Literature DB >> 28947151

Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective IRAK4 inhibitors.

Rajeev S Bhide1, Alec Keon2, Carolyn Weigelt3, John S Sack3, Robert J Schmidt2, Shuqun Lin2, Hai-Yun Xiao2, Steven H Spergel2, James Kempson2, William J Pitts2, Julie Carman4, Michael A Poss2.   

Abstract

The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay.
Copyright © 2017 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  4,6-Diaminonicotinamide; Autoimmune disease; IRAK4; Rheumatoid arthritis

Mesh：

Substances：

Year:  2017        PMID： 28947151     DOI： 10.1016/j.bmcl.2017.09.029

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  3 in total

1.  Optimization of Nicotinamides as Potent and Selective IRAK4 Inhibitors with Efficacy in a Murine Model of Psoriasis.

Authors:  Satheesh Nair; Sreekantha Ratna Kumar; Venkatram Reddy Paidi; Ramesh Sistla; Durgarao Kantheti; Subba Rao Polimera; Soodamani Thangavel; Amrita Jha Mukherjee; Mitalee Das; Rajeev S Bhide; William J Pitts; Natesan Murugesan; Shailesh Dudhgoankar; Jignesh Nagar; Siva Subramani; Debarati Mazumder; Julie A Carman; Deborah A Holloway; Xin Li; Mark P Fereshteh; Stefan Ruepp; Kamalavenkatesh Palanisamy; T Thanga Mariappan; Srinivas Maddi; Ajay Saxena; Paul Elzinga; Anjaneya Chimalakonda; Qian Ruan; Kaushik Ghosh; Sucharita Bose; John Sack; Chunhong Yan; Susan E Kiefer; Dianlin Xie; John A Newitt; S Pon Saravanakumar; Richard A Rampulla; Joel C Barrish; Percy H Carter; John Hynes
Journal:  ACS Med Chem Lett       Date:  2020-06-10       Impact factor: 4.345

2.  Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1.

Authors:  Andrew P Degnan; Godwin K Kumi; Christopher W Allard; Erika V Araujo; Walter L Johnson; Kurt Zimmermann; Bradley C Pearce; Steven Sheriff; Alan Futran; Xin Li; Gregory A Locke; Dan You; John Morrison; Karen E Parrish; Caitlyn Stromko; Anwar Murtaza; Jinqi Liu; Benjamin M Johnson; Gregory D Vite; Mark D Wittman
Journal:  ACS Med Chem Lett       Date:  2021-02-19       Impact factor: 4.345

3.  Design of Novel IRAK4 Inhibitors Using Molecular Docking, Dynamics Simulation and 3D-QSAR Studies.

Authors:  Swapnil P Bhujbal; Weijie He; Jung-Mi Hah
Journal:  Molecules       Date:  2022-09-24       Impact factor: 4.927
  3 in total

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