Anastrozol
Descripción general
Descripción
- Específicamente, es eficaz en el tratamiento del cáncer de mama positivo para receptores hormonales. Además, se ha empleado como medida preventiva para aquellos con alto riesgo de desarrollar cáncer de mama .
Anastrozol: es un medicamento antiestrogénico que pertenece a la clase de los inhibidores de la aromatasa. Se comercializa comúnmente bajo el nombre de marca y se usa junto con otros tratamientos para el cáncer de mama.
Mecanismo De Acción
Supresión de Estrógenos: El anastrozol inhibe la enzima aromatasa, que convierte los andrógenos en estrógenos. Al bloquear este proceso, reduce los niveles de estrógeno en el cuerpo.
Dianas Moleculares: La aromatasa en sí es la diana molecular principal. Al inhibirla, el this compound interrumpe la síntesis de estrógenos.
Aplicaciones Científicas De Investigación
Química: El anastrozol sirve como una herramienta valiosa en la química medicinal, particularmente en el campo de la investigación del cáncer.
Biología: Los investigadores estudian sus efectos sobre el metabolismo del estrógeno y su impacto en los cánceres dependientes de hormonas.
Medicina: Más allá del tratamiento del cáncer de mama, se explora el this compound para otras afecciones relacionadas con las hormonas.
Industria: Sus aplicaciones industriales se extienden a la fabricación farmacéutica y al desarrollo de medicamentos.
Análisis Bioquímico
Biochemical Properties
Anastrozole works by inhibiting the enzyme aromatase, which is responsible for the conversion of androgens to estrogens in peripheral tissues . This inhibition prevents the synthesis of estrogen from adrenal androgens, primarily androstenedione and testosterone . By reducing the amount of estrogen in the body, Anastrozole slows the growth of tumors that require estrogen to grow .
Cellular Effects
Anastrozole has a significant impact on various types of cells and cellular processes. It reduces the risk of early breast cancer recurrence and controls breast cancer that has come back or spread to other parts of the body . Anastrozole can also reduce the risk of breast cancer development if a person’s family history or a genetic test shows they have a higher risk of breast cancer .
Molecular Mechanism
Anastrozole exerts its effects at the molecular level by blocking the production of estrogens in the body, hence having antiestrogenic effects . It does this by reversibly binding to the aromatase enzyme, and through competitive inhibition, blocks the conversion of androgens to estrogens in peripheral (extragonadal) tissues .
Temporal Effects in Laboratory Settings
Anastrozole is generally safe to take for a long time . It can make bones weaker and more likely to break (osteoporosis). Bone density (DEXA) scans may be conducted to check the strength of the bones before starting Anastrozole treatment, 1 or 2 years into treatment, and again after the treatment finishes .
Dosage Effects in Animal Models
Based on findings from animal studies and its mechanism of action, Anastrozole can cause fetal harm when administered to a pregnant woman . Anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (AUC) .
Metabolic Pathways
Anastrozole is primarily metabolized in the liver via oxidation and glucuronidation to a number of inactive metabolites, including hydroxyanastrozole (both free and glucuronidated) and anastrozole glucuronide . Oxidation to hydroxyanastrozole is catalyzed predominantly by CYP3A4 (as well as CYP3A5 and CYP2C8, to a lesser extent) and the direct glucuronidation of anastrozole is catalyzed mainly by UGT1A4 .
Transport and Distribution
Anastrozole is rapidly absorbed and T max is typically reached within 2 hours of dosing under fasted conditions . Once absorbed, Anastrozole is widely distributed throughout the body, with about 40% being bound to plasma proteins .
Subcellular Localization
The subcellular localization of Anastrozole is not explicitly mentioned in the literature. Given its mechanism of action, it can be inferred that Anastrozole likely interacts with the aromatase enzyme in the endoplasmic reticulum of cells, where the enzyme is located. This is because aromatase is a membrane-bound enzyme, and its active site is located in the endoplasmic reticulum .
Métodos De Preparación
Rutas de Síntesis: El anastrozol se sintetiza mediante un proceso de varios pasos. El paso clave implica el acoplamiento de 1,2,4-triazol con un grupo fenilmetilo, seguido de la adición de nitrilo. La secuencia general de la reacción conduce a la formación del compuesto.
Producción Industrial: El this compound se produce industrialmente utilizando rutas de síntesis eficientes.
Análisis De Reacciones Químicas
Reactividad: El anastrozol experimenta diversas reacciones químicas debido a sus características estructurales. Estas incluyen reacciones de oxidación, reducción y sustitución.
Reactivos y Condiciones Comunes: Los reactivos y condiciones específicos dependen de la transformación deseada. Por ejemplo
Productos Principales: Los productos formados a partir de estas reacciones incluyen derivados modificados del this compound, que pueden tener propiedades farmacológicas alteradas.
Comparación Con Compuestos Similares
Propiedades
IUPAC Name |
2-[3-(2-cyanopropan-2-yl)-5-(1,2,4-triazol-1-ylmethyl)phenyl]-2-methylpropanenitrile |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C17H19N5/c1-16(2,9-18)14-5-13(8-22-12-20-11-21-22)6-15(7-14)17(3,4)10-19/h5-7,11-12H,8H2,1-4H3 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
YBBLVLTVTVSKRW-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC(C)(C#N)C1=CC(=CC(=C1)CN2C=NC=N2)C(C)(C)C#N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C17H19N5 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID9022607 |
Source
|
| Record name | Anastrozole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID9022607 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
293.4 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 | Anastrozole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015348 | |
| 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 |
Freely soluble in methanol, acetone, ethanol, tetrahydrofuran; very soluble in acetonitrile., In water, 0.5 mg/mL at 25 °C; solubility is dependent of pH in the physiological range., 6.61e-02 g/L |
Source
|
| Record name | Anastrozole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01217 | |
| 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 | ANASTROZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7462 | |
| 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 | Anastrozole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015348 | |
| 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 |
Anastrazole exerts its anti-estrogenic effects via selective and competitive inhibition of the aromatase enzyme found predominantly in the adrenal glands, liver, and fatty tissues. Many breast cancers are hormone receptor-positive, meaning their growth is stimulated and/or maintained by the presence of hormones such as estrogen or progesterone. In postmenopausal women, estrogen is primarily derived from the conversion of adrenally-produced androgens into estrogens by the aromatase enzyme - by competitively inhibiting the biosynthesis of estrogen at these enzymes, anastrozole effectively suppresses circulating estrogen levels and, subsequently, the growth of hormone receptor-positive tumours., Anastrozole is a nonsteroidal aromatase inhibitor that interferes with estradiol production in peripheral tissues. Adrenally generated androstenedione, the chief source of circulating estrogen in postmenopausal women, is converted by aromatase to estrone, which is further converted to estradiol. Growth of many breast cancer tumors containing estrogen receptors and aromatase can be promoted by estrogen., Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone., Because estrogen acts as a growth factor for hormone-dependent breast cancer cells, anastrozole-induced reduction of serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression. Anastrozole selectively inhibits the conversion of androgens to estrogens. In postmenopausal women, ovarian secretion of estrogen declines and conversion of adrenal androgens (mainly androstenedione and testosterone) to estrone and estradiol in peripheral tissues (adipose, muscle, and liver), catalyzed by the aromatase enzyme, is the principal source of estrogens. Anastrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P-450 unit of the enzyme; suppression of estrogen biosynthesis in all tissues reduces serum concentrations of circulating estrogens, including estrone, estradiol, and estrone sulfate. Anastrozole selectively inhibits synthesis of estrogens and does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone. In animals, anastrozole has not been shown to possess direct progestogenic, androgenic, or estrogenic activity, but alterations in the circulating concentrations of progesterone, androgens, and estrogens have been observed. |
Source
|
| Record name | Anastrozole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01217 | |
| 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 | ANASTROZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7462 | |
| 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 ethyl acetate/cyclohexane, Off-white powder | |
CAS No. |
120511-73-1 |
Source
|
| Record name | Anastrozole | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=120511-73-1 | |
| 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 | Anastrozole [USAN:USP:INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0120511731 | |
| 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 | Anastrozole | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01217 | |
| 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 | anastrozole | |
| Source | DTP/NCI | |
| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=759855 | |
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| Record name | anastrozole | |
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| URL | https://dtp.cancer.gov/dtpstandard/servlet/dwindex?searchtype=NSC&outputformat=html&searchlist=719344 | |
| 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. | |
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| Record name | Anastrozole | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID9022607 | |
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| Record name | 1,3-Benzenediacetonitrile, α1,α1,α3,α3-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl) | |
| Source | European Chemicals Agency (ECHA) | |
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| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/2Z07MYW1AZ | |
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| Record name | ANASTROZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7462 | |
| 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 | Anastrozole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015348 | |
| 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 |
81-82 °C, 130.14 °C |
Source
|
| Record name | ANASTROZOLE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/7462 | |
| 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 | Anastrozole | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015348 | |
| 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. | |
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Retrosynthesis Analysis
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Strategy Settings
| Precursor scoring | Relevance Heuristic |
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| 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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