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Rational Design, Synthesis and Evaluation of Novel C6 ‐Bicycloalkaneimidazole Containing Imidazo[1,2‐ b ]pyridazines for ASK1 Inhibition
Author(s) -
Lee Yujin,
Jang Jiyoon,
Bibi Maimoona,
Duggirala Krishna Babu,
Ji Sang Hee,
Lee Ji Hun,
Ahn Sunjoo,
Song Jin Sook,
Chae Chong Hak,
Kim Seong Hwan,
Lee Kwangho
Publication year - 2021
Publication title -
bulletin of the korean chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.237
H-Index - 59
ISSN - 1229-5949
DOI - 10.1002/bkcs.12275
Subject(s) - ask1 , kinase , chemistry , pyridazine , p38 mitogen activated protein kinases , map kinase kinase kinase , biochemistry , cyclin dependent kinase 2 , microbiology and biotechnology , pharmacology , protein kinase a , biology , stereochemistry
Apoptosis signal‐regulating kinase 1 (ASK1) is a member of mitogen‐activated protein kinase kinase kinase (MAP3K) family that involves downstream phosphorylation of MAP kinases, c‐Jun N‐terminal kinases, and p38 MAP kinases. ASK1 inhibitors could possibly be beneficial for ameliorating the development and progression of diseases. Especially, ASK1 has been of interest as one of therapeutic targets for nonalcoholic fatty liver disease as the most common chronic liver diseases including simple steatosis and nonalcoholic steatohepatitis. In this manuscript, novel ASK1 inhibitor lead KTA‐29 which has an imidazo[1,2‐ b ]pyridazine core with novel C6‐bicycloheptaneimidazole is disclosed. With the novel imidazo[1,2‐ b ]pyridazine core, structure‐activity‐relationship study for ASK1 potency is described and KTA‐29 affinity toward ASK1 with molecular modeling study is explained.