恩格列净
描述
恩格列净是一种口服药物，主要用于治疗2型糖尿病。它属于一类称为钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂的药物。通过抑制SGLT2，恩格列净减少肾脏对葡萄糖的重吸收，导致尿中葡萄糖排泄增加。 这有助于降低2型糖尿病患者的血糖水平 .
科学研究应用
恩格列净具有广泛的科学研究应用，包括：
糖尿病管理： 恩格列净主要用于通过降低血糖水平来治疗2型糖尿病
心血管益处： 研究表明，恩格列净可以降低2型糖尿病患者发生心血管事件（如心脏病发作和中风）的风险
肾脏保护： 已发现恩格列净具有肾脏保护作用，降低了肾脏疾病进展的风险.
心力衰竭： 该化合物也用于治疗心力衰竭，提供了超出血糖控制的益处.
作用机制
恩格列净通过抑制肾脏中的钠-葡萄糖协同转运蛋白2（SGLT2）发挥作用。这种抑制减少了肾小球滤液中葡萄糖的重吸收，导致尿中葡萄糖排泄增加。血糖水平的降低有助于控制2型糖尿病。 此外，恩格列净已被证明具有心脏保护作用和肾脏保护作用，这些作用被认为是通过减少氧化应激和改善内皮功能等机制介导的 .
准备方法
合成路线和反应条件： 恩格列净通过涉及多个关键中间体的多步合成过程合成。一种常见的合成路线包括以下步骤：
中间体I的形成： 初始步骤涉及4-氯-3-(4-(四氢呋喃-3-基氧基)苄基)苯基与合适的糖基供体反应，形成中间体I。
中间体II的形成： 中间体I经历进一步的反应，包括保护和脱保护步骤，以生成中间体II。
工业生产方法： 恩格列净的工业生产通常涉及使用优化反应条件的大规模合成，以确保高产率和纯度。该过程包括：
回流： 反应混合物回流以促进所需产物的形成。
化学反应分析
反应类型： 恩格列净经历各种化学反应，包括：
常见试剂和条件：
氧化降解： 过氧化氢或其他氧化剂等试剂可以诱导氧化降解。
主要形成的产物：
氧化降解产物： 根据所用条件和试剂的不同，可能会形成各种氧化产物。
水解产物： 水解会导致较小片段和降解产物的形成.
相似化合物的比较
恩格列净属于SGLT2抑制剂类药物。该类中的其他类似化合物包括：
达格列净： 该化合物也用于治疗2型糖尿病，并已获准用于治疗心力衰竭.
依格列净： 另一种作用机制类似但药代动力学特性不同的SGLT2抑制剂.
恩格列净的独特之处： 恩格列净在SGLT2上具有高度选择性，而对SGLT1的选择性较低，这有助于其疗效和安全性。 它还已被证明具有显著的心血管和肾脏益处，使其成为患有2型糖尿病和合并症患者的宝贵选择 .
属性
IUPAC Name |
(2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-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/C23H27ClO7/c24-18-6-3-14(23-22(28)21(27)20(26)19(11-25)31-23)10-15(18)9-13-1-4-16(5-2-13)30-17-7-8-29-12-17/h1-6,10,17,19-23,25-28H,7-9,11-12H2/t17-,19+,20+,21-,22+,23-/m0/s1 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
OBWASQILIWPZMG-QZMOQZSNSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1COCC1OC2=CC=C(C=C2)CC3=C(C=CC(=C3)C4C(C(C(C(O4)CO)O)O)O)Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Isomeric SMILES |
C1COC[C@H]1OC2=CC=C(C=C2)CC3=C(C=CC(=C3)[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)Cl |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C23H27ClO7 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID601026093 |
Source
|
| Record name | Empagliflozin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID601026093 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
450.9 g/mol |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Mechanism of Action |
The vast majority of glucose filtered through the glomerulus is reabsorbed within the proximal tubule, primarily via SGLT2 (sodium-glucose linked co-transporter-2) which is responsible for ~90% of the total glucose reabsorption within the kidneys. Na+/K+-ATPase on the basolateral membrane of proximal tubular cells utilize ATP to actively pump Na+ ions into the interstitium surrounding the tubule, establishing a Na+ gradient within the tubular cell. SGLT2 on the apical membrane of these cells then utilize this gradient to facilitate secondary active co-transport of both Na+ and glucose out of the filtrate, thereby reabsorbing glucose back into the blood – inhibiting this co-transport, then, allows for a marked increase in glucosuria and decrease in blood glucose levels. Empagliflozin is a potent inhibitor of renal SGLT2 transporters located in the proximal tubules of the kidneys and works to lower blood glucose levels via an increase in glucosuria. Empagliflozin also appears to exert cardiovascular benefits - specifically in the prevention of heart failure - independent of its blood glucose-lowering effects, though the exact mechanism of this benefit is not precisely understood. Several theories have been posited, including the potential inhibition of Na+/H+ exchanger (NHE) 1 in the myocardium and NHE3 in the proximal tubule, reduction of pre-load via diuretic/natriuretic effects and reduction of blood pressure, prevention of cardiac fibrosis via suppression of pro-fibrotic markers, and reduction of pro-inflammatory adipokines. |
Source
|
| Record name | Empagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB09038 | |
| 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. |
864070-44-0 |
Source
|
| Record name | Empagliflozin | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=864070-44-0 | |
| 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 | Empagliflozin [USAN:INN] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0864070440 | |
| 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 | Empagliflozin | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB09038 | |
| 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 | Empagliflozin | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID601026093 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-((S)-tetrahydrofuran-3-yloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol | |
| 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 | EMPAGLIFLOZIN | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/HDC1R2M35U | |
| 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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| Template Set | Pistachio/Bkms_metabolic/Pistachio_ringbreaker/Reaxys/Reaxys_biocatalysis |
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