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A sequencing of a finite group G is an ordering of its elements xi = e, x2, * . . , x, such that the partial products of its nonempty initial segments are all the elements of G (necessarily listed without repetition). Sequencings are related to some other interesting constructions, see e.g. [6]. They have been investigated for abelian groups [3], groups of(More)
Introduction. A celebrated reviewer once described a certain paper (in a phrase which never actually saw publication in Mathematical Reviews) as being concerned with the study of "valueless measures on pointless spaces". This article contains nothing about measures, valueless or otherwise; but I hope that by giving a historical survey of the subject known(More)
Successful drug discovery relies on the selection of drug candidates with good in vivo pharmacokinetic (PK) properties as well as appropriate preclinical efficacy and safety profiles. In vivo PK profiling is often a bottleneck in the discovery process. In this review, we focus on the tiered in vivo PK approaches implemented at the Genomics Institute of the(More)
With the extensive use of different strains of mice and rats in in vivo efficacy models, lack of relevant metabolic clearance data among strains has been a concern. Metabolic clearance is an important parameter impacting drug discovery, and it is often used as a compound selection filter. Metabolically stable compounds are often preferred, and will have a(More)
The 1,536-well microplate format has widely supplanted the 384-well microplate format for high-throughput screening and for IC(50) assays. Previously, liquid chromatography/mass spectrometry (LC/MS) analyses of such samples required manual transfers of the wells of interest from a 1,536-well plate into a 384-well plate. Because this manual transfer(More)
We report on the development of a parallel HPLC/MS purification system incorporating an indexed (i.e., multiplexed) ion source. In the method described, each of the flow streams from a parallel array of HPLC columns is directed toward the multiplexed (MUX) ion source and sampled in a time-dependent, parallel manner. A visual basic application has been(More)
Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of(More)
A novel family of 1H-imidazol-2-yl-pyrimidine-4,6-diamines has been identified with potent activity against the erythrocyte-stage of Plasmodium falciparum (Pf), the most common causative agent of malaria. A systematic SAR study resulted in the identification of compound 40 which exhibits good potency against both wild-type and drug resistant parasites and(More)
On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a(More)