Identification
- Generic Name
- Rifalazil
- DrugBank Accession Number
- DB04934
- Background
Rifalazil is a derivative of the antibiotic rifamycin. It is being investigated by ActivBiotics for the treatment of various bacterial infections.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Rifalazil (DB04934)
- Weight
- Average: 941.088
Monoisotopic: 940.446988137 - Chemical Formula
- C51H64N4O13
- Synonyms
- 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin
- Rifalazil
- Rifalazilo
- Rifalazilum
- External IDs
- ABI 1648
- KRM-1648
Pharmacology
- Indication
Investigated for use/treatment in atherosclerosis, bacterial infection, and peripheral vascular disease.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Rifalazil represents a new generation of ansamycins that contain a unique four-ring structure. Originally rifalazil was developed as a therapeutic agent to replace rifampin as part of a multiple drug regimen in the treatment of tuberculosis. As a result of its superior antimicrobial activity and high intracellular levels, rifalazil has potential to treat indications caused by the intracellular pathogen, Chlamydia trachomatis, which causes non-gonococcal urethritis and cervicitis, often leading to pelvic inflammatory disease. Rifalazil also has potential to treat the related microorganism, Chlamydia pneumoniae, which may be involved in chronic inflammatory processes thought to be partly responsible for atherosclerosis. Due to its favourable antimicrobial spectrum and other positive attributes, rifalazil may also prove valuable in the treatment of gastric ulcer disease, caused by Helicobacter pylori, and antibiotic-associated colitis, the result of toxin production following the growth of Clostridium difficile in the colon. The potential value of rifalazil in the treatment of these indications will be assessed in human clinical trials.
- Mechanism of action
The potent antimycobacterial activity of rifalazil is due to inhibition of bacterial RNA polymerase.
Target Actions Organism UDNA-directed RNA polymerase subunit beta Not Available Escherichia coli (strain K12) - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
The major metabolites of rifalazil in human are 25-deacetyl-benzoxazinorifamycin and 32-hydroxy-benzoxazinorifamycin. The enzyme responsible for the benzoxazinorifamycin-25-deacetylation is a B-esterase while the enzyme responsible for the benzoxazinorifamycin-32-hydroxylation is CYP3A4.
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Rifalazil can be increased when it is combined with Abametapir. Acenocoumarol The risk or severity of bleeding can be increased when Rifalazil is combined with Acenocoumarol. Ambroxol The risk or severity of methemoglobinemia can be increased when Rifalazil is combined with Ambroxol. Amiodarone The metabolism of Rifalazil can be decreased when combined with Amiodarone. Amprenavir The metabolism of Rifalazil can be decreased when combined with Amprenavir. - Food Interactions
- Not Available
Products
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- Rifalazil
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenoxazines. These are polycyclic aromatic compounds containing a phenoxazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a 1,4-oxazine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzoxazines
- Sub Class
- Phenoxazines
- Direct Parent
- Phenoxazines
- Alternative Parents
- Macrolactams / Naphthofurans / N-arylpiperazines / Naphthols and derivatives / Benzofurans / Coumarans / Aryl alkyl ketones / Dialkylarylamines / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids show 18 more
- Substituents
- 1,4-diazinane / 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / 1-naphthol / Acetal / Alcohol / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl alkyl ketone show 39 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Bacteria
Chemical Identifiers
- UNII
- S1976TE8QK
- CAS number
- 129791-92-0
- InChI Key
- UEFHFKKWYKVLDC-HTQYORAHSA-N
- InChI
- InChI=1S/C51H64N4O13/c1-24(2)23-54-16-18-55(19-17-54)32-21-33(57)39-35(22-32)67-48-40(52-39)36-37-44(60)30(8)47-38(36)49(62)51(10,68-47)65-20-15-34(64-11)27(5)46(66-31(9)56)29(7)43(59)28(6)42(58)25(3)13-12-14-26(4)50(63)53-41(48)45(37)61/h12-15,20-22,24-25,27-29,34,42-43,46,57-60H,16-19,23H2,1-11H3,(H,53,63)/b13-12+,20-15+,26-14-/t25-,27+,28+,29+,34-,42-,43+,46+,51-/m0/s1
- IUPAC Name
- (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,32-tetrahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-30-[4-(2-methylpropyl)piperazin-1-yl]-6,23,37-trioxo-8,27,38-trioxa-24,34-diazahexacyclo[23.11.1.1^{4,7}.0^{5,36}.0^{26,35}.0^{28,33}]octatriaconta-1,3,5(36),9,19,21,25,28,30,32,34-undecaen-13-yl acetate
- SMILES
- CO[C@H]1\C=C\O[C@@]2(C)OC3=C(C)C(O)=C4C(=O)C(NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@@H]1C)=C1OC5=CC(=CC(O)=C5N=C1C4=C3C2=O)N1CCN(CC(C)C)CC1
References
- General References
- Mae T, Inaba T, Konishi E, Hosoe K, Hidaka T: Identification of enzymes responsible for rifalazil metabolism in human liver microsomes. Xenobiotica. 2000 Jun;30(6):565-74. [Article]
- Rothstein DM, Hartman AD, Cynamon MH, Eisenstein BI: Development potential of rifalazil. Expert Opin Investig Drugs. 2003 Feb;12(2):255-71. [Article]
- External Links
- KEGG Drug
- D02550
- PubChem Compound
- 6540558
- PubChem Substance
- 175426909
- ChemSpider
- 16736451
- ChEMBL
- CHEMBL236297
- ZINC
- ZINC000169677007
- Wikipedia
- Rifalazil
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Unknown Status Treatment Intermittent Claudication / Peripheral Vascular Disease Patient 1 2 Completed Treatment Chlamydia Trachomatis Infection 1 2 Unknown Status Not Available Cerebrovascular Diseases / Coronary Artery Disease (CAD) / Peripheral Vascular Disease Patient 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0116 mg/mL ALOGPS logP 5.16 ALOGPS logP 4.48 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 4.52 Chemaxon pKa (Strongest Basic) 8.63 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 15 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 226.22 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 260.84 m3·mol-1 Chemaxon Polarizability 99.78 Å3 Chemaxon Number of Rings 7 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.7494 Blood Brain Barrier - 0.9076 Caco-2 permeable - 0.5979 P-glycoprotein substrate Substrate 0.7333 P-glycoprotein inhibitor I Inhibitor 0.5525 P-glycoprotein inhibitor II Non-inhibitor 0.7461 Renal organic cation transporter Non-inhibitor 0.89 CYP450 2C9 substrate Non-substrate 0.801 CYP450 2D6 substrate Non-substrate 0.8338 CYP450 3A4 substrate Substrate 0.6903 CYP450 1A2 substrate Non-inhibitor 0.5611 CYP450 2C9 inhibitor Non-inhibitor 0.5582 CYP450 2D6 inhibitor Non-inhibitor 0.8682 CYP450 2C19 inhibitor Non-inhibitor 0.6166 CYP450 3A4 inhibitor Non-inhibitor 0.7363 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7914 Ames test Non AMES toxic 0.5689 Carcinogenicity Non-carcinogens 0.8451 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6963 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9942 hERG inhibition (predictor II) Non-inhibitor 0.8326
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 298.00888 predictedDeepCCS 1.0 (2019) [M+H]+ 299.66208 predictedDeepCCS 1.0 (2019) [M+Na]+ 305.81894 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Unknown
- General Function
- Ribonucleoside binding
- Specific Function
- DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
- Gene Name
- rpoB
- Uniprot ID
- P0A8V2
- Uniprot Name
- DNA-directed RNA polymerase subunit beta
- Molecular Weight
- 150631.165 Da
References
- Fujii K, Saito H, Tomioka H, Mae T, Hosoe K: Mechanism of action of antimycobacterial activity of the new benzoxazinorifamycin KRM-1648. Antimicrob Agents Chemother. 1995 Jul;39(7):1489-92. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase 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 react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Mae T, Inaba T, Konishi E, Hosoe K, Hidaka T: Identification of enzymes responsible for rifalazil metabolism in human liver microsomes. Xenobiotica. 2000 Jun;30(6):565-74. [Article]
Drug created at October 21, 2007 22:23 / Updated at February 21, 2021 18:51