Alteration of the Dihydrothiazine Ring Moiety

Murphy, C. F.; Webber, J. A.

doi:10.1016/b978-0-12-261450-7.50009-5

Cited by 11 publications

(19 citation statements)

References 40 publications

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“…Compound 3b crystallized in the monoclinic space group P2, with a unit cell having the dimensions a = 7.228 (4) A, b = 10.328 (4) A, c = 15.436 (8) A, 0 = 90.415 (5)" and a calculated density of 1.39 g ~m -~. Compound 3b crystallized in the monoclinic space group P2, with a unit cell having the dimensions a = 7.228 (4) A, b = 10.328 (4) A, c = 15.436 (8) A, 0 = 90.415 (5)" and a calculated density of 1.39 g ~m -~.…”

Section: Discussionmentioning

confidence: 99%

3-exo-Methylenecephalosporins: structure and thermodynamics by experiment and theory

Wirth¹,

Deeter²

1991

J. Org. Chem.

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1-0-Benzoyl-myo-inositol(13): white solid; m p 84-87 "C (hexane-methanol); 'H NMR (DMSO-d6 + D 2 0 ) 6 8.03-7.51 (m, 5 H, aromatics), 4.65 (dd, 1 H, J = 2.6 Hz, J = 10.3 Hz, H-l), 3.93 (br s, H-2), 3.73 (t, 1 H), 3.43 (t, 1 H, J = 9.3 Hz), 3.26 (dd, 1 H, J = 2.4 Hz, J = 9.5 Hz, H-3), 3.06 (t, 1 H, J = 9.0 Hz); I3C NMR (DMSO-d6) 6 165.6 (oca), 133.0, 130.3, 129.4, 128.4 (aromatics), 1-0-(p-Methoxybenzoy1)-myo-inositol (14): white solid; m p 185-187 "C (methanol); 'H NMR (DMSO-d, + D20) 6 7.95 aromatics), 4.59 (dd, 1 H, J = 2.7 Hz, J = 10.1 Hz, H -l ) , 3.90 (t, 1 H, J = 2.6 Hz , H-2), 3.80 (s, 3 H, CH,O), 3.71 (t, 1 H), 3.41 (t, 20.7 (3 CHaCO). 75.1, 72.3, 72.2, 71.3, 71.2, 70.1 (C-1-C-6). (d, 2 H, Jortho = 8.9 Hz, aromatics), 7.01 (d, 2 H, Joeho = 8.9 Hz, 1 H, J = 9.5 Hz), 3.24 (dd, 1 H, J = 2.6 Hz, J = 9.8 Hz, H-3) 3.04 (t, 1 H, J = 9.1 Hz); 13C NMR (DMSO-d6 + D2O) 6 165.3 (OCO), 162.9 (para aromatics), 131.5 (ortho aromatics), 122.6 (meta aromatics), 113.7 (ipso aromatics), 75.1, 72.3, 71.4, 70.1, 70.0 75.5,

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Section: Discussionmentioning

confidence: 99%

3-exo-Methylenecephalosporins: structure and thermodynamics by experiment and theory

Wirth¹,

Deeter²

1991

J. Org. Chem.

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“…Oxidation of cephalosporins having a C-7 amide hydrogen takes place selectively to form the more hindered /3-sulfoxide. 23 While sulfoxide oxygen appears to direct metalation by strong bases in aprotic solvents, 24 experiments with conformationally constrained systems25 reveal that deprotonation by hydroxide and alkoxide bases in protic solvents occurs with marked stereoelectronic preference for sulfinyl anion formation anti to the S-O bond.26 Indeed when 7-(phenoxyacetyljdeacetoxycephalosporin C-1 /3-oxide (5) and N-(tertbutoxycarbonyljcephalosporin C-l/3-oxide (6) in deuterium oxide 7 X = OH (pH 8.11 and 7.60,27 respectively, 25 mM phosphate buffer, 32 ± 1 °C) were examined by NMR spectroscopy and the disappearance of the C-2 hydrogens was treated as parallel pseudo-first-order processes,28 it was found that HA exchanged roughly 10 times faster than HB. 29 Analogous experiments with the -sulfoxide corresponding to 5 gave only a slight difference in the relative rates of exchange, favoring now HB over HA.…”

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confidence: 99%

Stereochemical fate of chiral methyl of valine in the ring expansion of penicillin N to deacetoxycephalosporin C

Townsend¹,

Theis²,

Neese³

et al. 1985

J. Am. Chem. Soc.

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“…Isomerization has also been observed in homogenates of small intestine, liver and in plasma from mice [5]. d3-Cefotiam is devoid of antibacterial activity [21].…”

Section: Discussionmentioning

confidence: 94%

Skin tissue fluid levels of cefotiam in healthy man following oral cefotiam hexetil

Körting¹,

Schäfer‐Korting

Kees

et al. 1990

Eur J Clin Pharmacol

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Summary.Cefotiam hexetil is a pro-drug of cefotiam available for oral administration. To evaluate cefotiam concentrations at the active site in skin and soft-tissue infections, drug levels in skin suction blister fluid (SBF), cantharides blister fluid (CBF) and serum were determined. Six healthy subjects received oral cefotiam 400 mg as cefotiam hexetil. On an other day 200 mg was injected intravenously.Following the oral dose, the bioavailability of cefotiam was 45.5%, and the maximum concentration in serum of 2.6mg-1 -~ was obtained at 2.1 h. Peak concentrations in both types of blister fluid (0.9 mg. 1-1) were significantly lower than after the iv dose (SBF 1.4 mg.1 -I, CBF 1.5 mg. 1 -1), and the peak levels occurred later (3.3 versus 1.5 h in CBF). Despite the delay, the extent of penetration was about 100% following either mode of administration (SBE iv dose 112%, oral dose 117%). The cefotiam level in skin blister fluids declined significantly more slowly than the serum level. Following the oral dose, the mean terminal half life was serum 0.8 h, SBF 2.6 h and CBF 4.6h.Cefotiam concentrations in the blister fluids were close to the MIC90 of Staphylococcus aureus, S. epidermis and H. influenzae and exceeded the MIC90 of Streptococci, E. coli and Proteus mirabilis.Thus, the oral administration of cefotiam 400 mg t. i. d. should be curative in the majority of bacterial infections of the skin and soft-tissues.

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Alteration of the Dihydrothiazine Ring Moiety

Cited by 11 publications

References 40 publications

3-exo-Methylenecephalosporins: structure and thermodynamics by experiment and theory

3-exo-Methylenecephalosporins: structure and thermodynamics by experiment and theory

Stereochemical fate of chiral methyl of valine in the ring expansion of penicillin N to deacetoxycephalosporin C

Skin tissue fluid levels of cefotiam in healthy man following oral cefotiam hexetil

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