Details
Stereochemistry | ACHIRAL |
Molecular Formula | C6H6Cl2N2O4S2 |
Molecular Weight | 305.159 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NS(=O)(=O)C1=CC(=C(Cl)C(Cl)=C1)S(N)(=O)=O
InChI
InChIKey=GJQPMPFPNINLKP-UHFFFAOYSA-N
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)
Molecular Formula | C6H6Cl2N2O4S2 |
Molecular Weight | 305.159 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including https://www.urmc.rochester.edu/news/story/4461/new-drug-for-periodic-paralysis-has-roots-in-urmc-research.aspx
Curator's Comment: description was created based on several sources, including https://www.urmc.rochester.edu/news/story/4461/new-drug-for-periodic-paralysis-has-roots-in-urmc-research.aspx
Diclorphenamide, a carbonic anhydrase inhibitor, was initially developed for the treatment of glaucome, however, now it is used for patients suffering from primary hypokalemic and hyperkalemic periodic paralysis. The exact mechanism of diclorphenamide in periodic paralysis is unknown.
Originator
Sources: https://www.urmc.rochester.edu/news/story/4461/new-drug-for-periodic-paralysis-has-roots-in-urmc-research.aspx
Curator's Comment: # Merck & Co
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2095180 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | KEVEYIS Approved UseKeveyis is an oral carbonic anhydrase inhibitor indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants. Launch Date1958 |
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Primary | KEVEYIS Approved UseKeveyis is an oral carbonic anhydrase inhibitor indicated for the treatment of primary hyperkalemic periodic paralysis, primary hypokalemic periodic paralysis, and related variants. Launch Date1958 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3030 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29762909 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
DICHLORPHENAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
66456 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29762909 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
DICHLORPHENAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
41 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29762909 |
200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: |
DICHLORPHENAMIDE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12% |
DICHLORPHENAMIDE plasma | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Disc. AE: Hypokalemia, Weight loss... AEs leading to discontinuation/dose reduction: Hypokalemia (mild, 83.3%) Sources: Weight loss (16.7%) Itchy throat (16.7%) Tachycardia (16.7%) Gait instability (moderate, 16.7%) Toothache (moderate, 16.7%) |
200 mg 1 times / day multiple, oral (total daily dose) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Primary hyperkalemic periodic paralysis|Primary hypokalemic periodic paralysis Sources: |
Disc. AE: Hypersensitivity, Hypokalemia... AEs leading to discontinuation/dose reduction: Hypersensitivity Sources: Hypokalemia Metabolic acidosis Fall |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Itchy throat | 16.7% Disc. AE |
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Tachycardia | 16.7% Disc. AE |
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Weight loss | 16.7% Disc. AE |
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Hypokalemia | mild, 83.3% Disc. AE |
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Gait instability | moderate, 16.7% Disc. AE |
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Toothache | moderate, 16.7% Disc. AE |
400 mg 2 times / day multiple, oral Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: |
healthy, 38.1±12.1 n = 6 Health Status: healthy Age Group: 38.1±12.1 Sex: M+F Population Size: 6 Sources: |
Fall | Disc. AE | 200 mg 1 times / day multiple, oral (total daily dose) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Primary hyperkalemic periodic paralysis|Primary hypokalemic periodic paralysis Sources: |
Hypersensitivity | Disc. AE | 200 mg 1 times / day multiple, oral (total daily dose) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Primary hyperkalemic periodic paralysis|Primary hypokalemic periodic paralysis Sources: |
Hypokalemia | Disc. AE | 200 mg 1 times / day multiple, oral (total daily dose) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Primary hyperkalemic periodic paralysis|Primary hypokalemic periodic paralysis Sources: |
Metabolic acidosis | Disc. AE | 200 mg 1 times / day multiple, oral (total daily dose) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Condition: Primary hyperkalemic periodic paralysis|Primary hypokalemic periodic paralysis Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 5.0 |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 9.0 |
no | |||
Page: 8.0 |
no | |||
Page: 8.0 |
no | |||
Page: 8.0 |
no | |||
Page: 8.0 |
no | |||
Page: 8.0 |
no | |||
Page: 8.0 |
no | |||
Page: 8.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 9.0 |
no | |||
Page: 6.0 |
yes | |||
Page: 6.0 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Carbonic anhydrase inhibitors and osmotic agents in glaucoma. Carbonic anhydrase inhibitors. | 1968 Aug |
|
[Diclofenamide Reference Standard (Control 891) of National Institute of Hygienic Sciences]. | 1991 |
|
Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis. | 2000 Jan |
|
Long-term management of a glaucomatous eye in a dog treated with medical therapy alone. | 2001 Dec |
|
Generation and evaluation of a CYP2C9 heteroactivation pharmacophore. | 2003 Dec |
|
Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. | 2003 Mar 10 |
|
Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides. | 2003 Mar 24 |
|
Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives. | 2003 May 22 |
|
Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. | 2004 Apr |
|
Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. | 2004 Jan 19 |
|
Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. | 2004 Jan 5 |
|
Carbonic anhydrase inhibitors. Inhibition of cytosolic isozyme XIII with aromatic and heterocyclic sulfonamides: a novel target for the drug design. | 2004 Jul 16 |
|
Benzolamide is not a membrane-impermeant carbonic anhydrase inhibitor. | 2004 Jun |
|
Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides. | 2004 Jun 21 |
|
Theoretical study of gas-phase acidity, pKa, lipophilicity, and solubility of some biologically active sulfonamides. | 2004 Oct 15 |
|
[Diclofenamide]. | 2005 Apr 15 |
|
Expression of a novel carbonic anhydrase, CA XIII, in normal and neoplastic colorectal mucosa. | 2005 Apr 18 |
|
Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation. | 2005 Aug |
|
A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G). | 2005 Feb |
|
Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. | 2005 Feb 15 |
|
Carbonic anhydrase inhibitors. Inhibition of the human cytosolic isozyme VII with aromatic and heterocyclic sulfonamides. | 2005 Feb 15 |
|
Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs? | 2005 Feb 15 |
|
Carbonic anhydrase inhibitors: inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with benzo[b]thiophene 1,1-dioxide sulfonamides. | 2005 Nov 1 |
|
Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. | 2005 Sep 1 |
|
Carbonic anhydrase inhibitors: cloning and sulfonamide inhibition studies of a carboxyterminal truncated alpha-carbonic anhydrase from Helicobacter pylori. | 2006 Apr 15 |
|
Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. | 2006 Jan |
|
[Diuretic therapy in heart failure]. | 2006 Jan-Feb |
|
Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs. | 2006 Mar 23 |
|
Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. | 2006 Nov 30 |
|
The development of topically acting carbonic anhydrase inhibitors as anti-glaucoma agents. | 2007 |
|
Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. | 2007 Dec 1 |
|
Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition studies of the human secretory isoform VI, a new target for sulfonamide and sulfamate inhibitors. | 2007 Jan 25 |
|
The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. | 2008 |
|
Practical aspects in the management of hypokalemic periodic paralysis. | 2008 Apr 21 |
|
Muscle channelopathies and electrophysiological approach. | 2008 Jan |
|
Treatment for periodic paralysis. | 2008 Jan 23 |
|
Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited--old leads for new applications? | 2008 Jul 21 |
|
Acetazolamide prevents vacuolar myopathy in skeletal muscle of K(+) -depleted rats. | 2008 May |
|
Treatment of neuromuscular channelopathies: current concepts and future prospects. | 2008 Oct |
|
QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme XIV with sulfonamides using PRECLAV software. | 2009 Apr |
|
Molecular cloning, characterization, and inhibition studies of the Rv1284 beta-carbonic anhydrase from Mycobacterium tuberculosis with sulfonamides and a sulfamate. | 2009 Apr 23 |
|
Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. | 2009 Jul 15 |
|
Biodegradable fumarate-based drug-delivery systems for ophthalmic applications. | 2009 Mar 15 |
|
Carbonic anhydrase inhibitors. Cloning, characterization, and inhibition studies of a new beta-carbonic anhydrase from Mycobacterium tuberculosis. | 2009 May 14 |
|
Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy. | 2009 Nov 1 |
|
Increased expression of carbonic anhydrase I in the synovium of patients with ankylosing spondylitis. | 2010 Dec 8 |
Substance Class |
Chemical
Created
by
admin
on
Edited
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by
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on
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Record UNII |
VVJ6673MHY
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175517
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WHO-ATC |
S01EC02
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EU-Orphan Drug |
EU/3/16/1677
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FDA ORPHAN DRUG |
314210
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NCI_THESAURUS |
C29577
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WHO-VATC |
QS01EC02
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NCI_THESAURUS |
C47796
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SUB07093MIG
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DB01144
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3353
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m4357
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3038
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DICLOFENAMIDE
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CHEMBL17
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100000082917
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639
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |