- 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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- TRIAZOLONES DERIVATIVES FOR USE IN THE TREATMENT, AMELIORATION OR PREVENTION OF A VIRAL DISEASE
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The present invention relates to a compound having the general formula (I), optionally in the form of a pharmaceutically acceptable salt, solvate, polymorph, prodrug, tautomer, racemate, codrug, cocrystal, enantiomer, or diastereomer or mixture thereof, which is useful in treating, ameloriating or preventing a viral disease. Furthermore, specific combination therapies are disclosed.
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Page/Page column 54; 55
(2017/04/18)
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- ISOINDOLINONE COMPOUNDS AS GPR119 MODULATORS FOR THE TREATMENT OF DIABETES, OBESITY, DYSLIPIDEMIA AND RELATED DISORDERS
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The present invention relates to isoindolinone compounds. The isoindolinone compounds are GPR119 modulators and useful for the prevention and/or treatment of diabetes, obesity, dyslipidemia and related disorders. The invention furthermore relates to the u
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Page/Page column 75; 76
(2015/11/02)
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- PHARMACEUTICALS CONTAINING NOVEL 1-POSITION SUBSTITUTED INDAZOLE DERIVATIVE
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PROBLEM TO BE SOLVED: To provide pharmaceuticals containing a compound having strong effect of modulating α7 nicotinic acetylcholine receptor (α7nAChR) and useful as treatment agent for diseases related to cholinergic in central nervous system (CNS) and/o
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Paragraph 0121
(2016/10/09)
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- NOVEL 1-SUBSTITUTED INDAZOLE DERIVATIVE
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A medicament for treating diseases associated with cholinergic properties in the central nervous system (CNS) and/or peripheral nervous system (PNS), diseases associated with smooth muscle contraction, endocrine disorders, neurodegenerative disorders and
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Paragraph 0228-0230
(2014/05/08)
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- COMPOUNDS FOR THE TREATMENT OF INFLAMMATORY DISORDERS
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This invention relates to compounds of the Formula (I): (Chemical formula should be inserted here as it appears on abstract in paper form) (I) or a pharmaceutically acceptable salt, solvate or isomer thereof, which can be useful for the treatment of diseases or conditions mediated by MMPs, ADAMs, TACE, aggrecanase, TNF- or combinations thereof.
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Page/Page column 109-110
(2010/06/11)
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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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- NEW CONVENIENT METHODS FOR THE SYNTHESIS OF 1,2-DIHYDRO-3H-INDAZOL-3-ONE AND ITS 1-ACYL DERIVATIVES
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The acid hydrolysis of the readily obtainable 3-(o-carboxyphenyl)sydnones (6a-d) afforded 3-indazolones (3a-d) in yields over 90 percent. By transacylation between 1-acyl-3-acyloxyindazoles (11a-d) and 3-indazolones (3a, c), the corresponding 1-acyl-3-indazolones 10a-d resulted in pure state and yields also over 90 percent.
- Dumitrascu, Florea,Plaveti, Marieta,Raileanu, Dan
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p. 917 - 924
(2007/10/03)
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- The Structure of Indazolinone and Derivatives in the Solid State and in Solution: an X-Ray and Nuclear Magnetic Resonance Study
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The structure of indazolinone and some of its derivatives was obtained by the combined use of crystallography, 13C CP/MAS, and 15N n.m.r.It was concluded that indazolinone exists as such in the solid state but only as a minor tautomer (15percent) in DMSO solution, where the 3-hydroxyindazole tautomer predominates (85percent).The result of bromination of indazolinone is reported.Two acylhydrazines, as open analogues of indazolinone, were studied as model compounds.
- Ballesteros, Paloma,Elguero, Jose,Claramunt, Rosa Maria,Faure, Robert,Foces-Foces, Ma de la Concepcion,et al.
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p. 1677 - 1682
(2007/10/02)
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