224452-66-8 Usage
Uses
Used in Pharmaceutical Industry:
Retapamulin is used as a topical antibiotic for treating skin infections caused by both E. coli and S. aureus with similar potencies. Its unique mechanism of action, which involves binding to domain V of 23S rRNA, results in no cross-resistance to existing antibiotic classes, making it the first pleuromutilin approved for human use.
Used in Veterinary Medicine:
Retapamulin's predecessors, tiamulin and valnemulin, were developed for veterinary use and have been shown to interact uniquely with bacterial ribosomes. This interaction, which involves high affinity binding to a site on the 50S subunit, interferes with ribosomal peptidyl transferase activity, blocks P-site interactions, and prevents the evolution of active 50S ribosomal subunits.
Brand Name:
Altabax
Originator
GlaxoSmithKline (US)
Pharmaceutical Applications
A semisynthetic pleuromutilin formulated as a 1% ointment
for topical use. It is active against staphylococci
(MIC 0.12 mg/L), including methicillin-resistant strains, and
against streptococci (MIC 0.03–0.25 mg/L), including Str.
pyogenes and Str. pneumoniae. Most enterococci and Gramnegative
bacilli are resistant. Propionibacteria are susceptible,
suggesting that it might be useful in acne. Early indications
suggest that resistance does not emerge readily, but experience
with veterinary pleuromutilins indicates that chromosomal
resistance may develop with extended use.
It is metabolized in the liver and rapidly excreted, precluding
use in systemic infection. Systemic exposure is said to be
low following topical application and it appears safe, but there
are few data on absorption through broken and unbroken skin.
Principal side effects noted include local irritation and occasional
allergic reactions. Licensed use is presently restricted to
the treatment of impetigo and uncomplicated skin infections.
Possible value in methicillin-resistant Staph. aureus (MRSA)
infection or carriage has not yet been established.
Side effects
The most frequent adverse event was application site irritation, but other side effects, occurring in o2% of patients, included headache, diarrhea, nausea, and nasopharyngitis. While there are no contraindications, it is recommended that pregnant women only use retapamulin when the potential benefits outweigh the potential risks since animal reproductive studies are not always predictive of human response. Likewise, nursing mothers are cautioned about the unknown possibility of retapamulin excretion in breast milk.
Synthesis
The synthesis of retapamulin begins with generation of the mesylate of pleuromutilin, isolated through fermentation of Clitopilus passeckerianus, followed by nucleophilic substitution with exo-8-methyl-8-azabicyclo[3.2.1]octan-3-thiol under basic conditions Shridhar Hegde and Michelle Schmidt (potassium-tert-butoxide in ethanol or tetrabutylammonium hydrogen sulfate in dichloromethane/water and sodium hydroxide at pH 12.5). The azabicyclic thiol derivative may be prepared via a Mitsunobu reaction between tropine and thioacetic acid.
references
[1] jones r n, fritsche t r, sader h s, et al. activity of retapamulin (sb-275833), a novel pleuromutilin, against selected resistant gram-positive cocci. antimicrobial agents and chemotherapy, 2006, 50(7): 2583-2586.[2] rittenhouse s, biswas s, broskey j, et al. selection of retapamulin, a novel pleuromutilin for topical use. antimicrobial agents and chemotherapy, 2006, 50(11): 3882-3885.
Check Digit Verification of cas no
The CAS Registry Mumber 224452-66-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,2,4,4,5 and 2 respectively; the second part has 2 digits, 6 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 224452-66:
(8*2)+(7*2)+(6*4)+(5*4)+(4*5)+(3*2)+(2*6)+(1*6)=118
118 % 10 = 8
So 224452-66-8 is a valid CAS Registry Number.
InChI:InChI=1/C30H47NO4S/c1-7-28(4)16-22(24(27(34)35)36-21-14-19-8-9-20(15-21)31(19)6)29(5)17(2)10-12-30(18(3)26(28)33)13-11-23(32)25(29)30/h7,17-22,24-26,33H,1,8-16H2,2-6H3,(H,34,35)/p-1/t17-,18+,19-,20+,21+,22+,24?,25+,26+,28-,29+,30+/m1/s1
224452-66-8Relevant articles and documents
Novel method for preparing retapamulin
-
, (2017/10/22)
The invention provides a novel method for preparing an externally applied antibacterial medicine retapamulin. According to the method, tiamulin is used as an initial raw material, and is subjected to five steps of physical chemical reactions and a purifying process to prepare the retapamulin; the initial raw material has controllable quality, and is suitable for new medicine research, development and application; and the method is simple in operation, controllable in condition, low in preparation cost and convenient for industrial production, and is a great innovation for the retapamulin synthesis method.
A prepares switzerland he Moline method
-
Paragraph 0023; 0069; 0070; 0071, (2017/08/31)
The invention discloses a method for preparing retapamulin. The method comprises the following steps that a compound of a formula 3 and a compound of a formula 4 are subjected to a nucleophilic substitution reaction to obtain a compound of a formula 5; the compound of the formula 5 is subjected to a hydrolysis reaction to obtain beta-tropine mercaptan shown in a formula 6; the beta-tropine mercaptan shown in the formula 6 is not separated and purified to be subjected to condensation with a compound of a formula 2 to obtain retapamulin 1; the reaction formula is shown in the specification, wherein M in the compound of the formula 4 is a metal ion of a potassium ion or a sodion or a calcium ion or an iron ion or an ammonium ion, n corresponds to the valence of the metal ion M and is 1 or 2 or 3, and R is alkyl groups C1-C3 or a phenyl group or a substituted phenyl group or a benzyl group or a substituted benzyl group. The method is easy and convenient to implement, a cheap reagent is adopted, the influences on the environment are greatly reduced, intermediate products are easy to purify, no column chromatography is needed, the defects of reported methods for preparing beta-tropine mercaptan and retapamulin are overcome, and the method has obvious positive and progressive effects and practical application value.
A Swedish he Moline synthesis method
-
, (2017/07/11)
The present invention provides a synthesis method for Retapamulin. The method comprises: using pleuromutilin as a starting material of one segment; obtaining PLM-TS by condensation reaction between the starting material and toluenesulfonyl chloride; using tropenol as a raw material of the other segment; obtaining TRP-MS by reaction between the raw material and toluenesulfonyl chloride; after performing substitution reaction between TRP-MS that uses water as a solvent and potassium ethyl xanthate, performing acidification between the substance and sulfuric acid to obtain an intermediate TRP-XAN; TRP-XAN undergoing hydrolysis in an ethanol NaOH solution; performing acidification between the substance and sulfuric acid to obtain an intermediate TRP-THI; the two segments TRP-THI and PLM-TS undergoing condensation reaction under alkaline conditions to obtain the final product, Retapamulin. The synthesis method for Retapamulin provided by the present invention is simple, environmentally friendly, easy in controlling the quality of intermediates of all steps, and suitable for the Retapamulin synthesis process in industrialized production.
Process for the preparation of Retapamulin and its intermediates
-
Page/Page column 3; 5; 6, (2009/06/27)
Processes for preparing tropine derivatives of the following Formula B are provided where LG represents a leaving group. The tropine derivatives may be used to prepare Retapamulin, preferably in substantially pure form. Also provided are processes for preparing Retapamulin comprising combining a base, tropine thiol in a free base or salt form, an organic solvent, and a pleuromutilin derivative of Formula A:
