Jennifer Tran

Design at the atomic level: design of biaryloxazolidinones as potent orally active antibiotics.

We have developed a first generation of hybrid sparsomycin-linezolid compounds into a new family of orally bioavailable biaryloxazolidinones that have activity against both linezolid-susceptible and -resistant gram-positive bacteria as well as the fastidious gram-negative bacteria Haemophilus influenzae and Moraxella catarrahalis. The convergent synthesis of these new compounds is detailed.

Design at the atomic level : Generation of novel hybrid biaryloxazolidinones as promising new antibiotics

From the X-ray crystal structures of linezolid and the non-selective antibiotic sparsomycin, we have derived a new family of hybrid oxazolidinones. From this initial compound set we have developed a new biaryloxazolidinone scaffold that shows both potent antimicrobial activity as well as selective inhibition of ribosomal translation. The synthesis of these compounds is outlined.

The SAR of 6-(N-alkyl-N-acyl)-2-propyl-3-[(2′-tetrazol-5-yl)biphen-4-yl)methyl]-quinazolinones as balanced affinity antagonists of the human AT1 and AT2 receptors

Abstract Modification of the 6-N-alkyl-N-acyl groups of L-159,689, 6 6-(N-benzoyl-N-pentyl)-amino-2-propyl-3-[(2′-(tetrazol-5-yl)biphen-4-yl)methyl]quinazolin-4-(3H)one led to the identification of the 6-(N-benzoyl-N-(3-pyridylmethyl)) analog (L-162,537). L-162,537 had improved aqueous solubility and oral bioavailability in the dog. The SAR of this class of AT1 and AT2 ligands is discussed.