TY  - JOUR
AU  - Orgován, Zoltán
AU  - Ferenczy, György
AU  - Steinbrecher, Thomas
AU  - Szilágyi, Bence
AU  - Bajusz, Dávid
AU  - Keserű, György Miklós
TI  - Validation of tautomeric and protomeric binding modes by free energy calculations. A case study for the structure based optimization of d-amino acid oxidase inhibitors
JF  - JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
J2  - J COMPUT AID MOL DES
VL  - 32
PY  - 2018
IS  - 2
SP  - 331
EP  - 345
PG  - 15
SN  - 0920-654X
DO  - 10.1007/s10822-018-0097-y
UR  - https://m2.mtmt.hu/api/publication/3333356
ID  - 3333356
N1  - Megjegyzés-27191071
N1 Funding details: K111862, AHF, American Hungarian Foundation
N1 Funding text: Program (project KTIA NAP_13) and by the Hungarian Science Foundation OTKA (project K111862) is gratefully acknowledged.
Megjegyzés-27191022
N1 Funding details: K111862, AHF, American Hungarian Foundation
N1 Funding text: Program (project KTIA NAP_13) and by the Hungarian Science Foundation OTKA (project K111862) is gratefully acknowledged.
Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, Budapest, 1117, Hungary            
            Schrödinger GmbH, Dynamostr. 13, Mannheim, 68165, Germany            
            Cited By :7            
            Export Date: 6 September 2021            
            CODEN: JCADE            
            Correspondence Address: Keserű, G.M.; Medicinal Chemistry Research Group, Magyar tudósok krt. 2, Hungary; email: gy.keseru@ttk.mta.hu
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Szilágyi, Bence
AU  - Kovacs, P
AU  - Ferenczy, György
AU  - Rácz, Anita
AU  - Németh, Krisztina
AU  - Benéné Visy, Júlia
AU  - Szabó, Pál Tamás
AU  - Ilas, J
AU  - Balogh, György Tibor
AU  - Monostory, Katalin
AU  - Vincze, István
AU  - Tábi, Tamás
AU  - Szökő, Éva
AU  - Keserű, György Miklós
TI  - Discovery of isatin and 1H-indazol-3-ol derivatives as d-amino acid oxidase (DAAO) inhibitors
JF  - BIOORGANIC & MEDICINAL CHEMISTRY
J2  - BIOORGAN MED CHEM
VL  - 26
ET  - 0
PY  - 2018
IS  - 8
SP  - 1579
EP  - 1587
PG  - 9
SN  - 0968-0896
DO  - 10.1016/j.bmc.2018.02.004
UR  - https://m2.mtmt.hu/api/publication/3344151
ID  - 3344151
N1  - Megjegyzés-27393542
N1 Funding details: KTIA NAP_13
N1 Funding text: This study was supported by the National Brain Research Program grant (project KTIA NAP_13). Celesztina Domonkos is acknowledged for help in biological measurements, Katalin Tóth and Máté Déri for performing in vitro pharmacokinetic studies and Judit Müller for the performing PAMPA tests. A
AB  - 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.
LA  - English
DB  - MTMT
ER  -