- PHTHALAZINE AND PYRIDO [3,4-D] PYRIDAZ INE COMPOUNDS AS H1 RECEPTOR ANTAGONISTS
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The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various diseases, such as allergic rhinitis.
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Page/Page column 50
(2009/05/30)
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- Synthesis and use of sulfonamide-, sulfoxide-, or sulfone-containing aminoglycoside-CoA bisubstrates as mechanistic probes for aminoglycoside N-6′-acetyltransferase
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Aminoglycoside-coenzyme A conjugates are challenging synthetic targets because of the wealth of functional groups and high polarity of the starting materials. We previously reported a one-pot synthesis of amide-linked aminoglycoside-CoA bisubstrates. These molecules are nanomolar inhibitors of aminoglycoside N-6′-acetyltransferase Ii (AAC(6′)-Ii), an important enzyme involved in bacterial resistance to aminoglycoside antibiotics. We report here the synthesis and biological activity of five new aminoglycoside-CoA bisubstrates containing sulfonamide, sulfoxide, or sulfone groups. Interestingly, the sulfonamide-linked bisubstrate, which was expected to best mimic the tetrahedral intermediate, does not show improved inhibition when compared with amide-linked bisubstrates. On the other hand, most of the sulfone- and sulfoxide-containing bisubstrates prepared are nanomolar inhibitors of AAC(6′)-Ii.
- Gao, Feng,Yan, Xuxu,Zahr, Omar,Larsen, Aaron,Vong, Kenward,Auclair, Karine
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supporting information; experimental part
p. 5518 - 5522
(2009/05/30)
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