Literature DB >> 21316221

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

Yuanjun He1, Theodore M Kamenecka, Youseung Shin, Xinyi Song, Rong Jiang, Romain Noel, Derek Duckett, Weimin Chen, Yuan Yuan Ling, Michael D Cameron, Li Lin, Susan Khan, Marcel Koenig, Philip V LoGrasso.   

Abstract

Quinazoline 3 was discovered as a novel c-jun N-terminal kinase (JNK) inhibitor with good brain penetration and pharmacokinetic (PK) properties. A number of analogs which were potent both in the biochemical and cellular assays were discovered. Quinazoline 13a was found to be a potent JNK3 inhibitor (IC(50)=40 nM), with >500-fold selectivity over p38, and had good PK and brain penetration properties. With these properties, 13a is considered a potential candidate for in vivo evaluation.
Copyright © 2011 Elsevier Ltd. All rights reserved.

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Year:  2011        PMID： 21316221      PMCID： PMC3052630          DOI： 10.1016/j.bmcl.2011.01.079

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


  23 in total

1.  Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.

Authors:  Bruce G Szczepankiewicz; Christi Kosogof; Lissa T J Nelson; Gang Liu; Bo Liu; Hongyu Zhao; Michael D Serby; Zhili Xin; Mei Liu; Rebecca J Gum; Deanna L Haasch; Sanyi Wang; Jill E Clampit; Eric F Johnson; Thomas H Lubben; Michael A Stashko; Edward T Olejniczak; Chaohong Sun; Sarah A Dorwin; Kristi Haskins; Cele Abad-Zapatero; Elizabeth H Fry; Charles W Hutchins; Hing L Sham; Cristina M Rondinone; James M Trevillyan
Journal:  J Med Chem       Date:  2006-06-15       Impact factor: 7.446

2.  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

3.  Design and synthesis of 2'-anilino-4,4'-bipyridines as selective inhibitors of c-Jun N-terminal kinase-3.

Authors:  Britt-Marie Swahn; Yafeng Xue; Erwan Arzel; Elisabet Kallin; Angelika Magnus; Niklas Plobeck; Jenny Viklund
Journal:  Bioorg Med Chem Lett       Date:  2005-12-05       Impact factor: 2.823

4.  Inhibitors of c-jun-N-terminal kinase (JNK).

Authors:  Philip LoGrasso; Theodore Kamenecka
Journal:  Mini Rev Med Chem       Date:  2008-07       Impact factor: 3.862

5.  Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.

Authors:  Ted Kamenecka; Rong Jiang; Xinyi Song; Derek Duckett; Weimin Chen; Yuan Yuan Ling; Jeff Habel; John D Laughlin; Jeremy Chambers; Mariana Figuera-Losada; Michael D Cameron; Li Lin; Claudia H Ruiz; Philip V LoGrasso
Journal:  J Med Chem       Date:  2010-01-14       Impact factor: 7.446

6.  Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors.

Authors:  Mahbub Alam; Rebekah E Beevers; Tom Ceska; Richard J Davenport; Karen M Dickson; Mara Fortunato; Lewis Gowers; Alan F Haughan; Lynwen A James; Mark W Jones; Natasha Kinsella; Christopher Lowe; Johannes W G Meissner; Anne-Lise Nicolas; Benjamin G Perry; David J Phillips; William R Pitt; Adam Platt; Andrew J Ratcliffe; Andrew Sharpe; Laura J Tait
Journal:  Bioorg Med Chem Lett       Date:  2007-03-30       Impact factor: 2.823

7.  AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils.

Authors:  S Carboni; U Boschert; P Gaillard; J-P Gotteland; J-Y Gillon; P-A Vitte
Journal:  Br J Pharmacol       Date:  2007-11-19       Impact factor: 8.739

8.  Structure-activity relationships and X-ray structures describing the selectivity of aminopyrazole inhibitors for c-Jun N-terminal kinase 3 (JNK3) over p38.

Authors:  Ted Kamenecka; Jeff Habel; Derek Duckett; Weimin Chen; Yuan Yuan Ling; Bozena Frackowiak; Rong Jiang; Youseung Shin; Xinyi Song; Philip LoGrasso
Journal:  J Biol Chem       Date:  2009-03-04       Impact factor: 5.157

9.  3,5-Disubstituted quinolines as novel c-Jun N-terminal kinase inhibitors.

Authors:  Rong Jiang; Derek Duckett; Weiming Chen; Jeff Habel; Yuan Yuan Ling; Philip LoGrasso; Theodore M Kamenecka
Journal:  Bioorg Med Chem Lett       Date:  2007-08-26       Impact factor: 2.823

10.  Synthesis and SAR of 4-substituted-2-aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors.

Authors:  Paul S Humphries; Jennifer A Lafontaine; Charles S Agree; David Alexander; Ping Chen; Quyen-Quyen T Do; Lilian Y Li; Elizabeth A Lunney; Ranjan J Rajapakse; Karen Siegel; Sergei L Timofeevski; Tianlun Wang; David M Wilhite
Journal:  Bioorg Med Chem Lett       Date:  2009-03-13       Impact factor: 2.823
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  13 in total

Review 1.  JNK signalling in cancer: in need of new, smarter therapeutic targets.

Authors:  Concetta Bubici; Salvatore Papa
Journal:  Br J Pharmacol       Date:  2014-01       Impact factor: 8.739

2.  Identification and characterization of a novel class of c-Jun N-terminal kinase inhibitors.

Authors:  Igor A Schepetkin; Liliya N Kirpotina; Andrei I Khlebnikov; Tracey S Hanks; Irina Kochetkova; David W Pascual; Mark A Jutila; Mark T Quinn
Journal:  Mol Pharmacol       Date:  2012-03-20       Impact factor: 4.436

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

Authors:  Yuanjun He; Derek Duckett; Weimin Chen; Yuan Yuan Ling; Michael D Cameron; Li Lin; Claudia H Ruiz; Philip V Lograsso; Theodore M Kamenecka; Marcel Koenig
Journal:  Bioorg Med Chem Lett       Date:  2013-12-04       Impact factor: 2.823

4.  Pyridopyrimidinone Derivatives as Potent and Selective c-Jun N-Terminal Kinase (JNK) Inhibitors.

Authors:  Ke Zheng; Chul Min Park; Sarah Iqbal; Pamela Hernandez; HaJeung Park; Philip V LoGrasso; Yangbo Feng
Journal:  ACS Med Chem Lett       Date:  2015-03-02       Impact factor: 4.345

5.  Epidrugs in Amyotrophic Lateral Sclerosis/Frontotemporal Dementia: Contextualizing a Role for Histone Kinase Inhibition in Neurodegenerative Disease.

Authors:  Samantha N Cobos; Mariana P Torrente
Journal:  ACS Pharmacol Transl Sci       Date:  2022-01-21

6.  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 7.  Interleukins in glioblastoma pathophysiology: implications for therapy.

Authors:  Y T Yeung; K L McDonald; T Grewal; L Munoz
Journal:  Br J Pharmacol       Date:  2013-02       Impact factor: 8.739

8.  ULK1 and JNK are involved in mitophagy incurred by LRRK2 G2019S expression.

Authors:  Yuangang Zhu; Chunyan Wang; Mei Yu; Jie Cui; Liang Liu; Zhiheng Xu
Journal:  Protein Cell       Date:  2013-09-10       Impact factor: 14.870

9.  A small molecule bidentate-binding dual inhibitor probe of the LRRK2 and JNK kinases.

Authors:  Yangbo Feng; Jeremy W Chambers; Sarah Iqbal; Marcel Koenig; HaJeung Park; Lisa Cherry; Pamela Hernandez; Mariana Figuera-Losada; Philip V LoGrasso
Journal:  ACS Chem Biol       Date:  2013-06-10       Impact factor: 5.100

10.  JNK isoforms differentially regulate neurite growth and regeneration in dopaminergic neurons in vitro.

Authors:  Lars Tönges; Veronique Planchamp; Jan-Christoph Koch; Thomas Herdegen; Mathias Bähr; Paul Lingor
Journal:  J Mol Neurosci       Date:  2011-04-06       Impact factor: 3.444
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