Literature DB >> 24332487

Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors.

Yuanjun He1, Derek Duckett1, Weimin Chen1, Yuan Yuan Ling1, Michael D Cameron1, Li Lin1, Claudia H Ruiz1, Philip V Lograsso1, Theodore M Kamenecka1, Marcel Koenig2.   

Abstract

The design and synthesis of isoxazole 3 is described, a potent JNK inhibitor with two fold selectivity over p38. Optimization of this scaffold led to compounds 27 and 28 which showed greatly improved selectivity over p38 by maintaining the JNK3 potency of compound 3. Extensive SAR studies will be described as well as preliminary in vivo data of the two lead compounds.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  Isoxazole; JNK; Kinase; c-Jun

Mesh：

Substances：

Year:  2013        PMID： 24332487      PMCID： PMC4540177          DOI： 10.1016/j.bmcl.2013.11.052

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


  48 in total

Review 1.  MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein.

Authors:  Matthew R Lee; Celia Dominguez
Journal:  Curr Med Chem       Date:  2005       Impact factor: 4.530

2.  Highly selective c-Jun N-terminal kinase (JNK) 3 inhibitors with in vitro CNS-like pharmacokinetic properties II. Central core replacement.

Authors:  R Jeffrey Neitz; Andrei W Konradi; Hing L Sham; Wes Zmolek; Karina Wong; Ann Qin; Colin Lorentzen; David Nakamura; Kevin P Quinn; John-Michael Sauer; Kyle Powell; Lany Ruslim; David Chereau; Zhao Ren; John Anderson; Frédérique Bard; Ted A Yednock; Irene Griswold-Prenner
Journal:  Bioorg Med Chem Lett       Date:  2011-04-27       Impact factor: 2.823

3.  N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3.

Authors:  Richard M Angell; Francis L Atkinson; Murray J Brown; Tsu Tshen Chuang; John A Christopher; Maria Cichy-Knight; Allison K Dunn; Kendra E Hightower; Susanna Malkakorpi; James R Musgrave; Margarete Neu; Paul Rowland; Robyn L Shea; Jeffery L Smith; Donald O Somers; Sonia A Thomas; Gladstone Thompson; Ruolan Wang
Journal:  Bioorg Med Chem Lett       Date:  2006-12-15       Impact factor: 2.823

4.  Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3.

Authors:  Britt-Marie Swahn; Fernando Huerta; Elisabet Kallin; Jonas Malmström; Tatjana Weigelt; Jenny Viklund; Patrick Womack; Yafeng Xue; Liselotte Ohberg
Journal:  Bioorg Med Chem Lett       Date:  2005-11-15       Impact factor: 2.823

5.  JNK Inhibition Protects Dopamine Neurons and Provides Behavioral Improvement in a Rat 6-hydroxydopamine Model of Parkinson's Disease.

Authors:  Candice E Crocker; Susan Khan; Michael D Cameron; Harold A Robertson; George S Robertson; Philip Lograsso
Journal:  ACS Chem Neurosci       Date:  2011-04-20       Impact factor: 4.418

Review 6.  p38 mitogen-activated protein kinase pathways in asthma and COPD.

Authors:  Kian Fan Chung
Journal:  Chest       Date:  2011-06       Impact factor: 9.410

Review 7.  p38 MAP kinase inhibitors: many are made, but few are chosen.

Authors:  Celia Dominguez; David A Powers; Nuria Tamayo
Journal:  Curr Opin Drug Discov Devel       Date:  2005-07

8.  Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes.

Authors:  Stefan A Laufer; Gerd K Wagner; Dunja A Kotschenreuther; W Albrecht
Journal:  J Med Chem       Date:  2003-07-17       Impact factor: 7.446

9.  Synthesis and SAR of piperazine amides as novel c-jun N-terminal kinase (JNK) inhibitors.

Authors:  Youseung Shin; Weiming Chen; Jeff Habel; Derek Duckett; Yuan Yuan Ling; Marcel Koenig; Yuanjun He; Tomas Vojkovsky; Philip LoGrasso; Theodore M Kamenecka
Journal:  Bioorg Med Chem Lett       Date:  2009-03-26       Impact factor: 2.823

10.  The synthesis of highly substituted isoxazoles by electrophilic cyclization: an efficient synthesis of valdecoxib.

Authors:  Jesse P Waldo; Richard C Larock
Journal:  J Org Chem       Date:  2007-11-03       Impact factor: 4.354
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  6 in total

1.  N-Aromatic-Substituted Indazole Derivatives as Brain-Penetrant and Orally Bioavailable JNK3 Inhibitors.

Authors:  Yangbo Feng; HaJeung Park; Jae Cheon Ryu; Sung Ok Yoon
Journal:  ACS Med Chem Lett       Date:  2021-09-21       Impact factor: 4.632

Review 2.  Advances in Immunosuppressive Agents Based on Signal Pathway.

Authors:  Zhiqing Xu; Ming Chu
Journal:  Front Pharmacol       Date:  2022-05-26       Impact factor: 5.988

Review 3.  Selective inhibitors for JNK signalling: a potential targeted therapy in cancer.

Authors:  Qinghua Wu; Wenda Wu; Vesna Jacevic; Tanos C C Franca; Xu Wang; Kamil Kuca
Journal:  J Enzyme Inhib Med Chem       Date:  2020-12       Impact factor: 5.051

4.  Structural Optimization of a Pyridinylimidazole Scaffold: Shifting the Selectivity from p38α Mitogen-Activated Protein Kinase to c-Jun N-Terminal Kinase 3.

Authors:  Francesco Ansideri; Joana T Macedo; Michael Eitel; Ahmed El-Gokha; Dhafer S Zinad; Camilla Scarpellini; Mark Kudolo; Dieter Schollmeyer; Frank M Boeckler; Bärbel S Blaum; Stefan A Laufer; Pierre Koch
Journal:  ACS Omega       Date:  2018-07-12

5.  DNA Methylation Patterns of Chronic Explosive Breaching in U.S. Military Warfighters.

Authors:  Zhaoyu Wang; Caroline M Wilson; Yongchao Ge; Jeffrey Nemes; Christina LaValle; Angela Boutté; Walter Carr; Gary Kamimori; Fatemeh Haghighi
Journal:  Front Neurol       Date:  2020-10-23       Impact factor: 4.003

6.  Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway.

Authors:  Heon-Su Kim; Jung-Soo Suh; Yoon-Kwan Jang; Sang-Hyun Ahn; Ganesan Raja; Jin-Chul Kim; Youngmi Jung; Sang Hoon Jung; Tae-Jin Kim
Journal:  Sci Rep       Date:  2020-10-22       Impact factor: 4.379
  6 in total

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