Details

Autor(en) / Beteiligte

• Hurley, Christopher A.
• Blair, Wade S.
• Bull, Richard J.
• Chang, Christine
• Crackett, Peter H.
• Deshmukh, Gauri
• Dyke, Hazel J.
• Fong, Rina
• Ghilardi, Nico
• Gibbons, Paul
• Hewitt, Peter R.
• Johnson, Adam
• Johnson, Tony
• Kenny, Jane R.
• Kohli, Pawan Bir
• Kulagowski, Janusz J.
• Liimatta, Marya
• Lupardus, Patrick J.
• Maxey, Robert J.
• Mendonca, Rohan
• Narukulla, Raman
• Pulk, Rebecca
• Ubhayakar, Savita
• van Abbema, Anne
• Ward, Stuart I.
• Waszkowycz, Bohdan
• Zak, Mark

Titel

Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2013-06, Vol.23 (12), p.3592-3598

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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).