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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:50 UTC
Update Date2020-02-26 21:40:17 UTC
HMDB IDHMDB0014753
Secondary Accession Numbers
  • HMDB14753
Metabolite Identification
Common NameRifabutin
DescriptionRifabutin belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides. Of the five metabolites that have been identified, 25-O-desacetyl and 31-hydroxy are the most predominant. Rifabutin is a very strong basic compound (based on its pKa). Rifabutin is a potentially toxic compound. The former metabolite has an activity equal to the parent drug and contributes up to 10% to the total antimicrobial activity. Clinical experience with rifamycins suggests that gastric lavage to evacuate gastric contents (within a few hours of overdose), followed by instillation of an activated charcoal slurry into the stomach, may help absorb any remaining drug from the gastrointestinal tract. Rifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%. About 30% of the dose is excreted in the feces.
Structure
Data?1582753217
SynonymsNot Available
Chemical FormulaC46H62N4O11
Average Molecular Weight847.0047
Monoisotopic Molecular Weight846.441508846
IUPAC Name(7S,9Z,11S,12R,13S,14R,15R,16R,17S,18S,19Z,21Z)-2,15,17,23-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,32-dioxo-8,33-dioxa-24,27,29-triazaspiro[pentacyclo[23.6.1.1^{4,7}.0^{5,31}.0^{26,30}]tritriacontane-28,4'-piperidine]-1(31),2,4,9,19,21,23,25,29-nonaen-13-yl acetate
Traditional Name(7S,9Z,11S,12R,13S,14R,15R,16R,17S,18S,19Z,21Z)-2,15,17,23-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-1'-(2-methylpropyl)-6,32-dioxo-8,33-dioxa-24,27,29-triazaspiro[pentacyclo[23.6.1.1^{4,7}.0^{5,31}.0^{26,30}]tritriacontane-28,4'-piperidine]-1(31),2,4,9,19,21,23,25,29-nonaen-13-yl acetate
CAS Registry Number72559-06-9
SMILES
[H]\C1=C([H])\[C@]([H])(OC)[C@@]([H])(C)[C@@]([H])(OC(C)=O)[C@]([H])(C)[C@]([H])(O)[C@]([H])(C)[C@@]([H])(O)[C@@]([H])(C)\C([H])=C(\[H])/C(/[H])=C(C)\C(O)=NC2=C3NC4(CCN(CC(C)C)CC4)N=C3C3=C(C(O)=C(C)C4=C3C(=O)[C@](C)(O4)O1)C2=O
InChI Identifier
InChI=1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12-,20-15-,24-14-/t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1
InChI KeyATEBXHFBFRCZMA-DVAZEERGSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolactams
Sub ClassNot Available
Direct ParentMacrolactams
Alternative Parents
Substituents
  • Naphthofuran
  • Macrolactam
  • Azaspirodecane
  • Naphthalene
  • Benzofuran
  • Coumaran
  • Aryl ketone
  • Aryl alkyl ketone
  • Ketal
  • Piperidine
  • Benzenoid
  • 3-imidazoline
  • Vinylogous amide
  • Vinylogous acid
  • Lactam
  • Ketimine
  • Amino acid or derivatives
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxylic acid ester
  • Ketone
  • Carboxamide group
  • Secondary alcohol
  • Acetal
  • Carboxylic acid derivative
  • Dialkyl ether
  • Secondary aliphatic amine
  • Enamine
  • Ether
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Monocarboxylic acid or derivatives
  • Polyol
  • Secondary amine
  • Organic oxygen compound
  • Organopnictogen compound
  • Imine
  • Carbonyl group
  • Organic oxide
  • Alcohol
  • Hydrocarbon derivative
  • Amine
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
Physiological effect

Health effect:

Disposition

Source:

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.017 g/LNot Available
LogP4.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.017 g/LALOGPS
logP4.31ALOGPS
logP3.44ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)5.29ChemAxon
pKa (Strongest Basic)7.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area209.04 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity233.17 m³·mol⁻¹ChemAxon
Polarizability91.1 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-06vi-2000000290-b6c2e05a4e08c21c8009Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-8000002970-8db040b5d2c5d1c7f870Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9000003500-61568975d849f4e01490Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-1000000390-013052b1c69581676709Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0kbs-2000000790-222783e8f7fc477df855Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000m-3000001910-593444223c16d943f93eSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00615 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00615 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRifabutin
METLIN IDNot Available
PubChem Compound46783538
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Ekins S, Bravi G, Wikel JH, Wrighton SA: Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates. J Pharmacol Exp Ther. 1999 Oct;291(1):424-33. [PubMed:10490933 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
General function:
Involved in ATP binding
Specific function:
Molecular chaperone. Has ATPase activity
Gene Name:
HSP90AA1
Uniprot ID:
P07900
Molecular weight:
84659.0
References
  1. Schnaider T, Somogyi J, Csermely P, Szamel M: The Hsp90-specific inhibitor geldanamycin selectively disrupts kinase-mediated signaling events of T-lymphocyte activation. Cell Stress Chaperones. 2000 Jan;5(1):52-61. [PubMed:10701840 ]
  2. Neckers L, Schulte TW, Mimnaugh E: Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity. Invest New Drugs. 1999;17(4):361-73. [PubMed:10759403 ]
  3. Srethapakdi M, Liu F, Tavorath R, Rosen N: Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product-dependent G1 arrest. Cancer Res. 2000 Jul 15;60(14):3940-6. [PubMed:10919672 ]
  4. Munster PN, Srethapakdi M, Moasser MM, Rosen N: Inhibition of heat shock protein 90 function by ansamycins causes the morphological and functional differentiation of breast cancer cells. Cancer Res. 2001 Apr 1;61(7):2945-52. [PubMed:11306472 ]
  5. Yang J, Yang JM, Iannone M, Shih WJ, Lin Y, Hait WN: Disruption of the EF-2 kinase/Hsp90 protein complex: a possible mechanism to inhibit glioblastoma by geldanamycin. Cancer Res. 2001 May 15;61(10):4010-6. [PubMed:11358819 ]