Canagliflozin
Descripción general
Descripción
Canagliflozina es un medicamento que se utiliza principalmente para tratar la diabetes mellitus tipo 2. Pertenece a la clase de inhibidores del cotransportador de sodio-glucosa 2 (SGLT2), que funcionan al prevenir la reabsorción de glucosa en los riñones, lo que aumenta la excreción de glucosa a través de la orina . Este mecanismo ayuda a reducir los niveles de azúcar en sangre en personas con diabetes tipo 2. Canagliflozina fue aprobada para uso médico en los Estados Unidos, la Unión Europea y Australia en 2013 .
Mecanismo De Acción
Canagliflozina ejerce sus efectos al inhibir el cotransportador de sodio-glucosa 2 (SGLT2) en los túbulos proximales de los riñones . Esta inhibición previene la reabsorción de glucosa desde la luz tubular renal, lo que conduce a una mayor excreción de glucosa a través de la orina . Los objetivos moleculares involucrados en este mecanismo incluyen las proteínas SGLT2, que son responsables de la reabsorción de glucosa en los riñones .
Compuestos Similares:
- Dapagliflozina
- Empagliflozina
- Metformina
- Ozempic (semaglutida)
Comparación:
- Eficacia: Se ha demostrado que Canagliflozina tiene una eficacia similar en la reducción de los niveles de HbA1c en comparación con empagliflozina y dapagliflozina . canagliflozina puede tener una eficacia ligeramente mayor en la reducción de HbA1c en comparación con dapagliflozina .
- Seguridad: Los perfiles de seguridad de canagliflozina, dapagliflozina y empagliflozina son comparables, con efectos secundarios comunes que incluyen infecciones del tracto urinario e infecciones genitales .
- Singularidad: Canagliflozina es única en su capacidad para reducir la hinchazón del cerebro en la isquemia cerebral, una propiedad que no se asocia comúnmente con otros inhibidores de SGLT2 .
Análisis Bioquímico
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 .
Métodos De Preparación
Rutas Sintéticas y Condiciones de Reacción: La síntesis de canagliflozina involucra múltiples pasos, comenzando con la preparación de intermediarios clave. Uno de los métodos incluye la formación de un sistema de suspensión de canagliflozina en agua o un disolvente mixto, seguido de cristalización . Otro método implica disolver intermediarios en disolventes como tetrahidrofurano y metanol, seguido de hidrólisis usando ácido clorhídrico .
Métodos de Producción Industrial: La producción industrial de canagliflozina generalmente implica la optimización de la solubilidad y la biodisponibilidad del compuesto. Se emplean técnicas como los preconcentrados de microemulsión para mejorar la solubilidad y la biodisponibilidad oral de canagliflozina . La formulación optimizada se evalúa por su tasa de disolución, tasa de permeación y biodisponibilidad oral.
Análisis De Reacciones Químicas
Tipos de Reacciones: Canagliflozina sufre varias reacciones químicas, incluida la oxidación y la glucuronidación. Las principales vías metabólicas implican la formación de metabolitos de O-glucurónido y productos de oxidación .
Reactivos y Condiciones Comunes:
Oxidación: Canagliflozina se puede oxidar para formar metabolitos como M8 y M9.
Glucuronidación: Esta reacción implica la adición de ácido glucurónico a canagliflozina, formando metabolitos como M5, M7 y M17.
Principales Productos: Los principales productos formados a partir de estas reacciones incluyen metabolitos de O-glucurónido y productos de oxidación, que luego se excretan del cuerpo .
Aplicaciones Científicas De Investigación
Canagliflozina tiene una amplia gama de aplicaciones de investigación científica:
Comparación Con Compuestos Similares
- 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 .
Propiedades
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
AI-Powered Synthesis Planning: Our tool employs the Template_relevance Pistachio, Template_relevance Bkms_metabolic, Template_relevance Pistachio_ringbreaker, Template_relevance Reaxys, Template_relevance Reaxys_biocatalysis model, leveraging a vast database of chemical reactions to predict feasible synthetic routes.
One-Step Synthesis Focus: Specifically designed for one-step synthesis, it provides concise and direct routes for your target compounds, streamlining the synthesis process.
Accurate Predictions: Utilizing the extensive PISTACHIO, BKMS_METABOLIC, PISTACHIO_RINGBREAKER, REAXYS, REAXYS_BIOCATALYSIS database, our tool offers high-accuracy predictions, reflecting the latest in chemical research and data.
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
Descargo de responsabilidad e información sobre productos de investigación in vitro
Tenga en cuenta que todos los artículos e información de productos presentados en BenchChem están destinados únicamente con fines informativos. Los productos disponibles para la compra en BenchChem están diseñados específicamente para estudios in vitro, que se realizan fuera de organismos vivos. Los estudios in vitro, derivados del término latino "in vidrio", involucran experimentos realizados en entornos de laboratorio controlados utilizando células o tejidos. Es importante tener en cuenta que estos productos no se clasifican como medicamentos y no han recibido la aprobación de la FDA para la prevención, tratamiento o cura de ninguna condición médica, dolencia o enfermedad. Debemos enfatizar que cualquier forma de introducción corporal de estos productos en humanos o animales está estrictamente prohibida por ley. Es esencial adherirse a estas pautas para garantizar el cumplimiento de los estándares legales y éticos en la investigación y experimentación.
![1,4-Bis[(4-chlorophenyl)phenylmethyl]piperazine dihydrochloride](/img/structure/B192774.png)
