Ifosfamida
Descripción general
Descripción
La ifosfamida es un medicamento de quimioterapia utilizado para tratar varios tipos de cáncer, incluido el cáncer testicular, el sarcoma de tejidos blandos, el osteosarcoma, el cáncer de vejiga, el cáncer de pulmón de células pequeñas, el cáncer cervical y el cáncer de ovario . Pertenece a la familia de medicamentos alquilantes y mostaza nitrogenada . La this compound funciona interrumpiendo la duplicación del ADN y la creación de ARN, inhibiendo así el crecimiento de las células cancerosas .
Mecanismo De Acción
La ifosfamida requiere biotransformación en el hígado por el sistema del citocromo P450 antes de que se active . Los metabolitos activos de la this compound forman enlaces cruzados de ADN en la posición N-7 de guanina, lo que lleva a daño celular y muerte . Esta interrupción de la replicación del ADN y la producción de ARN inhibe el crecimiento y la proliferación de las células cancerosas . Los objetivos moleculares exactos y las vías involucradas en la citotoxicidad de la this compound aún se están estudiando, pero se sabe que interfiere con la síntesis de ADN y ARN .
Aplicaciones Científicas De Investigación
La ifosfamida se utiliza ampliamente en la investigación científica, particularmente en los campos de la química, la biología, la medicina y la industria. En medicina, se utiliza como agente quimioterapéutico para tratar varios cánceres . En biología, se utiliza para estudiar los mecanismos de daño y reparación del ADN, así como los efectos de los agentes alquilantes en los procesos celulares . En química, sirve como compuesto modelo para estudiar la reactividad de las mostazas nitrogenadas y el desarrollo de nuevos agentes anticancerígenos . Las aplicaciones industriales incluyen el desarrollo de portadores lipídicos nanoestructurados para la administración oral de this compound, que tienen como objetivo mejorar su estabilidad y biodisponibilidad .
Análisis Bioquímico
Biochemical Properties
Ifosfamide is metabolized by the liver CYP450 enzymes to its active metabolites . These metabolites, phosphoramide mustard derivatives and acrolein, bind to the DNA inhibiting DNA synthesis . The metabolism of Ifosfamide in vivo and in rat liver microsomes is mediated by different CYP isoenzymes: 3A (CYP3A) plus CYP2B1/ CYP2C11 and CYP3A, respectively .
Cellular Effects
Ifosfamide and its metabolites can cause toxicity of normal cells due to induction of oxidative stress . This can lead to hematological toxicity and liver injury .
Molecular Mechanism
The molecular mechanism of Ifosfamide involves its metabolites binding to the DNA, which inhibits DNA synthesis . This action is facilitated by the liver CYP450 enzymes .
Temporal Effects in Laboratory Settings
In most clinical pharmacokinetic studies, the phenomenon of autoinduction has been observed, but the mechanism is not completely understood .
Dosage Effects in Animal Models
The effects of Ifosfamide vary with different dosages in animal models . High doses of Ifosfamide can cause hematological toxicity, oxidative stress, inflammation, and hepatotoxicity .
Metabolic Pathways
Ifosfamide is involved in various metabolic pathways, interacting with enzymes such as CYP3A, CYP2B1, and CYP2C11 . The specific isoenzymes responsible for Ifosfamide metabolism may lead to an improved efficacy/toxicity ratio by modulation of the metabolic pathways .
Transport and Distribution
Whether Ifosfamide is specifically transported by erythrocytes and which activated Ifosfamide metabolites play a key role in this transport is currently being debated .
Subcellular Localization
The subcellular localization of Ifosfamide and its metabolites is a complex process that involves various enzymes and transporters .
Métodos De Preparación
La ifosfamida se puede sintetizar a través de varias rutas. Un método implica hacer reaccionar un intermedio de this compound con un agente clorante, seguido de ciclización bajo la acción de una base orgánica . Otro método utiliza aziridina como material de partida, que sufre ciclización y reacciones subsecuentes para formar this compound . Los métodos de producción industrial a menudo implican la optimización de estas rutas sintéticas para garantizar un alto rendimiento y pureza al tiempo que se minimiza el uso de productos químicos tóxicos y explosivos .
Análisis De Reacciones Químicas
La ifosfamida sufre varias reacciones químicas, incluida la oxidación, la reducción y la sustitución. Se metaboliza en el hígado por las enzimas del citocromo P450, lo que lleva a la formación de metabolitos activos e inactivos . Los reactivos comunes utilizados en estas reacciones incluyen oxidasas de función mixta y bases orgánicas . Los principales productos formados a partir de estas reacciones incluyen cloroacetaldehído y otros metabolitos que contribuyen a los efectos terapéuticos y tóxicos del fármaco .
Comparación Con Compuestos Similares
La ifosfamida está químicamente relacionada con otras mostazas nitrogenadas, como la ciclofosfamida, la trofosfamida, la mafosfamida, la sufosfamida y la glufosfamida . En comparación con estos compuestos, la this compound tiene propiedades farmacocinéticas únicas, incluida una vida media más larga y diferentes vías metabólicas . Su capacidad para formar enlaces cruzados de ADN y su efectividad en el tratamiento de una amplia gama de cánceres la convierten en un valioso agente quimioterapéutico .
Propiedades
IUPAC Name |
N,3-bis(2-chloroethyl)-2-oxo-1,3,2λ5-oxazaphosphinan-2-amine |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C7H15Cl2N2O2P/c8-2-4-10-14(12)11(6-3-9)5-1-7-13-14/h1-7H2,(H,10,12) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
HOMGKSMUEGBAAB-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1CN(P(=O)(OC1)NCCCl)CCCl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C7H15Cl2N2O2P |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID7020760 |
Source
|
| Record name | Ifosfamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID7020760 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
261.08 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 | Ifosfamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015312 | |
| 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 |
Soluble in water, 1.50e+01 g/L |
Source
|
| Record name | Ifosfamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01181 | |
| 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 | IFOSFAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7023 | |
| 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. | |
| Record name | Ifosfamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015312 | |
| 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 mechanism of ifosfamide has not been determined, but appears to be similar to other alkylating agents. Ifosfamide requires biotransformation in the liver by mixed-function oxidases (cytochrome P450 system) before it becomes active. After metabolic activation, active metabolites of ifosfamide alkylate or bind with many intracellular molecular structures, including nucleic acids. The cytotoxic action is primarily through the alkylation of DNA, done by attaching the N-7 position of guanine to its reactive electrophilic groups. The formation of inter and intra strand cross-links in the DNA results in cell death., Mechanism of action: metabolites cause alkylation of DNA. /from table/, Ifosfamide, a structural analog of cyclophosphamide, belongs to the oxazaphosphorine class of antitumor alkylating agents which must be activated by the mixed function oxidase system of the liver. The 4-hydroxy oxazaphosphorines are a reactive species capable of interacting with nucleic acids & cellular materials to cause cell damage & death. The 4-hydroxy metabolite spontaneously liberates acrolein in many sites throughout the body & it is this substance that is responsible for oxazaphosphorine urotoxicity. Both ifosfamide & cyclophosphamide produce cystitis characterized by tissue edema & ulceration followed by sloughing of mucosal epithelial cells, necrosis of smooth muscle fibers & arteries, & culminating in focal hemorrhage. The selective urotoxicity of oxazaphosphorine occurs because the bladder contains a very low concn of thiol cmpds (glutathione, cysteine) which, by virtue of their nucleophilic sulfhydryl groups, are able to react & neutralize many reactive chemicals. Because the metabolic activation of ifosfamide proceeds more slowly than that of cyclophosphamide, doses of ifosfamide are 3-4 times higher than those of cyclophosphamide. This explains the higher incidence of urotoxicity associated with ifosfamide. |
Source
|
| Record name | Ifosfamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01181 | |
| 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 | IFOSFAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7023 | |
| 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. | |
Color/Form |
Crystals from anhyd ether, White crystalline powder | |
CAS No. |
3778-73-2 |
Source
|
| Record name | Ifosfamide | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=3778-73-2 | |
| 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 | Ifosfamide [USAN:USP:INN:BAN:JAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0003778732 | |
| 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 | Ifosfamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01181 | |
| 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 | ifosfamide | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=759154 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | ifosfamide | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=109724 | |
| Description | The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents. | |
| Explanation | Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source. | |
| Record name | Ifosfamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID7020760 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Ifosfamide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.021.126 | |
| 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 | IFOSFAMIDE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/UM20QQM95Y | |
| 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 | IFOSFAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7023 | |
| 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. | |
| Record name | Ifosfamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015312 | |
| 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 |
39-41 °C, 39 - 41 °C |
Source
|
| Record name | Ifosfamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01181 | |
| 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 | IFOSFAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7023 | |
| 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. | |
| Record name | Ifosfamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015312 | |
| 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
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.
![4-N-(4-chlorophenyl)sulfonyl-1-N-[(2S)-3-methyl-1-oxo-1-[[(2S)-1-(1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)pyrrolidine-2-carbonyl]amino]butan-2-yl]benzene-1,4-dicarboxamide](/img/new.no-structure.jpg)
![(2S)-N-[(2S)-3-(1H-imidazol-5-yl)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-(1H-imidazol-5-yl)-2-(2-methylpropanoylamino)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]propanoyl]-4-methyl-2-(methylamino)pentanamide](/img/structure/B1674352.png)
