- Compounds and methods of use
-
Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, Y, A, L1, L2, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.
- -
-
Page/Page column 478; 479
(2021/08/04)
-
- Discovery of dap-3 polymyxin analogues for the treatment of multidrug-resistant gram-negative nosocomial infections
-
We report novel polymyxin analogues with improved antibacterial in vitro potency against polymyxin resistant recent clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa. In addition, a human renal cell in vitro assay (hRPTEC) was used to inform structure-toxicity relationships and further differentiate analogues. Replacement of the Dab-3 residue with a Dap-3 in combination with a relatively polar 6-oxo-1-phenyl-1,6-dihydropyridine-3- carbonyl side chain as a fatty acyl replacement yielded analogue 5x, which demonstrated an improved in vitro antimicrobial and renal cytotoxicity profiles relative to polymyxin B (PMB). However, in vivo PK/PD comparison of 5x and PMB in a murine neutropenic thigh model against P. aeruginosa strains with matched MICs showed that 5x was inferior to PMB in vivo, suggesting a lack of improved therapeutic index in spite of apparent in vitro advantages.
- Magee, Thomas V.,Brown, Matthew F.,Starr, Jeremy T.,Ackley, David C.,Abramite, Joseph A.,Aubrecht, Jiri,Butler, Andrew,Crandon, Jared L.,Dib-Hajj, Fadia,Flanagan, Mark E.,Granskog, Karl,Hardink, Joel R.,Huband, Michael D.,Irvine, Rebecca,Kuhn, Michael,Leach, Karen L.,Li, Bryan,Lin, Jian,Luke, David R.,Macvane, Shawn H.,Miller, Alita A.,McCurdy, Sandra,McKim, James M.,Nicolau, David P.,Nguyen, Thuy-Trinh,Noe, Mark C.,O'Donnell, John P.,Seibel, Scott B.,Shen, Yue,Stepan, Antonia F.,Tomaras, Andrew P.,Wilga, Paul C.,Zhang, Li,Xu, Jinfeng,Chen, Jinshan Michael
-
p. 5079 - 5093
(2013/07/26)
-
- CO-CRYSTALS AND SALTS OF CCR3-INHIBITORS
-
This invention relates to co-crystals and salts of CCR3 inhibitors of formula (1), pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases related with the CCR3-receptor.
- -
-
Page/Page column 32-33
(2012/04/23)
-
- Synthesis of heteroarenes using cascade radical cyclisation via iminyl radicals
-
Cascade radical cyclisation involving homolytic aromatic substitution has been used to synthesise new tetracycles. Treatment of vinyl iodide radical precursors with Me3Sn radicals (from hexamethylditin) yielded intermediate vinyl radicals which
- Bowman, W. Russell,Cloonan, Martin O.,Fletcher, Anthony J.,Stein, Tobias
-
p. 1460 - 1467
(2007/10/03)
-