双氯芬酰胺
作用机制
双氯芬酰胺通过抑制碳酸酐酶发挥作用。这种抑制会减少眼睛中房水的分泌，从而降低眼内压。 此过程涉及的确切分子靶标和途径尚不完全清楚，但已知碳酸酐酶抑制剂（如双氯芬酰胺）会部分抑制房水的分泌 .
科学研究应用
双氯芬酰胺具有广泛的科学研究应用：
化学： 它用作各种化学反应的试剂，以及作为研究磺酰胺化学的标准品。
生物学： 双氯芬酰胺用于生物学研究，以了解碳酸酐酶抑制剂在细胞过程中的作用。
医学： 除了用于治疗青光眼和癫痫外，双氯芬酰胺还用于治疗原发性低钾血症和高钾血症周期性麻痹.
工业： 双氯芬酰胺用于制药行业开发新药和配方.
生化分析
Biochemical Properties
Dichlorphenamide interacts with carbonic anhydrase, an enzyme that plays a crucial role in regulating pH and fluid balance in the body . By inhibiting this enzyme, Dichlorphenamide can reduce the production of aqueous humor, thereby lowering intraocular pressure .
Cellular Effects
Dichlorphenamide influences cell function by altering the activity of carbonic anhydrase. This can affect various cellular processes, including fluid balance and ion transport . The inhibition of carbonic anhydrase can also impact cell signaling pathways and gene expression related to these processes .
Molecular Mechanism
Dichlorphenamide exerts its effects at the molecular level by binding to carbonic anhydrase and inhibiting its activity . This can lead to changes in ion transport and fluid balance within cells, as well as alterations in gene expression related to these processes .
Metabolic Pathways
Dichlorphenamide is involved in the carbonic anhydrase pathway, where it interacts with the carbonic anhydrase enzyme . This can affect metabolic flux and metabolite levels, particularly those related to fluid balance and ion transport .
Subcellular Localization
The subcellular localization of Dichlorphenamide and its effects on activity or function would depend on its interactions with carbonic anhydrase and other biomolecules within the cell
准备方法
双氯芬酰胺的合成涉及 4,5-二氯苯-1,3-二磺酰氯与氨的反应。该反应通常在受控条件下进行，以确保形成所需产物。 工业生产方法可能涉及使用类似反应条件的大规模合成，但针对更高的产量和纯度进行了优化 .
化学反应分析
双氯芬酰胺会经历各种化学反应，包括：
取代反应： 在适当条件下，双氯芬酰胺中的氯原子可以被其他亲核试剂取代。
氧化还原： 双氯芬酰胺可以发生氧化还原反应，虽然这些反应在其典型应用中不太常见。
这些反应中常用的试剂包括强酸、碱和亲核试剂。形成的主要产物取决于所用的特定反应条件和试剂。
相似化合物的比较
双氯芬酰胺因其特定的结构和性质而在碳酸酐酶抑制剂中独一无二。类似化合物包括：
乙酰唑胺： 另一种用于治疗青光眼和高原病的碳酸酐酶抑制剂。
甲磺酰胺： 用于治疗青光眼，类似于双氯芬酰胺，但药代动力学性质不同。
布林佐胺： 一种用于治疗眼内压升高的局部碳酸酐酶抑制剂.
属性
IUPAC Name |
4,5-dichlorobenzene-1,3-disulfonamide |
Source
|
|---|---|---|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI |
InChI=1S/C6H6Cl2N2O4S2/c7-4-1-3(15(9,11)12)2-5(6(4)8)16(10,13)14/h1-2H,(H2,9,11,12)(H2,10,13,14) |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
InChI Key |
GJQPMPFPNINLKP-UHFFFAOYSA-N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Canonical SMILES |
C1=C(C=C(C(=C1S(=O)(=O)N)Cl)Cl)S(=O)(=O)N |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
Molecular Formula |
C6H6Cl2N2O4S2 |
Source
|
| Source | PubChem | |
| URL | https://pubchem.ncbi.nlm.nih.gov | |
| Description | Data deposited in or computed by PubChem | |
DSSTOX Substance ID |
DTXSID1022922 |
Source
|
| Record name | Dichlorphenamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID1022922 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
Molecular Weight |
305.2 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 | Dichlorphenamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015275 | |
| 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 |
PRACTICALLY INSOL IN WATER; SOL IN ALKALINE SOLN, FREELY SOL IN PYRIDINE & IN 1 N NAOH; SOL IN ALCOHOL; SOL IN 2 N SODIUM CARBONATE; SLIGHTLY SOL IN ETHER, 3.98e-01 g/L |
Source
|
| Record name | DICHLORPHENAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3267 | |
| 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 | Dichlorphenamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015275 | |
| 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 |
Carbonic anhydrase inhibitors reduce intraocular pressure by partially suppressing the secretion of aqueous humor (inflow), although the mechanism by which they do this is not fully understood. Evidence suggests that HCO3- ions are produced in the ciliary body by hydration of carbon dioxide under the influence of carbonic anhydrase and diffuse into the posterior chamber which contains more Na+ and HCO3- ions than does plasma and consequently is hypertonic. Water is then attracted to the posterior chamber by osmosis, resulting in a drop in pressure., PHOSPHATURIA MAY BE RELATED TO DIRECT STIMULATION...OF CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE...PRODN BY KIDNEY. ...DRUG ACTS SIMILARLY TO PARATHYROID HORMONE IN ENHANCING URINARY EXCRETION OF PHOSPHATE & CYCLIC AMP, IN CONTRAST TO ITS ANTAGONISM OF ACTION OF HORMONE ON BONE. /ACETAZOLAMIDE/, ...INHIBITION OF...CARBONIC ANHYDRASE. ...IS NONCOMPETITIVE. ...ENZYME IS NORMALLY PRESENT IN TISSUES IN HUGE EXCESS. MORE THAN 99% OF ENZYME ACTIVITY IN KIDNEY MUST BE INHIBITED BEFORE PHYSIOLOGICAL EFFECTS BECOME APPARENT. ENZYME...IS DOMINANT TISSUE COMPONENT TO WHICH INHIBITORS BECOME BOUND. /ACETAZOLAMIDE/, /CHANGES IN URINE/...MAY BE ATTRIBUTED TO INHIBITION OF (+)H SECRETION BY RENAL TUBULE. ... CURRENT EVIDENCE INDICATES GREATER EFFECT ON PROXIMAL THAN ON DISTAL TUBULE, WITH LITTLE OR NO EFFECT ON ASCENDING LIMB. ...PHOSPHATURIA...USED AS INDEX OF LOCALIZING DIURETIC ACTION... /ACETAZOLAMIDE/, ...INCR URINARY EXCRETION OF BICARBONATE & FIXED CATION, MOSTLY SODIUM. AS RESULT, CONCN OF BICARBONATE IN EXTRACELLULAR FLUID DECR & METABOLIC ACIDOSIS RESULTS. ...RENAL RESPONSE TO ACETAZOLAMIDE IS GREATLY REDUCED.../BUT/ DIURETIC RESPONSE IS ENHANCED. /ACETAZOLAMIDE/, DRUG LOWERS INTRAOCULAR PRESSURE BY REDUCING RATE OF SECRETION OF AQ HUMOR. |
Source
|
| Record name | Diclofenamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01144 | |
| 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 | DICHLORPHENAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3267 | |
| 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 |
NEEDLES FROM DIMETHYLSULFOXIDE + WATER, WHITE OR NEARLY WHITE, CRYSTALLINE POWDER | |
CAS No. |
120-97-8 |
Source
|
| Record name | Dichlorphenamide | |
| Source | CAS Common Chemistry | |
| URL | https://commonchemistry.cas.org/detail?cas_rn=120-97-8 | |
| 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 | Dichlorphenamide [USP] | |
| Source | ChemIDplus | |
| URL | https://pubchem.ncbi.nlm.nih.gov/substance/?source=chemidplus&sourceid=0000120978 | |
| 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 | Diclofenamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01144 | |
| 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 | Dichlorphenamide | |
| Source | EPA DSSTox | |
| URL | https://comptox.epa.gov/dashboard/DTXSID1022922 | |
| Description | DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology. | |
| Record name | Diclofenamide | |
| Source | European Chemicals Agency (ECHA) | |
| URL | https://echa.europa.eu/substance-information/-/substanceinfo/100.004.037 | |
| 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 | DICHLORPHENAMIDE | |
| Source | FDA Global Substance Registration System (GSRS) | |
| URL | https://gsrs.ncats.nih.gov/ginas/app/beta/substances/VVJ6673MHY | |
| 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 | DICHLORPHENAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3267 | |
| 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 | Dichlorphenamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015275 | |
| 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 |
239-241 °C, 228.7 °C |
Source
|
| Record name | Diclofenamide | |
| Source | DrugBank | |
| URL | https://www.drugbank.ca/drugs/DB01144 | |
| 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 | DICHLORPHENAMIDE | |
| Source | Hazardous Substances Data Bank (HSDB) | |
| URL | https://pubchem.ncbi.nlm.nih.gov/source/hsdb/3267 | |
| 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 | Dichlorphenamide | |
| Source | Human Metabolome Database (HMDB) | |
| URL | http://www.hmdb.ca/metabolites/HMDB0015275 | |
| 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
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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
Q1: What is the primary mechanism of action of dichlorphenamide?
A1: Dichlorphenamide acts as a carbonic anhydrase inhibitor. [, , ] It binds to the active site of carbonic anhydrase, preventing the enzyme from catalyzing the reversible hydration of carbon dioxide to bicarbonate and protons. This inhibition has significant effects on various physiological processes, particularly in the kidneys and eyes. [, , , , ]
Q2: How does dichlorphenamide affect the kidneys?
A2: By inhibiting carbonic anhydrase in the kidneys, dichlorphenamide reduces bicarbonate reabsorption in the proximal tubules. This leads to increased excretion of bicarbonate in the urine, resulting in metabolic acidosis. [, , ] This acidosis is thought to contribute to its therapeutic effects in periodic paralysis. [, ]
Q3: How does dichlorphenamide affect the eyes?
A4: Dichlorphenamide's inhibition of carbonic anhydrase in the ciliary body of the eye reduces aqueous humor production, leading to a decrease in intraocular pressure. [, , ] This effect makes it useful in treating glaucoma. [, , ]
Q4: What is the molecular formula and weight of dichlorphenamide?
A5: The molecular formula of dichlorphenamide is C6H6Cl2N2O4S2, and its molecular weight is 305.16 g/mol. []
Q5: Are there any known dimer impurities of dichlorphenamide?
A6: Yes, two dimeric impurities, 2,3-dichloro-5-(3,4-dichloro-5-sulfamoyl-phenyl)sulfonylbenzenesulfonamide (1,1′-dichlorphenamide dimer) and 2,3-dichloro-5-(2,3-dichloro-5-sulfamoylphenyl)sulfonyl-benzenesulfonamide (1,3′-dichlorphenamide dimer), have been identified and characterized. These impurities can form during the synthesis of dichlorphenamide. []
Q6: What analytical techniques are used to characterize and quantify dichlorphenamide?
A7: Dichlorphenamide can be analyzed using techniques like Gas Chromatography (GC) and Liquid Chromatography-Mass Spectrometry (LC-MS). [, ] For instance, electron-capture GLC with derivatization to tetramethyl derivatives was employed to determine dichlorphenamide levels in rabbit serum and aqueous humor. []
Q7: What is the pharmacokinetic profile of dichlorphenamide?
A9: Dichlorphenamide exhibits a relatively long half-life ranging from 32 to 68 hours. [] Following oral administration, it reaches maximum plasma concentration within 1.5–3 hours. [] The area under the curve and maximum concentration increase proportionally with dose. []
Q8: How is dichlorphenamide metabolized and excreted?
A10: While detailed metabolic pathways are not fully elucidated within the provided texts, its long half-life suggests potential for metabolism. [] Further research is necessary to characterize its metabolic fate and excretion routes.
Q9: What is the evidence for dichlorphenamide's efficacy in treating periodic paralysis?
A11: Multiple randomized, double-blind, placebo-controlled trials have demonstrated dichlorphenamide's efficacy in reducing attack frequency in patients with hypokalemic periodic paralysis. [, , , ] While results in hyperkalemic periodic paralysis appear promising, further research is needed due to smaller sample sizes in clinical trials. [, , ]
Q10: Are there specific patient populations where dichlorphenamide's efficacy varies?
A12: Research suggests potential for variable responses to dichlorphenamide. In a specific case, a patient with hypokalemic periodic paralysis and a NaV1.4pR222W mutation experienced increased attack frequency with dichlorphenamide. [] This highlights the complexity of treatment response and underscores the need for personalized medicine approaches.
Q11: How does dichlorphenamide compare to acetazolamide in treating periodic paralysis?
A13: While both dichlorphenamide and acetazolamide are carbonic anhydrase inhibitors used to treat periodic paralysis, there have been no head-to-head trials comparing their efficacy. [, , ] Some anecdotal reports suggest potential differences in patient response, with some individuals experiencing greater benefit from dichlorphenamide. []
Q12: What are the common adverse effects associated with dichlorphenamide?
A14: The most common adverse effects reported with dichlorphenamide include paresthesia (tingling sensations), confusion, and gastrointestinal disturbances. [, , ] These side effects are often dose-dependent. []
Q13: Are there any ongoing efforts to improve the delivery of dichlorphenamide to specific tissues?
A13: Research is exploring drug delivery strategies to enhance dichlorphenamide's targeting to specific tissues and improve its therapeutic index. This includes investigating novel formulations and delivery systems.
Q14: When was dichlorphenamide first introduced as a potential therapeutic agent?
A17: Dichlorphenamide's introduction as a therapeutic agent dates back to the mid-20th century. Early investigations highlighted its potential as a diuretic and its ocular hypotensive effects. [, ]
Q15: What were some key milestones in the research and development of dichlorphenamide?
A18: A key milestone in dichlorphenamide research was the FDA approval for treating primary periodic paralysis in 2015, based on the strength of randomized controlled trials demonstrating its efficacy. [, ] This approval marked a significant advancement in treatment options for this rare group of neuromuscular disorders.
Q16: Beyond its use in humans, are there other applications for dichlorphenamide?
A19: Dichlorphenamide has been investigated for potential applications in various fields. For instance, its insecticidal properties against Aedes aegypti and Drosophila melanogaster have been explored. []
Q17: What are some important areas for future research on dichlorphenamide?
A17: Future research should focus on:
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