335030-36-9Relevant articles and documents
An efficient one-pot synthesis of annulated pyridines utilising a directed ortho-metallation/transmetallation approach
Davies, Antony J.,Brands, Karel M. J.,Cowden, Cameron J.,Dolling, Ulf-H.,Lieberman, David R.
, p. 1721 - 1724 (2004)
The ortho-alkylation of Boc-protected aminopyridines with α,ω-dihaloalkanes followed by in situ cyclisation, resulted in the corresponding annulated pyridine derivatives in good to excellent yields. The effect of the alkylating and chelating agents, the transmetallation additives and the directing group was examined.
Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK
Seefeld, Mark A.,Miller, William H.,Newlander, Kenneth A.,Burgess, Walter J.,DeWolf Jr., Walter E.,Elkins, Patricia A.,Head, Martha S.,Jakas, Dalia R.,Janson, Cheryl A.,Keller, Paul M.,Manley, Peter J.,Moore, Terrance D.,Payne, David J.,Pearson, Stewart,Polizzi, Brian J.,Qiu, Xiayang,Rittenhouse, Stephen F.,Uzinskas, Irene N.,Wallis, Nicola G.,Huffman, William F.
, p. 1627 - 1635 (2007/10/03)
Bacterial enoyl-ACP reductase (FabI) is responsible for catalyzing the final step of bacterial fatty acid biosynthesis and is an attractive target for the development of novel antibacterial agents. Previously we reported the development of FabI inhibitor 4 with narrow spectrum antimicrobial activity and in vivo efficacy against Staphylococcus aureus via intraperitoneal (ip) administration. Through iterative medicinal chemistry aided by X-ray crystal structure analysis, a new series of inhibitors has been developed with greatly increased potency against FabI-containing organisms. Several of these new inhibitors have potent antibacterial activity against multidrug resistant strains of S. aureus, and compound 30 demonstrates exceptional oral (po) in vivo efficacy in a S. aureus infection model in rats. While optimizing FabI inhibitory activity, compounds 29 and 30 were identified as having low micromolar FabK inhibitory activity, thereby increasing the antimicrobial spectrum of these compounds to include the FabK-containing pathogens Streptococcus pneumoniae and Enterococcus faecalis. The results described herein support the hypothesis that bacterial enoyl-ACP reductases are valid targets for antibacterial agents.
