Hydroxychloroquine
Vue d'ensemble
Description
L’hydroxychloroquine est un médicament principalement utilisé pour prévenir et traiter le paludisme dans les régions où le paludisme reste sensible à la chloroquine. Il est également utilisé pour traiter la polyarthrite rhumatoïde, le lupus et la porphyrie cutanée tardive. L’this compound est prise par voie orale, souvent sous forme de sulfate d’this compound . Il appartient aux familles de médicaments antipaludiques et 4-aminoquinoléine .
Applications De Recherche Scientifique
Hydroxychloroquine has a wide range of scientific research applications. It is used in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus erythematosus . It has also been investigated for its potential antiviral properties, including its use in the treatment of COVID-19 . Additionally, this compound has applications in cancer research, where it is studied for its ability to inhibit autophagy and induce apoptosis in cancer cells .
Mécanisme D'action
L’hydroxychloroquine exerce ses effets par plusieurs mécanismes. Elle interfère avec l’activité lysosomale et l’autophagie, interagit avec la stabilité des membranes et modifie les voies de signalisation et l’activité transcriptionnelle . Ces actions se traduisent par l’inhibition de la production de cytokines et la modulation de certaines molécules co-stimulatrices . L’this compound supprime également l’activation des récepteurs Toll-like, qui jouent un rôle important dans la réponse immunitaire innée et les maladies auto-immunes .
Analyse Biochimique
Biochemical Properties
Hydroxychloroquine is a weak base that accumulates in acidic compartments such as lysosomes and inflamed tissues . It interferes with lysosomal activity and autophagy, interacts with membrane stability, and alters signaling pathways and transcriptional activity . This can result in inhibition of cytokine production and modulation of certain co-stimulatory molecules .
Cellular Effects
This compound has been shown to have a variety of effects on cells. It can inhibit terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry . ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry . This compound also acts by suppressing Toll-like receptors to trigger important immunomodulatory effects .
Temporal Effects in Laboratory Settings
In laboratory settings, severe laboratory abnormalities while taking this compound are rare, even in a population with a high rate of comorbidities . Among the abnormalities observed, the majority of them were likely due to disease progression or a medication other than this compound .
Dosage Effects in Animal Models
In animal models, this compound has been shown to be ineffective in preventing or treating SARS-CoV-2 infection, regardless of the dosage used . The LD50 (lethal dose, 50%) of this compound is approximately twice as high as that of chloroquine .
Metabolic Pathways
This compound is metabolized by CYP3A4, CYP2D6, and CYP2C8 in vitro . All three CYPs formed the primary metabolites desethylchloroquine (DCQ) and desethylthis compound (DHCQ) to various degrees .
Transport and Distribution
This compound is completely absorbed from the gastrointestinal tract, sequestered in peripheral tissues, metabolized in the liver to pharmacologically active by-products, and excreted via the kidneys and the feces . Plasma volumes of distribution up to 65,000 L for chloroquine and 44,257 L for this compound have been reported .
Subcellular Localization
This compound and its metabolites are primarily localized in the cytoplasm . In some cell lines, they accumulate in a specific region of the cytoplasm .
Méthodes De Préparation
Voies de synthèse et conditions de réaction : La préparation de l’hydroxychloroquine implique plusieurs étapes. Une méthode comprend la protection hydroxyle du 5-(N-éthyl-N-hydroxyethyl)-2-aminopentane en utilisant un réactif de silanisation. Les protons aminés sont ensuite éliminés dans le tétrahydrofurane ou le toluène en utilisant une solution de bis(triméthylsilyl)lithium amide pour former des anions amino. Ces anions subissent une réaction de substitution avec la 4,7-dichloroquinoléine pour générer de l’this compound . Le sulfate d’this compound est ensuite salifié avec de l’acide sulfurique dans une solution alcoolique pour générer du sulfate d’this compound .
Méthodes de production industrielle : Les méthodes de production industrielle du sulfate d’this compound consistent à condenser la 4,7-dichloroquinoléine avec une chaîne latérale d’this compound sous l’action d’un catalyseur pour obtenir de l’this compound. Ceci est suivi par la réaction de l’this compound avec de l’acide sulfurique pour préparer le sulfate d’this compound .
Analyse Des Réactions Chimiques
Types de réactions : L’hydroxychloroquine subit diverses réactions chimiques, notamment des réactions d’oxydation, de réduction et de substitution.
Réactifs et conditions courants : Les réactifs courants utilisés dans ces réactions comprennent le bis(triméthylsilyl)lithium amide pour l’élimination des protons aminés et l’acide sulfurique pour le processus de salification .
Principaux produits formés : Les principaux produits formés à partir de ces réactions comprennent l’this compound et le sulfate d’this compound .
Applications de la recherche scientifique
L’this compound a une large gamme d’applications de recherche scientifique. Elle est utilisée dans le traitement des maladies auto-immunes telles que la polyarthrite rhumatoïde et le lupus érythémateux . Elle a également été étudiée pour ses propriétés antivirales potentielles, y compris son utilisation dans le traitement du COVID-19 . En outre, l’this compound a des applications dans la recherche sur le cancer, où elle est étudiée pour sa capacité à inhiber l’autophagie et à induire l’apoptose dans les cellules cancéreuses .
Comparaison Avec Des Composés Similaires
L’hydroxychloroquine est similaire à la chloroquine, toutes deux étant des composés 4-aminoquinoléine utilisés pour traiter le paludisme et les maladies auto-immunes . L’this compound présente une incidence plus faible de toxicité oculaire/rétinienne potentiellement irréversible par rapport à la chloroquine . D’autres composés similaires comprennent la deséthylthis compound et l’oxichloroquine .
Propriétés
IUPAC Name |
2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-ethylamino]ethanol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C18H26ClN3O/c1-3-22(11-12-23)10-4-5-14(2)21-17-8-9-20-18-13-15(19)6-7-16(17)18/h6-9,13-14,23H,3-5,10-12H2,1-2H3,(H,20,21) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
XXSMGPRMXLTPCZ-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CCN(CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl)CCO |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C18H26ClN3O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Related CAS |
747-36-4 (sulfate (1:1) salt) |
Source
|
| Record name | Hydroxychloroquine [INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000118423 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
DSSTOX Substance ID |
DTXSID8023135 |
Source
|
| Record name | Hydroxychloroquine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8023135 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
335.9 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Physical Description |
Solid |
Source
|
| Record name | Hydroxychloroquine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015549 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Solubility |
2.61e-02 g/L |
Source
|
| Record name | Hydroxychloroquine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015549 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Mechanism of Action |
The exact mechanisms of hydroxychloroquine are unknown. It has been shown that hydroxychloroquine accumulates in the lysosomes of the malaria parasite, raising the pH of the vacuole. This activity interferes with the parasite's ability to proteolyse hemoglobin, preventing the normal growth and replication of the parasite. Hydroxychloroquine can also interfere with the action of parasitic heme polymerase, allowing for the accumulation of the toxic product beta-hematin. Hydroxychloroquine accumulation in human organelles also raise their pH, which inhibits antigen processing, prevents the alpha and beta chains of the major histocompatibility complex (MHC) class II from dimerizing, inhibits antigen presentation of the cell, and reduces the inflammatory response. Elevated pH in the vesicles may alter the recycling of MHC complexes so that only the high affinity complexes are presented on the cell surface. Self peptides bind to MHC complexes with low affinity and so they will be less likely to be presented to autoimmune T cells. Hydroxychloroquine also reduces the release of cytokines like interleukin-1 and tumor necrosis factor, possibly through inhibition of Toll-like receptors. The raised pH in endosomes, prevent virus particles (such as SARS-CoV and SARS-CoV-2) from utilizing their activity for fusion and entry into the cell. Hydroxychloroquine inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry. ACE2 that is not in the glycosylated state may less efficiently interact with the SARS-CoV-2 spike protein, further inhibiting viral entry. |
Source
|
| Record name | Hydroxychloroquine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01611 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
CAS No. |
118-42-3 |
Source
|
| Record name | Hydroxychloroquine | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=118-42-3 | |
| Description | CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society. | |
| Explanation | The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated. | |
| Record name | Hydroxychloroquine [INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000118423 | |
| Description | ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system. | |
| Record name | Hydroxychloroquine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01611 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Hydroxychloroquine | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID8023135 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Hydroxychloroquine | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.003.864 | |
| Description | The European Chemicals Agency (ECHA) is an agency of the European Union which is the driving force among regulatory authorities in implementing the EU's groundbreaking chemicals legislation for the benefit of human health and the environment as well as for innovation and competitiveness. | |
| Explanation | Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page. | |
| Record name | HYDROXYCHLOROQUINE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/4QWG6N8QKH | |
| Description | The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions. | |
| Explanation | Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required. | |
| Record name | Hydroxychloroquine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015549 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Melting Point |
89-91, 90 °C |
Source
|
| Record name | Hydroxychloroquine | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01611 | |
| Description | The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. | |
| Explanation | Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode) | |
| Record name | Hydroxychloroquine | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015549 | |
| Description | The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body. | |
| Explanation | HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications. | |
Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
|---|---|
| Min. plausibility | 0.01 |
| Model | Template_relevance |
| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
| Top-N result to add to graph | 6 |
Feasible Synthetic Routes
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Veuillez noter que tous les articles et informations sur les produits présentés sur BenchChem sont destinés uniquement à des fins informatives. Les produits disponibles à l'achat sur BenchChem sont spécifiquement conçus pour des études in vitro, qui sont réalisées en dehors des organismes vivants. Les études in vitro, dérivées du terme latin "in verre", impliquent des expériences réalisées dans des environnements de laboratoire contrôlés à l'aide de cellules ou de tissus. Il est important de noter que ces produits ne sont pas classés comme médicaments et n'ont pas reçu l'approbation de la FDA pour la prévention, le traitement ou la guérison de toute condition médicale, affection ou maladie. Nous devons souligner que toute forme d'introduction corporelle de ces produits chez les humains ou les animaux est strictement interdite par la loi. Il est essentiel de respecter ces directives pour assurer la conformité aux normes légales et éthiques en matière de recherche et d'expérimentation.
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