Bioorganic & medicinal chemistry letters
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Bioorg. Med. Chem. Lett. · Jun 2013
LetterNovel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1.
The identification of a novel fused triazolo-pyrrolopyridine scaffold, optimized derivatives of which display nanomolar inhibition of Janus kinase 1, is described. Prototypical example 3 demonstrated lower cell potency shift, better permeability in cells and higher oral exposure in rat than the corresponding, previously reported, imidazo-pyrrolopyridine analogue 2. Examples 6, 7 and 18 were subsequently identified from an optimization campaign and demonstrated modest selectivity over JAK2, moderate to good oral bioavailability in rat with overall pharmacokinetic profiles comparable to that reported for an approved pan-JAK inhibitor (tofacitinib).
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Bioorg. Med. Chem. Lett. · Jun 2013
An analysis of the synthetic tryptamines AMT and 5-MeO-DALT: emerging 'Novel Psychoactive Drugs'.
Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of two widely marketed tryptamine-derived NPDs, namely alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine.