Acetohydroxamic acid

Identification

Summary

Acetohydroxamic acid is a synthetic urea derivative used to treat urea splitting bacterial infections of the urinary tract.

Brand Names
Lithostat
Generic Name
Acetohydroxamic acid
DrugBank Accession Number
DB00551
Background

Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly. It is used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 75.0666
Monoisotopic: 75.032028409
Chemical Formula
C2H5NO2
Synonyms
  • Acethydroxamsaeure
  • Acetic acid, oxime
  • Acetohydroxamate
  • Acetohydroxamic acid
  • Acetohydroximic acid
  • Acetyl hydroxyamino
  • Acetylhydroxamic acid
  • Acide acetohydroxamique
  • Acido acetohidroxamico
  • Acidum acetohydroxamicum
  • AHA
  • Cetohyroxamic acid
  • Methylhydroxamic acid
  • N-Acetyl hydroxyacetamide
  • N-Acetylhydroxylamine
  • N-Hydroxyacetamide

Pharmacology

Indication

Used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.

Pharmacology
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Associated Conditions
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Contraindications
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Pharmacodynamics

Acetohydroxamic Acid, a synthetic drug derived from hydroxylamine and ethyl acetate, is similar in structure to urea. In the urine, it acts as an antagonist of the bacterial enzyme urease. Acetohydroxamic Acid has no direct antimicrobial action and does not acidify urine directly.

Mechanism of action

Acetohydroxamic Acid reversibly inhibits the bacterial enzyme urease. This inhibits the hydrolysis of urea and production of ammonia in urine infected with urea-splitting organisms, leading to a decrease in pH and ammonia levels. As antimicrobial agents are more effective in such conditions, the effectiveness of these agents is amplified, resulting in a higher cure rate.

TargetActionsOrganism
AUrease subunit alpha
inhibitor
Enterobacter aerogenes
UMacrophage metalloelastase
inhibitor
Humans
Absorption

Well absorbed from the GI tract following oral administration.

Volume of distribution

Not Available

Protein binding

No known binding

Metabolism

35-65% of oral dose excreted unchanged in urine (which provides the drug's therapeutic effect).

Route of elimination

Not Available

Half-life

5-10 hours in patients with normal renal function

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Oral, rat: LD50 = 4.8gm/kg. Symptoms of overdose include anorexia, malaise, lethargy, diminished sense of wellbeing, tremor, anxiety, nausea, and vomiting.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
EthanolThe risk or severity of rash can be increased when Ethanol is combined with Acetohydroxamic acid.
Interactions
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Food Interactions
  • Avoid alcohol. Concomitant use of acetohydroxamic acid with alcohol may cause a rash.
  • Avoid iron supplements. Acetohydroxamic acid chelates iron, therefore oral supplementation of iron will reduce levels of both iron and acetohydroxamic acid.
  • Take on an empty stomach.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LithostatTablet250 mg/1OralMission Pharmacal Company1983-05-31Not applicableUS flag

Categories

ATC Codes
G04BX03 — Acetohydroxamic acid
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as acetohydroxamic acids. These are organic compounds that contain a hydroxamic acid group carrying a methyl group attached to its carbon center.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Carboxylic acid derivatives
Direct Parent
Acetohydroxamic acids
Alternative Parents
Acetamides / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Acetamide / Acetohydroxamic acid / Aliphatic acyclic compound / Carbonyl group / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organonitrogen compound / Organooxygen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
carbohydroximic acid (CHEBI:49029)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
4RZ82L2GY5
CAS number
546-88-3
InChI Key
RRUDCFGSUDOHDG-UHFFFAOYSA-N
InChI
InChI=1S/C2H5NO2/c1-2(4)3-5/h5H,1H3,(H,3,4)
IUPAC Name
N-hydroxyacetamide
SMILES
CC(=O)NO

References

Synthesis Reference

Teresio Tamietto, "Process for the preparation of an indole-3-acetohydroxamic acid." U.S. Patent US4186133, issued November, 1971.

US4186133
General References
  1. Link [Link]
Human Metabolome Database
HMDB0014691
KEGG Drug
D00220
KEGG Compound
C06808
PubChem Compound
1990
PubChem Substance
46508546
ChemSpider
1913
BindingDB
50099857
RxNav
16728
ChEBI
49029
ChEMBL
CHEMBL734
ZINC
ZINC000004658603
Therapeutic Targets Database
DAP001277
PharmGKB
PA164749213
PDBe Ligand
HAE
Drugs.com
Drugs.com Drug Page
Wikipedia
Acetohydroxamic_acid
PDB Entries
1am6 / 1e9y / 1fwe / 1os2 / 1utt / 1utz / 1y93 / 2hu6 / 2ow9 / 2ozr
show 19 more
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2Not Yet RecruitingTreatmentArgininosuccinate Synthetase Deficiency (Citrullinemia) / Argininosuccinic Acid Lyase Deficiency (Argininosuccinic Aciduria) / Carbamyl-Phosphate Synthase I Deficiency / Ornithine Transcarbamylase Deficiency1
1, 2TerminatedTreatmentDeficiencies in enzymes of the urea cycle1

Pharmacoeconomics

Manufacturers
  • Mission pharmacal co
Packagers
  • Mission Pharmacal
Dosage Forms
FormRouteStrength
SolutionAuricular (otic)3 mg
SolutionParenteral200 mg
InjectionIntravenous0.1 g
SolutionParenteral100 mg
SolutionParenteral10 mg
SolutionIntravenous10 mg
SolutionIntravenous100 mg
TabletOral250 mg/1
SolutionIntravenous200 mg
Prices
Unit descriptionCostUnit
Lithostat 250 mg tablet1.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)90.5 °CPhysProp
water solubility1E+006 mg/LNot Available
logP-1.59HANSCH,C ET AL. (1995)
pKa8.7 (at 25 °C)SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
PropertyValueSource
Water Solubility509.0 mg/mLALOGPS
logP-1.5ALOGPS
logP-1ChemAxon
logS0.83ALOGPS
pKa (Strongest Acidic)8.94ChemAxon
pKa (Strongest Basic)-5.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area49.33 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity16.23 m3·mol-1ChemAxon
Polarizability6.6 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9856
Blood Brain Barrier+0.9906
Caco-2 permeable-0.5723
P-glycoprotein substrateNon-substrate0.8815
P-glycoprotein inhibitor INon-inhibitor0.9466
P-glycoprotein inhibitor IINon-inhibitor0.9824
Renal organic cation transporterNon-inhibitor0.9583
CYP450 2C9 substrateNon-substrate0.8167
CYP450 2D6 substrateNon-substrate0.8386
CYP450 3A4 substrateNon-substrate0.6646
CYP450 1A2 substrateNon-inhibitor0.912
CYP450 2C9 inhibitorNon-inhibitor0.9364
CYP450 2D6 inhibitorNon-inhibitor0.91
CYP450 2C19 inhibitorNon-inhibitor0.9083
CYP450 3A4 inhibitorNon-inhibitor0.9757
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9735
Ames testAMES toxic0.9108
CarcinogenicityCarcinogens 0.5892
BiodegradationNot ready biodegradable0.6152
Rat acute toxicity1.5791 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9935
hERG inhibition (predictor II)Non-inhibitor0.9644
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.83 KB)
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

Targets

Drugtargets2
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Kind
Protein
Organism
Enterobacter aerogenes
Pharmacological action
Yes
Actions
Inhibitor
General Function
Urease activity
Specific Function
Not Available
Gene Name
ureC
Uniprot ID
P18314
Uniprot Name
Urease subunit alpha
Molecular Weight
60304.12 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. [Article]
  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. [Article]
  3. Palinska KA, Jahns T, Rippka R, Tandeau De Marsac N: Prochlorococcus marinus strain PCC 9511, a picoplanktonic cyanobacterium, synthesizes the smallest urease. Microbiology. 2000 Dec;146 Pt 12:3099-107. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydropho...
Gene Name
MMP12
Uniprot ID
P39900
Uniprot Name
Macrophage metalloelastase
Molecular Weight
54001.175 Da
References
  1. Mannino C, Nievo M, Machetti F, Papakyriakou A, Calderone V, Fragai M, Guarna A: Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors. Bioorg Med Chem. 2006 Nov 15;14(22):7392-403. Epub 2006 Aug 8. [Article]
  2. Bertini I, Calderone V, Cosenza M, Fragai M, Lee YM, Luchinat C, Mangani S, Terni B, Turano P: Conformational variability of matrix metalloproteinases: beyond a single 3D structure. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5334-9. Epub 2005 Apr 4. [Article]
  3. Bertini I, Calderone V, Fragai M, Giachetti A, Loconte M, Luchinat C, Maletta M, Nativi C, Yeo KJ: Exploring the subtleties of drug-receptor interactions: the case of matrix metalloproteinases. J Am Chem Soc. 2007 Mar 7;129(9):2466-75. Epub 2007 Feb 2. [Article]
  4. Fukuda M, Peppas NA, McGinity JW: Floating hot-melt extruded tablets for gastroretentive controlled drug release system. J Control Release. 2006 Oct 10;115(2):121-9. Epub 2006 Jul 21. [Article]

Drug created on June 13, 2005 13:24 / Updated on August 07, 2021 00:25