Acetohydroxamic acid

Details

Stereochemistry	ACHIRAL
Molecular Formula	C2H5NO2
Molecular Weight	75.0666
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)NO

InChI

InChIKey=RRUDCFGSUDOHDG-UHFFFAOYSA-N

InChI=1S/C2H5NO2/c1-2(4)3-5/h5H,1H3,(H,3,4)

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/cdi/acetohydroxamic-acid.html | https://www.drugbank.ca/drugs/DB00551 | https://www.ncbi.nlm.nih.gov/pubmed/6854890

Acetohydroxamic acid (also known as AHA or by the trade name Lithostat) is 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 is used to lower the level of ammonia in the urine, which may help with some types of urinary infections. 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. In 1983 the US Food and Drug Administration approved acetohydroxamic acid (AHA) as an orphan drug for "prevention of so-called struvite stones" under the newly enacted Orphan Drug Act of 1983.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial urease 4 Target ID: CHEMBL2364683 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8214097\|https://www.ncbi.nlm.nih.gov/pubmed/29913313\|https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6660b616-a82d-9109-19ce-2bdf9747acea#nlm34090-1\|https://www.ncbi.nlm.nih.gov/pubmed/29894891	Inhibitor 8504		27.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
chronic urea-splitting urinary infection 1 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6660b616-a82d-9109-19ce-2bdf9747acea	Palliative		Approved 8583	LITHOSTAT Approved Use Acetohydroxamic acid (AHA) is indicated as adjunctive therapy in patients with chronic urea-splitting urinary infection. AHA is intended to decrease urinary ammonia and alkalinity, but it should not be used in lieu of curative surgical treatment (for patients with stones) or antimicrobial treatment. Long-term treatment with AHA may be warranted to maintain urease inhibition as long as urea-splitting infection is present. Experience with AHA does not go beyond 7 years. A patient package insert should be distributed to each patient who receives AHA. Launch Date 1983

C_max

Value	Dose	Co-administered	Analyte	Population
9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3928387/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		ACETOHYDROXAMIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
21.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3928387/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		ACETOHYDROXAMIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 g 1 times / day multiple, oral Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/	unhealthy, 49 ± 1 Health Status: unhealthy Age Group: 49 ± 1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/	Disc. AE: Anemia, Tremulousness... AEs leading to discontinuation/dose reduction: Anemia Tremulousness Headache Nausea Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/
1.8 g 1 times / day multiple, oral Highest studied dose Dose: 1.8 g, 1 times / day Route: oral Route: multiple Dose: 1.8 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23442/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23442/	Disc. AE: Anemia, Reticulocytosis... AEs leading to discontinuation/dose reduction: Anemia Reticulocytosis Sources: https://pubmed.ncbi.nlm.nih.gov/23442/

AEs

AE	Significance	Dose	Population
Anemia	Disc. AE	1 g 1 times / day multiple, oral Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/	unhealthy, 49 ± 1 Health Status: unhealthy Age Group: 49 ± 1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/
Headache	Disc. AE	1 g 1 times / day multiple, oral Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/	unhealthy, 49 ± 1 Health Status: unhealthy Age Group: 49 ± 1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/
Nausea	Disc. AE	1 g 1 times / day multiple, oral Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/	unhealthy, 49 ± 1 Health Status: unhealthy Age Group: 49 ± 1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/
Tremulousness	Disc. AE	1 g 1 times / day multiple, oral Recommended Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/	unhealthy, 49 ± 1 Health Status: unhealthy Age Group: 49 ± 1 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/3294442/
Anemia	Disc. AE	1.8 g 1 times / day multiple, oral Highest studied dose Dose: 1.8 g, 1 times / day Route: oral Route: multiple Dose: 1.8 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23442/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23442/
Reticulocytosis	Disc. AE	1.8 g 1 times / day multiple, oral Highest studied dose Dose: 1.8 g, 1 times / day Route: oral Route: multiple Dose: 1.8 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23442/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/23442/

PubMed

Title	Date	PubMed
Inhibition of urease by miscellaneous ions and compounds. Implications for the therapy of infection-induced urolithiasis.	1977 Sep	903216
Purification, properties, kinetics, and mechanism of beta-N-acetylglucosamidase from Aspergillus niger.	1980 Dec 25	7440573
Microsome- and hepatocyte-mediated mutagenicity of hydroxyurea and related aliphatic hydroxamic acids in V79 Chinese hamster cells.	1985 Nov-Dec	4069149
Synergistic binding of ligands to angiotensin-converting enzyme.	1988 Mar 25	2831219
Receptor mediated targeting of lectin conjugated gliadin nanoparticles in the treatment of Helicobacter pylori.	2003 Aug	15203930
Jackbean, soybean and Bacillus pasteurii ureases: biological effects unrelated to ureolytic activity.	2004 Apr	15030486
Acetohydroxamate inhibition of the activity of urease from dehusked seeds of water melon (Citrullus vulgaris).	2004 Aug	15558957
Synthesis, antiprotozoal and cytotoxic activities of new N-(3,4-dimethyl-5-isoxazolyl)-1,2-naphthoquinone-4-amino derivatives.	2004 Jun	15178304
Urease-induced alkalinization of extracellular pH and its antitumor activity in human breast and lung cancers.	2005	16475272
Release of iron from ferritin by aceto- and benzohydroxamic acids.	2005 Apr 18	15819556
DFT study of the V(IV)/V(V) oxidation mechanism in the presence of N-hydroxyacetamide.	2005 Aug	16038979
Ternary ligand-zinc-hydroxamate complexes.	2005 Jan 10	15627358
Neutral acetohydroxamic acid coordination to a mononuclear Ni(II) center stabilized by an intramolecular hydrogen-bonding interaction.	2005 Jan 28	15654379
Dimerization of the keto tautomer of acetohydroxamic acid-infrared matrix isolation and theoretical study.	2005 May	15820882
Application of Fourier transform infrared spectroscopy for monitoring hydrolysis and synthesis reactions catalyzed by a recombinant amidase.	2005 Nov 1	16185648
Hard and soft X-ray absorption spectroscopic investigation of aqueous Fe(III)-hydroxamate siderophore complexes.	2005 Nov 17	16833318
Chemistry of a Ni(II) acetohydroxamic acid complex: formation, reactivity with water, and attempted preparation of zinc and cobalt analogues.	2005 Oct 3	16180888
Towards third generation matrix metalloproteinase inhibitors for cancer therapy.	2006 Apr 10	16538215
Alcohol and oxidative liver injury.	2006 Feb	16447273
Pb(II)-binding capability of aminohydroxamic acids: primary hydroxamic acid derivatives of alpha-amino acids as possible sequestering agents for Pb(II).	2006 Jan	16274742
Characterization and optimization of experimental variables within a reproducible bladder encrustation model and in vitro evaluation of the efficacy of urease inhibitors for the prevention of medical device-related encrustation.	2006 Jan	16206254
Heterocyclic zinc-binding groups for use in next-generation matrix metalloproteinase inhibitors: potency, toxicity, and reactivity.	2006 Mar	16391944
A new role for old ligands: discerning chelators for zinc metalloproteinases.	2006 Mar 15	16522091
Synthesis and antibacterial activity of novel oxazolidinones bearing N-hydroxyacetamidine substituent.	2006 May 1	16488606
Di-, tri-, and tetranuclear zinc hydroxamate complexes as structural models for the inhibition of zinc hydrolases by hydroxamic acids.	2006 May 29	16711700
Synthesis of bicyclic molecular scaffolds (BTAa): an investigation towards new selective MMP-12 inhibitors.	2006 Nov 15	16899369
Infrared spectroscopic studies of siderophore-related hydroxamic acid ligands adsorbed on titanium dioxide.	2006 Nov 21	17107007
Floating hot-melt extruded tablets for gastroretentive controlled drug release system.	2006 Oct 10	16959356
Near edge X-ray absorption fine structure spectroscopy of bacterial hydroxamate siderophores in aqueous solutions.	2006 Oct 26	17048812
Interaction of imidazole containing hydroxamic acids with Fe(III): hydroxamate versus imidazole coordination of the ligands.	2007	18274616
Simultaneous Determination of Cobalt(II) and Nickel(II) by Fourth-Order Derivative Spectrophotometric Method Using 2-Hydroxy-3-Methoxy Benzaldehyde Thiosemicarbazone.	2007	17671609
Preparation and in vitro characterization of gellan based floating beads of acetohydroxamic acid for eradication of H. pylori.	2007 Dec	18165186
Vasorelaxant activity of some oxime derivatives.	2007 Dec 1	17706962
Laccase induction in fungi and laccase/N-OH mediator systems applied in paper mill effluent.	2007 Jan	16376074
Spectroscopic study of the uranyl-acetohydroxamate adduct with tributyl phosphate.	2007 Jul	17697472
Exploring the subtleties of drug-receptor interactions: the case of matrix metalloproteinases.	2007 Mar 7	17269766
Jack bean urease: the effect of active-site binding inhibitors on the reactivity of enzyme thiol groups.	2007 Oct	17418881
A membrane associated metalloprotease cleaves Cry3Aa Bacillus thuringiensis toxin reducing pore formation in Colorado potato beetle brush border membrane vesicles.	2007 Sep	17643388
Chelated iron sources are inhibitors of Pseudomonas aeruginosa biofilms and distribute efficiently in an in vitro model of drug delivery to the human lung.	2008 Aug	18284482
Lipoamide dehydrogenase and diaphorase catalyzed conversion of some NO donors to NO and reduction of NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO).	2009 Dec	20097961
The interaction of zinc(II) and hydroxamic acids and a metal-triggered Lossen rearrangement.	2009 Dec 14	19937618
Adsorption of hydroxamate siderophores and EDTA on goethite in the presence of the surfactant sodium dodecyl sulfate.	2009 Jun 13	19523232
Synthesis, molecular docking and biological evaluation of metronidazole derivatives as potent Helicobacter pylori urease inhibitors.	2009 Nov 1	19804978
13[C]-urea breath test as a novel point-of-care biomarker for tuberculosis treatment and diagnosis.	2010 Aug 27	20805989
Synthesis, structures, and urease inhibitory activities of three copper(II) and zinc(II) complexes with 2-{[2-(2-hydroxyethylamino)ethylimino]methyl}-4-nitrophenol.	2010 Jul	20362357
Inhibitors of human histone deacetylase: synthesis and enzyme assay of hydroxamates with piperazine linker.	2010 Mar	20217840
X-ray absorption spectroscopy of aqueous aluminum-organic complexes.	2010 May 27	20443586
Entropic contribution to the linking coefficient in fragment based drug design: a case study.	2010 May 27	20415416
The synthesis, structure and activity evaluation of pyrogallol and catechol derivatives as Helicobacter pylori urease inhibitors.	2010 Nov	20801557
Synthesis, molecular docking and biological evaluation of Schiff base transition metal complexes as potential urease inhibitors.	2010 Oct	20691510

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Urinary Tract Infection Starting dose: 12 mg/kg/day administered at 6 to 8 hour intervals at a time when the stomach is empty. Then progress to one tablet orally 3 to 4 times a day in a total daily dose of 10 to 15 mg/kg/day. The maximum daily dose should be no more than 1.5 grams, regardless of body weight.

Route of Administration: Oral

Name

Type

Language

Acetohydroxamic acid

Official Name

English

LITHOSTAT

Preferred Name

English

NSC-176136

Code

English

N-ACETYL HYDROXYACETAMIDE

Systematic Name

English

ACETOHYDROXAMIC ACID [HSDB]

Common Name

English

ACETOHYDROXAMIC ACID [USAN]

Common Name

English

Acetohydroxamic acid [WHO-DD]

Common Name

English

acetohydroxamic acid [INN]

Common Name

English

ACETOHYDROXAMIC ACID [MI]

Common Name

English

ACETOHYDROXAMIC ACID [USP MONOGRAPH]

Common Name

English

ACETOHYDROXAMIC ACID [USP-RS]

Common Name

English

ACETOHYDROXAMIC ACID [ORANGE BOOK]

Common Name

English

ACETOHYDROXAMIC ACID [MART.]

Common Name

English

N-HYDROXYACETAMIDE

Systematic Name

English

ACETOHYDROXAMIC ACID [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-ATC

G04BX03