Synthesis and structure-activity relationship of ribofuranosyl echiguanine analogs as inhibitors of phosphatidylinositol 4-kinase

Add time:07/15/2019    Source:sciencedirect.com

N-Substituted-2-amino-4(3H)-7H-oxopyrrolo[2,3-d]pyrimidine-5-carboxamides and their ribofuranosyl and 2′,3′-dideoxyribofuranosyl derivatives were prepared as membrane permeable echiguanine analogs and tested for their ability to inhibit phosphatidylinositol (PI) 4-kinase. Compounds 5 and 6 were found to inhibit the enzyme approximately at the same level as echiguanines A and B. It is noteworthy that ribofuranosides 18, 19, and 20 and dideoxyribofuranoside 29 effectively inhibited PI 4-kinase. Thus, the terminal amide and related structures may be preferable for inhibition of the enzyme in echiguanine analogs with or without ribofuranoside.

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