258497-35-7

Upstream product

• 76-83-5 trityl chloride 
• 258497-34-6 4-hydroxymethyl-3-mercaptopyridine 
• 18103-75-8 3-mercaptoisonicotinic acid 

Downstream Products

• 258497-36-8 [2-(3-tritylsulfanyl-pyridin-4-ylmethylsulfanyl)-ethyl]-carbamic acid tert-butyl ester 
• 258497-39-1 (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 

Relevant academic research and scientific papers

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).

7-acylamino-3-heteroarylthio-3-cephem carboxylic acid antibiotics and prodrugs thereof

The present invention relates to a cephem prodrug having formula III or formula IV: or a pharmaceutically acceptable salt thereof, wherein R′1is selected from the group consisting of hydrogen and —C(O)CH(NH2)CH3and R′2is selected from the group consisting of hydrogen and an acyl group that is cleaved by an enzyme found in mammals, with the proviso that, when either R′1or R′2is hydrogen, the other is not. A, B, L, G, E, and J are each independently nitrogen or carbon such that the respective rings are selected from the group consisting of provided that the group —CH2—S—CH2CH2NHR′2is attached only to a carbon atom of said heterocyclic group, and Q is selected from the group consisting of nitrogen and —CX, wherein X is selected from the group consisting of hydrogen and chlorine.

Cephalosporin antibiotics

The present invention includes novel compounds of formula where G, H, J, L and M are carbon or nitrogen, R99 is selected from the group consisting of sulfur, SO, SO2, NH, N-alkyl, oxygen, C 3BOND C (cis or trans), and C 3BOND C, and R12 is NR13R14, The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to beta -lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.

Cephalosporin antibiotics

The present invention includes novel compounds of formula where A, B, D, and E are selected from the group consisting of carbon, nitrogen and sulfur, R99 is selected from the group consisting of sulfur, SO, S02, NH, N-alkyl, oxygen, C=C (cis or trans), and C 3BOND C, and R12 is NR13R14, The invention also includes the pharmacologically acceptable salts which exhibit antibiotic activity against a wide spectrum of organisms including organisms which are resistant to beta -lactam antibiotics and are useful as antibacterial agents. The invention also relates to novel intermediates useful for making the novel compounds of the present invention and to novel methods for producing the novel compounds and intermediate compounds.