Clarithromycin structure

Therapeutic Function Antibiotic Chemical Name Erythromycin, 6-O-methyl-Common Name Clarithromycin Structural Formula ... 

X-ray crystal structures of the three 14-metnbered macrolides, erythromydn, clarithromycin and roxithromycin have been solved bound to the Deinococcus radiodu-rans (Dr) large subunit [4]. They bind at about the same location as the 15- and... 

The basic structure of the macrohde antibiotics is characterized by a lactonic cycle with two osidic chains, and they are classified according to the number of carbon atoms in the cycle 14-membered macrohdes (for example clarithromycin, dirithromycin, erythromycin, roxithromycin, troleandomycin), 15-membered macrolides (for example azithromycin), and 16-membered macrolides (for example josamycin, midecamycin, spiramycin). 

Researchers at Rib-X Pharmaceuticals, in addition to reaching Phase II with an oxazolidinone, have also capitalized on the structure of available ribosome macrolide complexes [81-84]. Macrolides (Scheme 4) such as azithromycin (1), clarithromycin (10), and telithromycin (Ketek, 12) are positioned near to linezolid in the PTC region, again binding mostly to RNA. The structures of azithromycin (PDB 1M1K, 1YHQ) and linezolid led to a series of compounds that extended the structure of the macrolides in ways medicinal chemistry had previously considered undesirable. 

Figure 6.8. The structures of the macrolides erythromycin, clarithromycin, and azithromycin.

Azithromycin is a macrolide (erythromycin, clarithromycin, and azithromycin) that interferes with microbial protein synthesis. It is indicated in the following conditions. Adults treatment of infections of the respiratory tract, acute bacterial sinusitis, acute bacterial exacerbations of COPD, community-acquired pneumonia, Mycobacterium avium complex, pelvic inflammatory disease, pharyngitis/tonsilli-tis, skin and skin structure infections, and sexually transmitted diseases caused by susceptible organisms. Children treatment of acute bacterial sinusitis, acute otitis media caused by susceptible organisms, community-acquired pneumonia, pharyngitis/tonsillitis caused by S. pyogenes in patients who cannot use first-line therapy. 

Clarithromycin is an H. pylori agent/macrolide, which inhibits microbial protein synthesis. Clarithromycin is indicated in the treatment of infections of the respiratory tract, skin and skin structure treatment of disseminated atypical mycobacterial infections caused by susceptible strains of specific microorganisms and prevention of disseminated Mycobacterium avium complex disease in patients with advanced HIV infection. Clarithromycin in combination with omeprazole is indicated in the treatment of patients with an active duodenal ulcer associated with H. pylori infection. In children it is used in acute otitis media. Macrolides are erythromycin, clarithromycin, and azithromycin. 

Macrolide antibiotics contain a many-membered lactone ring (14-membered rings for erythromycin and clarithromycin, and a 15-membered ring for azithromycin) to which are attached one or more deoxy sugars. Clarithromycin differs from erythromycin only by methylation of the hydroxyl group at the 6 position, and azithromycin differs by the addition of a methyl-substituted nitrogen atom into the lactone ring. These structural modifications improve acid stability and tissue penetration and broaden the spectrum of activity. 

Numerous studies have compared clarithromycin to loracarbef, amoxicillin/ clavulanate, amoxicillin suspension, and cefaclor in the treatment of acute otitis media in children with similar clinical outcomes and side effects [37-41]. In mild to moderate skin and skin structure infections, clarithromycin was not significantly better than erythromycin (96-88% eradication rate), with similar GI-related events [42-47]. 

Clarithromycin was compared to cefadroxil and erythromycin in two large multicenter studies of patients with mild to moderate skin and skin structure infections. Clarithromycin was as effective and safe as cefadroxil and erythromycin, both in adults and children [45,47]. 

Northcutt, V. J., Craft, J. C., and Pichotta, P. (1990). Safety and efficacy of clarithromycin (C) compared to erythromycin (E) in the treatment (tx) of bacterial skin or skin structure infections (SSTIs). Presented at 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (Atlanta). Abstr. No. 1339. 

Parish, L. C. (1993). Clarithromycin in the treatment of skin and skin structure infections Two multicenter clinical studies. Clarithromycin Study Group. Int. J. Dermatol. 32,528-532. 

Gupta, S., and Siepman, H. (1992). Comparative safety and efficacy of clarithromycin vs. standard agents in the treatment of mild to moderate bacterial skin or skin structure infections. Presented at First International Conference on the Macrolides, AzaUdes and Streptogramins (Santa Fe, NM). 

Hebert, A. A., Still, J. G., and Reuman, P. D. (1993). Comparative safety and efficacy of clarithromycin and cefadroxil suspensions in the treatment of mild to moderate skin and skin structure infections in children. Pediatr. Infect. Dis. J. 12, S112-S117. 

The cyclic 11,12-carbonate of erythromycin represents a previously recognized method for stabilization of erythromycin by maintaining an equilibrium between the 6-hydroxy-9-keto and 6,9-hemiketal forms [44]. A new direction within this approach was recently reported with a series of cyclic 11,12-carbamate derivatives of erythromycin and clarithromycin (see Fig. 5), prepared by a general sequence of 10,11-dehydration, 12-0-carbamoylation, and intramolecular cyclization [45, 46]. Other structural modifications within this part of the erythromycin molecule include 10,11-anhydroerythromycin, previously synthesized from the cyclic 11,12-carbonate [47],... 

Among the related substances in many antibiotics are various structurally related components in the drug substance, the composite mixture of which is obtained in the synthetic or semisynthetic scheme and which gives rise to the drug efficacy. Control of the relative content of components is therefore necessary for these drugs. Test specification limits for the components are normally stated in terms of area percent of each, as maximum, minimum or a range of values for each or for the sums of several components. The types of components seen in these antibiotics were studied as impurities in the semisynthetic antibiotic clarithromycin, where detection limits of 0.1% w/w were found. Normalization factors were determined for each of 15 known related substances using ratios of the slope of linear calibrations for each substance to that for the reference impurity. 

Figure 17 (a) Molecular structure of clarithromycin, 4. (b) Densely packed zigzag arrangement of molecnles of snblimed 4 with... 

Chanically, the macrolide antibiotics comprise a laige cyclic lactone ring slnicture with one or more molecules of the unusual sugars, L-cladinose and D-desosamine, attached by glycosidic linkage. The lactone ring structure may be from 12- to 16-membered—clarithromycin, dirithromycin,... 

---