Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors

Mei Liu; Zhili Xin; Jill E Clampit; Sanyi Wang; Rebecca J Gum; Deanna L Haasch; James M Trevillyan; Cele Abad-Zapatero; Elizabeth H Fry; Hing L Sham; Gang Liu

doi:10.1016/j.bmcl.2006.02.046

Synthesis and SAR of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as novel, selective c-Jun N-terminal kinase inhibitors

Bioorg Med Chem Lett. 2006 May 15;16(10):2590-4. doi: 10.1016/j.bmcl.2006.02.046. Epub 2006 Mar 9.

Authors

Mei Liu¹, Zhili Xin, Jill E Clampit, Sanyi Wang, Rebecca J Gum, Deanna L Haasch, James M Trevillyan, Cele Abad-Zapatero, Elizabeth H Fry, Hing L Sham, Gang Liu

Affiliation

¹ Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6098, USA. [email protected]

PMID: 16527482
DOI: 10.1016/j.bmcl.2006.02.046

Abstract

A novel class of 1,9-dihydro-9-hydroxypyrazolo[3,4-b]quinolin-4-ones as c-Jun-N-terminal kinase (JNK) inhibitors is described. These compounds were synthesized via the condensation of 2-nitrobenzaldehydes and hydroxypyrazoles. The structure-activity relationships (SAR) and kinase selectivity profile of the inhibitors are also discussed. Compound 16 was identified as a potent JNK inhibitor with good cellular potency.

MeSH terms

Crystallography, X-Ray
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Molecular Structure
Quinolones / chemistry
Quinolones / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Quinolones
JNK Mitogen-Activated Protein Kinases