Abiraterone
描述
作用机制
阿比特龙通过选择性且不可逆地抑制酶 17α-羟化酶/C17,20-裂解酶 (CYP17) 来发挥作用，该酶对雄激素生物合成至关重要 . 通过阻断这种酶，阿比特龙减少了睾酮和其他雄激素的产生，从而抑制了雄激素依赖性前列腺癌细胞的生长 . 分子靶标包括肾上腺、睾丸和前列腺肿瘤 .
类似化合物：
阿比特龙的独特性： 阿比特龙的独特性在于其作用机制。 它在酶水平上抑制雄激素生物合成，而像比卡鲁胺和恩扎鲁胺这样的其他化合物在受体水平上起作用 . 这使得阿比特龙在雄激素受体信号传导抑制剂效果不佳的情况下特别有效。
生化分析
Biochemical Properties
Abiraterone plays a significant role in biochemical reactions as it selectively and irreversibly inhibits CYP17 (17 alpha-hydroxylase/C17,20-lyase), an enzyme required for androgen biosynthesis . This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues . The inhibition of CYP17 by this compound leads to a decrease in the formation of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione .
Cellular Effects
This compound has profound effects on various types of cells, particularly cancer cells. By inhibiting androgen synthesis, this compound reduces the availability of androgens, which are essential for the growth and survival of prostate cancer cells . This influences cell function, including impacts on cell signaling pathways, gene expression, and cellular metabolism .
Molecular Mechanism
The molecular mechanism of action of this compound involves its binding to the CYP17 enzyme, thereby inhibiting its activity . This prevents the conversion of pregnenolone and progesterone to DHEA and androstenedione, respectively . As a result, the levels of these androgens are reduced, leading to decreased stimulation of androgen receptors and changes in gene expression in prostate cancer cells .
Temporal Effects in Laboratory Settings
In laboratory settings, the effects of this compound have been observed to change over time . The pharmacokinetics of this compound have been studied in healthy volunteers, with results indicating that the maximum plasma concentration was achieved under fasting conditions .
Dosage Effects in Animal Models
The effects of this compound in animal models vary with different dosages
Metabolic Pathways
This compound is involved in the metabolic pathway of androgen biosynthesis . It interacts with the CYP17 enzyme, which is a key enzyme in this pathway .
准备方法
合成路线和反应条件： 醋酸阿比特龙的合成通常包括从脱氢表雄酮开始的四步过程 . 关键步骤包括：
缩合： 脱氢表雄酮与水合肼在乙醇中使用硫酸作为催化剂缩合形成腙中间体。
碘化： 在 1,1,3,3-四甲基胍存在下，用碘处理中间体，得到 17-碘雄甾-5,16-二烯-3β-醇。
铃木偶联： 碘化化合物与 3-(二乙基硼基)吡啶使用钯催化剂进行铃木交叉偶联，形成阿比特龙。
乙酰化： 最后，阿比特龙被乙酰化生成醋酸阿比特龙.
工业生产方法： 醋酸阿比特龙的工业生产涉及类似的合成路线，但针对大规模生产进行了优化。 采用溶剂蒸发、直接压片和熔融制粒等技术来增强最终产品的生物利用度和稳定性 .
化学反应分析
反应类型： 阿比特龙会经历各种化学反应，包括：
氧化： 阿比特龙可以被氧化形成羟基化的衍生物。
还原： 还原反应可以将阿比特龙转化为其相应的醇类。
常见试剂和条件：
氧化： 通常使用高锰酸钾或三氧化铬等试剂。
还原： 硼氢化钠或氢化铝锂是典型的还原剂。
取代： 卤化剂如碘或溴在温和条件下使用.
科学研究应用
阿比特龙具有广泛的科学研究应用：
化学： 它被用作研究类固醇酶抑制剂的模型化合物。
生物学： 阿比特龙用于研究雄激素生物合成及其抑制。
相似化合物的比较
Uniqueness of this compound: this compound’s uniqueness lies in its mechanism of action. It inhibits androgen biosynthesis at the enzymatic level, whereas other compounds like bicalutamide and enzalutamide act at the receptor level . This makes this compound particularly effective in cases where androgen receptor signaling inhibitors are less effective.
属性
IUPAC Name |
(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-pyridin-3-yl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-ol |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C24H31NO/c1-23-11-9-18(26)14-17(23)5-6-19-21-8-7-20(16-4-3-13-25-15-16)24(21,2)12-10-22(19)23/h3-5,7,13,15,18-19,21-22,26H,6,8-12,14H2,1-2H3/t18-,19-,21-,22-,23-,24+/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
GZOSMCIZMLWJML-VJLLXTKPSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
CC12CCC(CC1=CCC3C2CCC4(C3CC=C4C5=CN=CC=C5)C)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
C[C@]12CC[C@@H](CC1=CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CC=C4C5=CN=CC=C5)C)O |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C24H31NO |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID80879993 |
Source
|
| Record name | Abiraterone | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID80879993 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
349.5 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Mechanism of Action |
Abiraterone is an orally active inhibitor of the steroidal enzyme CYP17A1 (17 alpha-hydroxylase/C17,20 lyase). It inhibits CYP17A1 in a selective and irreversible manner via covalent binding mechanism. CYP17A1 is an enzyme that catalyzes the biosynthesis of androgen and is highly expressed in testicular, adrenal, and prostatic tumor tissue. More specifically, abiraterone inhibits the conversion of 17-hydroxyprognenolone to dehydroepiandrosterone (DHEA) by the enzyme CYP17A1 to decrease serum levels of testosterone and other androgens. |
Source
|
| Record name | Abiraterone | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB05812 | |
| 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) | |
CAS No. |
154229-19-3 |
Source
|
| Record name | Abiraterone | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=154229-19-3 | |
| 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 | Abiraterone [INN:BAN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0154229193 | |
| 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 | Abiraterone | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB05812 | |
| 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 | Abiraterone | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID80879993 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | (1S,2R,5S,10R,11S,15S)-2,15-dimethyl-14-(pyridin-3-yl)tetracyclo[8.7.0.0²,�.0¹¹,¹�] heptadeca-7,13-dien-5-ol | |
| 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 | ABIRATERONE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/G819A456D0 | |
| 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. | |
Retrosynthesis Analysis
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