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Identification
NameAcetohydroxamic Acid
Accession NumberDB00551  (APRD00774, EXPT01688)
TypeSmall Molecule
GroupsApproved
Description

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.

Structure
Thumb
Synonyms
Acethydroxamsaeure
Acethydroxamsaure
Acetic acid, oxime
Acetohydroxamate
Acetohydroxamic acid
Acetohydroximic acid
Acetyl hydroxyamino
Acetylhydroxamic acid
Acide acetohydroxamique
Acido acetohidroxamico
Acidum acetohydroxamicum
AHA
Cetohyroxamic acid
Lithostat
Methylhydroxamic acid
N-Acetyl hydroxyacetamide
N-Acetylhydroxylamine
N-Hydroxyacetamide
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Lithostattablet250 mg/1oralMission Pharmacal Company1983-05-312016-04-23Us
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII4RZ82L2GY5
CAS number546-88-3
WeightAverage: 75.0666
Monoisotopic: 75.032028409
Chemical FormulaC2H5NO2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassCarboxylic acid derivatives
Direct ParentAcetohydroxamic acids
Alternative Parents
Substituents
  • Acetohydroxamic acid
  • Acetamide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationUsed, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.
PharmacodynamicsAcetohydroxamic 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 actionAcetohydroxamic 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.
Related Articles
AbsorptionWell absorbed from the GI tract following oral administration.
Volume of distributionNot Available
Protein bindingNo known binding
Metabolism

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

Route of eliminationNot Available
Half life5-10 hours in patients with normal renal function
ClearanceNot Available
ToxicityOral, rat: LD50 = 4.8gm/kg. Symptoms of overdose include anorexia, malaise, lethargy, diminished sense of wellbeing, tremor, anxiety, nausea, and vomiting.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Mission pharmacal co
Packagers
Dosage forms
FormRouteStrength
Tabletoral250 mg/1
Prices
Unit descriptionCostUnit
Lithostat 250 mg tablet1.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point90.5 °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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (7.83 KB)
SpectraNot Available
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]
External Links
ATC CodesG04BX03
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (74 KB)
Interactions
Drug Interactions
Drug
EthanolThe risk or severity of adverse effects can be increased when Ethanol is combined with Acetohydroxamic Acid.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Enterobacter aerogenes
Pharmacological action
yes
Actions
inhibitor
General Function:
Urease activity
Specific Function:
Not Available
Gene Name:
ureC
Uniprot ID:
P18314
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. [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. 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. [PubMed:11101668 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
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 hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
Gene Name:
MMP12
Uniprot ID:
P39900
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. [PubMed:16899369 ]
  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. [PubMed:15809432 ]
  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. [PubMed:17269766 ]
  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. [PubMed:16959356 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11