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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2014-06-23 13:37:13 UTC
Update Date2019-07-23 07:17:04 UTC
HMDB IDHMDB0061725
Secondary Accession Numbers
  • HMDB61725
Metabolite Identification
Common NameRilpivirine
DescriptionRilpivirine, also known as TMC 278 or 278, TMC, belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent. Rilpivirine is a very strong basic compound (based on its pKa). Ripivirine treatment produces a significant and effective reduction in the viral load based on the study of HIV-1 RNA copies per ml or immunologic changes by the determination of counts of CD4+ and CD8+ cells. In humans, rilpivirine is involved in rilpivirine action pathway. Mainly hepatically metabolized by CYP3A. Rilpivirine was developed by Tilbotec, Inc. and FDA approved on May 20, 2011. It does not present activity against human DNA polymerases α, β and γ. It did not show any effect on mating or fertility in animal studies. The combinantion therapy (ripivirine and dolutegravir) presented the same viral supression found in previous three-drug therapies without integrase strand transfer inhibitor mutations or rilpivirine resistance. Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. The internal conformational flexibility of rilpivirine and the plasticity of it interacting binding site gives it a very high potency and an unlikely generation of resistance compared to other NNRTI's.
Structure
Data?1563866224
Synonyms
ValueSource
4-{[4-({4-[(e)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrileChEBI
TMC 278ChEBI
TMC278ChEBI
278, TMCHMDB
HCL, RilpivirineHMDB
Rilpivirine HCLHMDB
Rilpivirine hydrochlorideHMDB
Hydrochloride, rilpivirineHMDB
TMC-278HMDB
Chemical FormulaC22H18N6
Average Molecular Weight366.4185
Monoisotopic Molecular Weight366.159294606
IUPAC Name4-{[4-({4-[(1E)-2-cyanoeth-1-en-1-yl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile
Traditional Namerilpivirine
CAS Registry NumberNot Available
SMILES
CC1=CC(\C=C\C#N)=CC(C)=C1NC1=NC(NC2=CC=C(C=C2)C#N)=NC=C1
InChI Identifier
InChI=1S/C22H18N6/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19/h3-9,11-13H,1-2H3,(H2,25,26,27,28)/b4-3+
InChI KeyYIBOMRUWOWDFLG-ONEGZZNKSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzonitriles. These are organic compounds containing a benzene bearing a nitrile substituent.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzonitriles
Direct ParentBenzonitriles
Alternative Parents
Substituents
  • Benzonitrile
  • M-xylene
  • Xylene
  • Styrene
  • Aniline or substituted anilines
  • Aminopyrimidine
  • Hydropyrimidine
  • Pyrimidine
  • Imidolactam
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Nitrile
  • Carbonitrile
  • Organoheterocyclic compound
  • Amine
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateNot Available
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.012 g/LALOGPS
logP3.8ALOGPS
logP5.47ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)12.93ChemAxon
pKa (Strongest Basic)5.16ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area97.42 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity111.74 m³·mol⁻¹ChemAxon
Polarizability40.65 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-0649000000-96980e5526a79d124034Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0109000000-f0ca783d371380bc70e5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-1219000000-e52f83b92e47c660600dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zmj-4920000000-97a3c101caf2d43175bbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0109000000-b3b95eac39ccf546b147Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0629000000-e93c0f34e547e8a4da81Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-2910000000-04ece45ca32dd4273a60Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen LocationsNot Available
Tissue LocationsNot Available
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB08864
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 LinkRilpivirine
METLIN IDNot Available
PubChem Compound6451164
PDB IDNot Available
ChEBI ID68606
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
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  2. Dalton P: Researcher presents vexing information on rilpivirine. Proj Inf Perspect. 2008 Sep;(46):10-2. [PubMed:19048650 ]
  3. Fulco PP, McNicholl IR: Etravirine and rilpivirine: nonnucleoside reverse transcriptase inhibitors with activity against human immunodeficiency virus type 1 strains resistant to previous nonnucleoside agents. Pharmacotherapy. 2009 Mar;29(3):281-94. doi: 10.1592/phco.29.3.281. [PubMed:19249947 ]
  4. Hughes CA, Robinson L, Tseng A, MacArthur RD: New antiretroviral drugs: a review of the efficacy, safety, pharmacokinetics, and resistance profile of tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Expert Opin Pharmacother. 2009 Oct;10(15):2445-66. doi: 10.1517/14656560903176446. [PubMed:19678794 ]
  5. van 't Klooster G, Hoeben E, Borghys H, Looszova A, Bouche MP, van Velsen F, Baert L: Pharmacokinetics and disposition of rilpivirine (TMC278) nanosuspension as a long-acting injectable antiretroviral formulation. Antimicrob Agents Chemother. 2010 May;54(5):2042-50. doi: 10.1128/AAC.01529-09. Epub 2010 Feb 16. [PubMed:20160045 ]
  6. Macarthur RD: Clinical Trial Report: TMC278 (Rilpivirine) Versus Efavirenz as Initial Therapy in Treatment-Naive, HIV-1-Infected Patients. Curr Infect Dis Rep. 2011 Feb;13(1):1-3. doi: 10.1007/s11908-010-0148-6. [PubMed:21308448 ]
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  8. Schrijvers R, Desimmie BA, Debyser Z: Rilpivirine: a step forward in tailored HIV treatment. Lancet. 2011 Jul 16;378(9787):201-3. doi: 10.1016/S0140-6736(11)60992-6. [PubMed:21763920 ]
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  16. Reinheimer C, Doerr HW, Sturmer M: Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database. J Clin Virol. 2012 Mar;53(3):248-50. doi: 10.1016/j.jcv.2011.12.012. Epub 2011 Dec 30. [PubMed:22209291 ]
  17. Hussar DA, Snell CW: Boceprevir, telaprevir, and rilpivirine hydrochloride. J Am Pharm Assoc (2003). 2012 Jan-Feb;52(1):120-6. doi: 10.1331/JAPhA.2012.12506. [PubMed:22257626 ]
  18. Cohen CJ, Molina JM, Cahn P, Clotet B, Fourie J, Grinsztejn B, Wu H, Johnson MA, Saag M, Supparatpinyo K, Crauwels H, Lefebvre E, Rimsky LT, Vanveggel S, Williams P, Boven K: Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials. J Acquir Immune Defic Syndr. 2012 May 1;60(1):33-42. doi: 10.1097/QAI.0b013e31824d006e. [PubMed:22343174 ]
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  20. Diaz-Delfin J, Domingo P, Mateo MG, Gutierrez Mdel M, Domingo JC, Giralt M, Villarroya F: Effects of rilpivirine on human adipocyte differentiation, gene expression, and release of adipokines and cytokines. Antimicrob Agents Chemother. 2012 Jun;56(6):3369-75. doi: 10.1128/AAC.00104-12. Epub 2012 Mar 19. [PubMed:22430974 ]
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  23. O'Neal R: Rilpivirine and complera: new first-line treatment options. BETA. 2011 Fall-Winter;23(4):14-8. [PubMed:22567823 ]
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  25. Burugula L, Pilli NR, Makula A, Lodagala DS, Kandhagatla R: Liquid chromatography-tandem mass spectrometric assay for the non-nucleoside reverse transcriptase inhibitor rilpivirine in human plasma. Biomed Chromatogr. 2013 Feb;27(2):172-8. doi: 10.1002/bmc.2765. Epub 2012 Jun 22. [PubMed:22729755 ]
  26. Anta L, Llibre JM, Poveda E, Blanco JL, Alvarez M, Perez-Elias MJ, Aguilera A, Caballero E, Soriano V, de Mendoza C: Rilpivirine resistance mutations in HIV patients failing non-nucleoside reverse transcriptase inhibitor-based therapies. AIDS. 2013 Jan 2;27(1):81-5. doi: 10.1097/QAD.0b013e3283584500. [PubMed:22842995 ]
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  28. Lyseng-Williamson KA, Scott LJ: Emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen: a guide to its use in HIV-1 infection. Clin Drug Investig. 2012 Oct 1;32(10):715-22. doi: 10.2165/11209870-000000000-00000. [PubMed:22921088 ]
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