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The synthesis of a novel gut selective MTP inhibitor, 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), and its in vitro and in vivo profile are described. Dirlotapide (3) demonstrated excellent potency against MTP enzyme in HepG2 cells and canine hepatocytes. This novel MTP inhibitor(More)
A Free-Wilson analysis of the antibacterial activity found in a variety of quinoxaline 1,4-dioxides prepared and tested in these laboratories unexpectedly predicted that potent activity should be found in the case where the heterocyclic ring system was substituted with an acetyl group in the 2 position and a hydroxymethyl group in the 3 position (2). The(More)
3-Acetyl analogues of thiolactomycin, a thiotetronic acid natural product, were synthesized and profiled against livestock pathogens. Some analogues showed improved activity over thiolactomycin against Staphylococcus aureus and comparable activity against Pasteurella multocida. Several semisynthetically modified analogues of thiolactomycin showed no(More)
A new polyether antibiotic CP-84,657 (C45H78O14) was isolated by solvent extraction from the fermentation broth of Actinomadura sp. (ATCC 53708). Following purification by column chromatography and crystallization, the structure of CP-84,657 was elucidated by spectroscopic (NMR and MS) methods. The absolute stereochemistry was determined by a single crystal(More)
In a previous report, a plasmid, pIG1, which contained the loading domain from the Streptomyces avermitilis polyketide synthase (PKS), promoters from Streptomyces coelicolor and the DEBS1-TE truncated PKS from Saccharopolyspora erythraea, was integrated into the S. erythraea chromosome, effectively replacing the natural erythromycin loading domain with the(More)
Some 3-[(alkylthio)methyl]quinoxaline 1-oxide derivatives (1) have been synthesized and screened for antibacterial activity. 2-Acetyl-3-[(methylsulfonyl)methyl]quinoxaline 1-oxide (7a) was found to possess good in vitro activity against some pathogens important to veterinary medicine including Treponema hyodysenteriae, a causative agent in swine dysentery.(More)
The synthesis, separation, and structure determination of 6- and 7-acetyl--3-methyl-2-quinoxalinecarboxamide 1,4-dioxides are reported together with a comparison of their antibacterial activity. The structural assignment of these 6- and7-acetyl isomers was based on NMR analysis of related mono-N-oxide derivatives, which were obtained by treatment of the(More)
Interest in polyether antibiotics has remained at a high level for over 20 years, owing largely to the commercial importance of this class of drugs in veterinary medicine. For example, monensin1*, lasalocid1} and salmomycin2) are marketed as anticoccidial agents for poultry, and are used as growth permittants in cattle or swine. Narasin1} and maduramicin3)(More)
A new monocarboxylic acid ionophore antibiotic related to zincophorin, CP-78,545 (1), was found in the culture broth of Streptomyces sp. N731-45. CP-78,545 was extracted with organic solvents and purified by column chromatography. The metabolite, which is active in vitro against certain Gram-positive bacteria, as well as the anaerobe Treponema(More)