204122-20-3Relevant academic research and scientific papers
Discovery of orally efficacious RORγt inverse agonists. Part 2: Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives
Kono, Mitsunori,Oda, Tsuneo,Tawada, Michiko,Imada, Takashi,Banno, Yoshihiro,Taya, Naohiro,Kawamoto, Tetsuji,Tokuhara, Hidekazu,Tomata, Yoshihide,Ishii, Naoki,Ochida, Atsuko,Fukase, Yoshiyuki,Yukawa, Tomoya,Fukumoto, Shoji,Watanabe, Hiroyuki,Uga, Keiko,Shibata, Akira,Nakagawa, Hideyuki,Shirasaki, Mikio,Fujitani, Yasushi,Yamasaki, Masashi,Shirai, Junya,Yamamoto, Satoshi
, p. 470 - 482 (2018/01/05)
A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay.
Discovery of orally efficacious RORγt inverse agonists. Part 2: Design, synthesis, and biological evaluation of novel tetrahydroisoquinoline derivatives
Kono, Mitsunori,Oda, Tsuneo,Tawada, Michiko,Imada, Takashi,Banno, Yoshihiro,Taya, Naohiro,Kawamoto, Tetsuji,Tokuhara, Hidekazu,Tomata, Yoshihide,Ishii, Naoki,Ochida, Atsuko,Fukase, Yoshiyuki,Yukawa, Tomoya,Fukumoto, Shoji,Watanabe, Hiroyuki,Uga, Keiko,Shibata, Akira,Nakagawa, Hideyuki,Shirasaki, Mikio,Fujitani, Yasushi,Yamasaki, Masashi,Shirai, Junya,Yamamoto, Satoshi
, p. 470 - 482 (2019/05/09)
A series of tetrahydroisoquinoline derivatives were designed, synthesized, and evaluated for their potential as novel orally efficacious retinoic acid receptor-related orphan receptor-gamma t (RORγt)inverse agonists for the treatment of Th17-driven autoimmune diseases. We carried out cyclization of the phenylglycinamide core by structure-based drug design and successfully identified a tetrahydroisoquinoline carboxylic acid derivative 14 with good biochemical binding and cellular reporter activity. Interestingly, the combination of a carboxylic acid tether and a central fused bicyclic ring was crucial for optimizing PK properties, and the compound 14 showed significantly improved PK profile. Successive optimization of the carboxylate tether led to the discovery of compound 15 with increased inverse agonistic activity and an excellent PK profile. Oral treatment of mice with compound 15 robustly and dose-dependently inhibited IL-17A production in an IL23-induced gene expression assay.
Heterocyclic compound
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, (2016/10/08)
The present invention relates to compound (I) or a salt thereof which has a ROR γ t inhibitory action. wherein each symbol is as defined in the specification.
New generation dopaminergic agents. 2. Discovery of 3-OH-phenoxyethylamine and 3-OH-N1-phenylpiperazine dopaminergic templates
Mewshaw, Richard E.,Husbands, Morris,Gildersleeve, Elizabeth S.,Webb, Michael B.,Shi, Xiaojie,Mazandarani, Hossein,Cockett, Mark I.,Ochalski, Rafal,Brennan, Julie A.,Abou-Gharbia, Magid,Marquis, Karen,McGaughey, Georgia B.,Coupet, Joseph,Andree, Terrance H.
, p. 295 - 300 (2007/10/03)
Described in this report is a systematic study which led to the identification of two new dopamine D2 partial agonists (5 and 17). Phenols 5 and 17 represent prototypes of two new classes of D2 partial agonist as well as templates for the future design of novel dopaminergic agents.
