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Orexins are hypothalamic peptides that play an important role in maintaining wakefulness in mammals. Permanent deficit in orexinergic function is a pathophysiological hallmark of rodent, canine and human narcolepsy. Here we report that in rats, dogs and humans, somnolence is induced by pharmacological blockade of both orexin OX(1) and OX(2) receptors. When(More)
This paper presents a pulse-duration tunable Ultra-Wideband (UWB) generator that is developed using a variable edge-rate signal. Edge-rate variability is introduced by applying a step recovery diode (SRD) to compress the edges of the source and then employing a simple RC network to adjust the edge-rate. Afterwards, the compressed signal is differentiated(More)
Replacement of the dimethoxyphenyl moiety in the core skeleton of almorexant by appropriately substituted imidazoles afforded novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as potent dual orexin receptor antagonists. We describe in this Letter our efforts to further optimize the potency and brain penetration of these derivatives by(More)
BACKGROUND Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical(More)
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