diseases.

Preparation method and application of chiral chloroquine and phosphate thereof

The invention discloses a preparation method and application of chiral chloroquine and phosphate thereof. The method comprises the following steps: in a resolving solvent, salifying and crystallizing chloroquine racemate and a resolving agent to separate out crystals; performing primary recrystallizing, dissociating the crystals in an alkaline solution; filtering and separating out the resolving agent; performing extracting with an organic solvent, and drying and concentrating organic phases to respectively obtain corresponding (R)/(S)-chloroquine; and further salifying the (R)/(S)-chloroquine with phosphoric acid in the solvent to respectively obtain corresponding (R)/(S)-chloroquine phosphate. By adopting the method provided by the invention, the optical purity ee value of a finished product can be greater than 80% after primary crystallization, and the product with higher purity can be obtained by primary recrystallization. The crystals are good in crystal form and easy to filter and separate; the method is simple and convenient in resolution operation, free of tedious purification processes such as column separation, high in product optical purity, and relatively high in yield; and the resolving agent is reusable, so that production cost is low, and the method has a good industrial application prospect.

Preparation method of enantiomer pure chloroquine and chloroquine phosphate

The invention discloses a preparation method of enantiomer pure chloroquine and chloroquine phosphate, which comprises the following steps of: salifying racemic 2-amino-5-diethylaminopentane under theaction of single-configuration acid to form diastereomer salt, separating out the diastereomer salt from the solution to obtain single-configuration 2-amino- 5-diethylaminopentane intermediate salt,and the like. According to the method, racemic 2-amino- 5-diethylaminopentane is salified under the action of single-configuration acid to form diastereomer salt. On the basis of synthesizing chloroquine/chloroquine phosphate in the prior art, 2-amino-5-diethylaminopentane is used as a raw material to form diastereomer salt to resolve chiral raw materials. The method is high in purity, green and suitable for large-scale production, hazardous chemicals do not need to be introduced, salifying resolution is achieved, reaction energy barriers are reduced through catalyst application, the reactionrate is increased, side reactions are reduced, the optical purity of the product is improved through HPLC determination, the resolution cost is reduced, and the method is suitable for large-scale production.

Preparation method of chiral aminochloroquinoline

The invention discloses a preparation method of chiral aminochloroquinoline, which comprises the following steps: splitting a chiral side chain, preparing enantiomer salt, splitting the side chain andchiral acid crystals to obtain chiral acid salt, neutralizing the chiral acid salt to obtain free basic groups, and reacting the free basic groups with 4, 7-dichloroquinoline to obtain chiral aminochloroquinoline. The yield of the chiral aminochloroquinoline obtained by the method is high, and the purity reaches 99.7%.

Application of chiral chloroquine, hydroxychloroquine or salt of the chiral chloroquine and hydroxychloroquine as anti-coronavirus drug target 3CL hydrolase inhibitor for reducing cardiotoxicity

The invention discloses an application of chiral chloroquine, hydroxychloroquine or pharmaceutically acceptable salts of the chiral chloroquine and hydroxychloroquine in preparation of drugs used forpreventing and/or treating coronavirus pneumonia by using a coronavirus key drug target 3CL hydrolase (Mpro) as an action target. The chiral chloroquine and hydroxychloroquine have high bonding strength with the Mpro causing inflammation of the lung and the like; the activity of the Mpro can be significantly inhibited; and the chiral chloroquine and hydroxychloroquine are indicated to have the effect of preventing and treating pneumonia caused by coronaviruses and be able to be used as anti-pneumonia drugs. Through evaluation on the inhibitory activity of an hERG potassium ion channel, the concentration at which the chloroquine, hydroxychloroquine and enantiomers of the chloroquine and hydroxychloroquine are likely to generate cardiotoxicity to the hERG potassium ion channel is provided. The chiral chloroquine and hydroxychloroquine are prepared through chiral high-performance liquid chromatography and chiral synthesis; S-configuration chloroquine, hydroxychloroquine or salts of the chloroquine and hydroxychloroquine can be selected as a drug independently, or form a pharmaceutical composition for treating diseases caused by the coronaviruses; and due to higher activity and low cardiotoxicity of the chloroquine, hydroxychloroquine or salts of the chloroquine and hydroxychloroquine, the administration dosage range is greatly widened.

Chiral chloroquine, hydroxychloroquine and derivatives thereof as well as preparation method and application of chiral chloroquine, hydroxychloroquine and derivatives thereof

The invention belongs to the field of drug synthesis, and discloses a compound with a structure as shown in a formula I (See the specification) and pharmaceutically acceptable salt, tautomer, polymorphic substance, isomer and solvate thereof. Secondly, the invention discloses a method for preparing chiral chloroquine and hydroxychloroquine through chiral high performance liquid chromatography. Finally, the invention discloses application of chiral chloroquine, hydroxychloroquine and salt derivatives thereof in preparation of drugs for treating novel coronavirus pneumonia.

USE OF CHLOROQUINE AND CLEMIZOLE COMPOUNDS FOR TREATMENT OF INFLAMMATORY AND CANCEROUS CONDITIONS

Disclosed herein are methods for use of R-chloroquine or clemizole or combinations of R- chloroquine and clemizole for the treatment of a subject in need thereof. Uses include methods of treating inflammatory' conditions, treating liver cancer or reducing the risk of developing liver cancer in a subject. Uses also include methods of treating non-alcoholic steatohepatitis in a subject.

Asymmetric synthesis method of optically pure (R)/(S)-chloroquine

The invention discloses an asymmetric synthesis method of optically pure (R)/(S)-chloroquine. 4-amino-7-chloroquinoline and 5-diethylin-2-pentanone are taken as starting raw materials and are subjected to an asymmetric reductive ammoniation reaction under the catalysis of chiral acid, optically pure chloroquine is obtained, and the spatial configuration of a product is controlled through spatial configuration of the chiral acid. The method adopts simple steps, the raw materials are easy to obtain, the yield is higher, the stereoselectivity is good, the chiral construction cost is relatively lower, the operation is simple, and the method is environment-friendly and suitable for large-scale production.