Identification

Name
Chlormerodrin
Accession Number
DB00534  (APRD00864)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Chlormerodrin is a mercurial compound with toxic side effects that was previously used as a diuretic. The radiolabeled form has been used as a diagnostic and research tool. It is no longer used and has been replaced with new classes of diuretic drugs.

Structure
Thumb
Synonyms
  • {3-[(aminocarbonyl)amino]-2-methoxypropyl}chloromercury
  • 1-[3-(chloromercuri)-2-methoxypropyl]urea
  • Chlormerodrin
  • Chlormerodrina
  • Chlormerodrine
  • Chlormerodrinum
International/Other Brands
Mercloran (Parke Davis) / Ormerdan (Parke Davis)
Categories
UNII
99T5TWO621
CAS number
62-37-3
Weight
Average: 367.2
Monoisotopic: 368.021530917
Chemical Formula
C5H11ClHgN2O2
InChI Key
BJFGVYCULWBXKF-UHFFFAOYSA-M
InChI
InChI=1S/C5H11N2O2.ClH.Hg/c1-4(9-2)3-7-5(6)8;;/h4H,1,3H2,2H3,(H3,6,7,8);1H;/q;;+1/p-1
IUPAC Name
[3-(chloromercurio)-2-methoxypropyl]urea
SMILES
COC(CNC(N)=O)C[Hg]Cl

Pharmacology

Indication

Previously used as a diuretic. The radiolabeled form has been used as a diagnostic and research tool.

Pharmacodynamics

Chlormerodrin is a mercurial compound with toxic side effects. It is no longer used and has been replaced with new classes of diuretic drugs.

Mechanism of action

Chlormerodrin most likely acts by a direct renal action. Mercurial diuresis is presumed to occur through inhibition of reabsorption of water and electrolytes in the convoluted tubules, although the problem of whether the locus of action is primarily on the proximal or distal portion has not yet been settled. There is also evidence that mercurials interfere with the permeability of the membrane of tubular cells by increasing passive influx of Na+ ion, Cl- ion and water into the cells, without interfering with the active extrusion of Na+ ion. Lastly, there is some evidence that chlormerodrin inhibits succinic dehydrogenase, but the clinical significance of this binding is not known.

TargetActionsOrganism
ASolute carrier family 12 member 1
inducer
Human
USuccinate-semialdehyde dehydrogenase, mitochondrial
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

As chlormerodrin has been shown to increase the levels of mercury in the kidney to toxic levels, any symptoms of overdose will most likely correspond to symptoms experienced in exposure to mercury.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference

Foreman, E.L; U S . Patent 2,635,983; April 21,1953; assigned to Lakeside Laboratories, Inc.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014674
PubChem Compound
25210
PubChem Substance
46504793
ChemSpider
2615
ChEBI
59445
Therapeutic Targets Database
DAP000754
PharmGKB
PA164748977
Wikipedia
Chlormerodrin

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)152.5 °CPhysProp
water solubility1.1E+004 mg/L (at 25 °C)MERCK INDEX (1996)
logP-0.80HALBACH,S (1985)
Predicted Properties
PropertyValueSource
Water Solubility29.2 mg/mLALOGPS
logP-0.5ALOGPS
logP-0.86ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)14.05ChemAxon
pKa (Strongest Basic)-1.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area64.35 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity38.78 m3·mol-1ChemAxon
Polarizability18.42 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9659
Caco-2 permeable-0.5979
P-glycoprotein substrateNon-substrate0.6753
P-glycoprotein inhibitor INon-inhibitor0.899
P-glycoprotein inhibitor IINon-inhibitor0.9662
Renal organic cation transporterNon-inhibitor0.8512
CYP450 2C9 substrateNon-substrate0.7687
CYP450 2D6 substrateNon-substrate0.7764
CYP450 3A4 substrateNon-substrate0.6932
CYP450 1A2 substrateNon-inhibitor0.6985
CYP450 2C9 inhibitorNon-inhibitor0.7286
CYP450 2D6 inhibitorNon-inhibitor0.9078
CYP450 2C19 inhibitorNon-inhibitor0.6618
CYP450 3A4 inhibitorNon-inhibitor0.7519
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8039
Ames testAMES toxic0.5408
CarcinogenicityNon-carcinogens0.6151
BiodegradationNot ready biodegradable0.6354
Rat acute toxicity2.4805 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9194
hERG inhibition (predictor II)Non-inhibitor0.9225
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as isoureas. These are organic compounds containing the isourea group, with the general structure R1N(R2)C(=NR3)OR4, or its hydrocarbyl derivatives (R1,R2,R3,R4=H, alkyl, aryl).
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboximidic acids and derivatives
Sub Class
Carboximidic acids
Direct Parent
Isoureas
Alternative Parents
Organic transition metal salts / Organic metal halides / Dialkyl ethers / Carboximidamides / Organopnictogen compounds / Organic zwitterions / Organic oxides / Imines / Hydrochlorides / Hydrocarbon derivatives
Substituents
Isourea / Dialkyl ether / Ether / Organic metal halide / Carboximidamide / Organic transition metal salt / Organic nitrogen compound / Hydrocarbon derivative / Hydrochloride / Organic salt
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
ureas, organomercury compound (CHEBI:59445)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
General Function
Sodium:potassium:chloride symporter activity
Specific Function
Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
Gene Name
SLC12A1
Uniprot ID
Q13621
Uniprot Name
Solute carrier family 12 member 1
Molecular Weight
121449.13 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Tabern DL, Kearney J, Sohn H: The quantitative measurement of tubular chlormerodrin binding as an index of renal function: a study of 400 cases. Can Med Assoc J. 1970 Sep 26;103(6):601-7. [PubMed:5455277]
  4. Mannuzzu LM, Moronne MM, Macey RI: Estimate of the number of urea transport sites in erythrocyte ghosts using a hydrophobic mercurial. J Membr Biol. 1993 Apr;133(1):85-97. [PubMed:8391582]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Succinate-semialdehyde dehydrogenase [nad(p)+] activity
Specific Function
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Gene Name
ALDH5A1
Uniprot ID
P51649
Uniprot Name
Succinate-semialdehyde dehydrogenase, mitochondrial
Molecular Weight
57214.23 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Oda Y: [Experimental study on renal succinic dehydrogenase. 2. Age differences in renal succinic dehydrogenase in rats administered diuretics]. Nihon Shonika Gakkai Zasshi. 1968 Apr 1;72(4):370-80. [PubMed:5692397]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 05:24