An Alternate Synthesis of Camoquin<sup>1</sup>

Burckhalter, J. H.; DeWald, Horace A.; Tendick, Frank H.

doi:10.1021/ja01158a504

Cited by 11 publications

(15 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Burckhalter, as an alternative method for the synthesis of amodiaquine, employed a similar reverse strategy that provided amodiaquine in 80% yield . In terms of yield, this was to be a major improvement as the product 8 proved to be insoluble in cold ethanol and could be filtered and washed to give analytically pure material (monohydrochloride) without the need for chromatography.…”

Section: Resultsmentioning

confidence: 99%

Development of a Scalable Synthetic Route to GSK369796 (N-tert-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug

Lawrence¹,

Dennis²,

Hahn³

et al. 2008

Org. Process Res. Dev.

View full text Add to dashboard Cite

An improved process to the novel 4-aminoquinoline antimalarial GSK369796 is described. Although the initial synthetic route consisted of only two steps from readily available starting materials, the product isolated via the key Mannich reaction was hampered by both low yields and low purity. In addition to instability under the reaction conditions used for the Mannich reaction, the drug substance was found to decompose during attempts to purify by recrystallisation. Reaction conditions were developed that resolved these issues, culminating in the successful production of multi-kg quantities of GSK369796 in >98% a/a purity and in 57% overall yield.

show abstract

Section: Resultsmentioning

confidence: 99%

Development of a Scalable Synthetic Route to GSK369796 (N-tert-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug

Lawrence¹,

Dennis²,

Hahn³

et al. 2008

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…Amodiaquine was synthesized according to the method described by Burckhalter et al 14 4-(7-Fluoroquinolin-4-ylamino)-2-diethylaminomethylphenol is a novel compound and was synthesized by the following procedure. Briefly, 4-amino-2-[(diethylamino)methyl]phenol dihydrochloride (133.6 mg, 0.500 mmol) was dissolved in dry ethanol (2.0 ml) and 4-chloro-7-fluoroquinoline (95.3 mg, 0.525 mmol) was added to the solution, and the reaction mixture was refluxed for a further 3 h. The solvent was removed under reduced pressure, and the residue was dissolved in distilled water.…”

Section: Methodsmentioning

confidence: 99%

Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors

Baba

Toyama

Sakakibara

et al. 2017

Antivir Chem Chemother

View full text Add to dashboard Cite

AimsSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease. SFTS is epidemic in Asia, and its fatality rate is around 30% in Japan. The causative virus severe fever with thrombocytopenia syndrome virus (SFTSV) is a phlebovirus of the family Phenuiviridae (the order Bunyavirales). Although effective treatments are required, there are no antiviral agents currently approved for clinical use. Ribavirin and favipiravir were examined for their anti-SFTSV activity and found to be selective inhibitors of SFTSV replication in vitro. However, their activity was not sufficient. Therefore, it is mandatory to identify novel compounds active against SFTSV. To this end, we have established a safe and rapid assay system for screening selective inhibitors of SFTSV.MethodsThe virus was isolated from SFTS patients treated in Kagoshima University Hospital. Vero cells were infected with SFTSV and incubated in the presence of various concentrations of test compounds. After three days, the cells were examined for their intracellular viral RNA levels by real-time reverse transcription-PCR without extracting viral RNA. The cytotoxicity of test compounds was determined by a tetrazolium dye method.ResultsAmong the test compounds, the antimalarial agent amodiaquine was identified as a selective inhibitor of SFTSV replication. Its 50% effective concentration (EC50) and cytotoxic concentration (CC50) were 19.1 ± 5.1 and >100 µM, respectively. The EC50 value of amodiaquine was comparable to those of ribavirin and favipiravir.ConclusionAmodiaquine is considered to be a promising lead of novel anti-SFTSV agents, and evaluating the anti-SFTSV activity of its derivatives is in progress.

show abstract

“…However, TLC analysis showed incomplete conversion of 13 within 3 h, thus the reaction was continued for 24 h while monitoring progress at intervals of 2 h to afford the Mannich base (14) in a moderate yield of 60%. With the intention of reducing the reaction time, the reaction was repeated in methanol and 32% HCl, however, within 7 h, TLC analysis showed the formation of unidentifiable impurities.…”

Section: Preparation Of Amodiaquine Dihydrochloride Dihydratementioning

confidence: 99%

“…11 Despite the available antimalarial drugs such as amodiaquine (3), most of sub-Saharan Africa still lacks adequate access to good quality, affordable antimalarial drugs due to most active pharmaceutical ingredients (APIs) being imported from other countries. While published processes are available for ADQ and 4,7-DCQ, 9,10,[12][13][14][15][16][17][18][19][20] each of these methods have limitations such as low yields, formation of impurities, the use of expensive solvents or hazardous solvents or more unit operations are required for production of Amodiaquine, which drives up the energy requirements. 9,21 Additionally, no methods are reported for the removal of impurities or for the exact determination of the crystal water molecules in ADQ.…”

Section: Introductionmentioning

confidence: 99%

Process Development for the Manufacture of the Antimalarial Amodiaquine Dihydrochloride Dihydrate

Gohain¹,

Malefo²,

Kunyane³

et al. 2023

Preprint

View full text Add to dashboard Cite

A robust process technology for the manufacture of the active pharmaceutical ingredient (API) amodiaquine dihydrochloride dihydrate (ADQ, 3), an important antimalarial, is reported. The process consists of a three-step synthetic route that involves a Mannich reaction, condensation with 4,7-dichloroquinoline (DCQ, 5) and rehydration. Additionally, a cost-competitive process for the production of DCQ (5) is also reported wherein DCQ (5) was prepared in four steps from meta-chloroaniline (7). 4-Amido-2-(diethylaminomethyl)phenol (14), DCQ (5), and ADQ (3) were obtained in yields of 92, 89 and 90% respectively.

show abstract

An Alternate Synthesis of Camoquin¹

Cited by 11 publications

References 0 publications

Development of a Scalable Synthetic Route to GSK369796 (N-tert-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug

Development of a Scalable Synthetic Route to GSK369796 (N-tert-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug

Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors

Process Development for the Manufacture of the Antimalarial Amodiaquine Dihydrochloride Dihydrate

Contact Info

Product

Resources

About

An Alternate Synthesis of Camoquin1

Cited by 11 publications

References 0 publications

Development of a Scalable Synthetic Route to GSK369796 (N-tert-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug

Development of a Scalable Synthetic Route to GSK369796 (N-tert-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug

Establishment of an antiviral assay system and identification of severe fever with thrombocytopenia syndrome virus inhibitors

Process Development for the Manufacture of the Antimalarial Amodiaquine Dihydrochloride Dihydrate

Contact Info

Product

Resources

About

An Alternate Synthesis of Camoquin¹