- Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: Concurrent optimization of enzyme inhibitor potency and selectivity
-
The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki 100-fold selective) inhibitors. The iterative inhibitor design and evaluation with assistance of the selectivity screen served to differentiate otherwise indistinguishable inhibitors permitting the simultaneous optimization of potency and selectivity. Significantly, the simultaneous assessment of all potential competitive enzymes with the selectivity screen does not require the use of expressed or purified enzymes or a competitive substrate, no modification of the inhibitors is required, and the relative potency for competitive enzymes can be quantified (IC50's) including those that lack known substrates or function.
- Leung, Donmienne,Du, Wu,Hardouin, Christophe,Cheng, Heng,Hwang, Inkyu,Cravatt, Benjamin F.,Boger, Dale L.
-
-
Read Online
- Oxidation of sp3C—H bonds in N-alkylhydrazides: Access to 2,5-disubstituted 1,3,4-oxadiazole derivatives
-
The oxidation of sp3C[sbnd]H bonds in N-alkylhydrazides was achieved en route to the efficient synthesis of a broad series of 1,3,4-oxadiazoles. Mechanistic studies have revealed that N-acylhydrazone is a key intermediate in this catalytic transformation.
- Zhang, Liang,Zhao, Xiaolong,Jing, Xiaobi,Zhang, Xuewen,Lü, Shiwei,Luo, Liangliang,Jia, Xiaodong
-
supporting information
p. 5669 - 5672
(2016/11/29)
-
- C-H carboxylation of heteroarenes with ambient CO2
-
The C-H carboxylation of heteroarenes was achieved under transition metal-free reaction conditions with naturally abundant CO2 as the C1 source at relatively low temperature. The C-H carboxylation was mediated by KOt-Bu at atmospheric pressure
- Fenner, Sabine,Ackermann, Lutz
-
supporting information
p. 3804 - 3807
(2016/07/07)
-
- Hydroxamic Acids as Potent Inhibitors of FeII and MnII E. coli Methionine Aminopeptidase: Biological Activities and X-ray Structures of Oxazole Hydroxamate-EcMetAP-Mn Complexes
-
New series of acids and hydroxamic acids linked to five-membered heterocycles including furan, oxazole, 1,2,4- or 1,3,4-oxadiazole, and imidazole were synthesized and tested as inhibitors against the FeII, CoII, and MnII f
- Huguet, Florian,Melet, Armelle,Alves de Sousa, Rodolphe,Lieutaud, Aurelie,Chevalier, Jacqueline,Maigre, Laure,Deschamps, Patrick,Tomas, Alain,Leulliot, Nicolas,Pages, Jean-Marie,Artaud, Isabelle
-
scheme or table
p. 1020 - 1030
(2012/07/31)
-
- OXADIAZOLE KETONE INHIBITORS OF FATTY ACID AMIDE HYDROLASE
-
Certain oxadiazole ketone compounds are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity.
- -
-
Page/Page column 25
(2010/11/08)
-