205110-48-1 Usage
Description
Cethromycin, also known as ABT-773, is a ketolide antibiotic that was originally developed by Abbott in the late 1990s and is currently under development by Advanced Life Sciences since 2004. It is derived from erythromycin A and designed to overcome resistance to macrolides. Cethromycin is characterized by the absence of the neutral sugar L-cladinose at position 3 of the erythronolide ring, which is replaced by a keto group. This modification leads to better drug absorption, less gastric irritation, and improved acid stability. Cethromycin presents as a white crystalline powder and has been primarily used in clinical trials for upper and lower respiratory tract infections.
Uses
Used in Pharmaceutical Industry:
Cethromycin is used as an antibiotic for treating respiratory infections. Its development is primarily directed at upper and lower respiratory tract infections, making it a valuable addition to the arsenal of antibiotics for combating bacterial infections.
Used in Clinical Trials:
Cethromycin is used as a test subject in clinical trials to evaluate its efficacy and safety in treating respiratory infections. As it has not yet been approved for clinical use, these trials are essential for determining its potential role in the treatment of such infections.
Physical Properties:
Cethromycin is a 6-O-ketolide, which means that, compared to 11-N-ketolides like telithromycin, the linkage with the macrolactone ring is in the 6-O-position. It also features an O-propylallyl linkage instead of the aminopropyl linkage found in telithromycin. These structural differences contribute to its improved properties, such as better drug absorption and less gastric irritation.
Biological Activity
Oral bioavailability of cethromycin has been poorly studied in humans. Animal studies report values ranging from approximately 36% to 50%. Absorption of cethromycin appears to be dose dependent with time to Cmax increasing from 0.9 to 5.1 hours with increasing dosage. Food does not appear to exert meaningful effects on the pharmacokinetics of cethromycin, but this aspect deserves additional study. In a study on the effects of drug co-administration on the pharmacokinetics of cethromycin, ranitidine was found to significantly reduce cethromycin Cmax concentrations, by 25.7%. Conversely, sucralfate had no effect on cethromycin concentrations. The degree of serum protein binding is considered to approach 90%.
Mechanism of action
The mechanism of action is similar to macrolides and is based on interaction with the peptidyl transferase site of the 50S ribosomal subunit, thus inhibiting the translation of rRNAs and preventing the elongation step of protein synthesis. In addition, cethromycin also interferes at an earlier stage of protein synthesis by disrupting the assembling of 50S subunit precursors to block the formation of a functional 50S subunit. Ketolides in general (including cethromycin) inhibit protein synthesis by binding to the 50S ribosomal subunit, close to the peptidyl transferase site at the entrance of the ribosomal exit tunnel. The presence of a 3-keto group in place of the L-cladinose moiety, common to all ketolides, allows cethromycin to bind to the ribosomal target in the 23S rRNA domain V without causing expression of ribosomal mutations. The additional flexible side chain (in the 6-O position for cethromycin) attached to the macrocyclic ring allows binding to an additional ribosomal site. This dual binding affinity increases the binding affinity of cethromycin several-fold compared with that of erythromycin. It is probably also responsible for overcoming resistance mediated by both the ribosomal mutations (erm) and efflux pump (mef) mechanisms. This leads to an enhanced activity against S. pneumoniae, including most of the macrolide-resistant strains. Conversely, the methoxy group at position C-6 provides greater acid stability than that of other macrolides, and is related to greater gastrointestinal stability.
Drug interactions
Ketolides and macrolides are substrates and inhibitors of the
cytochrome P450 (CYP450) 3A4 system. So far, data available
specifically for cethromycin are very limited and mainly exist in
abstract form. It is expected that interactions are similar to other drugs
that are involved in this pathway. This is exemplified by ketoconazole,
a potent CYP3A4 inhibitor that caused a 5-fold increase in
cethromycin AUC and a 2.5-fold increase in drug Cmax, although
cethromycin’s main metabolite showed a decreased Cmax but no effect
on its AUC. Similarly, rifampicin (600 mg)
significantly affected the pharmacokinetics of cethromycin (300 mg),
with a 95% reduction in the ketolide’s AUC and its metabolite
N-desmethyl cethromycin.
Check Digit Verification of cas no
The CAS Registry Mumber 205110-48-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,0,5,1,1 and 0 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 205110-48:
(8*2)+(7*0)+(6*5)+(5*1)+(4*1)+(3*0)+(2*4)+(1*8)=71
71 % 10 = 1
So 205110-48-1 is a valid CAS Registry Number.
InChI:InChI=1/C42H59N3O10/c1-11-32-42(8)36(44-40(50)55-42)25(4)33(46)23(2)21-41(7,51-18-14-15-28-20-29-16-12-13-17-30(29)43-22-28)37(26(5)34(47)27(6)38(49)53-32)54-39-35(48)31(45(9)10)19-24(3)52-39/h12-17,20,22-27,31-32,35-37,39,48H,11,18-19,21H2,1-10H3,(H,44,50)/b15-14+/t23-,24-,25-,26+,27-,31+,32+,35-,36-,37-,39+,41-,42-/m1/s1
205110-48-1Relevant articles and documents
6-O-SUBSTITUTED KETOLIDES HAVING ANTIBACTERIAL ACTIVITY
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, (2016/10/27)
PROBLEM TO BE SOLVED: To provide 6-O-substituted ketolides with antibacterial activity, having acid stability and enhanced activity toward gram negative bacteria and macrolide resistant gram positive bacteria. SOLUTION: This invention provides 6-O-substituted erythromycin ketolide derivatives such as formula (II) and compositions comprising the compounds. [Y and Z together form a group X; X is ketone, hydroxyimino or the like; or, one of Y and Z is H and the other is hydrogen, hydroxy or the like; Ra is H, hydroxy; Rc is H or a hydroxy protective group; R is a substituted methyl group]. COPYRIGHT: (C)2015,JPOandINPIT
