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Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin

Jones, Peter, Storer, Ian, Sabnis, Yogesh A., Wakenhut, Florian M., Whitlock, Gavin A., England, Katherine S., Mukaiyama, Takasuke, Dehnhardt, Christoph M., Coe, Jotham W., Kortum, Steve W., and others. (2016) Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin. Journal of Medicinal Chemistry, 60 (2). pp. 767-786. ISSN 0022-2623. (doi:10.1021/acs.jmedchem.6b01634)

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http://dx.doi.org/10.1021/acs.jmedchem.6b01634

Abstract

By use of a structure-based computational method for identification of structurally novel Janus kinase (JAK) inhibitors predicted to bind beyond the ATP binding site, a potent series of indazoles was identified as selective pan-JAK inhibitors with a type 1.5 binding mode. Optimization of the series for potency and increased duration of action commensurate with inhaled or topical delivery resulted in potent pan-JAK inhibitor 2 (PF-06263276), which was advanced into clinical studies.

Item Type: Article
DOI/Identification number: 10.1021/acs.jmedchem.6b01634
Uncontrolled keywords: Structure Based Drug Design JAK inhibitors
Subjects: Q Science > QD Chemistry > QD431 Organic Chemistry- Biochemistry- Proteins, peptides, amino acids
Divisions: Faculties > Sciences > School of Biosciences > Protein Science Group
Depositing User: David Brown
Date Deposited: 23 Jan 2017 13:46 UTC
Last Modified: 30 Jan 2020 10:04 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/60028 (The current URI for this page, for reference purposes)
Brown, David G.: https://orcid.org/0000-0003-4605-4779
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