(4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide

• ChemBase ID: 139
• Molecular Formular: C22H24N2O8
• Molecular Mass: 444.43456
• Monoisotopic Mass: 444.15326574
• SMILES: [C@@H]12[C@](C(=C3[C@H]([C@@H]2O)[C@H](c2c(C3=O)c(ccc2)O)C)O)(C(=O)C(=C([C@H]1N(C)C)O)C(=O)N)O
• Canonical SMILES: CN([C@@H]1C(=C(C(=O)N)C(=O)[C@@]2([C@H]1[C@@H](O)[C@@H]1[C@@H](C)c3cccc(c3C(=O)C1=C2O)O)O)O)C
• InChI: InChI=1S/C22H24N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31)/t7-,10+,14+,15-,17-,22-/m0/s1
• InChIKey: JBIWCJUYHHGXTC-AKNGSSGZSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
• IUPAC Traditional name: vibramycin
• Brand Name: Alti-Doxycycline; Apo-Doxy; Atridox; Doryx; Doxy 100; Doxy-Caps; Doxy-Lemmon; Doxychel; Doxychel Hyclate; Doxycin; Doxylin; Doxytec; Jenacyclin; Monodox; Novo-Doxylin; Nu-Doxycycline; Periostat; Supracyclin; Vibra-Tabs; Vibramycin; Oracea
• Synonyms: (4R,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide; 6-Deoxy-4-epioxytetracycline; 4-Epi Doxycycline (>70%); Doxcycline anhydrous; Doxycycline Hyclate; Doxycycline Monohydrate; Doxytetracycline; Doxycycline

Database IDs

• CAS Number: 6543-77-7; 564-25-0
• PubChem SID: 46506491; 160963602
• PubChem CID: 5281011; 54671203

CALCULATED PROPERTIES

JChem

• Rotatable Bonds: 2
• Lipinski's Rule of Five: false
• Acid pKa: -2.235276
• H Acceptors: 9
• H Donor: 6
• LogD (pH = 5.5): -4.28254
• LogD (pH = 7.4): -6.187371
• Log P: -3.435637
• Molar Refractivity: 113.8919 cm^3
• Polarizability: 43.13817 Å^3
• Polar Surface Area: 181.62 Å^2

ALOGPS 2.1

• Solubility (Water): 6.30e-01 g/l
• Log P: -0.72
• LOG S: -2.85

PROPERTIES

Physical Property

• Solubility: 630 mg/L; Methanol; Pyridine
• Apperance: Yellow Solid
• Melting Point: >176°C (dec.)
• Hydrophobicity(logP): -0.2

Safety Information

• Storage Condition: Amber Vial, -20°C Freezer, Under Inert Atmosphere

DETAILS

DrugBank - DB00254

• Drug Groups: approved; investigational
• Description: A synthetic tetracycline derivative with similar antimicrobial activity. Animal studies suggest that it may cause less tooth staining than other tetracyclines. It is used in some areas for the treatment of chloroquine-resistant falciparum malaria (malaria, falciparum). [PubChem]
• Indication: Doxycycline is indicated for use in respiratory tract infections caused by Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Legionella spp., or Klebsiella spp. It is also used for prophylaxis of malaria. Doxycycline is indicated for a variety of bacterial infections, from Mycobacterium fortuitum and M. marinum, to susceptible E. coli and Brucella spp. It can be used as an alternative to treating plague, tetanus, Campylobacter fetus
• Pharmacology: Doxycycline, a long-acting tetracycline derived from oxytetracycline, is used to inhibit bacterial protein synthesis and treat non-gonococcal urethritis and cervicitis, exacerbations of bronchitis in patients with COPD, and adult periodontitis.
• Toxicity: Symptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia. LD₅₀=262 mg/kg (I.P. in rat).
• Affected Organisms: Enteric bacteria and other eubacteria
• Biotransformation: Hepatic
• Absorption: Completely absorbed following oral administration.
• Half Life: 18-22 hours
• Protein Binding: >90%
• Elimination: They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.
• References: Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ: Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 2006 Sep;50(9):3124-31. [Pubmed] ; Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Buttner DW: Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production. Med Microbiol Immunol. 2003 Nov;192(4):211-6. Epub 2003 Mar 5. [Pubmed] ; Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet. 2005 Jun 18-24;365(9477):2116-21. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - E585900

An alternative to doxycycline to control gene expression.

REFERENCES

• Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ: Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 2006 Sep;50(9):3124-31. Pubmed
• Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Buttner DW: Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production. Med Microbiol Immunol. 2003 Nov;192(4):211-6. Epub 2003 Mar 5. Pubmed
• Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet. 2005 Jun 18-24;365(9477):2116-21. Pubmed
• Schiffer, I., et al.: Cancer Res. 63, 7221 (2003)
• Eger, K., et al.: Biochem. Biophys. Res. Comm., 323, 979, (2004).