Synthetic Antimalarials. The Preparation of Certain 4-Aminoquinolines<sup>1</sup>

Drake, Nathan L.; Creech, Hugh J.; Garman, John A.; Haywood, Stuart T.; Peck, Richard M.; Hook, J. O. Van.; Walton, Edward

doi:10.1021/ja01211a021

Cited by 27 publications

(14 citation statements)

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“…The bisthiazolium salt, SAR97276 , was discovered and developed by Sanofi in 2005 [72], however further investigation was terminated in 2012 after Phase II trials (NCT01445938). AQ-13 is a chloroquine derivative that was first described in 1946 [73]. While only differing to CQ in the amine side-chain, this difference has been linked to its increased efficacy against CQ-resistant strains [74].…”

Section: Futurementioning

confidence: 99%

The past, present and future of anti-malarial medicines

Tse

Korsik

Todd

2019

Malar J

343

295

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Great progress has been made in recent years to reduce the high level of suffering caused by malaria worldwide. Notably, the use of insecticide-treated mosquito nets for malaria prevention and the use of artemisinin-based combination therapy (ACT) for malaria treatment have made a significant impact. Nevertheless, the development of resistance to the past and present anti-malarial drugs highlights the need for continued research to stay one step ahead. New drugs are needed, particularly those with new mechanisms of action. Here the range of anti-malarial medicines developed over the years are reviewed, beginning with the discovery of quinine in the early 1800s, through to modern day ACT and the recently-approved tafenoquine. A number of new potential anti-malarial drugs currently in development are outlined, along with a description of the hit to lead campaign from which it originated. Finally, promising novel mechanisms of action for these and future anti-malarial medicines are outlined.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2724-z) contains supplementary material, which is available to authorized users.

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Section: Futurementioning

confidence: 99%

The past, present and future of anti-malarial medicines

Tse

Korsik

Todd

2019

Malar J

343

295

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“…7 CQ, 7-chloro-4-(4-diethylamino-1-methylbutylamino)quinoline is made by reacting 4-diethylamino-1-methylbutylamine with 4, 7-dichloroquinoline at 180°C. 8 Each of the two components involved in CQ synthesis can be prepared in several ways (Figure 1). In 1946, HCQ sulfate was synthesized as a derivative of CQ by incorporating a hydroxyl group into CQ, and they both share comparable mechanisms of action as weak bases and immuno-modulators.…”

Section: Structure Of the Sars-cov-2 Virusmentioning

confidence: 99%

Chloroquine and Hydroxychloroquine for the Prevention and Treatment of COVID-19: A Fiction, Hope or Hype? An Updated Review

Saghir¹,

Al-Gabri²,

Alagawany³

et al. 2021

TCRM

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In December 2019, the novel coronavirus disease pandemic (COVID-19) that began in China had infected so far more than 109,217,366 million individuals worldwide and accounted for more than 2,413,912 fatalities. With the dawn of this novel coronavirus (SARS-CoV-2), there was a requirement to select potential therapies that might effectively kill the virus, accelerate the recovery, or decrease the case fatality rate. Besides the currently available antiviral medications for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), the chloroquine/hydroxychloroquine (CQ/HCQ) regimen with or without azithromycin has been repurposed in China and was recommended by the National Health Commission, China in mid-February 2020. By this time, the selection of this regimen was based on its efficacy against the previous SARS-CoV-1 virus and its potential to inhibit viral replication of the SARS-CoV-2 in vitro. There was a shortage of robust clinical proof about the effectiveness of this regimen against the novel SARS-CoV-2. Therefore, extensive research effort has been made by several researchers worldwide to investigate whether this regimen is safe and effective for the management of COVID-19. In this review, we provided a comprehensive overview of the CQ/HCQ regimen, summarizing data from in vitro studies and clinical trials for the protection against or the treatment of SARS-CoV-2. Despite the initial promising results from the in vitro studies and the widespread use of CQ/HCQ in clinical settings during the 1st wave of COVID-19, current data from well-designed randomized controlled trials showed no evidence of benefit from CQ/HCQ supplementation for the treatment or prophylaxis against SARS-CoV-2 infection. Particularly, the two largest randomized controlled trials to date (RECOVERY and WHO SOLIDARITY trials), both confirmed that CQ/HCQ regimen does not provide any clinical benefit for COVID-19 patients. Therefore, we do not recommend the use of this regimen in COVID-19 patients outside the context of clinical trials.

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“…AQ-13 is a chloroquine (CQ) derivative first described in 1946 [ 141 ]. It has CQ-like MoA and pharmacokinetic properties.…”

Section: Resistance To Artemisinin and Its Partners In Artemisinin Combination Therapies (Acts)mentioning

confidence: 99%

Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures

Erhunse

Sahal

2021

Journal of Pharmaceutical Analysis

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Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine (DHA-PPQ), Cambodia swapped the first line artemisinin-based combination therapy (ACT) from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine. However, triple mutants have now emerged, suggesting that drug rotations may not be adequate to keep resistance at bay. There is, therefore, an urgent need for alternative treatment strategies to tackle resistance and prevent its spread. A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement. This review highlights the role of the key players in artemisinin resistance, the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.

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Synthetic Antimalarials. The Preparation of Certain 4-Aminoquinolines¹

Cited by 27 publications

References 0 publications

The past, present and future of anti-malarial medicines

The past, present and future of anti-malarial medicines

Chloroquine and Hydroxychloroquine for the Prevention and Treatment of COVID-19: A Fiction, Hope or Hype? An Updated Review

Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures

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Synthetic Antimalarials. The Preparation of Certain 4-Aminoquinolines1

Cited by 27 publications

References 0 publications

The past, present and future of anti-malarial medicines

The past, present and future of anti-malarial medicines

Chloroquine and Hydroxychloroquine for the Prevention and Treatment of COVID-19: A Fiction, Hope or Hype? An Updated Review

Protecting future antimalarials from the trap of resistance: Lessons from artemisinin-based combination therapy (ACT) failures

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Synthetic Antimalarials. The Preparation of Certain 4-Aminoquinolines¹