The rising of bacterial strains thathave antibiotic resistance is causing the search for new antimicrobial agents.In recent years, there is a number of new agents to treat patogenic diseases.These agents show considerable improved activity against bacteria that haveresistance or show lower sensitivity to previous antimicrobialagents.
Changing the chemical structure of molecules and introduction ofmolecules with new chemical structure have provided agents able to overcome thepresent resistance mechanism. These search workings are especially atpenicillins, quinolones and macrolides.Eritromycin, the typical macrolide, wasdiscovered in early 1950s. After this, macrolide antibiotics used for thetherapy of Streptococcus pneumoniae infections.At the same time, macrolides showed broad spectrum antimicrobial activityagainst patogens.The one of the advantages of macrolides is that it is analternative treatment of b-lactam intolerant patients. But, in the last two decades, there isan increasing resistance to macrolides such as erythromycin, azithromycin andclathromycin.
To overcome this problem, ketolides were developed. Ketolides arenew major class of semisynthetic eritromycin derivatives with 10-fold greaterribosomal binding affinity because of secondary interaction.The main chemicalcharacteristics of a ketolide is the displacement of cladinose attached to the macrolidering of 6-O-methylerytromycin ring atC-3 position with a ketone moiety.Telithromycin is the first availableoral ketolide. It is approved by the US Food and Drug Administration (FDA) in2001 and it is introduced into clinical practice.
. Telithromycin was developedat Aventis and reached the market as Ketek. Telithromycin is used for treatmentof respiratory tract infections such as mild-to-moderately-severe CAP, chronicbronchitis and acute bacterial sinusitis. Also it is quite effective againstmacrolide resistant Streptecoccuspneumoniae.
2. CHEMICAL and PHYSICAL PROPERTIES of TELITHROMYCIN· Molecular formula of telithromycin is C43H65N5O10· Molecularweight of telithromycin is 812.018 g/mol.· Telithromycin has 1 hydrogen bond donor· Telithromycin has 13 hydrogen bond acceptor· Telithromycin has 11 rotatable bond· Formal charge of telithromycin is 0· Telithromycin has 13 defined atom stereocenter· Telithromycin has 1 covalently bonded unit· Telithromycin is canonicalized compound· Log P value of telithromycin is 3· Water solubility of telithromycin is 300 mg/L· Melting point of telithromycin is between 176 °C and 188 °C