(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.14,7.05,35.026,34.027,32]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34),28,30,32-undecaen-13-yl acetate

• ChemBase ID: 1090
• Molecular Formular: C43H51N3O11
• Molecular Mass: 785.87854
• Monoisotopic Mass: 785.35235947
• SMILES: [C@@H]1([C@@H]([C@H](OC(=O)C)[C@H]([C@@H](OC)/C=C/O[C@]2(Oc3c(c(c4c(c(NC(=O)/C(=C\C=C\[C@@H]([C@H](O)[C@H]1C)C)/C)c1c(c4c3C2=O)nc2n1ccc(c2)C)O)O)C)C)C)C)O
• Canonical SMILES: CO[C@H]1/C=C/O[C@@]2(C)Oc3c(C2=O)c2c(c(c3C)O)c(O)c(c3c2nc2n3ccc(c2)C)NC(=O)/C(=C\C=C\[C@@H]([C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@H]1C)OC(=O)C)C)O)C)O)C)/C
• InChI: InChI=1S/C43H51N3O11/c1-19-14-16-46-28(18-19)44-32-29-30-37(50)25(7)40-31(29)41(52)43(9,57-40)55-17-15-27(54-10)22(4)39(56-26(8)47)24(6)36(49)23(5)35(48)20(2)12-11-13-21(3)42(53)45-33(34(32)46)38(30)51/h11-18,20,22-24,27,35-36,39,48-51H,1-10H3,(H,45,53)/b12-11+,17-15+,21-13-/t20-,22+,23+,24+,27-,35-,36+,39+,43-/m0/s1
• InChIKey: NZCRJKRKKOLAOJ-XRCRFVBUSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1^4,^7.0^5,^3^5.0^2^6,^3^4.0^2^7,^3^2]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34),28,30,32-undecaen-13-yl acetate; (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1^{4,7}.0^{5,35}.0^{26,34}.0^{27,32}]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34),28,30,32-undecaen-13-yl acetate
• IUPAC Traditional name: rifaximin; @rifaximin; (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1^4,^7.0^5,^3^5.0^2^6,^3^4.0^2^7,^3^2]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34),28,30,32-undecaen-13-yl acetate
• Brand Name: Fatroximin; Normix; Rifacol; Ritacol; Xifaxan
• Synonyms: (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,36-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23-dioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1^{4,7}.0^{5,35}.0^{26,34}.0^ {27,32}]heptatriaconta-1,3,5(35),9,19,21,25(36),26(34), 28,30,32-undecaen-13-yl acetate; Rifaximin [USAN:INN]; Rifaximina [Spanish]; Rifaximine [French]; Rifaximinum [Latin]; Rifamycin L 105; Rifamycin L 105SV; Rifamixin; Rifaxidin; rifaximin; Rifaximin; Xifaxan; Rifacol; Fatroximin; 4-Deoxy-4’-methylpyridol[1’,2’-1,2]imidazo[5,4-c]rifamycin SV; L-105; Normix; Rifaximin

Database IDs

• CAS Number: 80621-81-4
• PubChem SID: 46508705; 160964553
• PubChem CID: 6436173

CALCULATED PROPERTIES

JChem

• Acid pKa: 6.0116086
• H Acceptors: 11
• H Donor: 5
• LogD (pH = 5.5): 4.1706524
• LogD (pH = 7.4): 3.8784153
• Log P: 4.372091
• Molar Refractivity: 216.6926 cm^3
• Polarizability: 84.08042 Å^3
• Polar Surface Area: 198.38 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.94
• LOG S: -5.03
• Solubility (Water): 7.38e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform
• Apperance: Red Solid
• Melting Point: >102°C (dec.)
• Hydrophobicity(logP): 2.6

Safety Information

• Storage Condition: -20°C; Hygroscopic, -20°C Freezer, Under inert atmosphere

Pharmacology Properties

• Mechanism of Action: Inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase

Product Information

• Salt Data: Free Base
• Application(s): Antibacterial agent; Antibiotic

DETAILS

DrugBank - DB01220

• Drug Groups: approved; investigational
• Description: Rifaximin is a semisynthetic, rifamycin-based non-systemic antibiotic, meaning that the drug will not pass the gastrointestinal wall into the circulation as is common for other types of orally administered antibiotics. It is used to treat diarrhea caused by E. coli.
• Indication: For the treatment of patients (≥12 years of age) with travelers' diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin is also designated an orphan drug by the Food and Drug Administration for the adjunctive treatment of hepatic encephalopathy to reduce blood ammonia concentrations and decrease severity of neurological manifestations.
• Pharmacology: Rifaximin is a structural analog of rifampin and a non-systemic, gastrointestinal site-specific antibiotic. This non-systemic property of the drug is due to the addition of a pyridoimidazole ring, which renders it non-absorbable. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis and contributes to restore intestinal microflora imbalance. Other studies have also shown rifaximin to be an pregnane X receptor (PXR) activator. As PXR is responsible for inhibiting the proinflammatory transcription factor NF-kappa B (NF-κB) and is inhibited in inflammatory bowel disease (IBD), rifaximin may prove to be effective for the treatment of IBD.
• Toxicity: LD₅₀ > 2 g/kg (orally, in rats)
• Affected Organisms: Enteric bacteria and other eubacteria
• Biotransformation: In vitro drug interactions studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/mL, did not inhibit human hepatic cytochrome P450 isoenzymes: 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4. In an in vitro hepa-tocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4), an isoenzyme which rifampin is known to induce.
• Absorption: Low absorption in both the fasting state and when administered within 30 minutes of a high-fat breakfast.
• Half Life: Approximately 6 hours.
• Elimination: In a mass balance study, after administration of 400 mg 14C-rifaximin orally to healthy volunteers, of the 96.94% total recovery, 96.62% of the administered radioactivity was recovered in feces almost exclusively as the unchanged drug and 0.32% was recovered in urine mostly as metabolites with 0.03% as the unchanged drug.Rifaximin accounted for 18% of radioactivity in plasma. This suggests that the absorbed rifaximin undergoes metabolism with minimal renal excretion of the unchanged drug
• References: Cottreau J, Baker SF, DuPont HL, Garey KW: Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections. Expert Rev Anti Infect Ther. 2010 Jul;8(7):747-60. [Pubmed] ; Williams R, Bass N: Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety. Rev Gastroenterol Disord. 2005;5 Suppl 1:S10-8. [Pubmed] ; Koo HL, DuPont HL: Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases. Curr Opin Gastroenterol. 2010 Jan;26(1):17-25. [Pubmed] ; Pakyz AL: Rifaximin: a new treatment for travelers' diarrhea. Ann Pharmacother. 2005 Feb;39(2):284-9. Epub 2004 Dec 14. [Pubmed] ; Jalan R: Rifaximin in hepatic encephalopathy: More than just a non-absorbable antibiotic? J Hepatol. 2010 May 31. [Pubmed] ; Lawrence KR, Klee JA: Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy. 2008 Aug;28(8):1019-32. [Pubmed] ; Layer P, Andresen V: Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of travellers' diarrhoea. Aliment Pharmacol Ther. 2010 Jun;31(11):1155-64. Epub 2010 Mar 11. [Pubmed] ; Ojetti V, Lauritano EC, Barbaro F, Migneco A, Ainora ME, Fontana L, Gabrielli M, Gasbarrini A: Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):675-82. [Pubmed] ; Scarpignato C, Pelosini I: Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 Suppl 1:36-66. [Pubmed] ; Gillis JC, Brogden RN: Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs. 1995 Mar;49(3):467-84. [Pubmed] ; Koo HL, Dupont HL, Huang DB: The role of rifaximin in the treatment and chemoprophylaxis of travelers' diarrhea. Ther Clin Risk Manag. 2009;5:841-8. Epub 2009 Nov 2. [Pubmed] ; DuPont HL: Systematic review: prevention of travellers' diarrhoea. Aliment Pharmacol Ther. 2008 May;27(9):741-51. Epub 2008 Feb 14. [Pubmed] ; Romero-Gomez M: Pharmacotherapy of hepatic encephalopathy in cirrhosis. Expert Opin Pharmacother. 2010 Jun;11(8):1317-27. [Pubmed] ; Scarpignato C, Pelosini I: Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13-27. Epub 2006 Feb 8. [Pubmed] ; Pimentel M: Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009 Mar;18(3):349-58. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1790

Research Area: Infection
Biological Activity:
Rifaximin(Xifaxan), an orally administered, semi-synthetic, nonsystemic antibiotic derived from rifamycin SV with antibacterial activity. Rifaximin binds to the beta-subunit of bacterial DNA-dependent RNA polymerase, inhibiting bacterial RNA synthesis and bacterial cell growth. As rifaximin is not well absorbed, its antibacterial activity is largely localized to the gastrointestinal tract. [1]

Toronto Research Chemicals - R509500

Non-absorbable semisynthetic Rifamycin antibiotic.

REFERENCES

• Romero-Gomez M: Pharmacotherapy of hepatic encephalopathy in cirrhosis. Expert Opin Pharmacother. 2010 Jun;11(8):1317-27. Pubmed
• Scarpignato C, Pelosini I: Experimental and clinical pharmacology of rifaximin, a gastrointestinal selective antibiotic. Digestion. 2006;73 Suppl 1:13-27. Epub 2006 Feb 8. Pubmed
• Pimentel M: Review of rifaximin as treatment for SIBO and IBS. Expert Opin Investig Drugs. 2009 Mar;18(3):349-58. Pubmed
• Cottreau J, Baker SF, DuPont HL, Garey KW: Rifaximin: a nonsystemic rifamycin antibiotic for gastrointestinal infections. Expert Rev Anti Infect Ther. 2010 Jul;8(7):747-60. Pubmed
• Williams R, Bass N: Rifaximin, a nonabsorbed oral antibiotic, in the treatment of hepatic encephalopathy: antimicrobial activity, efficacy, and safety. Rev Gastroenterol Disord. 2005;5 Suppl 1:S10-8. Pubmed
• Koo HL, DuPont HL: Rifaximin: a unique gastrointestinal-selective antibiotic for enteric diseases. Curr Opin Gastroenterol. 2010 Jan;26(1):17-25. Pubmed
• Pakyz AL: Rifaximin: a new treatment for travelers' diarrhea. Ann Pharmacother. 2005 Feb;39(2):284-9. Epub 2004 Dec 14. Pubmed
• Jalan R: Rifaximin in hepatic encephalopathy: More than just a non-absorbable antibiotic? J Hepatol. 2010 May 31. Pubmed
• Lawrence KR, Klee JA: Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy. 2008 Aug;28(8):1019-32. Pubmed
• Layer P, Andresen V: Review article: rifaximin, a minimally absorbed oral antibacterial, for the treatment of travellers' diarrhoea. Aliment Pharmacol Ther. 2010 Jun;31(11):1155-64. Epub 2010 Mar 11. Pubmed
• Ojetti V, Lauritano EC, Barbaro F, Migneco A, Ainora ME, Fontana L, Gabrielli M, Gasbarrini A: Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):675-82. Pubmed
• Scarpignato C, Pelosini I: Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 Suppl 1:36-66. Pubmed
• Gillis JC, Brogden RN: Rifaximin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential in conditions mediated by gastrointestinal bacteria. Drugs. 1995 Mar;49(3):467-84. Pubmed
• Koo HL, Dupont HL, Huang DB: The role of rifaximin in the treatment and chemoprophylaxis of travelers' diarrhea. Ther Clin Risk Manag. 2009;5:841-8. Epub 2009 Nov 2. Pubmed
• DuPont HL: Systematic review: prevention of travellers' diarrhoea. Aliment Pharmacol Ther. 2008 May;27(9):741-51. Epub 2008 Feb 14. Pubmed
• http://en.wikipedia.org/wiki/Rifaximin
• Brufani, M., et al.: J. Antibiot., 37, 1611 (1984)
• Gillis, J.C., et al.: Drugs, 49, 467 (1984)
• Huang, D.B., et al.: J. Infection, 50, 97 (1984)
• de Angelis, L., Drugs of the Future, 1982, 7, 260, (rev)
• Brufani, M. et al., J. Antibiot., 1984, 37, 1611, (synth, pmr, pharmacol)
• Marchi, E. et al., J. Med. Chem., 1985, 28, 960, (synth, pharmacol)
• Venturini, A.P. et al., Chemioterapia, 1986, 5, 257; 263, (pharmacol, tox)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 200
• Gillis, J.C. et al., Drugs, 1995, 49, 467, (rev)