A MurF inhibitor that disrupts cell wall biosynthesis in Escherichia coli.

MurF is an essential enzyme of bacterial cell wall biosynthesis. Few MurF inhibitors have been reported, and none have displayed measurable antibacterial activity. Through the use of a MurF binding assay, a series of 8-hydroxyquinolines that bound to the Escherichia coli enzyme and inhibited its activity was identified.

An azomethine ylide approach to complex alkaloid-like heterocycles.

The nitrone above is readily available via the intramolecular aza Diels-Alder reaction of an amino acid derived triene in acetic acid. Subsequent treatment of the nitrone in refluxing toluene with substituted actetylenes produced the pictured pyrrole. At lower temperatures a 2,3-dihydroisoxazole, which is the product of a 3+2 dipolar cycloaddition, is produced.

3-Acyl-2,6-diaminopyridines as cyclin-dependent kinase inhibitors: synthesis and biological evaluation.

A novel series of 2,6-diamino-3-acylpyridines were designed and synthesized as cyclin-dependent kinase (CDK) inhibitors. The representative compounds 2r and 11 showed potent CDK1 and CDK2 inhibitory activities and inhibited cellular proliferation in HeLa, HCT116, and A375 tumor cells.

A point mutation in influenza B neuraminidase confers resistance to peramivir and loss of slow binding.

The influenza neuraminidase (NA) inhibitors peramivir, oseltamivir, and zanamivir are potent inhibitors of NAs from both influenza A and B strains. In general, these inhibitors are slow, tight binders of NA, exhibiting time-dependent inhibition. A mutant of influenza virus B/Yamagata/16/88 which was resistant to peramivir was generated by passage of the virus in tissue culture, in the presence of increasing concentrations (0.

Benzoxazinones as PPARgamma agonists. part 1: SAR of three aromatic regions.

A series of benzoxazinones was synthesized as PPARgamma agonists. The compounds were obtained in seven steps, and SAR was developed by variations to the core shown below. The compounds were tested as functional agonists in the induction of the aP2 gene in preadipocytes, and the most potent compound in the series has an EC(50)=0.

Unusual Regioselectivity of the Dipolar Cycloaddition Reactions of Nitrile Oxides and Tertiary Cinnamides and Crotonamides(1).

Benzonitrile oxides undergo 1,3-dipolar cycloaddition reactions with methyl cinnamate to produce the 5-phenyl and 4-phenyl regioisomers in approximately an 80:20 ratio. However, use of N,N-diethylcinnamide as the dipolarophile unexpectedly resulted in the formation of the 5-phenyl and 4-phenyl regioisomers in a 23:77 ratio. Studies have shown that this phenomena occurs only for tertiary cinnamides.