1589476-75-4Relevant academic research and scientific papers
Antibacterial activity of a series of N2, N4- disubstituted quinazoline-2,4-diamines
Van Horn, Kurt S.,Burda, Whittney N.,Fleeman, Renee,Shaw, Lindsey N.,Manetsch, Roman
, p. 3075 - 3093 (2014/05/06)
A series of N2,N4-disubstituted quinazoline-2,4- diamines has been synthesized and tested against multidrug resistant Staphylococcus aureus. A structure-activity and structure-property relationship study was conducted to identify new hit compounds. This study led to the identification of N2,N4-disubstituted quinazoline-2,4- diamines with minimum inhibitory concentrations (MICs) in the low micromolar range in addition to favorable physicochemical properties. Testing of biological activity revealed limited potential for resistance to these agents, low toxicity, and highly effective in vivo activity, even with low dosing regimens. Collectively, these characteristics make this compound series a suitable platform for future development of antibacterial agents.
Antileishmanial activity of a series of N2, N 4-disubstituted quinazoline-2,4-diamines
Van Horn, Kurt S.,Zhu, Xiaohua,Pandharkar, Trupti,Yang, Sihyung,Vesely, Brian,Vanaerschot, Manu,Dujardin, Jean-Claude,Rijal, Suman,Kyle, Dennis E.,Wang, Michael Zhuo,Werbovetz, Karl A.,Manetsch, Roman
, p. 5141 - 5156 (2014/07/08)
A series of N2,N4-disubstituted quinazoline-2,4- diamines has been synthesized and tested against Leishmania donovani and L. amazonensis intracellular amastigotes. A structure-activity and structure-property relationship study was conducted in part using the Topliss operational scheme to identify new lead compounds. This study led to the identification of quinazolines with EC50 values in the single digit micromolar or high nanomolar range in addition to favorable physicochemical properties. Quinazoline 23 also displayed efficacy in a murine model of visceral leishmaniasis, reducing liver parasitemia by 37% when given by the intraperitoneal route at 15 mg kg-1 day-1 for 5 consecutive days. Their antileishmanial efficacy, ease of synthesis, and favorable physicochemical properties make the N2,N 4-disubstituted quinazoline-2,4-diamine compound series a suitable platform for future development of antileishmanial agents.
