Macrolide Inspired Macrocycles as Modulators of the IL-17A/IL-17RA Interaction.

Journal of Medicinal Chemistry
Sanja KoštrunMartin Stahlhut

Abstract

Interleukin 17 (IL-17) cytokines promote inflammatory pathophysiology in many autoimmune diseases, including psoriasis, multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. Such broad involvement of IL-17 in various autoimmune diseases makes it an ideal target for drug discovery. Psoriasis is a chronic inflammatory disease characterized by numerous defective components of the immune system. Significantly higher levels of IL-17A have been noticed in lesions of psoriatic patients, if compared to non-lesion parts. Therefore, this paper is focused on the macrolide inspired macrocycles as potential IL-17A/IL-17RA modulators and covers the molecular design, synthesis, and in vitro profiling. Macrocycles are designed to diversify and enrich chemical space through different ring sizes and a variety of three-dimensional shapes. Inhibitors in the nM range were identified in both target-based and phenotypic assays. In vitro ADME as well as in vivo PK properties are reported.

References

Oct 20, 2009·Journal of Molecular Biology·Stefan GerhardtCaroline Russell
Dec 17, 2009·Seminars in Immunopathology·Allen W Ho, Sarah L Gaffen
Jan 7, 2011·Journal of Medicinal Chemistry·Višnja StepanićVesna Munić
Aug 27, 2011·Chemical Reviews·Ayman El-Faham, Fernando Albericio
Dec 14, 2011·European Journal of Medicinal Chemistry·Višnja StepanićSanja Koštrun
Sep 28, 2012·The Journal of Investigative Dermatology·Rosa ParisiUNKNOWN Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team
May 23, 2013·Nature Communications·Shenping LiuMatthew C Griffor
Sep 21, 2013·Journal of Medicinal Chemistry·Fabrizio Giordanetto, Jan Kihlberg
Mar 10, 2011·ACS Medicinal Chemistry Letters·Tomohiro Sugimoto, Tetsuya Tanikawa
Dec 1, 2004·Drug Discovery Today. Technologies·Christopher A Lipinski
Jul 21, 2014·Nature Chemical Biology·Elizabeth A VillarAdrian Whitty
Sep 16, 2014·Angewandte Chemie·Daniel S NielsenDavid P Fairlie
Sep 23, 2014·Chemistry & Biology·Michelle R ArkinJames A Wells
Dec 18, 2014·Journal of the American Chemical Society·William M HewittR Scott Lokey
Jun 13, 2015·Future Medicinal Chemistry·Christopher L AhlbachR Scott Lokey
Feb 9, 2016·Journal of Medicinal Chemistry·Alfonso EspadaJeffrey A Dodge
Feb 20, 2016·Drug Discovery Today·Adrian WhittySandor Vajda
May 18, 2016·Scientific Reports·Shenping LiuLauren D Wood
May 20, 2016·Nature·Ian B SeipleAndrew G Myers
Aug 17, 2016·Scientific Reports·Shenping LiuAtli Thorarensen
Oct 21, 2016·ChemMedChem·Gabriela B SantosFlavio S Emery
Oct 5, 2016·Current Topics in Medicinal Chemistry·Hana Cipcic PaljetakMihaela Peric
Dec 5, 2016·Pathogens and Disease·Maria Valeri, Manuela Raffatellu
Mar 2, 2017·Current Opinion in Chemical Biology·Alessandro ZorziChristian Heinis
Apr 15, 2017·European Journal of Medicinal Chemistry·Sanja KoštrunSulejman Alihodžić
Apr 24, 2018·Progress in Medicinal Chemistry·Sulejman AlihodžićDinko Žiher
Jun 14, 1999·Angewandte Chemie·Moriz Mayer, Bernd Meyer
May 12, 2018·MedChemComm·Wenjia WangAlexander Dömling
Aug 4, 2018·Journal of Medicinal Chemistry·Richard L MackmanBrian E Schultz
Aug 16, 2018·Clinical Reviews in Allergy & Immunology·Andrew Blauvelt, Andrea Chiricozzi
Aug 22, 2018·Frontiers in Immunology·Nicolo Costantino BrembillaWolf-Henning Boehncke
Dec 1, 2018·Expert Opinion on Biological Therapy·Annika Silfvast-KaiserAlan Menter
Aug 27, 2019·Frontiers in Pharmacology·Lazaros I SakkasDimitrios P Bogdanos

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