864548-01-6Relevant academic research and scientific papers
IMIDAZOLE-BASED ANTIMICROBIAL AGENTS
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Page/Page column 189, (2016/06/28)
The present invention relates to novel therapeutic agents suitable for use in the treatment of mammalian disease and in particular to novel therapeutic agents suitable for use in the treatment of microbial infection in mammals. The present invention further relates to the use of pharmaceutical compositions comprising said agents in the treatment of medical conditions in mammals, in particular in the treatment of microbial infection. The agents and pharmaceutical compositions of the invention are of particular relevance in the treatment of diseases associated with antibiotic-resistant microbes.
Discovery and optimisation studies of antimalarial phenotypic hits
Mital, Alka,Murugesan, Dinakaran,Kaiser, Marcel,Yeates, Clive,Gilbert, Ian H.
, p. 530 - 538 (2015/10/12)
There is an urgent need for the development of new antimalarial compounds. As a result of a phenotypic screen, several compounds with potent activity against the parasite Plasmodium falciparum were identified. Characterization of these compounds is discussed, along with approaches to optimise the physicochemical properties. The in vitro antimalarial activity of these compounds against P. falciparum K1 had EC50 values in the range of 0.09e29 mM, and generally good selectivity (typically >100-fold) compared to a mammalian cell line (L6). One example showed no significant activity against a rodent model of malaria, and more work is needed to optimise these compounds.
Discovery and structure-activity relationships of pyrrolone antimalarials
Murugesan, Dinakaran,Mital, Alka,Kaiser, Marcel,Shackleford, David M.,Morizzi, Julia,Katneni, Kasiram,Campbell, Michael,Hudson, Alan,Charman, Susan A.,Yeates, Clive,Gilbert, Ian H.
supporting information, p. 2975 - 2990 (2013/05/23)
In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 ～ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
Phenylpyrroles, a new chemolibrary virtual screening class of 5-HT 7 receptor ligands
Paillet-Loilier, Magalie,Fabis, Frederic,Lepailleur, Alban,Bureau, Ronan,Butt-Gueulle, Sabrina,Dauphin, Francois,Delarue, Catherine,Vaudry, Hubert,Rault, Sylvain
, p. 3753 - 3757 (2007/10/03)
Virtual screening studies have identified a series of phenylpyrroles as novel 5-HT7 receptor ligands. The synthesis and the affinity for the 5-HT7 receptor of these phenylpyrroles are described. Some of these compounds exhibited high affinity for the 5-HT7 receptors.
Novel HIV-1 protease inhibitors active against multiple PI-Resistant viral strains: Coadministration with indinavir
Kevin, Nancy J.,Duffy, Joseph L.,Kirk, Brian A.,Chapman, Kevin T.,Schleif, William A.,Olsen, David B.,Stahlhut, Mark,Rutkowski, Carrie A.,Kuo, Lawrence C.,Jin, Lixia,Lin, Jiunn H.,Emini, Emilio A.,Tata, James R.
, p. 4027 - 4030 (2007/10/03)
HIV-1 protease inhibitors (PI) with an N-arylpyrrole moiety in the P 3 position afforded excellent antiviral potency and substantially improved aqueous solubility over previously reported variants. The rapid in vitro clearance of these compounds in human liver microsomes prompted oral coadministration with indinavir to hinder their metabolism by the cyctochrome P450 3A4 isozyme and allow for in vivo PK assessment.
