Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3

3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead c...

Descripción completa

Detalles Bibliográficos
Autores principales: Oh, Youri, Jang, Miyoung, Cho, Hyunwook, Yang, Songyi, Im, Daseul, Moon, Hyungwoo, Hah, Jung-Mi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968587/
https://www.ncbi.nlm.nih.gov/pubmed/31856610
http://dx.doi.org/10.1080/14756366.2019.1705294
_version_ 1783489166161477632
author Oh, Youri
Jang, Miyoung
Cho, Hyunwook
Yang, Songyi
Im, Daseul
Moon, Hyungwoo
Hah, Jung-Mi
author_facet Oh, Youri
Jang, Miyoung
Cho, Hyunwook
Yang, Songyi
Im, Daseul
Moon, Hyungwoo
Hah, Jung-Mi
author_sort Oh, Youri
collection PubMed
description 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC(50) value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.
format Online
Article
Text
id pubmed-6968587
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-69685872020-01-30 Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3 Oh, Youri Jang, Miyoung Cho, Hyunwook Yang, Songyi Im, Daseul Moon, Hyungwoo Hah, Jung-Mi J Enzyme Inhib Med Chem Short Communication 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC(50) value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3. Taylor & Francis 2019-12-19 /pmc/articles/PMC6968587/ /pubmed/31856610 http://dx.doi.org/10.1080/14756366.2019.1705294 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Oh, Youri
Jang, Miyoung
Cho, Hyunwook
Yang, Songyi
Im, Daseul
Moon, Hyungwoo
Hah, Jung-Mi
Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
title Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
title_full Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
title_fullStr Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
title_full_unstemmed Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
title_short Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3
title_sort discovery of 3-alkyl-5-aryl-1-pyrimidyl-1h-pyrazole derivatives as a novel selective inhibitor scaffold of jnk3
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968587/
https://www.ncbi.nlm.nih.gov/pubmed/31856610
http://dx.doi.org/10.1080/14756366.2019.1705294
work_keys_str_mv AT ohyouri discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3
AT jangmiyoung discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3
AT chohyunwook discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3
AT yangsongyi discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3
AT imdaseul discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3
AT moonhyungwoo discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3
AT hahjungmi discoveryof3alkyl5aryl1pyrimidyl1hpyrazolederivativesasanovelselectiveinhibitorscaffoldofjnk3

Ejemplares similares