- Rational design of 4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition
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Indoleamine 2,3-dioxygenase 1 (IDO1) is an important therapeutic target for the treatment of diseases such as cancer that involve pathological immune escape. Starting from the scaffold of our previously discovered IDO1 inhibitor 4-phenyl-1,2,3-triazole, we used computational structure-based methods to design more potent ligands. This approach yielded highly efficient low molecular weight inhibitors, the most active being of nanomolar potency both in an enzymatic and in a cellular assay, while showing no cellular toxicity and a high selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO). A quantitative structure-activity relationship based on the electrostatic ligand-protein interactions in the docked binding modes and on the quantum chemically derived charges of the triazole ring demonstrated a good explanatory power for the observed activities.
- R?hrig, Ute F.,Majjigapu, Somi Reddy,Grosdidier, Aurélien,Bron, Sylvian,Stroobant, Vincent,Pilotte, Luc,Colau, Didier,Vogel, Pierre,Van Den Eynde, Beno?t J.,Zoete, Vincent,Michielin, Olivier
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experimental part
p. 5270 - 5290
(2012/08/28)
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- NOVEL HETEROCYCLIC AMIDE DERIVATIVES HAVING DIHYDROOROTATE DEHYDROGENASE INHIBITING ACTIVITY
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Novel heterocyclic amide derivatives having pharmacological effects, that is, compounds represented by the general formula (1) or salts thereof: (1) wherein X1-X2 is S-CH2 or the like; R1 is alkyl or the like; p is 0 to 7; R2 is hydrogen, alkyl, or the like; R3 is hydrogen, alkyl, or the like; Y1-Y2 is CH=CH or the like; R4 is halogeno, alkyl, or the like; q is 0 to 4; and R5 is halogeno, hydrogen, alkyl, or the like.
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Page/Page column 60
(2010/10/20)
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- Formation of new alkynyl(phenyl)iodonium salts and their use in the synthesis of phenylsulfonyl indenes and acetylenes http://www.mdpi.org
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The preparation of phenylsulfonyl indene derivatives and phenylsulfonyl-acetylenes from readily available alkynyl(phenyl)iodonium tetrafluoroborates and triflates was investigated using phenylsulfinate as nucleophile.
- Koumbis, Alexandros E.,Kyzas, Christos M.,Savva, Antri,Varvoglis, Anastasios
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p. 1340 - 1350
(2007/10/03)
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