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Bioorg Med Chem Lett. 2016 Jan 1;26(1):60-7. doi: 10.1016/j.bmcl.2015.11.031. Epub 2015 Nov 12.

Identification of azabenzimidazoles as potent JAK1 selective inhibitors.

Author information

1
AstraZeneca R&D Boston, Oncology IMED, 35 Gatehouse Drive, Waltham, MA 02451, United States. Electronic address: melissa.vasbinder@astrazeneca.com.
2
AstraZeneca R&D Boston, Oncology IMED, 35 Gatehouse Drive, Waltham, MA 02451, United States.
3
Proteros Biostructures GmbH, Martinsried, D-82152, Germany.
4
AstraZeneca R&D Boston, Discovery Sciences, 35 Gatehouse Drive, Waltham, MA 02451, United States.
5
AstraZeneca R&D, Discovery Sciences, Darwin Building, 310 Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UK.

Abstract

We have identified a class of azabenzimidazoles as potent and selective JAK1 inhibitors. Investigations into the SAR are presented along with the structural features required to achieve selectivity for JAK1 versus other JAK family members. An example from the series demonstrated highly selective inhibition of JAK1 versus JAK2 and JAK3, along with inhibition of pSTAT3 in vivo, enabling it to serve as a JAK1 selective tool compound to further probe the biology of JAK1 selective inhibitors.

KEYWORDS:

Azabenzimidazoles; JAK selectivity; JAK1; JAK1 inhibitors

PMID:
26614408
DOI:
10.1016/j.bmcl.2015.11.031
[Indexed for MEDLINE]

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