title: Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors.
abstract: Imidazo[1,2-a]pyridine derivatives were designed, synthesized, and evaluated as inhibitors of the apoptosis signal-regulating kinase 1 (ASK1). These were based on a benzothiazole derivative that was discovered from high-throughput screening of our compound library. As a result, we identified potent, selective, and orally bioavailable ASK1 inhibitors for wide range of therapeutic targets.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan. yoshito.terao@takeda.com
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Terao
authors.forename: Hideo
authors.initials: H
authors.lastname: Suzuki
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshikawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yashiro
authors.forename: Shiro
authors.initials: S
authors.lastname: Takekawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Kengo
authors.initials: K
authors.lastname: Okada
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Shuhei
authors.initials: S
authors.lastname: Yao
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Uchikawa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D057166:High-Throughput Screening Assays; D048848:MAP Kinase Kinase Kinase 5 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011725:Pyridines; D048848:MAP Kinase Kinase Kinase 5; C001439:imidazo(1,2-a)pyridine