- Structure-based design, synthesis and evaluation of 2,4-diaminopyrimidine derivatives as novel caspase-1 inhibitors
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Interleukin-1β converting enzyme contributes in various inflammatory and autoimmune diseases by maturing pro-inflammatory cytokines IL-1β, IL-18 and IL-33. Therefore, inhibition caspase-1 may provide a potential therapeutic strategy for the treatment of chronic inflammatory diseases. Here we have reported structure-based design, synthesis and biological evaluation of 2,4-diaminopyrimidine derivatives (6a-6w) as potential caspase-1 inhibitors. Six compounds 6m, 6n, 6o, 6p, 6q and 6r showed significant enzymatic inhibition with IC5 0 ranging from 0.022 to 0.078 μM. These compounds also displayed excellent cellular potency at sub-micromolar concentration. Moreover, molecular docking studies provided the useful binding insights specific for caspase-1 inhibition. All these results indicated that compounds 6m, 6n and 6o could be potential leads for the development of newer caspase-1 inhibitors as anti-inflammatory agents.
- Patel, Shivani,Modi, Palmi,Ranjan, Vishal,Chhabria, Mahesh
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p. 258 - 268
(2018/04/05)
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- Reaction of N-aryl-3-oxobutanethioamides with bis(guanidinium) carbonate
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Reactions of N-aryl-3-oxobutanethioamides with bis(guanidinium) carbonate lead to the formation of N-aryl-3-guanidinobut-2-enethioamides, 4-arylamino-6-methylpyrimidin-2-amines, guanidinium acetate, and arylamines, depending on the temperature conditions.
- Britsun,Borisevich,Lozinskii
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p. 907 - 910
(2008/02/08)
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