258497-39-1

Basic information

• Product Name: (7R,6R)-7-[2-(2-amino-5-chloro-thiazol-4-yl)-2-(Z)-trityloxyimino-acetylamino]-3-[4-(2-tert-butoxycarbonylaminoethylsulfanylmethyl)-pyridin-3-ylsulfanyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester
• CAS NO: 258497-39-1
• Molecular Weight: 1110.8
• Mol File: 258497-39-1.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: (7R,6R)-7-[2-(2-amino-5-chloro-thiazol-4-yl)-2-(Z)-trityloxyimino-acetylamino]-3-[4-(2-tert-butoxycarbonylaminoethylsulfanylmethyl)-pyridin-3-ylsulfanyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (7R,6R)-7-[2-(2-amino-5-chloro-thiazol-4-yl)-2-(Z)-trityloxyimino-acetylamino]-3-[4-(2-tert-butoxycarbonylaminoethylsulfanylmethyl)-pyridin-3-ylsulfanyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester(258497-39-1)
• EPA Substance Registry System: (7R,6R)-7-[2-(2-amino-5-chloro-thiazol-4-yl)-2-(Z)-trityloxyimino-acetylamino]-3-[4-(2-tert-butoxycarbonylaminoethylsulfanylmethyl)-pyridin-3-ylsulfanyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester(258497-39-1)

Safety Data

• Hazardous Substances Data: 258497-39-1(Hazardous Substances Data)

Upstream product

• 258497-36-8 [2-(3-tritylsulfanyl-pyridin-4-ylmethylsulfanyl)-ethyl]-carbamic acid tert-butyl ester 
• 258497-37-9 thiocarbonic acid S-[4-(2-tert-butoxycarbonylaminoethylsulfanylmethyl)-pyridin-3-yl] ester O-tert-butyl ester 
• 258497-35-7 3-(triphenylmethylthio)-4-hydroxymethylpyridine 
• 258497-34-6 4-hydroxymethyl-3-mercaptopyridine 
• 18103-75-8 3-mercaptoisonicotinic acid 
• 67385-09-5 2-[(tert-butoxycarbonyl)amino]-1-ethanethiol 
• 258497-38-0 [2-(3-mercapto-pyridin-4-ylmethylsulfanyl)-ethyl]-carbamic acid tert-butyl ester 

Relevant articles and documents

Relationships between structure, antibacterial activity, serum stability, pharmacokinetics and efficacy in 3-(heteroarylthio)cephems. Discovery of RWJ-333441 (MC-04,546)

SAR studies in a series of related 3-(heteroarylthio)cephems determined that a relatively high chemical reactivity of the β-lactam ring, modulated by electronic effects of substituents at C-3 and C-7, is necessary to achieve high in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA). Such high reactivity results in lowered hydrolytic stability and concomitantly increases susceptibility to β-lactam ring opening mediated by serum enzymes. Therefore, optimization of anti-MRSA activity versus stability toward serum-mediated degradation required a fine balance of substituent effects. Serum stability studies (measured as percentage of parent drug degraded after 60 min incubation) revealed up to 80-fold difference in degradation rate in a series of closely related (3-heteroarylthio)cephems. Of the compounds evaluated, RWJ-333441 (MC-04,546) possessed the best balance of serum stability (6% degradation after 60 min incubation) and in vitro activity versus MRSA (S. aureus COL MIC=1 μg/mL). Accordingly, RWJ-333441 displayed excellent in vivo efficacy versus methicillin-susceptible Staphylococcus aureus (MSSA, ED50=0.39 mg/kg in mouse sepsis model with S. aureus Smith) and good pharmacokinetic properties in the rat (Cltotal=0.39 L/h/kg).