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Identification
Name Acetohydroxamic Acid
Accession Number DB00551 (APRD00774, EXPT01688)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Acethydroxamsaure
Acetic acid, oxime
Acetohydroxamate
Acetohydroximic acid
Acetyl hydroxyamino
Acetylhydroxamic acid
AHA
Cetohyroxamic acid
Methylhydroxamic acid
N-Hydroxyacetamide
Salts Not Available
Brand names
Name Company
Lithostat
Brand mixtures Not Available
Categories
  • Enzyme Inhibitors
CAS number 546-88-3
Weight Average: 75.0666
Monoisotopic: 75.032028409
Chemical Formula C2H5NO2
InChI Key InChIKey=RRUDCFGSUDOHDG-UHFFFAOYSA-N
InChI
InChI=1S/C2H5NO2/c1-2(4)3-5/h5H,1H3,(H,3,4)
Plain Text
IUPAC Name
N-hydroxyacetamide
SMILES
CC(=O)NO
Plain Text
Mass Spec show (7.83 KB)
Taxonomy
Kingdom Organic
Classes
  • Amino Ketones
Substructures
  • Hydroxy Compounds
  • Hydroxamic Acids
  • Amino Ketones
  • Carboxamides and Derivatives
Pharmacology
Indication Used, in addition to antibiotics or medical procedures, to treat chronic urea-splitting urinary infections.
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.
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
Toxicity Oral, 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Mission pharmacal co
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Lithostat 250 mg tablet 1.66 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 90.5 °C PhysProp
water solubility 1E+006 mg/L Not Available
logP -1.59 HANSCH,C ET AL. (1995)
pKa 8.7 (at 25 °C) SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
Property Value Source
water solubility 5.09e+02 g/l ALOGPS
logP -1.5 ALOGPS
logP -1 ChemAxon
logS 0.83 ALOGPS
pKa (strongest acidic) 8.94 ChemAxon
pKa (strongest basic) -5.4 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 49.33 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 16.23 ChemAxon
polarizability 6.6 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Link
External Links
Resource Link
KEGG Drug D00220 Link_out
KEGG Compound C06808 Link_out
PubChem Compound 1990 Link_out
PubChem Substance 46508546 Link_out
ChemSpider 1913 Link_out
ChEBI 27777 Link_out
ChEMBL 27777 Link_out
Therapeutic Targets Database DAP001277 Link_out
PharmGKB PA164749213 Link_out
HET HAE Link_out
Drugs.com http://www.drugs.com/cdi/acetohydroxamic-acid.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Acetohydroxamic_acid Link_out
ATC Codes
  • G04BX03
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (74 KB)
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Urease alpha subunit

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P18314 Link_out
Gene: ureC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Macrophage metalloelastase

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P39900 Link_out
Gene: MMP12 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19