Anastrozole
Vue d'ensemble
Description
- Plus précisément, il est efficace dans le traitement du cancer du sein positif aux récepteurs hormonaux. De plus, il a été utilisé comme mesure préventive chez les personnes présentant un risque élevé de développer un cancer du sein .
Anastrozole : est un médicament anti-œstrogénique qui appartient à la classe des inhibiteurs de l'aromatase. Il est généralement vendu sous la marque et est utilisé en association avec d'autres traitements contre le cancer du sein.
Mécanisme D'action
Target of Action
Anastrozole is a competitive, selective, non-steroidal aromatase inhibitor . Its primary target is the enzyme aromatase, which plays a crucial role in the biosynthesis of estrogen . Aromatase catalyzes the conversion of androgens to estrogen . By inhibiting this enzyme, this compound effectively decreases circulating estrogen levels .
Mode of Action
This compound works by selectively inhibiting aromatase . It binds to the active site of the enzyme and prevents it from interacting with its substrate, thereby blocking the conversion of androgens to estrogens . This leads to a decrease in estrogen levels, particularly in postmenopausal women, where the primary source of estrogen is through the aromatization of androgens .
Biochemical Pathways
The key biochemical pathway affected by this compound is the conversion of androgens to estrogens, catalyzed by aromatase . By inhibiting this enzyme, this compound disrupts this pathway, leading to a decrease in estrogen levels . This is particularly significant in estrogen-responsive breast cancer, where estrogen plays a role in tumor growth and progression .
Pharmacokinetics
This compound is primarily metabolized in the liver via oxidation and glucuronidation to a number of inactive metabolites . Its clearance is mainly via hepatic metabolism and can therefore be altered in patients with hepatic impairment . Patients with stable hepatic cirrhosis exhibit an apparent oral clearance approximately 30% lower compared with patients with normal liver function . Conversely, renal impairment has a negligible effect on total drug clearance as the renal route is a relatively minor clearance pathway for this compound .
Result of Action
The molecular effect of this compound’s action is the reduction of estrogen levels in the body . On a cellular level, this leads to a decrease in the growth and proliferation of hormone-dependent breast cancer cells . By reducing the levels of estrogen, this compound deprives these cells of a key growth stimulus, thereby inhibiting tumor growth .
Action Environment
The action of this compound can be influenced by environmental factors. For instance, patients with hepatic impairment may have altered drug clearance, affecting the drug’s efficacy . Furthermore, according to an environmental risk assessment, the use of this compound is predicted to present an insignificant risk to the environment . The Predicted Environmental Concentration (PEC) / Predicted No Effect Concentration (PNEC) ratio is 1.4x10-4, indicating that the environmental impact of this compound is minimal .
Applications De Recherche Scientifique
Chemistry: Anastrozole serves as a valuable tool in medicinal chemistry, particularly in the field of cancer research.
Biology: Researchers study its effects on estrogen metabolism and its impact on hormone-dependent cancers.
Medicine: Beyond breast cancer treatment, this compound is explored for other hormone-related conditions.
Industry: Its industrial applications extend to pharmaceutical manufacturing and drug development.
Analyse Biochimique
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, this compound slows the growth of tumors that require estrogen to grow .
Cellular Effects
This compound 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 . This compound 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
This compound 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
This compound 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 this compound 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, this compound can cause fetal harm when administered to a pregnant woman . This compound 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
This compound is primarily metabolized in the liver via oxidation and glucuronidation to a number of inactive metabolites, including hydroxythis compound (both free and glucuronidated) and this compound glucuronide . Oxidation to hydroxythis compound is catalyzed predominantly by CYP3A4 (as well as CYP3A5 and CYP2C8, to a lesser extent) and the direct glucuronidation of this compound is catalyzed mainly by UGT1A4 .
Transport and Distribution
This compound is rapidly absorbed and T max is typically reached within 2 hours of dosing under fasted conditions . Once absorbed, this compound is widely distributed throughout the body, with about 40% being bound to plasma proteins .
Subcellular Localization
The subcellular localization of this compound is not explicitly mentioned in the literature. Given its mechanism of action, it can be inferred that this compound 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 .
Méthodes De Préparation
Voies de synthèse : L'Anastrozole est synthétisé par un processus en plusieurs étapes. L'étape clé implique le couplage du 1,2,4-triazole avec un groupe phénylméthyle, suivi d'une addition de nitrile. La séquence réactionnelle globale conduit à la formation du composé.
Production industrielle : L'this compound est produit industriellement à l'aide de voies de synthèse efficaces.
Analyse Des Réactions Chimiques
Réactivité : L'Anastrozole subit diverses réactions chimiques en raison de ses caractéristiques structurales. Celles-ci comprennent les réactions d'oxydation, de réduction et de substitution.
Réactifs et conditions courants : Les réactifs et les conditions spécifiques dépendent de la transformation souhaitée. Par exemple
Principaux produits : Les produits formés à partir de ces réactions comprennent des dérivés modifiés de l'this compound, qui peuvent avoir des propriétés pharmacologiques modifiées.
Applications de la recherche scientifique
Chimie : L'this compound est un outil précieux en chimie médicinale, en particulier dans le domaine de la recherche sur le cancer.
Biologie : Les chercheurs étudient ses effets sur le métabolisme des œstrogènes et son impact sur les cancers hormono-dépendants.
Médecine : Au-delà du traitement du cancer du sein, l'this compound est exploré pour d'autres affections liées aux hormones.
Industrie : Ses applications industrielles s'étendent à la fabrication pharmaceutique et au développement de médicaments.
Mécanisme d'action
Suppression des œstrogènes : L'this compound inhibe l'enzyme aromatase, qui convertit les androgènes en œstrogènes. En bloquant ce processus, il réduit les niveaux d'œstrogènes dans l'organisme.
Cibles moléculaires : L'aromatase elle-même est la principale cible moléculaire. En l'inhibant, l'this compound perturbe la synthèse des œstrogènes.
Comparaison Avec Des Composés Similaires
Propriétés
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 | |
| 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 | anastrozole | |
| Source | DTP/NCI | |
| 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. | |
| 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 | 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. | |
| Record name | 1,3-Benzenediacetonitrile, α1,α1,α3,α3-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl) | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.129.723 | |
| 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 | ANASTROZOLE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/2Z07MYW1AZ | |
| 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 | 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. | |
Synthesis routes and methods I
Procedure details
Synthesis routes and methods II
Procedure details
Synthesis routes and methods III
Procedure details
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
Avertissement et informations sur les produits de recherche in vitro
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.
![(E)-3-[3-(1,3-benzothiazol-2-ylsulfanylmethyl)-4-hydroxy-5-methoxyphenyl]-2-cyanoprop-2-enamide](/img/structure/B1683695.png)
![Benzoic acid, 4-[[(2,5-dihydroxyphenyl)methyl]amino]-, methyl ester](/img/structure/B1683696.png)
