Canagliflozin
Vue d'ensemble
Description
La canagliflozine est un médicament principalement utilisé pour traiter le diabète de type 2. Elle appartient à la classe des inhibiteurs du cotransporteur sodium-glucose 2 (SGLT2), qui agissent en empêchant la réabsorption du glucose dans les reins, augmentant ainsi l’excrétion du glucose dans l’urine . Ce mécanisme contribue à abaisser la glycémie chez les personnes atteintes de diabète de type 2. La canagliflozine a été approuvée pour un usage médical aux États-Unis, dans l’Union européenne et en Australie en 2013 .
Mécanisme D'action
La canagliflozine exerce ses effets en inhibant le cotransporteur sodium-glucose 2 (SGLT2) dans les tubules proximaux des reins . Cette inhibition empêche la réabsorption du glucose depuis la lumière tubulaire rénale, ce qui conduit à une augmentation de l’excrétion du glucose dans l’urine . Les cibles moléculaires impliquées dans ce mécanisme comprennent les protéines SGLT2, qui sont responsables de la réabsorption du glucose dans les reins .
Composés similaires :
- Dapagliflozine
- Empagliflozine
- Metformine
- Ozempic (sémiglutide)
Comparaison :
- Efficacité : Il a été démontré que la canagliflozine a une efficacité similaire dans la réduction des taux d’HbA1c par rapport à l’empagliflozine et à la dapagliflozine . La canagliflozine peut avoir une efficacité légèrement supérieure dans la réduction de l’HbA1c par rapport à la dapagliflozine .
- Sécurité : Les profils de sécurité de la canagliflozine, de la dapagliflozine et de l’empagliflozine sont comparables, les effets secondaires courants incluant les infections des voies urinaires et les infections génitales .
- Unicité : La canagliflozine est unique en ce qu’elle peut réduire le gonflement du cerveau dans l’ischémie cérébrale, une propriété qui n’est généralement pas associée aux autres inhibiteurs du SGLT2 .
Applications De Recherche Scientifique
Canagliflozin has a wide range of scientific research applications:
Analyse Biochimique
Biochemical Properties
Canagliflozin promotes urinary glucose excretion by inhibiting renal proximal convoluted tubule . It interacts with SGLT2, a low capacity/high affinity Na+/K+ co-transporter predominantly located in proximal convoluted tubules (PCT) of kidneys .
Cellular Effects
This compound has been shown to impact the composition of gut microbiota and metabolites . It mainly increases Muribaculum, Ruminococcaceae_UCG_014, Lachnospiraceae-UCG-001, and decreases ursodeoxycholic acids (UDCA) and hyodeoxycholic acids (HDCA) .
Molecular Mechanism
The molecular mechanism of this compound involves the inhibition of SGLT2, which prevents reabsorption of glucose and thereby stimulates glucose excretion in the urine .
Temporal Effects in Laboratory Settings
The effects of this compound on intestinal flora and metabolites have been studied in diabetic mice over a period of 8 weeks . It was found that this compound significantly increased GLP-1 level and impacted on the composition of gut microbiota and metabolites .
Metabolic Pathways
This compound influences intestinal fatty acid and bile acid (BA) metabolism . It increases fatty acids metabolites in feces .
Méthodes De Préparation
Voies de synthèse et conditions de réaction : La synthèse de la canagliflozine implique plusieurs étapes, commençant par la préparation d’intermédiaires clés. L’une des méthodes comprend la formation d’un système de suspension de canagliflozine dans l’eau ou un solvant mixte, suivie d’une cristallisation . Une autre méthode consiste à dissoudre des intermédiaires dans des solvants comme le tétrahydrofurane et le méthanol, puis à effectuer une hydrolyse à l’aide d’acide chlorhydrique .
Méthodes de production industrielle : La production industrielle de la canagliflozine implique généralement l’optimisation de la solubilité et de la biodisponibilité du composé. Des techniques telles que les préconcentrés de microémulsions sont utilisées pour améliorer la solubilité et la biodisponibilité orale de la canagliflozine . La formulation optimisée est évaluée pour sa vitesse de dissolution, sa vitesse de perméation et sa biodisponibilité orale.
Analyse Des Réactions Chimiques
Types de réactions : La canagliflozine subit diverses réactions chimiques, notamment l’oxydation et la glucuronidation. Les principales voies métaboliques impliquent la formation de métabolites O-glucuronides et de produits d’oxydation .
Réactifs et conditions courantes :
Oxydation : La canagliflozine peut être oxydée pour former des métabolites tels que M8 et M9.
Glucuronidation : Cette réaction implique l’addition d’acide glucuronique à la canagliflozine, formant des métabolites comme M5, M7 et M17.
Principaux produits : Les principaux produits formés à partir de ces réactions comprennent les métabolites O-glucuronides et les produits d’oxydation, qui sont ensuite excrétés par l’organisme .
4. Applications de la recherche scientifique
La canagliflozine a un large éventail d’applications de recherche scientifique :
Comparaison Avec Des Composés Similaires
- Dapagliflozin
- Empagliflozin
- Metformin
- Ozempic (semaglutide)
Comparison:
- Efficacy: Canagliflozin has been shown to have similar efficacy in lowering HbA1c levels compared to empagliflozin and dapagliflozin . this compound may have a slightly higher efficacy at lowering HbA1c compared to dapagliflozin .
- Safety: The safety profiles of this compound, dapagliflozin, and empagliflozin are comparable, with common side effects including urinary tract infections and genital infections .
- Uniqueness: this compound is unique in its ability to reduce brain swelling in cerebral ischemia, a property not commonly associated with other SGLT2 inhibitors .
Propriétés
IUPAC Name |
(2S,3R,4R,5S,6R)-2-[3-[[5-(4-fluorophenyl)thiophen-2-yl]methyl]-4-methylphenyl]-6-(hydroxymethyl)oxane-3,4,5-triol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C24H25FO5S/c1-13-2-3-15(24-23(29)22(28)21(27)19(12-26)30-24)10-16(13)11-18-8-9-20(31-18)14-4-6-17(25)7-5-14/h2-10,19,21-24,26-29H,11-12H2,1H3/t19-,21-,22+,23-,24+/m1/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
XTNGUQKDFGDXSJ-ZXGKGEBGSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC1=C(C=C(C=C1)C2C(C(C(C(O2)CO)O)O)O)CC3=CC=C(S3)C4=CC=C(C=C4)F |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
CC1=C(C=C(C=C1)[C@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)O)CC3=CC=C(S3)C4=CC=C(C=C4)F |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C24H25FO5S |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID601004469 |
Source
|
| Record name | Canagliflozin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID601004469 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
444.5 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Boiling Point |
642.9±55.0 |
Source
|
| Record name | Canagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB08907 | |
| 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) | |
Solubility |
almost insoluble, Practically insoluble in aqueous media from pH 1.1 to pH 12.9 /Canagliflozin hemihydrate/ |
Source
|
| Record name | Canagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB08907 | |
| 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 | Canagliflozin | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/8284 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Mechanism of Action |
The sodium-glucose co-transporter2 (SGLT2), is found in the proximal tubules of the kidney, and reabsorbs filtered glucose from the renal tubular lumen. Canagliflozin inhibits the SGLT2 co-transporter. This inhibition leads to lower reabsorption of filtered glucose into the body and decreases the renal threshold for glucose (RTG), leading to increased glucose excretion in the urine., Sodium-glucose co-transporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), and thereby increases urinary glucose excretion (UGE). |
Source
|
| Record name | Canagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB08907 | |
| 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 | Canagliflozin | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/8284 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
CAS No. |
842133-18-0 |
Source
|
| Record name | Canagliflozin | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=842133-18-0 | |
| 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 | Canagliflozin | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0842133180 | |
| 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 | Canagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB08907 | |
| 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 | Canagliflozin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID601004469 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | (1S)-1,5-Anhydro-1-C-(3-{[5-(4-fluorophenyl)thiophen-2-yl]methyl]}-4-methylphenyl)-D-glucitol | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/information-on-chemicals | |
| 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 | CANAGLIFLOZIN ANHYDROUS | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/6S49DGR869 | |
| 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 | Canagliflozin | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/8284 | |
| Description | The Hazardous Substances Data Bank (HSDB) is a toxicology database that focuses on the toxicology of potentially hazardous chemicals. It provides information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. The information in HSDB has been assessed by a Scientific Review Panel. | |
Melting Point |
68-72 |
Source
|
| Record name | Canagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB08907 | |
| 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) | |
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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