- Discovery of isatin and 1H-indazol-3-ol derivatives as D-amino acid oxidase (DAAO) inhibitors
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D-Amino acid oxidase (DAAO) is a potential target in the treatment of schizophrenia as its inhibition increases brain D-serine level and thus contributes to NMDA receptor activation. Inhibitors of DAAO were sought testing [6+5] type heterocycles and identified isatin derivatives as micromolar DAAO inhibitors. A pharmacophore and structure-activity relationship analysis of isatins and reported DAAO inhibitors led us to investigate 1H-indazol-3-ol derivatives and nanomolar inhibitors were identified. The series was further characterized by pKa and isothermal titration calorimetry measurements. Representative compounds exhibited beneficial properties in in vitro metabolic stability and PAMPA assays. 6-fluoro-1H-indazol-3-ol (37) significantly increased plasma D-serine level in an in vivo study on mice. These results show that the 1H-indazol-3-ol series represents a novel class of DAAO inhibitors with the potential to develop drug candidates.
- Szilágyi, Bence,Kovács, Péter,Ferenczy, Gy?rgy G.,Rácz, Anita,Németh, Krisztina,Visy, Júlia,Szabó, Pál,Ilas, Janez,Balogh, Gy?rgy T.,Monostory, Katalin,Vincze, István,Tábi, Tamás,Sz?k?, éva,Keser?, Gy?rgy M.
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p. 1579 - 1587
(2018/02/23)
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- EGFR INHIBITOR, AND PREPARATION AND APPLICATION THEREOF
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A 4-substituted-2-(N-(5-substituted allyl amide)phenyl)amino)pyrimidine derivative as represented by formula (I), and a preparation and application thereof as an EGFR inhibitor. The compound has activity of inhibiting the L858R EGFR mutant, the T790M EGFR mutant and the exon 19 deletion activating mutant, may be used to treat diseases mediated alone or in part by EGFR mutant activity, and has a wide application in drugs preventing and treating cancers, particularly non-small cell lung cancer.
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Paragraph 0106; 0565; 0566
(2017/09/02)
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- Bacterial translation inhibitors, 1-acylindazol-3-ols as anthranilic acid mimics
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The discovery and initial optimization of a novel anthranilic acid derived class of antibacterial agents has been described in a recent series of papers. This paper describes the discovery of 1-acylindazol-3-ols as a novel bioisostere of an anthranilic acid. The synthesis and structure-activity relationships of the indazol bioisosteres are described herein.
- Stiff, Cory,Graber, David R.,Thorarensen, Atli,Wakefield, Brian D.,Marotti, Keith R.,Melchior, Earline P.,Sweeney, Michael T.,Han, Fusen,Rohrer, Douglas C.,Zurenko, Gary E.,Romero, Donna L.
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scheme or table
p. 6293 - 6297
(2009/07/18)
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- Hypolipidemic Activity of Phthalimide Derivatives. 7. Structure-Activity Studies of Indazolone Analogues
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The apparent benefit of limiting serum cholesterol and triglyceride levels either by dietary restriction or drug therapy has prompted work in our laboratories toward development of a suitable antihyperlipidemic agent.We have demonstrated the antihyperlipi
- Wyrick, Steven D.,Voorstad, P. Josee,Cocolas, George,Hall, Iris H.
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p. 768 - 772
(2007/10/02)
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