12-Fluoro-5-methylchrysene, which has a fluorine atom at a peri position, is less carcinogenic toward mouse skin than is 5-methylchrysene. To determine the basis for this observation, we identified metabolites of 12-fluoro-5-methylchrysene formed by rat liver in vitro, and used these as standards to study the metabolism of [3H]-12-fluoro-5-methylchrysene in mouse liver in vitro and in mouse epi...

The peripheral plasma content of the pulmonary metabolite, 13,14-dihydro-15-keto-prostaglandin E2, reflects prostaglandin E2 (PGE2) biosynthesis and disposition in vivo more reliably than the peripheral plasma content of PGE2 itself. However, the chemical instability of 13,14-dihydro-15-keto-PGE2 and the multiple fates of its degradation products hinder the development of quantitative assays fo...

Amides of pseudoephedrine and ephedrine are shown to undergo highly stereospecific, invertive cyclization to form 4,5-dihydro-3,4-dimethyl-5-phenyl-1,3-oxazolium triflate derivatives in the presence of triflic anhydride-pyridine. 1H NMR spectra of the unpurified reaction products are remarkably clean, with sharp, well-defined peaks, and allow for rapid assessment of the diastereomeric purities ...

Erythromycin A 11,12-methylene acetal (5) and the corresponding 9-methoxime, 9-dihydro, and 8-hydroxy derivatives have been prepared and their antibacterial activities compared with those of erythromycin A and its 11,12-cyclic carbonate. The simple methylene acetal 5 showed excellent activity against Gram-positive organisms in vitro.

The measurement of metabolites constitutes a useful tool for detection of exposure and in pharmacokinetic studies. Epoxidation with subsequent glutathione conjugation and mercapturic acid formation is an important deactivation pathway for naphthalene, a toxin which presumably causes lung disease. The mercapturic acid conjugates of naphthalene [NaphMA (1), N-acetyl-S-(1,2-dihydro-1-hydroxy-2-nap...

A route to cationic tungsten alkylidyne N-heterocyclic carbene (NHC) complexes of the general formula [W(CR)X2(NHC)(tBuCN)y+B(ArF)4–] (R = tBu, C6H4-4-OMe; X Br, Cl, OTf; NHC 1,3-dimesityl-1,3-dihydro-2H-imidazol-2-ylidene, IMes; 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene, IDipp; 1,3-dimesityl-4,5-dichloro-1,3-dihydro-2H-imidazol-2-ylidene, IMesCl2; y 1, 2; ArF 3,5-bis(tri...

A human cytochrome P-450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae and the microsomes containing P450 1B1 were used to examine the selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains, using the SOS response as an end point of DNA damage. We also determined and compar...

a group of regioisomeric 5-oxo-1,4,5,6,7,8 hexahydroquinoline derivatives possessing a cox-2 so2me pharmacophore at the para position of the c-2 or c-4 phenyl ring, in conjunction with a c-4 or c-2 phenyl (4-h) or substituted-phenyl ring (4-f,4-cl,4-br,4-ome,4-me, 4-no2), were designed for evaluation as selective cyclooxygenase-2 (cox-2) inhibitors. these target 5-oxo-1,4,5,6,7,8 hexahydroquino...