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Identification
NameAminosalicylic Acid
Accession NumberDB00233  (APRD00749, EXPT00693)
TypeSmall Molecule
GroupsApproved
Description

An antitubercular agent often administered in association with isoniazid. The sodium salt of the drug is better tolerated than the free acid. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-HYDROXY-4-aminobenzoic acidNot AvailableNot Available
4-aminosalicylateNot AvailableNot Available
4-aminosalicylic acidNot AvailableNot Available
Aminosalicylic acidNot AvailableNot Available
p-aminosalicylic acidNot AvailableNot Available
para-amino salicylic acidNot AvailableNot Available
para-aminosalicylic acidNot AvailableNot Available
PASNot AvailableNot Available
PaserNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pasergranule, delayed release4 goralJacobus Pharmaceutical Company, Inc.1995-02-15Not AvailableUs
Over the Counter ProductsNot Available
International Brands
NameCompany
PamisylParke-Davis
RexipasBristol-Myers Squibb
RezipasBristol-Myers Squibb
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Aminosalicylate Sodium
Thumb
  • InChI Key: FVVDKUPCWXUVNP-UHFFFAOYSA-M
  • Monoisotopic Mass: 175.024537738
  • Average Mass: 175.1172
DBSALT000354
Categories
CAS number65-49-6
WeightAverage: 153.1354
Monoisotopic: 153.042593095
Chemical FormulaC7H7NO3
InChI KeyWUBBRNOQWQTFEX-UHFFFAOYSA-N
InChI
InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)
IUPAC Name
4-amino-2-hydroxybenzoic acid
SMILES
NC1=CC(O)=C(C=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminosalicylic acids. These are salicylic acids carrying an amino group on the benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentAminosalicylic acids
Alternative Parents
Substituents
  • Aminosalicylic acid
  • Salicylic acid
  • Aminobenzoic acid or derivatives
  • Aminobenzoic acid
  • Benzoic acid
  • Substituted aniline
  • Benzoyl
  • Aminophenol
  • Phenol
  • Aniline
  • Primary aromatic amine
  • Vinylogous acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of tuberculosis
PharmacodynamicsAminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.
Mechanism of actionThere are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding50-60%
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityLD50=4 gm/kg (orally in mice); LD50=3650 mg/kg (orally in rabbits)
Affected organisms
  • Mycobacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9356
Blood Brain Barrier-0.7101
Caco-2 permeable-0.852
P-glycoprotein substrateNon-substrate0.8405
P-glycoprotein inhibitor INon-inhibitor0.9777
P-glycoprotein inhibitor IINon-inhibitor0.9905
Renal organic cation transporterNon-inhibitor0.9337
CYP450 2C9 substrateNon-substrate0.8174
CYP450 2D6 substrateNon-substrate0.8358
CYP450 3A4 substrateNon-substrate0.7782
CYP450 1A2 substrateNon-inhibitor0.8645
CYP450 2C9 substrateNon-inhibitor0.8281
CYP450 2D6 substrateNon-inhibitor0.9627
CYP450 2C19 substrateInhibitor0.5778
CYP450 3A4 substrateNon-inhibitor0.7324
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9157
Ames testNon AMES toxic0.9388
CarcinogenicityNon-carcinogens0.8045
BiodegradationReady biodegradable0.6246
Rat acute toxicity1.5761 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9689
hERG inhibition (predictor II)Non-inhibitor0.9676
Pharmacoeconomics
Manufacturers
  • Century pharmaceuticals inc
  • Hexcel chemical products
  • Panray corp sub ormont drug and chemical co inc
  • Lannett co inc
  • Consolidated midland corp
  • Jacobus pharmaceutical co
  • Bristol myers squibb co
Packagers
Dosage forms
FormRouteStrength
Granule, delayed releaseoral4 g
Prices
Unit descriptionCostUnit
Paser granules 4 gm packet3.59USD packet
Aminosalicylic acid powder2.4USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point150.5 dec °CPhysProp
water solubility1690 mg/L (at 23 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.89SANGSTER (1994)
pKa2.05 (at 25 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
Water Solubility11.8 mg/mLALOGPS
logP0.62ALOGPS
logP0.83ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)2.19ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area83.55 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity40 m3·mol-1ChemAxon
Polarizability14.29 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.18 KB)
SpectraNot Available
References
Synthesis Reference

Thomas M. Parkinson, Joseph P. Brown, Robert E. Wingard, Jr., “Pharmaceutical preparations containing a polymeric agent for releasing 5-aminosalicylic acid or its salts into the gastrointestinal tract.” U.S. Patent US4298595, issued January, 1975.

US4298595
General ReferenceNot Available
External Links
ATC CodesJ04AA01
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (73.6 KB)
Interactions
Drug Interactions
Drug
AzathioprineAminosalicylic acid may increase the toxicity of thiopurine, azathioprine.
MercaptopurineAminosalicylic acid may increase the toxicity of thiopurine, mercaptopurine.
SulindacRisk of additive toxicity (e.g. bleed risk). Aminosalicylic acid may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
Tiaprofenic acidIncreased risk of gastrointestinal bleeding.
TioguanineAminosalicylic acid may increase the toxicity of thiopurine, thioguanine.
TolmetinAdditive effects increase the risk of GI bleeding. Monitor for increased bleeding risk during concomitant therapy.
TrandolaprilThe salicylate, Aminosalicylic acid, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Aminosalicylic acid is initiated, discontinued or dose changed.
TreprostinilThe prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the salicylate, Aminosalicylic acid. Monitor for increased bleeding during concomitant thearpy.
WarfarinThe antiplatelet effects of aminosalicylic acid may increase the bleed risk associated with warfarin.
Food Interactions
  • Take without regard to meals.

Targets

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Mifflin RC, Saada JI, Di Mari JF, Valentich JD, Adegboyega PA, Powell DW: Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8. Pubmed
  2. Generini S, Fiori G, Matucci Cerinic M: Therapy of spondylarthropathy in inflammatory bowel disease. Clin Exp Rheumatol. 2002 Nov-Dec;20(6 Suppl 28):S88-94. Pubmed
  3. Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Russo G, Caliendo G, Santagada V, Cirino G, Wallace JL, Fiorucci S: 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. J Pharmacol Exp Ther. 2006 Oct;319(1):447-58. Epub 2006 Jul 19. Pubmed
  4. Cipolla G, Crema F, Sacco S, Moro E, de Ponti F, Frigo G: Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res. 2002 Jul;46(1):1-6. Pubmed
  5. Pruzanski W, Stefanski E, Vadas P, Ramamurthy NS: Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity. Biochem Pharmacol. 1997 Jun 15;53(12):1901-7. Pubmed

2. Inhibitor of nuclear factor kappa-B kinase subunit alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Inhibitor of nuclear factor kappa-B kinase subunit alpha O15111 Details

References:

  1. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000 Dec;95(12):3452-7. Pubmed
  2. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. Pubmed
  3. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM: Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000 Nov;119(5):1209-18. Pubmed

3. Arachidonate 5-lipoxygenase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Arachidonate 5-lipoxygenase P09917 Details

References:

  1. Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci. 1987 Jun;32(6):577-82. Pubmed
  2. Allgayer H, Eisenburg J, Paumgartner G: Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine. Eur J Clin Pharmacol. 1984;26(4):449-51. Pubmed
  3. Sircar JC, Schwender CF, Carethers ME: Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983 Jan 1;32(1):170-2. Pubmed

4. Group IIE secretory phospholipase A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
Group IIE secretory phospholipase A2 Q9NZK7 Details

References:

  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

5. 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase

Kind: protein

Organism: Mycobacterium tuberculosis

Pharmacological action: unknown

Actions: unknown

Components

Name UniProt ID Details
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase P64143 Details

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

Enzymes

1. Myeloperoxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Myeloperoxidase P05164 Details

References:

  1. von Ritter C, Grisham MB, Granger DN: Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum. Gastroenterology. 1989 Mar;96(3):811-6. Pubmed
  2. Gorgulu S, Yagci G, Kaymakcioglu N, Ozkara M, Kurt B, Ozcan A, Kaya O, Sadir S, Tufan T: Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats. Dig Dis Sci. 2006 Mar;51(3):480-7. Pubmed]

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08