Dirithromycin

Title: Dirithromycin
CAS Registry Number: 62013-04-1
CAS Name: (1R,2R,3R,6R,7S,8S,9R,10R,12R,13S,15R,17S)-7-[(2,6-Dideoxy-3-C-methyl-3-O-methyl-a-L-ribo-hexopyranosyl)oxy]-3-ethyl-2,10-dihydroxy-15-[(2-methoxyethoxy)methyl]-2,6,8,10,12,17-hexamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-b-D-xylo-hexopyranosyl]oxy]-4,16-dioxa-14-azabicyclo[11.3.1]heptadecan-5-one
Additional Names: [9S(R)]-9-deoxo-11-deoxy-9,11-[imino[2-(2-methoxyethoxy)ethylidene]oxy]erythromycin
Manufacturers' Codes: LY-237216; AS-E 136
Trademarks: Dynabac (Lilly); Noriclan (Lilly); Nortron (Lilly); Valodin (Ferrer)
Molecular Formula: C42H78N2O14
Molecular Weight: 835.07
Percent Composition: C 60.41%, H 9.41%, N 3.35%, O 26.82%
Literature References: Semi-synthetic derivative of erythromycin, q.v. Prepn: BE 840431 (1976 to Thomae); R. Maier et al., US 4048306 (1977 to Boehringer, Ing.). Synthesis, 1H- and 13C-NMR, and antimicrobial evaluation: F. T. Counter et al., Antimicrob. Agents Chemother. 35, 1116 (1991). X-ray structure determn: P. Luger, R. Maier, J. Cryst. Mol. Struct. 9, 329 (1979). HPLC determn in plasma: G. W. Whitaker, T. D. Lindstrom, J. Liq. Chromatogr. 11, 3011 (1988). Symposium on antibacterial activity, pharmacology, and clinical experience: J. Antimicrob. Chemother. 31, Suppl. C, 1-185 (1993).
Properties: Crystals from ethanol/water, mp 186-189° (dec) (Counter). pKa 9.0 in 66% aq dimethyl fluoride. LD50 in mice (g/kg): >1 s.c.; >1 orally (Maier).
Melting point: mp 186-189° (dec) (Counter)
pKa: pKa 9.0 in 66% aq dimethyl fluoride
Toxicity data: LD50 in mice (g/kg): >1 s.c.; >1 orally (Maier)
Therap-Cat: Antibacterial.
Keywords: Antibacterial (Antibiotics); Macrolides.
Discodermolide Disilane Disodium Dihydrogen Hypophosphate Disodium Phenyl Phosphate Disofenin

Dirithromycin
Dirithromycin.svg
Systematic (IUPAC) name
(2R,3R,6R,7S,8S,9R,10R,12R,13S,15R,17S)-9-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-3-ethyl-2,10-dihydroxy-7-{[(2R,4R,5S,6S)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy}-15-[(2-methoxyethoxy)methyl]-2,6,8,10,12,17-hexamethyl-4,16-dioxa-14-azabicyclo[11.3.1]heptadecan-5-one
Clinical data
Trade names Dynabac
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a604026
Licence data US FDA:link
Pregnancy cat. B
Legal status  ?
Routes Oral
Pharmacokinetic data
Bioavailability 10%
Protein binding 15 to 30%
Metabolism Hyrolized to erythromycyclamine in 1.5 hours
Identifiers
CAS number 62013-04-1 YesY
ATC code J01FA13
PubChem CID 6917067
DrugBank DB00954
ChemSpider 5292341 YesY
UNII 1801D76STL YesY
KEGG D03865 YesY
ChEBI CHEBI:474014 N
ChEMBL CHEMBL1200505 N
Chemical data
Formula C42H78N2O14 
Mol. mass 835.074 g/mol
 N (what is this?)  (verify)

Dirithromycin is a macrolide glycopeptide antibiotic.

Dirithromycin (Dynabac) is a more lipid-soluble prodrug derivative of 9S-erythromycyclamine prepared by condensation of the latter with 2-(2-methoxyethoxy)acetaldehyde. The 9N, 11O-oxazine ring thus formed is a hemi-aminal that is unstable under both acidic and alkaline aqueous conditions and undergoes spontaneous hydrolysis to form erythromycyclamine. Erythromycyclamine is a semisynthetic derivative of erythromycin in which the 9-ketogroup of the erythronolide ring has been converted to an amino group. Erythromycyclamine retains the antibacterial properties of erythromycin oral administration. The prodrug, dirithromycin, is provided as enteric coated tablets to protect it from acid catalyzed hydrolysis in the stomach. Orally administered dirithromycin is absorbed rapidly into the plasma, largely from the small intestine. Spontaneous hydrolysis to erythromycyclamine occurs in the plasma. Oral bioavailability is estimated to be about 10%, but food does not affect absorption of the prodrug.