85870-47-9Relevant articles and documents
Discovery of the Bruton's Tyrosine Kinase Inhibitor Clinical Candidate TAK-020 (S)-5-(1-((1-Acryloylpyrrolidin-3-yl)oxy)isoquinolin-3-yl)-2,4-dihydro-3 H-1,2,4-triazol-3-one, by Fragment-Based Drug Design
Sabat, Mark,Dougan, Douglas R.,Knight, Beverly,Lawson, J. David,Scorah, Nicholas,Smith, Christopher R.,Taylor, Ewan R.,Vu, Phong,Wyrick, Corey,Wang, Haixia,Balakrishna, Deepika,Hixon, Mark,Madakamutil, Loui,McConn, Donavon
supporting information, p. 12893 - 12902 (2021/09/13)
This publication details the successful use of FBDD (fragment-based drug discovery) principles in the invention of a novel covalent Bruton's tyrosine kinase inhibitor, which ultimately became the Takeda Pharmaceuticals clinical candidate TAK-020. Describe
Antifungal activity, mode of action variability, and subcellular distribution of coumarin-based antifungal azoles
Elias, Rebecca,Benhamou, Raphael I.,Jaber, Qais Z.,Dorot, Orly,Zada, Sivan Louzoun,Oved,Pichinuk, Edward,Fridman
supporting information, p. 779 - 790 (2019/07/10)
Azole antifungals inhibit the biosynthesis of ergosterol, the fungal equivalent of cholesterol in mammalian cells. Here we report an investigation of the activity of coumarin-substituted azole antifungals. Screening against a panel of Candida pathogens, including a mutant lacking CYP51, the target of antifungal azoles, revealed that this enzyme is inhibited by triazole-based antifungals, whereas imidazole-based derivatives have more than one mode of action. The imidazole-bearing antifungals more effectively reduced trailing growth associated with persistence and/or recurrence of fungal infections than triazole-based derivatives. The imidazole derivatives were more toxic to mammalian cells and more potently inhibited the activity of CYP3A4, which is one of the main causes of azole toxicity. Using live cell imaging, we showed that regardless of the type of azole ring fluorescent 7-diethylaminocoumarin-based azoles localized to the endoplasmic reticulum, the organelle that harbors CYP51. This study suggests that the coumarin is a promising scaffold for development of novel azole-based antifungals that effectively localize to the fungal cell endoplasmic reticulum.
FLUORESCENT DYE AGENT AND CARBOSTYRIL COMPOUND
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Paragraph 0137; 0138, (2019/04/03)
PROBLEM TO BE SOLVED: To provide a novel fluorescent dye agent. SOLUTION: A fluorescent dye agent contains a carbostyril compound represented by formula (1) [in the formula (1), R1 is H, a halogen atom, a hydroxyl group, a cyano group, a nitro group or the like; R2 is O; R3 is a halogen atom, a carboxyl group, an ester group, an amide group or the like; R4-R6 and R8 independently represent H, a halogen atom, a nitro group, a cyano group or the like, where mutually adjacent groups of R4-R8 may be bound to form a ring; R7 is H, a substituted or unsubstituted aliphatic group or the like]. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
