93068-78-1

Upstream product

• 16133-26-9 pyridine-3-thiol 
• 93068-72-5 (6R,7R)-7-tert-Butoxycarbonylamino-5,8-dioxo-3-[(E)-2-(pyridin-3-ylsulfanyl)-vinyl]-5λ⁴-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 

Downstream Products

• 288379-65-7 7β-[2-(Z)-(2-aminothiazol-4-yl)-2-(trityloxyimino)acetamido]-3-[(E)-2-(3-pyridyl)thiovinyl]-3-cephem-4-carboxylic acid 

Relevant academic research and scientific papers

Studies on anti-MRSA parenteral cephalosporins. IV. A novel water-soluble N-phosphono type prodrug for parenteral administration

A systematic approach for improving the water-solubility of anti-MRSA (methicillin-resistant Staphylococcus aureus) cephalosporin derivatives is described. We first tried to improve the water-solubility of 7β-[2- (5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-fluoromethoxyimino-acetamido]- 3-[(E)-2-(1-methylimidazo[1,2-b]pyridazinium-6-yl)thiovinyl]- 3-cephem-4-carboxylate (1a) by substitution of the C-3′ pharmacophore. Replacement of the C-3′ pharmacophore with a 1-methyl-4-pyridinio group improved the water-solubility without decreasing the anti-MRSA activity. Furthermore, we applied the N-modified prodrug strategy to the C-7 acyl group in order to enhance the water-solubility drastically. Among the compounds prepared, the N-phosphono type prodrugs 2a (1-methylimidazo [1,2-b]pyridazinium derivative) and 2b (1-methyl-4-pyridinio derivative) showed water-solubility appropriate for a product intended for intravenous injection and in vivo anti-MRSA activity comparable to that of vancomycin.

Orally active cephalosporins. Part 2: Synthesis, structure-activity relationships and oral absorption of cephalosporins having a C-3 pyridyl side chain

A series of 7β-[(Z)-2-(2-aminothiazol-4-yl)-2- hydroxyiminoacetamido]cephalosporins having a pyridine ring connected through various spacer moieties at the C-3 position was designed and synthesized and evaluated for antibacterial activity and oral absorption in rats. All compounds showed potent antibacterial activity against Staphylococcus aureus, whereas antibacterial activity against Gram-negative bacteria was markedly influenced by the spacer moiety between the pyridine and cephem nucleus. Oral absorption was influenced by the position of the pyridine nitrogen as well as by the spacer moiety. Among these compounds, FR86830 (14), having a 4- pyridylmethylthio moiety at the C-3 position, showed the most well balanced activity and moderate oral absorption. (C) 2000 Elsevier Science Ltd.