760981-83-7 Usage
Pharmaceutical Applications
A 2-fluoroketolide. The side chain substituting the C11–C12 carbamate is composed of a substituted triazolyl (aminophenyl) ring. It displays good in-vitro and in-vivo activity against Streptococcus spp., including Str. pneumoniae (MIC 0.0015–0.25 mg/L), Str. pyogenes (MIC ≤0.008–0.015 mg/L)and viridians group streptococci (MIC ≤0.008–0.06 mg/L). Activity against H. influenzae is close to that of azithromycin (MIC 1.0–2.0 mg/L). Vancomycin-susceptible strains of E. faecalis are inhibited by 0.003–2.0 mg/L and E. faecium by 0.25–2.0 mg/L. It exhibits good activity against Ch. pneumoniae (MIC 0.25–1.0 mg/L), C. trachomatis (MIC 0.123–0.5 mg/L) and Mycoplasma spp. (MIC ≤0.0008 mg/L). In vitro H. pylori is susceptible (MIC 0.006–0.25 mg/L), but C. jejuni less so (MIC 1–4 mg/L). It is extremely active in vitro against B. anthracis (MIC <0.008–0.015 mg/L) and other agents of bioterrorism such as Francisella tularensis (MIC <0.08–4.0 mg/L), Yersinia pestis and Burkholderia mallei (MIC 0.25–2.0 mg/L). It exhibits a good activity against the M. avium complex.In healthy adult volunteers the proposed therapeutic dose of 400 mg achieved a peak plasma concentration of 0.78 mg/L after 4 h. The apparent elimination half-life was 5.1 h.
Biological Activity
solithromycin (cem-101) is a new, potent and broad-spectrum fluoroketolide antibiotic [1][2].antibiotic is an antimicrobial used in the treatment and prevention of bacterial infection.solithromycin (cem-101) is a broad-spectrum fluoroketolide antibiotic. cem-101 exhibited high potency against diverse groups of gram-positive and gram-negative bacteria, including mycoplasma and ureaplasma, as well as bacteria associated with respiratory tract infections and skin infections, with mic50 values of 0.015 μg/ml and 4 μg/ml, respectively [1]. solithromycin (cem-101) bound to the large 50s subunit of the ribosome and inhibited protein biosynthesis. in streptococcus pneumoniae, staphylococcus aureus, and haemophilus influenzae, solithromycin inhibited cell viability, protein synthesis, and growth rate with ic50 values of 7.5, 40, and 125 ng/ml. solithromycin also inhibition the formation of the 50s subunit [3]. in monocytic u937 cells, solithromycin inhibited tnfα/cxcl8 production and mmp9 activity. in pbmc isolated from chronic obstructive pulmonary disease (copd) patients, solithromycin (10 μm) inhibited tnfα release and mmp9 activity. in monocytic u937 cells, solithromycin (10 μm) significantly inhibited nf-κb activity activated by oxidative stress [4].in c57bl/6j mice, solithromycin also inhibited cigarette smoke-induced neutrophilia and pro-mmp9 production [4]. cem-101 was also an effective antimicrobial for the prevention and treatment of intrauterine infection [2].
references
[1]. putnam sd, castanheira m, moet gj, et al. cem-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of gram-positive and gram-negative bacteria. diagn microbiol infect dis, 2010, 66(4): 393-401. [2]. keelan ja, kemp mw, payne ms, et al. maternal administration of solithromycin, a new, potent, broad-spectrum fluoroketolide antibiotic, achieves fetal and intra-amniotic antimicrobial protection in a pregnant sheep model. antimicrob agents chemother, 2014, 58(1): 447-454.[3]. rodgers w, frazier ad, champney ws. solithromycin inhibition of protein synthesis and ribosome biogenesis in staphylococcus aureus, streptococcus pneumoniae, and haemophilus influenzae. antimicrob agents chemother, 2013, 57(4): 1632-1637.[4]. kobayashi y, wada h, rossios c, et al. a novel macrolide solithromycin exerts superior anti-inflammatory effect via nf-κb inhibition. j pharmacol exp ther, 2013, 345(1): 76-84.
Check Digit Verification of cas no
The CAS Registry Mumber 760981-83-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,6,0,9,8 and 1 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 760981-83:
(8*7)+(7*6)+(6*0)+(5*9)+(4*8)+(3*1)+(2*8)+(1*3)=197
197 % 10 = 7
So 760981-83-7 is a valid CAS Registry Number.
760981-83-7Relevant articles and documents
Ribosome-Templated Azide-Alkyne Cycloadditions: Synthesis of Potent Macrolide Antibiotics by in Situ Click Chemistry
Glassford, Ian,Teijaro, Christiana N.,Daher, Samer S.,Weil, Amy,Small, Meagan C.,Redhu, Shiv K.,Colussi, Dennis J.,Jacobson, Marlene A.,Childers, Wayne E.,Buttaro, Bettina,Nicholson, Allen W.,MacKerell, Alexander D.,Cooperman, Barry S.,Andrade, Rodrigo B.
, p. 3136 - 3144 (2016)
Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered by combinatorial copper-catalyzed click chemistry, was synthesized in situ by incubating either E. coli 70S ribosomes or 50S subunits with macrolide-functionalized azide 2 and 3-ethynylaniline (3) precursors. The ribosome-templated in situ click method was expanded from a binary reaction (i.e., one azide and one alkyne) to a six-component reaction (i.e., azide 2 and five alkynes) and ultimately to a 16-component reaction (i.e., azide 2 and 15 alkynes). The extent of triazole formation correlated with ribosome affinity for the anti (1,4)-regioisomers as revealed by measured Kd values. Computational analysis using the site-identification by ligand competitive saturation (SILCS) approach indicated that the relative affinity of the ligands was associated with the alteration of macrolactone+desosamine-ribosome interactions caused by the different alkynes. Protein synthesis inhibition experiments confirmed the mechanism of action. Evaluation of the minimal inhibitory concentrations (MIC) quantified the potency of the in situ click products and demonstrated the efficacy of this method in the triaging and prioritization of potent antibiotics that target the bacterial ribosome. Cell viability assays in human fibroblasts confirmed 2 and four analogues with therapeutic indices for bactericidal activity over in vitro mammalian cytotoxicity as essentially identical to solithromycin (1).
Synthesis, Biological Evaluation, and Computational Analysis of Biaryl Side-Chain Analogs of Solithromycin
Daher, Samer S.,Lee, Miseon,Jin, Xiao,Teijaro, Christiana N.,Wheeler, Steven E.,Jacobson, Marlene A.,Buttaro, Bettina,Andrade, Rodrigo B.
supporting information, p. 3368 - 3373 (2021/09/06)
There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π-stacking and H-bonding) between from the biaryl side-chain of the drug and key residues in the 50S ribosomal subunit. We have designed and synthesized a library of solithromycin analogs to study their structure-activity relationships (SAR) in tandem with new computational studies. The biological activity of each analog was evaluated in terms of ribosomal affinity (Kd determined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H-bonding interactions that modulate the potency of solithromycin analogs.
Method for preparing Solithromycin compound
-
, (2017/08/28)
The invention provides a method for preparing a macrolide antibiotic, namely Solithromycin. The method includes the steps of fluorination, side chain condensation, deprotection and the like or includes the steps of side chain condensation, fluorination, deprotection and the like. Time when triazole side chains large in polarity are introduced is late, the defect that purification is not easy is avoided, and cost of Solithromycin is also reduced.
