- Discovery and structure-activity relationships of pyrrolone antimalarials
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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.
- 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.
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supporting information
p. 2975 - 2990
(2013/05/23)
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- HETEROCYCLIC MCHr1 ANTAGONISTS AND THEIR USE IN THERAPY
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Compounds of formula I depicted below, pharmaceutical compositions containing them, processes for preparing the compounds, and their use in the treatment of obesity, type II diabetes, metabolic syndrome, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy and related conditions, neurological disorders such as dementia, multiple sclerosis, Parkinson's disease, Huntington's chorea and Alzheimer's disease, and pain related disorders. The compounds are melanin concentrating hormone receptor 1 (MCHr1) antagonists.
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Page/Page column 43
(2008/06/13)
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- N-PIPERIDINE DERIVATES AS CCR3 MODULATORS
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Compounds of formula I, processes for preparing such compounds, their use in the treatment of obesity, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy, and related conditions, and neurological disorders such as dement
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Page/Page column 50
(2008/06/13)
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- THERAPEUTIC AGENTS I
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Compounds of formula(I), processes for preparing such compounds, their use in the treatment of obesity, psychiatric disorders, cognitive disorders, memory disorders, schizophrenia, epilepsy, and related conditions, and neurological disorders such as dementia, multiple sclerosis, Parkinson's disease, Huntington's chorea and Alzheimer's disease and pain related disorders, and pharmaceutical compositions containing them.
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Page/Page column 46
(2010/02/12)
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- Novel HIV-1 protease inhibitors active against multiple PI-Resistant viral strains: Coadministration with indinavir
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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.
- 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.
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p. 4027 - 4030
(2007/10/03)
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- A convenient rearrangement of 1-phenylpyrrole-2-carboxaldehydes into their 3-isomers
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1-Phenylpyrrole-2-carboxaldehydes are selectively and in high yield converted by treatment with trifluoromethanesulfonic acid (triflic acid) to 1-phenylpyrrole-3-carboxaldehydes.
- Dallemagne,Rault,Fabis,Dumoulin,Robba
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p. 1855 - 1857
(2007/10/02)
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