(3aR,4S,7R,9R,10R,11R,13R,15R,15aR)-10-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-{4-[4-(pyridin-3-yl)-1H-imidazol-1-yl]butyl}-tetradecahydro-1H-oxacyclotetradeca[4,3-d][1,3]oxazole-2,6,8,14-tetrone

• ChemBase ID: 851
• Molecular Formular: C43H65N5O10
• Molecular Mass: 812.0037
• Monoisotopic Mass: 811.47314331
• SMILES: O1[C@@]2([C@H](N(C1=O)CCCCn1cc(nc1)c1cccnc1)[C@H](C(=O)[C@@H](C[C@@](OC)([C@H](O[C@@H]1O[C@@H](C[C@H](N(C)C)[C@H]1O)C)[C@H](C(=O)[C@H](C(=O)O[C@H]2CC)C)C)C)C)C)C
• Canonical SMILES: CC[C@@H]1OC(=O)[C@H](C)C(=O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@@H]([C@H]2O)N(C)C)[C@](C[C@H](C(=O)[C@@H]([C@@H]2[C@@]1(C)OC(=O)N2CCCCn1cnc(c1)c1cccnc1)C)C)(C)OC
• InChI: InChI=1S/C43H65N5O10/c1-12-33-43(8)37(48(41(53)58-43)19-14-13-18-47-23-31(45-24-47)30-16-15-17-44-22-30)27(4)34(49)25(2)21-42(7,54-11)38(28(5)35(50)29(6)39(52)56-33)57-40-36(51)32(46(9)10)20-26(3)55-40/h15-17,22-29,32-33,36-38,40,51H,12-14,18-21H2,1-11H3/t25-,26-,27+,28+,29-,32+,33+,36-,37-,38-,40+,42-,43+/m1/s1
• InChIKey: LJVAJPDWBABPEJ-RMNISARHSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3aR,4S,7R,9R,10R,11R,13R,15R,15aR)-10-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-{4-[4-(pyridin-3-yl)-1H-imidazol-1-yl]butyl}-tetradecahydro-1H-oxacyclotetradeca[4,3-d][1,3]oxazole-2,6,8,14-tetrone
• IUPAC Traditional name: (3aR,4S,7R,9R,10R,11R,13R,15R,15aR)-10-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-{4-[4-(pyridin-3-yl)imidazol-1-yl]butyl}-octahydrooxacyclotetradeca[4,3-d][1,3]oxazole-2,6,8,14-tetrone
• Brand Name: Ketek
• Synonyms: telithromycin; Telithromycin

Database IDs

• CAS Number: 191114-48-4
• PubChem SID: 160964314
• PubChem CID: 70789201

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.410063
• H Acceptors: 11
• H Donor: 1
• LogD (pH = 5.5): 3.1206694
• LogD (pH = 7.4): 3.7969615
• Log P: 5.3681536
• Molar Refractivity: 214.6835 cm^3
• Polarizability: 86.46801 Å^3
• Polar Surface Area: 171.85 Å^2
• Rotatable Bonds: 11
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.0
• LOG S: -4.46
• Solubility (Water): 2.83e-02 g/l

PROPERTIES

Physical Property

• Solubility: 300 mg/L
• Hydrophobicity(logP): 3

DETAILS

DrugBank - DB00976

• Drug Groups: approved
• Description: Telithromycin, a semi-synthetic erythromycin derivative, belongs to a new chemical class of antibiotics called ketolides. Ketolides have been recently added to the macrolide-lincosamide-streptogramin class of antibiotics. Similar to the macrolide antibiotics, telithromycin prevents bacterial growth by interfering with bacterial protein synthesis. Telithromycin binds to the 50S subunit of the 70S bacterial ribosome and blocks further peptide elongation. Binding occurs simultaneously at to two domains of 23S RNA of the 50S ribosomal subunit, domain II and V, where older macrolides bind only to one. It is used to treat mild to moderate respiratory infections.
• Indication: For the treatment of Pneumococcal infection, acute sinusitis, acute bacterial tonsillitis, acute bronchitis and bronchiolitis, lower respiratory tract infection and lobar (pneumococcal) pneumonia.
• Pharmacology: Telithromycin is a ketolide antibiotic which has an antimicrobial spectrum similar or slightly broader than that of penicillin. It is often used as an alternative in patients who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. Telithromycin prevents bacterial growth by binding to bacterial 50S ribosomal subunits and interfering with bacterial peptide translocation and elongation.
• Toxicity: LD50>2000 mg/kg (PO in rats). Adverse effects are similar to those of clarithormycin and erithromycin and include diarrhea, nausea, vomiting, loose stools, abdominal pain, flatulence and dyspepsia. It may also cause dizziness, headache and taste disturbances.
• Affected Organisms: Enteric bacteria and other eubacteria
• Biotransformation: Hepatic - estimated 50% metabolized by CYP3A4 and 50% metabolized independent of cytochrome P450
• Absorption: Absolute bioavailability is approximately 57%. Maximal concentrations are reached 0.5 - 4 hours following oral administration. Food intake does not affected absorption.
• Half Life: Main elimination half-life is 2-3 hours; terminal elimination half-life is 10 hours
• Protein Binding: 60 - 70% bound primarily to human serum albumin
• Elimination: The systemically available telithromycin is eliminated by multiple pathways as follows: 7% of the dose is excreted unchanged in feces by biliary and/or intestinal secretion; 13% of the dose is excreted unchanged in urine by renal excretion; and 37% of the dose is metabolized by the liver.
• Distribution: * 2.9 L/kg
• References: Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP 3rd, Banks PM: Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006 Mar 21;144(6):415-20. Epub 2006 Feb 15. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

REFERENCES

• Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP 3rd, Banks PM: Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006 Mar 21;144(6):415-20. Epub 2006 Feb 15. Pubmed