Discovery of orally bioavailable inhibitors of MALT1 with in vivo activity for psoriasis

[Display omitted] We report the design, synthesis, and biological activity of a series of compounds that exhibit potent mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) inhibition. Structural transformation of the substructures of a starting compound gave amidomethyl derivatives an...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Bioorganic & medicinal chemistry letters 2023-02, Vol.82, p.129155-129155, Article 129155
Hauptverfasser: Nunettsu Asaba, Ken, Okimura, Keiichi, Adachi, Yohei, Tokumaru, Kazuyuki, Goto, Yasufumi, Fujii, Shigeo, Watanabe, Akira, Sakai, Chizuka, Sakurada, Eri, Amikura, Kazutoshi, Aoki, Takumi
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:[Display omitted] We report the design, synthesis, and biological activity of a series of compounds that exhibit potent mucosa-associated lymphoid tissue lymphoma translocation 1 (MALT1) inhibition. Structural transformation of the substructures of a starting compound gave amidomethyl derivatives and sulfonylguanidine derivatives that exhibited potent inhibition of MALT1. Compound 37 had good oral bioavailability and showed anti-psoriatic activity in an imiquimod-induced psoriasis mouse model after oral administration.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2023.129155