There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium… (More)
The authors report a case of an anaplastic astrocytoma which on magnetic resonance imaging and direct visualisation was continuous with an area of gliosis in the left frontal lobe. This gliosis was secondary to a head injury received 19 years earlier that required evacuation of an intracerebral haematoma. This case largely meets the accepted criteria for… (More)
The antiplasmodial activity, DMPK properties, and efficacy of a series of quinoline-4-carboxamides are described. This series was identified from a phenotypic screen against the blood stage of Plasmodium falciparum (3D7) and displayed moderate potency but with suboptimal physicochemical properties and poor microsomal stability. The screening hit (1, EC50 =… (More)
In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a… (More)
A rare case of retro-odontoid disc sequestration causing significant cord compression and progressive neurological deterioration is presented. The clinical history, radiology, treatment and pathogenesis of the case are described, along with a review of the relevant literature.